Enzymatic pretreatment of low-grade oils for biodiesel production.

The alkaline process for making biodiesel (fatty acid methyl esters, or FAME) is highly efficient at the transesterification of glycerides. However, its performance is poor when it comes to using oil that contain significant amounts of free fatty acids (FFA). The traditional approach to such feedstocks is to employ acid catalysis, which is slow and requires a large excess of methanol, or to evaporate FFA and convert that in a separate process. An attractive option would be to convert the FFA in oil feedstocks to FAME, before introducing it into the alkaline process. The high selectivity of enzyme catalysis makes it a suitable basis for such a pretreatment process. In this work, we present a characterization of the pretreatment of high-FFA rapeseed oil using immobilized Candida antarctica lipase B (Novozym 435), focused on the impact of initial FFA and methanol concentration. Based on experimental results, we have identified limitations for the process in terms of FFA concentration in the feedstock and make suggestions for process operation. It was found that, using 5% catalyst and 4% methanol at 35°C, the FFA concentration could be reduced to 0.5% within an hour for feedstock containing up to 15% FFA. Further, the reaction was observed to be under kinetic control, in that the biocatalyst converts FFA (and FAME) at a much higher rate than glyceride substrates. There is thus, both a minimum and a maximum reaction time for the process to achieve the desired concentration of FFA. Finally, an assessment of process stability in a continuous packed bed system indicates that as much as 15 m(3) oil could potentially be pretreated by 1 kg of biocatalyst at the given process conditions.

Catheter ablation of a difficult accessory pathway guided by coronary sinus venography and 3D electroanatomical mapping.

A 38-year-old man with history of unsuccessful catheter ablation of paraseptal accessory pathway (AP) and cardiac arrest was referred for reablation. Coronary sinus (CS) venography and detailed three-dimensional electroanatomical mapping demonstrated a large diverticulum near the CS ostium. A single radiofrequency ablation at the neck of the diverticulum eliminated conduction in the AP completely.

Biventricular pacing preserves left ventricular performance in patients with high-grade atrio-ventricular block: a randomized comparison with DDD(R) pacing in 50 consecutive patients.

AIMS: We aimed to investigate whether biventricular (BiV) pacing minimizes left ventricular (LV) dyssynchrony and preserves LV ejection fraction (LVEF) as compared with standard dual-chamber DDD(R) pacing in consecutive patients with high-grade atrio-ventricular (AV) block. METHODS AND RESULTS: Fifty patients were randomized to DDD(R) pacing or BiV pacing. LVEF was measured using three-dimensional echocardiography. Tissue-Doppler imaging was used to quantify LV dyssynchrony in terms of number of segments with delayed longitudinal contraction (DLC). LVEF was not different between groups after 12 months (P = 0.18). In the DDD(R) group LVEF decreased significantly from 59.7(57.4-61.4)% at baseline to 57.2(52.1-60.6)% at 12 months of follow-up (P = 0.03), whereas LVEF remained unchanged in the BiV group [58.9(47.1-61.7)% at baseline vs. 60.1(55.2-63.3)% after 12 months (P = 0.15)]. Dyssynchrony was more prominent in the DDD(R) group than in the BiV group at baseline (2.2 +/- 2.2 vs. 1.4 +/- 1.3 segments with DLC per patient, P = 0.10); and at 12 month follow-up (1.8 +/- 1.9 vs. 0.8 +/- 0.9 segments with DLC per patient, P = 0.02). NT-proBNP was unchanged in the DDD(R) group during follow-up (122 +/- 178 pmol/L vs. 91 +/- 166 pmol/L, NS) but decreased significantly in the BiV-group (from 198 +/- 505 pmol/L to 86 +/- 95 pmol/L after 12 months, P = 0.02). CONCLUSION: BiV pacing minimizes LV dyssynchrony, preserves LV function, and reduces NT-proBNP in contrast to DDD(R) pacing in patients with high-grade AV block.

Sequential versus simultaneous biventricular resynchronization for severe heart failure: evaluation by tissue Doppler imaging.

