A new simplified electrocardiographic score predicts clinical outcome in patients treated with CRT.

Aims: Cardiac Resynchronization Therapy (CRT) reduces morbidity and mortality for patients with heart failure and wide QRS complex, but up to 1/3 of patients are "non-responders" to the therapy. This study examines the ability of a simple standard electrocardiogram (ECG)-based scoring system to predict clinical outcome. Methods and results: Four hundred and ninety-one consecutive patients with CRT-implants (79% males, mean age 71 years, LVEF 24%, 59% with ischemic cardiomyopathy, 83% in NYHA class III) were included from a single large volume centre. All patients met standard indications for CRT, and were followed for 3 years after CRT implantation. Three ECG parameters were measured on the post-implant ECG, and compared to pre-implantation measurements: QRS duration, time to intrinsicoid deflection onset (ID) in V1 lead, amplitude change in V1 lead. Each positive ECG variable was given a numerical value of 1 to create the score (ranging 0-3). Clinical outcome was assessed as a composite of all-cause death, left ventricular assist device implantation, cardiac transplantation and HF hospitalization. Event-free survival was predicted by shortening of QRS duration ≥20 ms (HR 0.66 [95% CI 0.48-0.90] P = 0.009), ≥50% decreased summed R + S amplitude in V1 lead (HR 0.67 [0.49-0.90] P = 0.009) and ≤40 msec ID time in lead V1 during pacing (HR 0.63 [0.46-0.86] P = 0.004). The total score was an independent predictor for both event-free survival (HR 0.65 [0.54-0.77] P < 0.001) and for ≥10% left ventricular ejection fraction improvement (OR 1.7 [1.3-2.3] P < 0.001). Conclusions: Composite data from 12-lead ECG during CRT-treatment can be used in a simple score to predict long-term clinical outcome.

Impact of CT-apelin and NT-proBNP on identifying non-responders to cardiac resynchronization therapy.

CONTEXT: Assessment of response to cardiac resynchronization therapy (CRT) is essential. OBJECTIVE: To assess the predictive value of CT-apelin together with NT-proBNP in patients undergoing CRT. METHODS: Serum CT-apelin and NT-proBNP were measured by ELISA before, and six months after CRT. Primary endpoint was non-response (<4% increase in LVEF) after six months. RESULTS: From 81 patients, 15 proved to be non-responders. Six-month CT-apelin was superior compared to NT-proBNP in identifying non-responders by multivariate ROC (CT-apelin: p = 0.01, NT-proBNP: p = 0.13) and by logistic regression (CT-apelin: p = 0.01, NT-proBNP: p = 0.41) analyses. CONCLUSION: Six-month CT-apelin might be a valuable novel biomarker in identifying non-responders to CRT that was superior to NT-proBNP.

T-wave area as biomarker of clinical response to cardiac resynchronization therapy.

AIMS: There is increasing evidence that left bundle branch block (LBBB) morphology on the electrocardiogram is a positive predictor for response to cardiac resynchronization therapy (CRT). We previously demonstrated that the vectorcardiography (VCG)-derived T-wave area predicts echocardiographic CRT response in LBBB patients. In the present study, we investigate whether the T-wave area also predicts long-term clinical outcome to CRT. METHODS AND RESULTS: This is a retrospective study consisting of 335 CRT recipients. Primary endpoint were the composite of heart failure (HF) hospitalization, heart transplantation, left ventricular assist device implantation or death during a 3-year follow-up period. HF hospitalization and death alone were secondary endpoints. The patient subgroup with a large T-wave area and LBBB 36% reached the primary endpoint, which was considerably less (P < 0.01) than for patients with LBBB and a small T-wave area or non-LBBB patients with a small or large T-wave area (48, 57, and 51%, respectively). Similar differences were observed for the secondary endpoints, HF hospitalization (31 vs. 51, 51, and 38%, respectively, P < 0.01) and death (19 vs. 42, 34, and 42%, respectively, P < 0.01). In multivariate analysis, a large T-wave area and LBBB were the only independent predictors of the combined endpoint besides high creatinine levels and use of diuretics. CONCLUSION: T-wave area may be useful as an additional biomarker to stratify CRT candidates and improve selection of those most likely to benefit from CRT. A large T-wave area may derive its predictive value from reflecting good intrinsic myocardial properties and a substrate for CRT.

