Long-term clinical outcomes and cost-effectiveness of catheter vs thoracoscopic surgical ablation in long-standing persistent atrial fibrillation using continuous cardiac monitoring: CASA-AF randomized controlled trial.

BACKGROUND: Long-term clinical outcomes of catheter ablation (CA) compared to thoracoscopic surgical ablation (SA) to treat patients with long-standing persistent atrial fibrillation (LSPAF) are not known. OBJECTIVE: The purpose of this study was to compare the long-term (36-month) clinical efficacy, quality of life, and cost-effectiveness of SA and CA in LSPAF. METHODS: Participants were followed up for 3 years using implantable loop recorders and questionnaires to assess the change in quality of life. Intention-to-treat analyses were used to report the findings. RESULTS: Of the 115 patients with LSPAF treated, 104 (90.4%) completed 36-month follow-up [CA: n = 57 (95%); SA: n = 47 (85%)]. After a single procedure without antiarrhythmic drugs, 7 patients (12%) in the CA arm and 5 (11%) in the SA arm [hazard ratio 1.22; 95% confidence interval (CI) 0.81-1.83; P = .41] were free from atrial fibrillation/tachycardia (AF/AT) ≥30 seconds at 36 months. Thirty-three patients (58%) in the CA arm and 26 (55%) in the SA arm (hazard ratio 1.04; 95% CI 0.57-1.88; P = .91) had their AF/AT burden reduced by ≥75%. The overall impact on health-related quality of life was similar, with mean quality-adjusted life year estimates of 2.45 (95% CI 2.31-2.59) for CA and 2.32 (95% CI 2.13-2.52) for SA. Estimated costs were higher for SA (mean £24,682; 95% CI £21,746-£27,618) than for CA (mean £18,002; 95% CI £15,422-£20,581). CONCLUSION: In symptomatic LSPAF, CA and SA were equally effective at achieving arrhythmia outcomes (freedom from AF/AT ≥30 seconds and ≥75% burden reduction) after a single procedure without antiarrhythmic drugs. However, SA is significantly more costly than CA. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04280042.

Left Atrial Function Predicts Atrial Arrhythmia Recurrence Following Ablation of Long-Standing Persistent Atrial Fibrillation.

BACKGROUND: Left atrial (LA) function following catheter or surgical ablation of de-novo long-standing persistent atrial fibrillation (AF) and its impact on AF recurrence was studied in patients participating in the CASA-AF trial (Catheter Ablation vs. Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation). METHODS: All patients underwent echocardiography preablation, 3 and 12 months post-ablation. LA structure and function were assessed by 2-dimensional volume and speckle tracking strain measurements of LA reservoir, conduit, and contractile strain. Left ventricular diastolic function was measured using transmitral Doppler filling velocities and myocardial tissue Doppler velocities to derive the e', E/e', and E/A ratios. Continuous rhythm monitoring was achieved using an implantable loop recorder. RESULTS: Eighty-three patients had echocardiographic data suitable for analysis. Their mean age was 63.6±9.7 years, 73.5% were male, had AF for 22.8±11.6 months, and had a mean LA maximum volume of 48.8±13.8 mL/m2. Thirty patients maintained sinus rhythm, and 53 developed AF recurrence. Ablation led to similar reductions in LA volumes at follow-up in both rhythm groups. However, higher LA emptying fraction (36.3±10.6% versus 27.9±9.9%; P<0.001), reservoir strain (22.6±8.5% versus 16.7±5.7%; P=0.001), and contractile strain (9.2±3.4% versus 5.6±2.5%; P<0.001) were noted in the sinus rhythm compared with AF recurrence group following ablation at 3 months. Diastolic function was better in the sinus rhythm compared with the AF recurrence group with an E/A ratio of 1.5±0.5 versus 2.2±1.2 (P<0.001) and left ventricular E/e' ratio of 8.0±2.1 versus 10.3±4.1 (P<0.001), respectively. LA contractile strain at 3 months was the only independent predictor of AF recurrence. CONCLUSIONS: Following ablation for long-standing persistent AF, improvement in LA function was greater in those who maintained sinus rhythm. LA contractile strain at 3 months was the most important determinant of AF recurrence following ablation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02755688.

The long-term outcomes of cardiac implantable electronic devices implanted via the femoral route.