BACKGROUND: Cardiac resynchronization therapy (CRT) by means of simultaneous biventricular pacing improves left ventricular systolic performance and synchrony in patients with heart failure and bundle-branch block. We used tissue tracking and 3D echocardiography to evaluate the impact of sequential CRT with individualized interventricular delay programming. METHODS AND RESULTS: Twenty consecutive patients with severe heart failure and left bundle-branch block were included. Tissue tracking and 3D echocardiography were carried out before and on the day after pacemaker implantation. Eleven different interventricular delays were examined in each patient. Patients were reexamined after 3 months. Simultaneous CRT immediately reduced the extent of myocardium displaying delayed longitudinal contraction (DLC) from 48.6+/-16% to 23.2+/-13% (P<0.01) and increased left ventricular ejection fraction percentage (LVEF%) from 22.4+/-6% to 29.7+/-5% (P<0.01). However, optimum sequential CRT caused a further reduction in the extent of DLC from 23.2+/-13% to 11.1+/-7.2% (P<0.01), with a simultaneous increase in LVEF% (from 29.7+/-5% to 33.9+/-6%, P<0.01). Three months of optimum sequential CRT further improved LVEF% (from 33.6+/-6% to 38.6+/-7.2%, P<0.01). Tissue tracking detected the segments with DLC, and their location determined optimum interventricular delay programming. Compared with simultaneous CRT, sequential CRT increased diastolic filling time by 7+/-2.5%. CONCLUSIONS: Compared with simultaneous CRT, sequential CRT significantly improves left ventricular systolic and diastolic performance. Tissue tracking can be used to select optimum interventricular delay during CRT.

A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome.

OBJECTIVES: A randomized trial was done to compare single-chamber atrial (AAI) and dual-chamber (DDD) pacing in patients with sick sinus syndrome (SSS). Primary end points were changes in left atrial (LA) size and left ventricular (LV) size and function as measured by M-mode echocardiography. BACKGROUND: In patients with SSS and normal atrioventricular conduction, it is still not clear whether the optimal pacing mode is AAI or DDD pacing. METHODS: A total of 177 consecutive patients (mean age 74 +/- 9 years, 73 men) were randomized to treatment with one of three rate-adaptive (R) pacemakers: AAIR (n = 54), DDDR with a short atrioventricular delay (n = 60) (DDDR-s), or DDDR with a fixed long atrioventricular delay (n = 63) (DDDR-l). Before pacemaker implantation and at each follow-up, M-mode echocardiography was done to measure LA and LV diameters. Left ventricular fractional shortening (LVFS) was calculated. Analysis was on an intention-to-treat basis. RESULTS: Mean follow-up was 2.9 +/- 1.1 years. In the AAIR group, no significant changes were observed in LA or LV diameters or LVFS from baseline to last follow-up. In both DDDR groups, LA diameter increased significantly (p < 0.05), and in the DDDR-s group, LVFS decreased significantly (p < 0.01). Atrial fibrillation was significantly less common in the AAIR group, 7.4% versus 23.3% in the DDDR-s group versus 17.5% in the DDDR-l group (p = 0.03, log-rank test). Mortality, thromboembolism, and congestive heart failure did not differ between groups. CONCLUSIONS: During a mean follow-up of 2.9 +/- 1.1 years, DDDR pacing causes increased LA diameter, and DDDR pacing with a short atrioventricular delay also causes decreased LVFS. No changes occur in LA or LV diameters or LVFS during AAIR pacing. Atrial fibrillation is significantly less common during AAIR pacing.

Tissue Doppler imaging predicts improved systolic performance and reversed left ventricular remodeling during long-term cardiac resynchronization therapy.

OBJECTIVES: We sought to evaluate the long-term impact of cardiac resynchronization therapy (CRT) on left ventricular (LV) performance and remodeling using three-dimensional echocardiography and tissue Doppler imaging (TDI). BACKGROUND: Three-dimensional echocardiography and TDI allow rapid and accurate evaluation of LV volumes and performance. METHODS: Twenty-five consecutive patients with severe heart failure and bundle branch block who underwent biventricular pacemaker implantation were included. Before and after implantation of the pacemaker, three-dimensional echocardiography and TDI were performed. These examinations were repeated at outpatient visits every six months. RESULTS: Five patients (20%) died during one-year follow-up. In the remaining 20 patients, significant reductions in LV end-diastolic volume and LV end-systolic volume of 9.6 +/- 14% and 16.5 +/- 15%, respectively (p < 0.01), could be demonstrated during long-term follow-up. Accordingly, LV ejection fraction increased by 21.7 +/- 18% (p < 0.01). According to a newly developed TDI technique-tissue tracking-all regional myocardial segments improved their longitudinal systolic shortening (p < 0.01). The extent of the LV base displaying delayed longitudinal contraction, as detected by TDI before pacemaker implantation, predicted long-term efficacy of CRT. The QRS duration failed to predict resynchronization efficacy. CONCLUSIONS: Cardiac resynchronization significantly improved LV function and reversed LV remodeling during long-term follow-up. Patients likely to benefit from CRT can be identified by TDI before implantation of a biventricular pacemaker.