T-wave area predicts response to cardiac resynchronization therapy in patients with left bundle branch block.

INTRODUCTION: Chronic heart failure patients with a left ventricular (LV) conduction delay, mostly due to left bundle branch block (LBBB), generally derive benefit from cardiac resynchronization therapy (CRT). However, 30-50% of patients do not show a clear response to CRT. We investigated whether T-wave analysis of the ECG can improve patient selection. METHODS AND RESULTS: The study population comprised 244 CRT recipients with baseline 12-lead electrocardiogram recordings. Echocardiographic response after 6-month CRT was defined as a ≥5% increase in LV ejection fraction (LVEF). Vectorcardiograms (VCGs) were constructed from the measured 12-lead ECGs using an adapted Kors algorithm on digitized ECGs. Logistic regression models indicated repolarization variables as good predictors of CRT response. The VCG-derived T-wave area predicted CRT response (odds ratio [OR] per 10 µVs increase 1.172 [P < 0.001]) even better than QRS-wave area (OR = 1.116 [P = 0.001]). T-wave area had especially predictive value in the LBBB patient group (OR = 2.77 in LBBB vs. 1.09 in non-LBBB). This predictive value persisted after adjustment of multiple covariates, such as gender, ischemia, age, hypertension, coronary artery bypass graft, and the usage of diuretics and ß-blockers. In LBBB patients, the increase in LVEF was 6.1 ± 9.7% and 11.3 ± 9.1% in patients with T-wave area below and above the median value, respectively (P < 0.01). CONCLUSION: In patients with LBBB morphology of the QRS complex, a larger baseline T-wave area is an important independent predictor of LVEF increase following CRT.

High-volume lesions using a new second-generation open irrigation radiofrequency catheter are associated with the development of inhomogeneous lesions.

BACKGROUND: After catheter ablation there is often a discrepancy between acute and chronic success rates. We aimed to evaluate major determinants for lesion quality and understand different manifestations of lesion structures. METHODS: In a canine thigh muscle model radiofrequency (RF) current was delivered for 60 seconds at 30 W (n = 39) or 50 W (n = 18) with 15-g contact force. A second-generation 12-hole gold open irrigation catheter (SGIT) and a first-generation six-hole platinum-iridium catheter (FGIT; Biotronik, Berlin, Germany) were used. Electrode and tissue temperatures (at the surface and 3.5-mm and 7-mm depth) were recorded and lesion dimensions were measured. Lesions with steam pops were excluded. Histological examination was performed to evaluate homogeneity of the lesions. Inhomogeneity was defined as a visual multiband lesion pattern indicating different histological characteristics. RESULTS: In total 57 lesions were created. Seventeen lesions were excluded (steam pops) and 40 lesions were analyzed. A total number of 11 homogeneous and 29 inhomogeneous lesions were identified. Using the SGIT catheter 16.7% of the lesions was homogeneous and 83.3% inhomogeneous; for FGIT it was 43.8% and 56.2% (P = 0.065), respectively. Homogeneous lesions had lower volumes as compared to inhomogeneous lesions (514.0 ± 198.8 vs 914.8 ± 399.1 mm, P = 0.003). Multiple logistic regression analysis indicated that the SGIT catheter is a significant predictor for inhomogeneous lesions (odds ratio 6.5, 95% confidence interval 1.1-38.8; P = 0.040) independent from power setting and flow rate. CONCLUSIONS: The development of inhomogeneous lesions after acute RF ablation is associated with higher lesion volumes and the use of the second-generation irrigation gold-tip catheter.

Radiofrequency ablation at low irrigation flow rates using a novel 12-hole gold open-irrigation catheter.