BACKGROUND: Conventional superior access for cardiac implantable electronic devices (CIEDs) is not always possible and femoral CIEDs (F-CIED) are an alternative option when leadless systems are not suitable. The long-term outcomes and extraction experiences with F-CIEDs, in particular complex F-CIED (ICD/CRT devices), remain poorly understood. METHODS: Patients referred for F-CIEDs implantation between 2002 and 2019 at two tertiary centers were included. Early complications were defined as ≤30 days following implant and late complications >30 days. RESULTS: Thirty-one patients (66% male; age 56 ± 20 years; 35% [11] patients with congenital heart disease) were implanted with F-CIEDs (10 ICD/CRT and 21 pacemakers). Early complications were observed in 6.5% of patients: two lead displacements. Late complications at 6.8 ± 4.4 years occurred in 29.0% of patients. This was higher with complex F-CIED compared to simple F-CIED (60.0% vs. 14.3%, p = .02). Late complications were predominantly generator site related (n = 8, 25.8%) including seven infections/erosions and one generator migration. Eight femoral generators and 14 leads (median duration in situ seven [range 6-11] years) were extracted without complication. CONCLUSIONS: Procedural success with F-CIEDs is high with clinically acceptable early complication rates. There is a notable risk of late complications, particularly involving the generator site of complex devices following repeat femoral procedures. Extraction of chronic F-CIED in experienced centers is feasible and safe.

Follow the Lead: The Challenges of Cardiogenic Shock in Device-Related Infective Endocarditis.

We present the challenging case of a young man with congenital heart disease who survived severe device-related infective endocarditis and new pulmonary hypertension. He required prolonged mechanical circulatory support and had multiple significant complications. His case posed a management dilemma that was successfully resolved by effective multidisciplinary, tertiary center care. (Level of Difficulty: Beginner.).

Catheter ablation vs. thoracoscopic surgical ablation in long-standing persistent atrial fibrillation: CASA-AF randomized controlled trial.

AIMS: Long-standing persistent atrial fibrillation (LSPAF) is challenging to treat with suboptimal catheter ablation (CA) outcomes. Thoracoscopic surgical ablation (SA) has shown promising efficacy in atrial fibrillation (AF). This multicentre randomized controlled trial tested whether SA was superior to CA as the first interventional strategy in de novo LSPAF. METHODS AND RESULTS: We randomized 120 LSPAF patients to SA or CA. All patients underwent predetermined lesion sets and implantable loop recorder insertion. Primary outcome was single procedure freedom from AF/atrial tachycardia (AT) ≥30 s without anti-arrhythmic drugs at 12 months. Secondary outcomes included clinical success (≥75% reduction in AF/AT burden); procedure-related serious adverse events; changes in patients' symptoms and quality-of-life scores; and cost-effectiveness. At 12 months, freedom from AF/AT was recorded in 26% (14/54) of patients in SA vs. 28% (17/60) in the CA group [OR 1.128, 95% CI (0.46-2.83), P = 0.83]. Reduction in AF/AT burden ≥75% was recorded in 67% (36/54) vs. 77% (46/60) [OR 1.13, 95% CI (0.67-4.08), P = 0.3] in SA and CA groups, respectively. Procedure-related serious adverse events within 30 days of intervention were reported in 15% (8/55) of patients in SA vs. 10% (6/60) in CA, P = 0.46. One death was reported after SA. Improvements in AF symptoms were greater following CA. Over 12 months, SA was more expensive and provided fewer quality-adjusted life-years (QALYs) compared with CA (0.78 vs. 0.85, P = 0.02). CONCLUSION: Single procedure thoracoscopic SA is not superior to CA in treating LSPAF. Catheter ablation provided greater improvements in symptoms and accrued significantly more QALYs during follow-up than SA. CLINICAL TRIAL REGISTRATION: ISRCTN18250790 and ClinicalTrials.gov: NCT02755688.

Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF): study protocol for a randomised controlled trial.

