Biomedical subjects

Jiunn-Lee Lin

Publications and source records attributed to Jiunn-Lee Lin.

At least 19 recordsLinked to original sources

PubMed2006

Renin-angiotensin system gene polymorphisms and coronary artery disease in a large angiographic cohort: detection of high order gene-gene interaction.

There have been many reports regarding the association between renin-angiotensin system (RAS) gene polymorphisms and coronary artery disease (CAD) or acute myocardial infarction (AMI), but the results are inconsistent. In the present study, we used several new approaches with multilocus data to reappraise this issue in a large and relatively homogeneous Taiwanese population. A total of 1254 consecutive patients who underwent cardiac catheterization (735 with documented coronary artery disease and 519 without) between 1996 and 2003 were recruited. Angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A and G-217A polymorphisms of the angiotensinogen gene; and A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In single-locus analyses, no locus was associated with CAD, history of AMI and three-vessel CAD, either with or without adjustment for conventional CAD risk factors. For multilocus analyses, we recreated a balanced population, with the controls individually matched to the cases regarding the conventional CAD risk factors. We found that the angiotensinogen gene haplotype profile was significantly different between the cases and controls (chi2=31.6, P=0.030) in haplotype analyses. Furthermore, significant three-locus (G-217A, M235T and I/D) gene-gene interactions were detected by multifactor-dimensionality reduction method (highest cross-validation consistency 10.0, lowest prediction error 40.56%, P=0.017) and many even higher order gene-gene interactions by multilocus genotype disequilibrium tests (16 genotype disequilibria exclusively found in the controls, all of which included at least two genes among AGT, ACE and AT1R genes). Our study is the first to demonstrate epistatic, high-order, gene-gene interactions between RAS gene polymorphisms and CAD. These results are compatible with the concept of multilocus and multi-gene effects in complex diseases that would be missed with conventional approaches.

Aged↗

PubMed2006

Altered expression of FHL1, CARP, TSC-22 and P311 provide insights into complex transcriptional regulation in pacing-induced atrial fibrillation.

Atrial fibrillation (AF) is the most common progressive disease in patients with cardiac arrhythmia. AF is accompanied by complex atrial remodeling and changes in gene expression, but only a limited number of transcriptional regulators have been identified. Using a low-density cDNA array, we identified 31 genes involved in transcriptional regulation, signal transduction or structural components, which were either significantly upregulated or downregulated in porcine atria with fibrillation (induced by rapid atrial pacing at a rate of 400-600 bpm for 4 weeks that was then maintained without pacing for 2 weeks). The genes for four and a half LIM domains protein-1 (FHL1), transforming growth factor-beta (TGF-beta)-stimulated clone 22 (TSC-22), and cardiac ankyrin repeat protein (CARP) were significantly upregulated, and chromosome 5 open reading frame gene 13 (P311) was downregulated in the fibrillating atria. FHL1 and CARP play important regulatory roles in cardiac remodeling by transcriptional regulation and myofilament assembly. Induced mRNA expression of both FHL1 and CARP was also observed when cardiac H9c2 cells were treated with an adrenergic agonist. Increasing TSC-22 and marked P311 deficiency could enhance the activity of TGF-beta signaling and the upregulated TGF-beta1 and -beta2 expressions were identified in the fibrillating atria. These results implicate that observed alterations of underlying molecular events were involved in the rapid-pacing induced AF, possibly via activation of the beta-adrenergic and TGF-beta signaling.

Animals↗

PubMed2006

Septal pacing preserving better left ventricular mechanical performance and contractile synchronism than apical pacing in patients implanted with an atrioventricular sequential dual chamber pacemaker.