Ablation of atrial tachycardia after surgery for congenital and acquired heart disease using an electroanatomic mapping system: Which circuits to expect in which substrate?

OBJECTIVES: The purpose of this study was to compare atrial tachycardia circuits after a range of cardiac operations. BACKGROUND: Knowledge of circuits occurring in a given postsurgical substrate should help to ablate these challenging tachycardias and develop potential preventive strategies. METHODS: We analyzed tachycardia circuits in 83 consecutive patients (60 males; median age 47 years, range 9-73) after atrial incisions undergoing ablation of atrial tachycardias. A combined strategy of electroanatomic (CARTO) and entrainment mapping was used. Fifty-two patients (63%) underwent operation for congenital and 31 (37%) for acquired heart disease. Patients were divided into subgroups based on the intervention performed in the atria: right lateral atriotomy (39 patients), left atrial (11) and superior transseptal (10) approach to the mitral valve, biatrial heart transplantation (8), Mustard (8) and Fontan (4) procedure, and other interventions (3). RESULTS: Most of the 119 tachycardias mapped were isthmus-dependent atrial flutter (66) and incisional tachycardia (30). Isthmus-dependent atrial flutter was the most frequent arrhythmia in all subgroups except for Fontan patients, in whom incisional tachycardia was most frequent. The distribution of tachycardia circuits did not differ significantly among groups. CONCLUSIONS: The observed circuits did not differ among the postsurgical substrates. Isthmus-dependent atrial flutter should be the first circuit considered in patients after atrial incisions.

Pacemaker implantation after congenital heart surgery: risk and prognosis in a population-based follow-up study.

OBJECTIVE: Although earlier a feared complication of congenital cardiac surgery, the incidence of heart-block and sinus node dysfunction has been lowered to 1-4% due to improved surgical techniques and better anatomical understanding of the cardiac conduction system. Development of feasible pacemaker technologies has further lowered mortality and morbidity. However, pacemaker implantation in paediatric patients is in itself associated with significant morbidity due to pacemaker system failure and replacement. The aim of the present study was to examine prognostic factors of mortality, failure of systems and timing of implantation after surgery in post-surgical pacemaker patients. METHODS: We carried out a historical prospective follow-up analysis of all patients (age less than 18 years) who underwent pacemaker implantation due to post-surgical heart-block or sinus node dysfunction in the period 1981-2002 at our institution. Data was extracted from the Danish Pacemaker Register and hospital records. Kaplan-Meier survival time estimates and Cox proportional hazards analysis (Relative Risk, RR) were used to identify prognostic factors. RESULTS: High RACHS score (RR, 16.57), low age at implantation (RR, 0.22), low age at operation (RR, 0.06) and epicardial lead (RR, 0.18) were significant predictors for early mortality. Similarly, high RACHS score (RR, 4.84), low age at implantation (RR, 0.32), low age operation (RR, 0.38) and epicardial lead (RR, 0.40) were significant predictors failure of 1st pacemaker system. CONCLUSIONS: We identified a number of prognostic factors of patient mortality and failure of systems. One factor, high RACHS score, was previously shown to predict mortality and length of ICU stay in paediatric cardiac surgery; however, this study is the first to show a correlation between RACHS score and mortality as well as failure of pacemaker systems. This may have future implications for preoperative risk stratification of patients and counselling of parents to patients with congenital heart disease.

Genetic and phenotypic characterization of mutations in myosin-binding protein C (MYBPC3) in 81 families with familial hypertrophic cardiomyopathy: total or partial haploinsufficiency.