BACKGROUND: Atrial fibrillation is the commonest arrhythmia which raises the risk of heart failure, thromboembolic stroke, morbidity and death. Pharmacological treatments of this condition are focused on heart rate control, rhythm control and reduction in risk of stroke. Selective ablation of cardiac tissues resulting in isolation of areas causing atrial fibrillation is another treatment strategy which can be delivered by two minimally invasive interventions: percutaneous catheter ablation and thoracoscopic surgical ablation. The main purpose of this trial is to compare the effectiveness and safety of these two interventions. METHODS/DESIGN: Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF) is a prospective, multi-centre, randomised controlled trial within three NHS tertiary cardiovascular centres specialising in treatment of atrial fibrillation. Eligible adults (n = 120) with symptomatic, long-standing, persistent atrial fibrillation will be randomly allocated to either catheter ablation or thoracoscopic ablation in a 1:1 ratio. Pre-determined lesion sets will be delivered in each treatment arm with confirmation of appropriate conduction block. All patients will have an implantable loop recorder (ILR) inserted subcutaneously immediately following ablation to enable continuous heart rhythm monitoring for at least 12 months. The devices will be programmed to detect episodes of atrial fibrillation and atrial tachycardia ≥ 30 s in duration. The patients will be followed for 12 months, completing appropriate clinical assessments and questionnaires every 3 months. The ILR data will be wirelessly transmitted daily and evaluated every month for the duration of the follow-up. The primary endpoint in the study is freedom from atrial fibrillation and atrial tachycardia at the end of the follow-up period. DISCUSSION: The CASA-AF Trial is a National Institute for Health Research-funded study that will provide first-class evidence on the comparative efficacy, safety and cost-effectiveness of thoracoscopic surgical ablation and conventional percutaneous catheter ablation for long-standing persistent atrial fibrillation. In addition, the results of the trial will provide information on the effects on patients' quality of life. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN18250790 . Registered on 24 April 2015.

Pacing in congenital heart disease - A four-decade experience in a single tertiary centre.

BACKGROUND: The increased risk of brady- and tachy-arrhythmias in the congenital heart disease (CHD) population means that cardiac rhythm management devices are often required at an early age and expose patients to device-related complications. The present study drew upon four decades of experience at a tertiary adult congenital heart disease ACHD center and aimed to investigate the indication for cardiac implantable electronic devices (CIEDs) and predictors of late device-related complication requiring re-intervention. METHODS: A retrospective review of pacing records of ACHD patients over forty years was carried out. The primary outcome measure was device related complication requiring re-intervention. RESULTS: Between 1970 and 2009, 238 structural CHD patients who received CIEDs with follow-up data were identified (structural group). As a comparator group, 98 patients with congenital conduction disease or long QT syndrome with a structurally normal heart (electrical group) were included in the study. During a mean follow-up of 9.6±8.5years, 72 (21%) patients (44 structural group, 28 electrical group) required ≥1 re-intervention due to device related complications. Multivariate analysis showed that age at the time of device implant was an independent predictor of late device-related complications (HR 0.77, 95% CI 0.60-0.98, p=0.04). Sub-analysis of the structural group showed that ACHD complexity (Bethesda guideline) was the only predictor late device-related complication in the structural group (HR 2.96, 95% CI: 1.67-5.26, p<0.01). CONCLUSION: Increasing age at device implant was inversely associated with late device-related complications. ACHD patients with complex anatomy are at increased risk of device-related complications at mid and long-term follow-up.

Outcomes and costs of left atrial appendage closure from randomized controlled trial and real-world experience relative to oral anticoagulation.

