Leif-Hendrik Boldt

Steerable Versus Nonsteerable Sheath Technology in Atrial Fibrillation Ablation A Prospective, Randomized Study

Background— Steerable sheath technology is designed to facilitate catheter access, stability, and tissue contact in target sites of atrial fibrillation (AF) catheter ablation. We hypothesized that rhythm control after interventional AF treatment is more successful using a steerable as compared with a nonsteerable sheath access. Methods and Results— One hundred thirty patients with paroxysmal or persistent drug-refractory AF undergoing their first ablation procedure were prospectively included in a randomized fashion in 2 centers. Ablation was performed by 10 operators with different levels of clinical experience. Treatment outcome was measured with serial 7-day Holter ECGs and additional symptom-based arrhythmia documentation. Single procedure success (freedom from AF and/or atrial macroreentrant tachycardia) was significantly higher in patients ablated with a steerable sheath (78% versus 55% after 3 months, P=0.005; 76% versus 53% after 6 months, P=0.008). Rate of pulmonary vein isolation, procedure duration, and radiofrequency application time did not differ significantly, whereas fluoroscopy time was lower in the steerable sheath group (33±14 minutes versus 45±17 minutes, P<0.001). Complication rates showed no significant difference (3.2% versus 5%, P=0.608). On multivariable analysis, steerable sheath usage remained the only powerful predictor for rhythm outcome after 6 months of follow-up (hazard ratio, 2.837 [1.197 to 6.723]). Conclusions— AF catheter ablation using a manually controlled, steerable sheath for catheter navigation resulted in a significantly higher clinical success rate, with comparable complication rates and with a reduction in periprocedural fluoroscopy time. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00469638.

Normal values and clinical relevance of left atrial myocardial function analysed by speckle-tracking echocardiography: multicentre study

AIMS The aim of this multicentre study was to determine the normal range and the clinical relevance of the myocardial function of the left atrium (LA) analysed by 2D speckle-tracking echocardiography (2DSTE). METHODS AND RESULTS We analysed 329 healthy adult subjects prospectively included in 10 centres and a validation group of 377 patients with left ventricular diastolic dysfunction (LVDD). LA myocardial function was analysed by LA strain rate peak during LA contraction (LA-SRa) and LA strain peak during LA relaxation (LA-Strain). The range of values of LA myocardial function in healthy subjects was LA-SRa -2.11 ± 0.61 s(-1) and LA-Strain 45.5 ± 11.4%, and the lowest expected values of these LA analyses (calculated as -1.96 SD from the mean of healthy subjects) were LA-SRa -0.91 s(-1) and LA-Strain 23.1%. Concerning the clinical relevance of these LA myocardial analyses, LA-SRa and LA-Strain detected subtle LA dysfunction in patients with LVDD, even though LA volumetric measurements were normal. In addition, in these patients we found that the functional class (dyspnoea-NYHA classification) was inversely related to both LA-Strain and LA-SRa. CONCLUSION In the present multicentre study analysing a large cohort of healthy subjects and patients with LVDD, the normal range and the clinical relevance of the myocardial function of the LA using 2DSTE have been determined.

Genetic deletion of arginine 14 in phospholamban causes dilated cardiomyopathy with attenuated electrocardiographic R amplitudes

BACKGROUND Familial dilated cardiomyopathy is a highly heterogeneous genetic disease. Thus, identification of disease-causing mutations is a challenging and time-consuming task. Genotype-phenotype associations may alleviate identification of the underlying mutation. OBJECTIVE The purpose of this study was to investigate cardiac phenotypes within a family harboring a familial dilated cardiomyopathy-related mutation in the gene encoding phospholamban. METHODS Complete genetic and clinical analyses were performed in a family with familial dilated cardiomyopathy due to the PLN-R14Del mutation. Family relatives were studied by ECG, Holter ECG, echocardiography, ECG body surface potential mapping, and cardiac magnetic resonance imaging. RESULTS A candidate gene approach resulted in identification of a heterozygous deletion of arginine 14 in the gene encoding phospholamban (PLN-R14Del) segregating with dilated cardiomyopathy in the family pedigree. Mutation carriers suffered from familial dilated cardiomyopathy associated with cardiac death between the ages of 26 and 50 years. Interestingly, all adult mutation carriers revealed strikingly attenuated R amplitudes on standard ECG, regardless of the absence or presence of echocardiographic abnormalities. Gadolinium-enhanced cardiac magnetic resonance imaging showed late enhancement in PLN-R14Del carriers with preserved ejection fraction. Late enhancement was regionally related to areas of most pronounced R-amplitude attenuation as assessed by body surface potential mapping. CONCLUSION Attenuated R amplitudes were identified as an early ECG phenotype in a family with familial dilated cardiomyopathy due to the PLN-R14Del mutation. All adults harboring PLN-R14Del had attenuated R waves irrespective of echocardiographic abnormalities. The study findings suggest a mutation-related remodeling process preceding ventricular dysfunction.