BACKGROUND: High irrigation rates during radiofrequency (RF) ablation may cause fluid overload and limit lesion size. This in vivo animal study assessed the safety and efficacy of RF ablation at low irrigation rates using a novel 12-hole gold catheter. METHODS: A total of 103 lesions, created on the thigh of five mongrel dogs, were analyzed. Lesions were created using a 12-hole irrigated gold-tip (Au) and a six-hole irrigated platinum-iridium (PtIr) catheter (both 7F/3.5-mm electrode; BIOTRONIK SE & CO, KG, Berlin, Germany) in parallel and perpendicular orientation. RF current was delivered for 60 seconds at 30 W using 8 mL/min and 15 mL/min irrigation. Electrode temperature, steam pops, lesion dimensions, and coagulum formation were recorded. RESULTS: Electrode temperatures were lower for Au compared to PtIr in parallel (8 mL/min: 38.1 ± 1.7°C vs 48.0 ± 4.8°C, P < 0.0001; 15 mL/min: 36.0 ± 1.5°C vs 46.9 ± 5.4°C, P < 0.0001) and perpendicular position (15 mL/min: 35.5 ± 1.2°C vs 38.4 ± 2.5°C, P = 0.003). The number of steam pops between Au and PtIr was comparable for parallel (8 mL/min: 14% vs 27%, P = 0.65; 15 mL/min: 14% vs 43%, P = 0.21) and perpendicular orientation (8 mL/min: 25% vs 17%, P = 1.00; 15 mL/min: 18% vs 0%, P = 0.48). Au created larger volumes than PtIr at 8 mL/min irrigation (861 ± 251 mm(3) vs 504 ± 212 mm(3) , P = 0.004); however, for 15 mL/min, volumes were comparable (624 ± 269 mm(3) vs 768 ± 466 mm(3) , P = 0.46). No coagulum formation was observed for any of the catheters on the surface and catheter tip. CONCLUSION: RF ablation at low flow rate using a novel 12-hole irrigation Au catheter is safe and results in larger lesions than with a PtIr electrode.

The role of ablation of the atrioventricular junction in patients with heart failure and atrial fibrillation.

Ablation of the atrioventricular junction (AVJ) is a technically easy procedure that is safe and has a high success rate as an intervention for effective ventricular rate control in patients in symptomatic atrial fibrillation. AVJ ablation has been reported to improve quality of life, left ventricular ejection fraction, and exercise duration in these patients and minimize the incidence of inappropriate shocks. Because right ventricular pacing after AVJ ablation may result in decrease in left ventricular function and worsening of heart failure symptoms, there is increasing evidence to support the effectiveness of cardiac resynchronization therapy in atrial fibrillation populations.

Anemia and its association with clinical outcome in heart failure patients undergoing cardiac resynchronization therapy.

PURPOSE: Although a substantial proportion of patients with heart failure (HF) have anemia, there is a paucity of data evaluating the impact of anemia on clinical outcome in CRT patients. Our goal was to examine the ability of baseline hemoglobin (Hb) level and change in Hb level over time to predict clinical 2-year outcome and echocardiographic response to CRT. METHODS: Three hundred consecutive CRT patients (median 72 years [interquartile range (IQR) 16 years], 19% female) with baseline and follow-up hematological profiles available were examined. Baseline anemia was defined as Hb <12 g/dL in women and <13 g/dL in men, and patients were grouped into equal quartiles based on change in Hb. Two-year clinical outcome was determined using a composite endpoint that included HF hospitalization, left ventricular assist device (LVAD) placement, heart transplantation, and all-cause mortality. Echocardiographic reverse remodeling was examined at 6-month follow-up. RESULTS: One hundred fifty-one anemic patients were compared to 149 non-anemic patients. Changes in left ventricular dimensions and ejection fraction were similar for both groups. Univariate predictors of 2-year clinical outcome included baseline creatinine level, diuretic usage, and anemia; in multivariable regression, baseline anemia was an independent predictor for outcome (hazard ratio [HR] 1.79, 95% confidence interval [CI] [1.22-2.63], p = 0.003). The quartile with the most negative change in Hb concentration over time (≤-1.00 g/dL) had poorer event-free 2-year survival (HR 1.84, CI [1.13-3.00], p = 0.014). CONCLUSIONS: Baseline anemia and early postimplantation decline in Hb levels are associated with a worse 2-year prognosis in CRT patients, even though the magnitude of left ventricular reverse remodeling is similar compared to non-anemic patients.