AIMS: The aim of this study was to analyse randomized controlled study and real-world outcomes of patients with non-valvular atrial fibrillation (NVAF) undergoing left atrial appendage closure (LAAC) with the Watchman device and to compare costs with available antithrombotic therapies. METHODS AND RESULTS: Registry data of LAAC from two centres were prospectively collected from 110 patients with NVAF at risk of stroke, suitable and unsuitable for long-term anticoagulation (age 71.3 ± 9.2 years, CHADS2 2.8 ± 1.2, CHA2DS2-VASc 4.5 ± 1.6, and HAS-BLED 3.8 ± 1.1). Outcomes from PROTECT AF and registry study LAAC were compared with warfarin, dabigatran, rivaroxaban, apixaban, aspirin, and no treatment using a network meta-analysis. Costs were estimated over a 10-year horizon. Uncertainty was assessed using sensitivity analyses. The procedural success rate was 92% (103/112). Follow-up was 24.1 ± 4.6 months, during which annual rates of stroke, major bleeding, and all-cause mortality were 0.9% (2/223 patient-years), 0.9% (2/223 patient-years), and 1.8% (4/223 patient-years), respectively. Anticoagulant therapy was successfully stopped in 91.2% (93/102) of implanted patients by 12 months. Registry study LAAC stroke and major bleeding rates were significantly lower than PROTECT AF results: mean absolute difference of stroke, 0.89% (P = 0.02) and major bleeding, 5.48% (P < 0.001). Left atrial appendage closure achieved cost parity between 4.9 years vs. dabigatran 110 mg and 8.4 years vs. warfarin. At 10 years, LAAC was cost-saving against all therapies (range £1162-£7194). CONCLUSION: Left atrial appendage closure in NVAF in a real-world setting may result in lower stroke and major bleeding rates than reported in LAAC clinical trials. Left atrial appendage closure in both settings achieves cost parity in a relatively short period of time and may offer substantial savings compared with current therapies. Savings are most pronounced among higher risk patients and those unsuitable for anticoagulation.

Outcomes of defibrillator therapy in catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by adrenergically induced ventricular arrhythmias in patients with structurally normal hearts. Initiating triggered arrhythmias, such as bidirectional ventricular tachycardia, often degenerate into reentrant arrhythmias, such as ventricular fibrillation (VF). OBJECTIVE: To determine whether the effectiveness of implantable cardioverter-defibrillator (ICD) shocks is dependent on rhythm type. METHODS: It is a retrospective study of patients with CPVT who had undergone ICD implantation. Thirteen patients received ICDs (median age 15 years; range 9-43 years): 7 of 13 (54%) for cardiac arrest and 6 of 13 (46%) for syncope despite drug therapy. The median follow-up duration was 4.0 years (range 1.7-19.9 years). Nineteen reinterventions occurred, excluding generator replacements. Ten patients received 96 shocks (median 4 shocks; range 1-30 shocks). Eighty-seven shock electrograms were reviewed. Sixty-three (72%) shocks were appropriate, and 24 (28%) were inappropriate (T-wave oversensing 7 [29%], supraventricular arrhythmia 16 [67%], after self-terminating VF 1 [4%]). RESULTS: Among appropriate shocks, 20 (32%) were effective in terminating sustained arrhythmia and 43 (68%) were ineffective. Shocks delivered to triggered arrhythmias nearly always failed (1 of 40 [3%] effective), while shocks delivered to VF were usually successful (19 of 23 [83%] effective; P < .001). Four patients received 17 appropriate antitachycardia pacing therapies for ventricular tachycardia: only 2 (12%) were effective. No patient died. CONCLUSIONS: The effectiveness of ICD shock therapy in CPVT depends on the mechanism of the rhythm treated. Shocks delivered to initiating triggered arrhythmias nearly always fail, whereas those for subsequent VF are usually effective. ICD programming in these patients is exceptionally challenging.

Clinical experience of entirely subcutaneous implantable cardioverter-defibrillators in children and adults: cause for caution.

AIMS: This paper describes our clinical experience of using an entirely subcutaneous implantable cardioverter-defibrillator (S-ICD) in children and adults. Maintaining lead integrity and long-term vascular access are critical challenges of ICD therapy, especially in younger patients. The S-ICD has considerable theoretical advantages in selected patients without pacing indications, particularly children and young adults. Although sensing in an S-ICD may be influenced by age, pathology, and posture, there are currently few published data on clinical sensing performance outside the setting of intra-operative testing or in younger patients. METHODS AND RESULTS: Patients were selected by a multi-disciplinary team on clinical grounds for S-ICD implantation from a broad population at risk of sudden arrhythmic death. Sixteen patients underwent implantation [median age 20 years (range 10-48 years)]. Twelve had primary electrical disease and four had congenital structural heart disease. There were no operative complications, and ventricular fibrillation (VF) induction testing was successful in all cases. During median follow-up of 9 months (range 3-15 months), three children required re-operation. Eighteen clinical shocks were delivered in six patients. Ten shocks in four patients were inappropriate due to T-wave over-sensing. Within the eight shocks for ventricular arrhythmia, three were delivered for VF, among which two had delays in detection with time to therapy of 24 and 27 s. CONCLUSION: The S-ICD is an important new option for some patients. However, these data give cause for caution in light of the limited published data regarding clinical sensing capabilities, particularly among younger patients.