Mutations in the cardiac transcription factor GATA4 in patients with lone atrial fibrillation

Familial recurrence of atrial fibrillation (AF) is reported in up to 15% of patients with lone AF. Recently, it was proposed that congenital defects in the morphogenesis of the pulmonary vein myocardium are involved in genetic pathogenesis of lone AF. GATA4 is a cardiac transcription factor essentially involved in myocardial development. Mutations in GATA4 are associated with congenital cardiac malformations. To investigate whether GATA4 mutations represent a genetic origin for AF the coding region of GATA4 was sequenced in 96 patients with lone AF. We found a GATA4 mutation (M247T) in a patient with familial lone AF and atrial septal aneurysm without interatrial shunts. The mutation affects a deeply conserved domain adjacent to the first zinc finger domain of GATA4 and was not reported before. A second GATA4 mutation (A411V) was found in a female patient with sporadic lone AF. This variant was previously reported in patients with cardiac septal defects. However, no anomalies of the atrial or ventricular septa were noted in the AF patient harboring A411V. We report for the first time that mutations in the cardiac transcription factor GATA4 may represent a genetic origin of lone AF. The study proposes that lone AF may share a common genetic origin with congenital cardiac malformations.

Atrial fibrillation-induced cardiac troponin I release

BACKGROUND Cardiac troponin I (cTnI) is highly specific for myocardial damage and for the diagnosis of acute coronary syndrome. We investigated cTnI utility and predictive value in patients with atrial fibrillation (AF) in the acute setting. METHOD We studied 354 consecutive patients with the primary diagnosis of AF and clinical symptoms suggestive of myocardial ischemia presenting to our emergency department. cTnI was obtained on presentation. Patients with ST-segment elevation myocardial infarction were excluded. Coronary angiography was performed in 100 patients. RESULTS cTnI was elevated (>0.09 μg/L) in 51 of 354 (15%) patients. The mean cTnI in these patients was 0.37 μg/L (0.09-3.14). In 23 of 100 patients undergoing coronary angiography, cTnI was elevated. Only 6 of these 23 patients (26%) had significant stenosis. In 77 of 100 patients undergoing coronary angiography, cTnI was normal, revealing significant stenosis in 25 patients (33%). The positive predictive value of elevated cTnI for a coronary intervention was 26% and the negative predictive value was 68%. Using multivariate logistic regression, we found that heart rate on presentation, the presence of angina pectoris, left ventricular ejection fraction, serum creatinine, and hemoglobin independently predicted elevated cTnI level. CONCLUSION These data are the first to show that AF in the acute setting is frequently associated with cTnI elevations. AF patients with high heart rate and/or angina pectoris often show false elevated cTnI levels. These findings are relevant for clinicians evaluating patients with acute AF and myocardial ischemia symptoms. Appropriate clinical guidelines must be established that also consider AF-related elevations in cTnI.

Potential lifetime cost-effectiveness of catheter-based renal sympathetic denervation in patients with resistant hypertension

AIMS Recent studies have demonstrated the safety and efficacy of catheter-based renal sympathetic denervation (RDN) for the treatment of resistant hypertension. We aimed to determine the cost-effectiveness of this approach separately for men and women of different ages. METHODS AND RESULTS A Markov state-transition model accounting for costs, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness was developed to compare RDN with best medical therapy (BMT) in patients with resistant hypertension. The model ran from age 30 to 100 years or death, with a cycle length of 1 year. The efficacy of RDN was modelled as a reduction in the risk of hypertension-related disease events and death. Analyses were conducted from a payers perspective. Costs and QALYs were discounted at 3% annually. Both deterministic and probabilistic sensitivity analyses were performed. When compared with BMT, RDN gained 0.98 QALYs in men and 0.88 QALYs in women 60 years of age at an additional cost of €2589 and €2044, respectively. As the incremental cost-effectiveness ratios increased with patient age, RDN consistently yielded more QALYs at lower costs in lower age groups. Considering a willingness-to-pay threshold of €35 000/QALY, there was a 95% probability that RDN would remain cost-effective up to an age of 78 and 76 years in men and women, respectively. Cost-effectiveness was influenced mostly by the magnitude of effect of RDN on systolic blood pressure, the rate of RDN non-responders, and the procedure costs of RDN. CONCLUSION Renal sympathetic denervation is a cost-effective intervention for patients with resistant hypertension. Earlier treatment produces better cost-effectiveness ratios.