Mutations in the MYBPC3 gene, encoding the sarcomere protein myosin-binding protein C, are among the most frequent causes of autosomal dominant familial hypertrophic cardiomyopathy (FHC). We studied the frequency, type, and pathogenetic mechanism of MYBPC3 mutations in an unselected cohort of 81 FHC families, consecutively enrolled at a tertiary referral center. Nine mutations, six of which were novel, were found in 10 (12.3%) of the families using single-strand conformation polymorphism and DNA sequencing. A frameshift mutation in exon 2 clearly suggests that haploinsufficiency is a pathogenetic mechanism in FHC. In addition, splice site mutations in exon 6 and intron 31, a deletion in exon 13, and a nonsense mutation in exon 25, all lead to premature termination codons, most likely causing loss of function and haploinsufficiency. Furthermore, there were two missense mutations (D228N and A833 T) and one in-frame deletion (DeltaLys813). A considerable intrafamilial variation in phenotypic expression of MYBPC3-based FHC was noted, and we suggest that mutations influencing stability of mRNA could play a role in the variable penetrance and expressivity of the disease, perhaps via partial haploinsuffciency.

Long-term outcome of ablative therapy of postoperative supraventricular tachycardias in patients with univentricular heart: a European multicenter study.

BACKGROUND: Catheter ablation has evolved as a possible curative treatment modality for supraventricular tachycardias (SVT) in patients with univentricular heart. However, the long-term outcome of ablation procedures is unknown. We evaluated the procedural and long-term outcome of ablative therapy of late postoperative SVT in patients with univentricular heart. METHODS AND RESULTS: Patients with univentricular heart (n=19, 11 male; age, 29+/-9 years) referred for ablation of SVT were studied. Ablation was guided by 3D electroanatomic mapping in all but 2 procedures. A total of 41 SVT were diagnosed as intra-atrial reentrant tachycardia (n=30; cycle length, 310+/-68 ms), typical atrial flutter (n=4; cycle length, 288+/-42 ms), focal atrial tachycardia (n=6; cycle length, 400+/-60 ms), and atrial fibrillation (n=1). Ablation was successful in 73% of intra-atrial reentrant tachycardia, 75% of atrial flutter, and all focal atrial tachycardia and focal atrial fibrillation. During the follow-up period of 53+/-34 months, 2 patients were lost to follow-up, 3 died of heart failure, 2 underwent heart transplantation, and 1 underwent conduit replacement. Of the remaining group, 8 had sinus rhythm and 3 had SVT. CONCLUSIONS: Focal and reentrant mechanisms underlie postoperative SVT in patients with univentricular heart. Successive SVT developing over time may be caused by different mechanisms. Ablative therapy is potentially curative, with a procedural success rate of 78%. In patients who had multiple ablation procedures, the SVT originated from different atrial sites, suggesting that these new SVT were caused by progressive atrial disease. Despite recurrent SVT, sinus rhythm at the end of the follow-up period was achieved in 72%.

Prevention of atrial flutter with cryoablation may be proarrhythmogenic.

BACKGROUND: Atrial flutter is a serious problem after surgery for congenital heart disease. METHODS: We performed an intraoperative linear one-minute cryolesion between a right atriotomy and the tricuspid annulus to prevent atrial flutter in 17 consecutive adult patients undergoing surgery for congenital heart disease. Coronary angiography and electrophysiology study using an electroanatomic mapping system to assess the conduction across the line and to try to induce atrial flutter were performed three months after the operation in 15 patients. RESULTS: Eleven patients had bidirectional block in the cryolesion, four patients did not, and two patients refused the electrophysiology study and coronary angiography. All patients with terminal temperature below -151 degrees C had bidirectional block, while only one patient with terminal temperature above -151 degrees C had bidirectional block. No patient with bidirectional block and all patients without bidirectional block had inducible or spontaneous atrial flutter (p = 0.0007). No lesion of the right coronary artery was detected at coronary angiography. CONCLUSIONS: The success rate was suboptimal and the intervention is potentially proarrhythmogenic in patients without block. Preventive strategies targeting atrial flutter should be validated with regard to the block rate achieved.

Superior transseptal approach to mitral valve is associated with a higher need for pacemaker implantation than the left atrial approach.