Stem cell infusion into the vein of Marshall.

The vein of Marshall (VOM) and related cardiac ganglia have been clearly implicated in atrial fibrillation. Electrophysiological procedures have targeted these sites of autonomic innervation. However, targeting the exact sites has proven technically challenging. Identifying the VOM and infusing stem cells may ablate related ganglia autonomic function and offer an innovative treatment for atrial fibrillation.

C-type natriuretic peptide production by the human kidney is blunted in chronic heart failure.

CNP (C-type natriuretic peptide) is a vasodilatory peptide produced by vascular endothelium and the human heart with a short half-life. CNP has been identified within the human kidney; however, few results are available on whether the human kidney is a systemic source of CNP. The aim of the present study was to establish whether CNP is secreted by the human kidney and if synthesis is blunted in CHF (chronic heart failure). A total of 20 male subjects (age, 57+/-2 years; mean+/-S.E.M.) undergoing CHF assessment (n=13) or investigation of paroxysmal supraventricular arrhythmia (normal left ventricular function in sinus rhythm during procedure) (n=7) were recruited. Renal CNP production was determined from concomitant plasma concentrations in the aorta and renal vein. When considering all subjects, a significant step-up in plasma CNP was found from the aorta to renal vein (3.0+/-0.3 compared with 8.3+/-2.4 pg/ml respectively; P=0.0045). The mean increase in CNP was 5.3+/-2.4 pg/ml (range, -0.9 to +45.3 pg/ml). In patients with CHF, the aortic concentration was 3.3+/-0.4 pg/ml compared with a renal vein concentration of 4.3+/-0.6 pg/ml (P=0.11). In those with normal left ventricular function, the respective values were 2.5+/-0.5 and 15.7+/-6.0 pg/ml (P=0.01). In conclusion, CNP is synthesized and secreted into the circulation by the normal human kidney, where it may have paracrine actions. Net renal secretion of CNP appears to be blunted in patients with CHF.

Paced ventricular electrogram fractionation predicts sudden cardiac death in hypertrophic cardiomyopathy.

AIMS: Paced electrogram fractionation analysis (PEFA) has been assessed for the prediction of sudden cardiac death (SCD) in a large-scale, prospective study of patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: We determined the positive predictive value (PPV) of PEFA in relation to other risk factors for SCD and outcomes in 179 patients with HCM and no prior history of cardiac arrest. Patients were followed over a mean 4.3 years (range: 1.1-6.3 years). Thirteen patients had SCD-equivalent events: four of these patients died suddenly, three were resuscitated from ventricular fibrillation (VF), and six had implantable cardioverter-defibrillator (ICD) discharges in response to VF. PEFA identified nine of these patients and another 14 non-VF patients yielding a censored PPV of between 0.19 and 0.59 that was greater than the PPV that was the formal stopping point of the trial (0.18). Eighty per cent of patients were followed for 4 years or more. The PPV for the identification of SCD in this group was 0.38 (0.17-0.59). The use of two or more conventional markers to predict SCD identified five patients with SCD-equivalent events in the 4-year follow-up group and 42 other patients without events yielding a PPV of 0.106 (confidence limits 0.02-0.15). CONCLUSION: PEFA identifies HCM patients at risk of SCD with greater accuracy than non-invasive techniques and may have an important role in determining indications for ICD prescription.

Implantation of a biventricular implantable cardioverter defibrillator via the femoral vein.

Permanent pacing with access gained via the femoral vein has been described since 1980. Here we describe implantation of a biventricular implantable cardioverter defibrillator (ICD) in a case where normal implantation using thoracic venous access was not possible due to anatomical anomalies. The advantages of this technique over epicardial pacing in such a case are discussed, as are the practical difficulties involved when applying this technique to the implantation of a biventricular ICD.

Comparison of segmental and global markers of dyssynchrony in predicting clinical response to cardiac resynchronization.