BACKGROUND: Permanent pacing is the treatment for chronotropically incompetent hearts. However, the right ventricular (RV) apical pacing-induced asynchrony, even maintaining the atrioventricular (AV) sequential activation, has depressed left ventricular contractility. Whether RV septal pacing would less compromise the electromechanical performance of the left ventricle and the chronotropic effect on myocardial contractility, is unknown. METHODS: We prospectively studied 42 patients without structural heart diseases and with symptomatic bradycardia. There were 10 patients receiving atrial pacing (AAI) pacemakers, 18 patients having AV sequential pacing at RV apex (DDDapx) and 14 patients being AV sequentially paced at septum (DDDspt). Echocardiography was performed before and within 72 h after the pacemaker implantation. The ventricular mechanical performance and asynchrony was compared in conditions of programmed rates of 60, 80 and 100/min. RESULTS: Myocardial performance index was significantly better in DDDspt than in DDDapx patients (p=0.003). With faster programmed rate, the QRS/RR increased (p<0.05) in DDDapx patients with more inter- and intraventricular asynchrony, implicating the disadvantage of prolonged depolarization time. The DDDspt group demonstrated comparable parameters of diastolic function to AAI patients and preserved mechanical performance during accelerated pacing. CONCLUSIONS: RV septal pacing showed the advantages of shorter depolarization time, less ventricular contractile asynchrony, better mechanical performance and preserved chronotropic response on myocardial contractility in comparison with apical pacing.

Aged↗

PubMed2006

The association of human connexin 40 genetic polymorphisms with atrial fibrillation.

BACKGROUND: There is evidence showing that genetic factors contribute to the pathogenesis of atrial fibrillation (Af). We investigated the association between Af and polymorphisms of the connexin 40 (Cx40) gene, which is important in the electrical coupling between atrial myocytes. METHODS: We performed an association study between two Cx40 single nucleotide polymorphisms (SNPs) (Cx40 -44 and +71 allele) and Af. We enrolled 173 patients with Af, and the control group consisted of 232 patients without Af. The luciferase assay was performed to evaluate the promoter activities of different Cx40 haplotypes in cultured atrial myocytes. RESULTS: We found that the two SNPs were both significantly associated with Af. In pairwise linkage disequilibrium analysis, the two SNPs were completely linked (Cx40 -44G always associated with Cx40 +71A; Cx40 -44A associated with Cx40 +71G, P<0.001). In haplotype analysis, we demonstrated that the frequency of Cx40 (-44A,+71G) was significantly higher in the Af group than that in the control group (P<0.006, odds ratio=1.514, 95% confidence interval 1.13-2.04). We also performed genotype analysis using several genetic models, finding that the recessive model showed the lowest P value (P<0.004) and the largest odds ratio (2.53, 95% confidence interval 1.23-5.19). In promoter activity studies using luciferase as the reporter, Cx40 (-44A,+71G) had significantly lower promoter activity than that of the Cx40 (-44G,+71A) in atrial myocytes. CONCLUSIONS: The two SNPs in the promoter region of the Cx40 gene were significantly associated with Af. The Cx40 (-44A +71G) haplotype was associated with a higher risk for Af. This haplotype also had significantly lower promoter activity in atrial myocytes.

Aged↗

PubMed2006

Measuring heart rate variability with wavelet thresholds and energy components in healthy subjects and patients with congestive heart failure.

BACKGROUND: Analysis of wavelet thresholds and energy components can be used to differentiate patients with congestive heart failure (CHF) from healthy subjects and to demonstrate the improvement of heart rate variability after treatment with beta-blockers in the patient group. METHODS: Nine patients with CHF without concurrent beta-blocker therapy and 15 healthy volunteers were recruited and received 24-hour Holter recording. Wavelet thresholds and energy components were calculated. The patients with CHF were then treated with atenolol for 3 months. Another Holter recording was repeated and associated wavelet parameters were estimated. RESULTS: Wavelet thresholds were statistically higher in normal subjects than those derived from patients with CHF (62.40 +/- 20.65 vs. 16.90 +/- 9.72, p < 0.001). The difference was still significant after control of heart rate and the total number of heart beats (74.85 +/- 22.68 vs. 32.51 +/- 18.73, p < 0.001). The energy component of HRV in the finest wavelet domain was also significantly higher in the normal subjects (243.01 +/- 237.69 x 10(-6) vs. 40.65 +/- 39.65 x 10(-6), p = 0.001). These two measures increased after treatment with beta-blockers in the patients with CHF, but not to the extent of those of normal subjects. CONCLUSION: Analysis of wavelet thresholds and energy components has provided robust and accurate measurements for background HRV.