Usefulness of hyponatremia as a predictor for adverse events in patients with heart failure receiving cardiac resynchronization therapy.

Hyponatremia portends a poor prognosis in patients with heart failure (HF). The aim of this study was to evaluate prognostic implication of hyponatremia on adverse events in patients with HF receiving cardiac resynchronization therapy (CRT). Additionally, the impact of improvement of hyponatremia after CRT device implantation was also evaluated. In this retrospective analysis, we included patients in whom a CRT device was implanted between April 2004 and April 2010 at our institution and had a baseline sodium level obtained within 72 hours of implantation. The patients were followed up for 3 years after implantation for subsequent primary composite end points, that is, hospitalization for HF, left ventricular assist device or heart transplant, and all-cause death. Sodium levels were followed up at 3 to 6 months after device implantation. Hyponatremia was defined as a serum sodium level of <135 mmol/L. A total of 402 patients were included (age 68.7 ± 12.3 years, women 20.9%). One hundred seventy-nine adverse events were noted in this period. In a Cox proportional hazards univariate model, hyponatremia (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.113 to 2.131, p = 0.009), creatinine (HR 1.267, 95% CI 1.156 to 1.389, p <0.001), and diuretics (HR 2.652, 95% CI 1.401 to 5.019, p = 0.003) were associated with occurrence of the composite end point. A total of 57.9% of patients with hyponatremia at baseline had the composite end point compared with 40.7% of those with normal sodium concentration (p = 0.004). Kaplan-Meier curve showed that hyponatremic patients fared worse. Also, patients in whom hyponatremia resolved after CRT device implantation had lower incidence of the composite end point compared with patients who had normal pre-CRT sodium levels but developed hyponatremia later. In conclusion, baseline hyponatremia is associated with poor prognosis in patients with HF. CRT can resolve hyponatremia in some patients after device implantation. Patients with postimplantation hyponatremia (either newly developed or persistent from baseline) have a poor clinical outcome. Post-CRT improvement of hyponatremia is associated with improved clinical outcomes.

Long-term experience with coronary sinus side branch stenting to stabilize left ventricular electrode position.

BACKGROUND: Despite technical advancements, implantation of coronary sinus (CS) leads may be challenging, and dislocation remains a relevant clinical problem. OBJECTIVE: The aim of this study was to investigate the effectiveness, safety, and long-term outcome of stent implantation to anchor the lead to the wall of the CS side branch. METHODS: Stenting of a CS side branch was performed in 312 patients. The procedure was performed because of postoperative lead dislocation in 16 patients and because of an intraoperative unstable lead position or phrenic nerve stimulation in 296 cases. A bare metal coronary stent was introduced over a second guide wire in the same CS sheath. The stent was deposited 5-35 mm proximal to the most proximal electrode. Mechanical damage of the CS side branch or pericardial effusion was not observed owing to stenting. RESULTS: During follow-up (median 28.4, interquartile range 15-37, maximum 70 months), a clinically important increase in the left ventricular pacing threshold was found in four cases and reoperation was necessary in only two patients (0.6%). Phrenic nerve stimulation was observed in 18 instances, and repositioning with an ablation catheter was performed in seven cases. Impedance measurements did not suggest lead insulation failure. Three stented leads were extracted without complication after 3-49 months owing to infection, while four leads were extracted easily during heart transplantation after 7-27 months. CONCLUSION: Stent implantation to stabilize CS lead position seems to be an effective and safe procedure in prevention and treatment of CS lead dislocation in selected cases.

Chaperone-related immune dysfunction: an emergent property of distorted chaperone networks.

Molecular chaperones (heat shock proteins) are important components of cellular networks, such as protein-protein and gene regulatory networks. Chaperones participate in the folding of immunologically important proteins, presentation of antigens and activation of the immune system. Here, we propose that chaperone-related immune dysfunction might be more general than was previously thought. Mutations and polymorphism of chaperones and the regulators of their synthesis, heat shock factor-1, chaperone diseases, sick chaperones and chaperone overload might all affect (mostly impairing) immune responses.