AIMS: Cardiac resynchronization therapy (CRT) reduces inter- and intraventricular dyssynchrony and shortens total isovolumic time (t-IVT). We compared the extent to which the values of ventricular dyssynchrony and t-IVT predict clinical benefits of CRT. METHODS AND RESULTS: Ventricular dyssynchrony was assessed in 39 patients with heart failure before and 6 months after CRT. Segmental dyssynchrony was identified from time to onset and peak systolic velocity of wall motion. T-IVT (s/min) was derived as [60-(total ejection time+total filling time)]. The difference between ventricular pre-ejection periods (D-PEP) was calculated. Outcome measures were fall in New York Heart Association (NYHA) class and increase in cardiac output (CO). Following CRT, NYHA class fell in 29/39 patients, CO increased (by 1.0 L/min, P < 0.001), and intraventricular delay (Intra-VD), interventricular delay (Inter-VD), t-IVT, and D-PEP shortened (by 25 ms, 72 ms, 6 s/min, and 38 ms, P < 0.01). NYHA class and CO were unchanged with CRT in 10/39, and Intra-VD, Inter-VD, t-IVT, and D-PEP lengthened (by 43 ms, 52 ms, 7 s/min, and 35 ms, P < 0.05). Though univariate predictors of CO increment with CRT were Intra-VD, Inter-VD, t-IVT, and D-PEP, only pre-CRT values of CO (P < 0.001), t-IVT (P < 0.001), and D-PEP (P = 0.025) were independent. CONCLUSION: Global, rather than segmental, measures of ventricular dyssynchrony are powerful, independent predictors of clinical response to CRT.

Mechanism of cardiac output gain from cardiac resynchronization therapy in patients with coronary artery disease or idiopathic dilated cardiomyopathy.

The mechanisms underlying cardiac resynchronization therapy have consistently been studied at rest and remain ill defined. Peak stress total isovolumic time (t-IVT) is a major determinant of cardiac output (CO) in chronic heart failure. In this study, pharmacologic stress was used to assess the effects of atrioventricular (AV) delay shortening and ventricular resynchronization elements of cardiac resynchronization therapy. Thirty patients undergoing cardiac resynchronization therapy were studied <6 months after implantation. t-IVT and CO were measured during native activation (left bundle branch block), AV delay shortening (right ventricular dual-chamber pacing), and full resynchronization (atrio-biventricular pacing). Full resynchronization shortened peak stress t-IVT by 9.4 +/- 6.2 s/min (p <0.001) and increased peak stress CO by 0.9 +/- 0.4 L/min (p <0.001), with the effects in individual patients showing a large correlation (r = -0.64, p <0.001). In contrast, simple AV delay shortening did not shorten peak stress t-IVT nor increase peak stress CO, nor was CO at rest affected by full resynchronization or AV delay shortening. Of all measurements during native activation, the best predictor of gain in peak stress CO from full resynchronization was peak stress t-IVT (r = 0.75, p <0.001), with every 5 s/min increment in peak stress t-IVT during native activation predicting a 6% gain in peak stress CO. No conventional measures during native activation at rest or during stress (including QRS duration, the Tei index, tissue Doppler intraventricular delay, and t-IVT at rest) added significant additional information. In conclusion, only during stress does resynchronization consistently increase CO. Second, little of this increment in CO is achieved by AV delay shortening alone. Third, under native activation, long t-IVT during peak stress is the single best predictor of resynchronization-mediated increment in peak stress CO.

Late recurrence of outflow tract obstruction seven years after septal ablation in hypertrophic cardiomyopathy.

We present a case of late recurrence of outflow tract obstruction 7 years after successful septal ablation in hypertrophic cardiomyopathy. In addition the debate over maximal versus minimal treatment is discussed.

Chronic heart failure patients with restrictive LV filling pattern have significantly less benefit from cardiac resynchronization therapy than patients with late LV filling pattern.

BACKGROUND: Cardiac resynchronization fails to improve symptoms in up to one third of patients meeting criteria for this treatment, for reasons which are unclear. Indeed, the very mechanism of benefit from resynchronization is controversial. Resynchronization may work by improving ventricular filling: we tested the hypothesis that benefit from resynchronization depends on filling pattern. METHODS AND RESULTS: We assessed symptoms (NYHA class) and LV filling of 40 patients with chronic heart failure and prolonged QRS who underwent resynchronization. Fifteen had restrictive filling pattern (E velocity>or=1.0 m/s, E/A ratio>1 and E wave deceleration time