Myocardial Systolic and Diastolic Performance Derived by 2-Dimensional Speckle Tracking Echocardiography in Heart Failure With Normal Left Ventricular Ejection Fraction

Background—The aim of this study was to investigate the myocardial systolic and diastolic performance of the left ventricle (LV) in patients with heart failure with normal LV ejection fraction (HFNEF) through novel LV myocardial indices, which assess the systolic and diastolic function of the whole myocardium of the LV. Methods and Results—LV myocardial systolic and diastolic performance were assessed as the average value of peak systolic strain and peak early-diastolic strain rate, respectively, in longitudinal, circumferential, and radial directions from all LV segments using 2-dimensional speckle-tracking echocardiography. We studied patients with HFNEF and a control group consisting of asymptomatic subjects with LV diastolic dysfunction of similar age, sex, and LV ejection fraction. A total of 322 patients were included (92 with HFNEF and 230 with asymptomatic LV diastolic dysfunction). Myocardial systolic and diastolic LV performance were significantly lower in HFNEF (20.13±6.02% and 1.14±0.27 s−1) than in patients with asymptomatic LV diastolic dysfunction (25.33±6.06% and 1.37±0.33 s−1, respectively; all P<0.0001). In addition, patients with HFNEF with low systolic and diastolic LV myocardial performance had significantly higher LV filling pressures (17.1±6.6 and 17.6±6.3 versus 12.0±5.1 and 11.7±4.7, respectively; all P<0.001) and lower cardiac output (4.8±1.0 L/min and 4.9±1.1 L/min versus 5.7±1.2 L/min and 5.8±1.1 L/min, respectively; all P<0.001) than patients with normal LV myocardial performance. In relation to these findings, the symptomatic status (ie, New York Heart Association functional class) was significantly altered in those patients with low systolic and diastolic LV myocardial performance. Conclusions—In patients with HFNEF, both systolic and diastolic LV myocardial performance are impaired, which is associated with increased LV filling pressures, decreased cardiac output, and worse New York Heart Association functional class. Therefore, the measurement of these myocardial parameters could be of great importance in HFNEF because these echocardiographic indices assess the multidirectional function of the whole myocardium of the LV, thereby allowing detection of an alteration of the global function of the LV which is associated with a worse symptomatic status in these patients.

Safety aspects of deep sedation during catheter ablation of atrial fibrillation.

Background:  The combination of intravenous propofol and midazolam is frequently used to provide unconscious sedation during catheter ablation of atrial fibrillation (AF), but only a very few reports are available on the influence of prolonged propofol infusion on arterial blood gas, blood pressure, and anesthesia‐associated complications during ablation of AF. The purpose of this study was to assess tolerance and safety of unconscious sedation with intravenous propofol and midazolam during catheter ablation of AF.

Effects of deep sedation on cardiac electrophysiology in patients undergoing radiofrequency ablation of supraventricular tachycardia: impact of propofol and ketamine

AIMS Propofol is commonly used as an anaesthetic during catheter ablation. Bradycardia and termination of supraventricular tachycardia (SVT) under propofol are reported. Ketamine is used for cardiac catheterization procedures and increases heart rate and blood pressure. Our study aimed to determine the effects of propopfol and ketamine on atrial electrophysiology. METHODS AND RESULTS Thirty-one patients undergoing electrophysiological study prior to SVT ablation were enrolled. Patients received a combination of propofol/midazolam (n = 10), ketamine/midazolam (n = 9), or midazolam alone (n = 12). Electrophysiological study was performed before and after administration of the anaesthetic agents. Blood pressure, corrected sinus node recovery time, Wenckebach cycle length, and atrial conduction time were measured. We found a significant increase in heart rate, systolic, and diastolic blood pressure and a significant shortening of atrial conduction time after administration of ketamine compared with propofol and the control. Results for ketamine, propofol and the control, respectively: mean (SD) change in heart rate was 12.4 (8.3), -1.4 (8), and 1 (7.5) b.p.m. (P = 0.002); mean (SD) change in systolic blood pressure was 19.2 (8.1), -22 (9), and 0.1 (5.7) mmHg (P < 0.001); mean (SD) change in diastolic blood pressure was 6.6 (9.7), -7.8 (2.9), and 2.3 (4.5) mmHg (P = 0.001); and mean (SD) change in atrial conduction time was -13.7 (16.4), 4.5 (11.1), and -0.3 (3.8) ms (P = 0.008). No significant affection of sinus node or antrioventricular node function was seen. CONCLUSION Our results show stimulatory effects of ketamine on heart rate, atrial conduction, and blood pressure. Ketamine, therefore, may be beneficial in patients with pre-existing hypotension and bradycardia.

Mutational analysis of the PITX2 and NKX2-5 genes in patients with idiopathic atrial fibrillation

Atrial fibrillation (AF) is the most frequently encountered arrhythmia in clinical practice. In a subgroup of patients, AF is regarded as idiopathic when no signs of structural heart disease or other causes of the arrhythmia can be identified during conventional clinical work-up. Recent studies have demonstrated that AF has a substantial genetic basis in a number of cases. The entire coding sequences, including intron-exon boundaries, of the genes PITX2 and NKX2-5 were screened for genetic variants by means of initial polymerase chain reaction followed by DNA sequencing in 96 patients with idiopathic AF. Although we detected a number of variants, our candidate gene approach did not result in identification of mutations associated with AF in the coding regions of PITX2 or NKX2-5 in our well characterized AF cohort.