BACKGROUND: Several studies suggest that the superior transseptal approach to mitral valve surgery leads to sinus node dysfunction. The clinical consequences are not known. METHODS: Consecutive patients undergoing surgery for mitral valve disease from November 16, 1994 through January 26, 2004 were retrospectively evaluated. The surgeons used either the superior transseptal (group A) or left atrial approach (group B). The risk of pacemaker implantation associated with the superior transseptal approach as compared with the left atrial approach was estimated using the multivariate Cox regression analysis to adjust for possible confounders. RESULTS: We included 577 patients, 150 in group A and 427 in group B. Forty-four patients had a pacemaker implanted after the surgery; 17 in group A and 27 in group B (p = 0.010). The superior transseptal approach was an independent risk factor of pacemaker implantation in multivariate analysis (hazard ratio 2.2 [1.2 to 4.1], p = 0.014). Nineteen patients had a pacemaker implanted because of sinus node dysfunction; 9 in group A and 10 in group B (p = 0.017). Group A was an independent predictor of pacemaker implantation because of sinus node dysfunction in bivariate analyses. The risk of pacemaker implantation because of atrioventricular conduction disturbances was not different between the groups (p = 0.178). CONCLUSIONS: The superior transseptal approach has a higher risk of clinically significant sinus node dysfunction than the left atrial approach.

The superior transseptal surgical approach to mitral valve creates slow conduction.

BACKGROUND: Atrial tachycardia is very frequent after mitral valve surgery using the superior transseptal approach. METHODS: Sixteen patients operated on for mitral valve disease (superior transseptal approach = Group A, n = 9, and left atrial approach = Group B, n = 7) underwent radiofrequency catheter ablation of atrial tachycardia guided by electroanatomic mapping. Twenty-six consecutive patients without previous cardiac surgery with typical atrial flutter served as controls (Group C). RESULTS: Atrial tachycardia occurred earlier after the operation in Group A than in Group B (median 97 vs 2,159 days, P = 0.003). Typical atrial flutter was the most frequent circuit in all groups (Group A-7 patients, Group B-5 patients, Group C-26 patients). Three patients in Group A developed right atrial incisional tachycardia. Ten of 14 tachycardia circuits (typical atrial flutter, n = 7, incisional tachycardia, n = 3) in Group A depended on the corridor between the right atrial part of the atriotomy and the tricuspid annulus. Slow conduction during typical atrial flutter was detected in this corridor in Group A, but not in the corresponding region in Groups B and C (P < 0.001). The cycle length of typical atrial flutter was longer in Groups A and B than in Group C (mean 283 ms and 282 ms vs 233 ms, P = 0.003). Patients in Group B with typical atrial flutter had larger right atria than patients in Group A or Group C (mean 156 mL vs 96 mL and 113 mL, P = 0.033). CONCLUSIONS: The superior transseptal incision may predispose to atrial tachycardia by creating slow conduction between the atriotomy and the tricuspid annulus.

Atrial incision affects the incidence of atrial tachycardia after mitral valve surgery.

BACKGROUND: Atrial fibrillation is common after mitral valve surgery. We do not know the incidence of atrial tachycardia and how it depends on the surgical approach used. METHODS: The subjects of the study were 213 consecutive patients who had surgery for mitral valve disease from January 1, 2001, through January 26, 2004. The surgeons used either the superior transseptal approach (69 patients, group A) or left atrial approach (144 patients, group B). An investigator, blinded for the approach used, analyzed all 12-lead electrocardiograms taken during the admission after the operation. The data were analyzed using the Cox regression analysis as time from the operation until documentation of atrial tachycardia or atrial fibrillation on a 12-lead electrocardiogram. Hazard ratio (95% confidence interval) is reported. RESULTS: The superior transseptal approach (2.0 [1.1 to 3.5], p = 0.023), age 60 years or more (2.3 [1.2 to 4.6], p = 0.015), and male sex (2.6 [1.3 to 5.2], p = 0.007) were independent predictors of atrial tachycardia. Age 60 years or more was the only independent predictor of atrial fibrillation (2.0 [1.2 to 3.3], p = 0.007). Although atrial tachycardia was less frequent than atrial fibrillation in group B (p < 0.001), atrial tachycardia was as common as atrial fibrillation in group A (p = 0.149). CONCLUSIONS: The superior transseptal approach has a higher risk of atrial tachycardia than the left atrial approach. Atrial tachycardia has different predictors than atrial fibrillation and constitutes a significant problem, especially after the superior transseptal approach. These results emphasize the need to distinguish between atrial tachycardia and atrial fibrillation-two entities with different pathophysiology, therapy, and also epidemiology.