Adrenergic beta-Antagonists↗

PubMed2006

A novel mutation (Arg169Gln) of the cardiac ryanodine receptor gene causing exercise-induced bidirectional ventricular tachycardia.

An 18-year-old woman presented with exercise induced sudden collapse. Series of cardiac work up revealed no structural cardiac abnormalities. Bidirectional ventricular tachycardia occurred during a treadmill exercise test. Under the impression of catecholaminergic polymorphic ventricular tachycardia, we screened the cardiac ryanodine receptor gene for mutation. We identified a novel heterozygous mutation at the 169th amino acid (Arg169Gln). This amino acid is highly conserved among many species and this mutation was not present in 50 normal control subjects. This patient was treated with a beta-block with good response.

Adolescent↗

PubMed2005

Denaturing high-performance liquid chromatography screening of the long QT syndrome-related cardiac sodium and potassium channel genes and identification of novel mutations and single nucleotide polymorphisms.

Mutations in cardiac potassium and sodium channel genes are responsible for several hereditary cardiac arrhythmia syndromes. We established a denaturing high-performance liquid chromatography (DHPLC) protocol for rapid mutation screening of these genes, and reported mutations and variations identified by this method. We included 28 patients with Brugada syndrome, 4 with congenital long QT syndrome (LQTS), 11 with drug-induced LQTS, 4 with idiopathic ventricular fibrillation, and 50 normal volunteers. Polymerase chain reactions were performed to amplify the entire coding region of these genes. DHPLC was used to screen for heteroduplexes then DNA sequencing was performed. With this method, we identified the mutation(s) in all four patients with congenital LQTS (KCNQ1 A341V, KCNH2 N633D, KCNH2 2768Cdel and KCNE1 K70 N Y81C double mutations). We also identified the SCN5A A551T mutation in 1 of the 28 patients with Brugada syndrome. All the above-mentioned mutations were novel except KCNQ1 A341V. No mutations were identified in patients with drug-induced LQTS or idiopathic ventricular fibrillation. In total, 25 single nucleotide polymorphisms were identified, 10 of which were novel. In conclusion, DHPLC is a sensitive and rapid method for detection of cardiac sodium and potassium channel gene mutations.

Chromatography, High Pressure Liquid↗

PubMed2005

Identification of good responders to rhythm control of paroxysmal and persistent atrial fibrillation by transthoracic and transesophageal echocardiography.

BACKGROUND: Identification of good responders to rhythm control in the management of atrial fibrillation (AF) is worthwhile in terms of increasing hemodynamic benefit and decreasing the likelihood of unstable anticoagulation even after the Atrial Fibrillation Follow-Up Investigation of Rhythm Management. METHODS: We tested the hypothesis that atrial substrate determines the risk of recurrence on rhythm control both in patients with paroxysmal AF (PAF) and in those with persistent or sustained AF (> or =1 week, SAF). There were 90 consecutive patients (mean age 63 +/- 12 years, 67 males and 23 females) with previous PAF (n = 66) or SAF (n = 24). They were maintained in sinus rhythm successfully for at least 1 month after conversion and then studied by transthoracic and transesophageal echocardiography. All of the patients were followed regularly by determination of symptoms, 12-lead ECG and intermittent Holter recording to determine recurrence of AF after echocardiographic study. RESULTS: After 9.1 +/- 3.8 (range 3-12) months of follow-up, 23 of the 90 (26%) patients had documented recurrence of AF (67 without recurrence). Univariate analysis of demographic characteristics, medications, ECG and echocardiographic parameters revealed that, compared with the group of patients without recurrent AF, the group of those with it included more members of the SAF group (11/27 vs. 13/67, p = 0.039), included more male subjects (22/23 vs. 45/67, p = 0.045), had a larger left atrial volume index (LAVI; 27 +/- 9 vs. 22 +/- 9 ml/m2, p = 0.024) and had lower LA appendage peak emptying velocity (LAAPEV; 42 +/- 15 vs. 55 +/- 22 cm/s, p = 0.01). Multivariate Cox proportional hazards regression analysis adjusted for age, gender and AF group revealed that patients with LAVI <30 ml/m2 and LAAPEV >46 cm/s had the least recurrence of AF (relative risk 0.18, 95% confidence interval 0.06-0.55, vs. with LAVI >30 ml/m2 or LAAPEV <46 cm/s, p = 0.002). Kaplan-Meier probability of freedom from AF recurrence was significantly better when LAVI <30 ml/m2 (log-rank p = 0.02), LAAPEV > 46 cm/s (p = 0.013) or both (p = 0.004). The superiority to predict the rate of sinus rhythm maintenance was the same in the PAF and SAF groups. CONCLUSIONS: Good responders to rhythm control in the PAF and SAF groups share the characteristics of smaller LA volume and better LAA contractile function, emphasizing the critical role of atrial substrate remodeling in recurrence of AF.

Adult↗

PubMed2005

Immediate impairment of left ventricular mechanical performance and force-frequency relation by rate-responsive dual-chamber, but not atrial pacing: Implications from intraventricular isovolumic relaxation flow.

BACKGROUND: Despite the maintenance of atrioventricular (AV) synchrony, the detrimental effect of left ventricular asynchronization on mechanical performance and intraventricular flow by nonphysiologic right ventricular apical pacing in dual-chamber pacing, with and without rate adaptation, is not clear. METHOD: Twenty-seven consecutive patients receiving permanent pacemakers for symptomatic bradyarrhythmias (18 with DDD and 9 with AAI mode pacemakers) were evaluated with standard and tissue Doppler echocardiography before and 24 h after pacemaker implantation. The rate-response effect of pacing was studied by programmed rate with increments of 20, from 60 to 100/min. RESULTS: Color M-mode echocardiography demonstrated that much more DDD patients developed new biphasic intraventricular flow during isovolumic relaxation period than AAI patients (13/18 versus 0/9, P<0.001). In DDD patients, the ventricular relaxation represented by mitral annulus velocity in early diastole significantly attenuated (before vs. after DDDR, 8.5+/-2.8 vs. 5.2+/-1.2 cm/s, P<0.05), and also the mitral flow propagation velocity (33+/-11 vs. 25+/-5 cm/s, P<0.01). The myocardial performance index increased after DDD (0.70+/-0.15 vs. 0.79+/-0.24, P<0.05) but not after AAI (0.61+/-0.1 vs. 0.59+/-0.08, P=NS). For both pacing groups, the accelerated pacing rate prolonged the isovolumic relaxation time and shortened the diastole period (P<0.001). However, only DDD patients had a decreased mitral flow propagation velocity (P=0.026) and an attenuated force-frequency relation in programmed rate acceleration. CONCLUSION: Despite the AV synchrony, right ventricular apical pacing immediately attenuates the left ventricular contraction and relaxation performance, which deteriorated further and suppressed the physiologically positive force-frequency relation after accelerated pacing rate.

Aged↗

PubMed2005

Successful radiofrequency catheter ablation of idiopathic ventricular fibrillation presented as recurrent syncope and diagnosed by an implanted loop recorder.

As a palliative therapy, an implantable cardioverter-defibrillator (ICD) could not prevent the occurrence of ventricular tachycardia or fibrillation (VT, VF), but only suppress it by overdrive pacing or direct current shocks. Recurrent VT or VF followed by frequent ICD shocks might thus put patients in a painful disaster. We presented a case of recurrent syncope diagnosed as recurrent VF by an implanted loop recorder (ILR). The VF was eliminated by radiofrequency catheter ablation (RFCA) of triggering ventricular premature complexes (VPCs).

Adult↗

PubMed2005

Radiofrequency ablation of a concealed right anterior accessory pathway associated with right atrial diverticulum in a child.

A 9-year-old boy had refractory supraventricular tachycardia and a right atrial (RA) diverticulum as diagnosed by ultrafast computed tomography. An electrophysiological study under transesophageal echocardiography guidance revealed a concealed right anterior accessory pathway passing through the body of the RA diverticulum. Radiofrequency ablation was performed to eliminate retrograde ventriculoatrial conduction.

Catheter Ablation↗

PubMed2005

Left atrial dysfunction in patients with atrial fibrillation after successful rhythm control for > 3 months.

BACKGROUND: Large-scale clinical trials have demonstrated that patients with atrial fibrillation (AF), when treated with a rhythm-control strategy, are still at risk for embolic events. We hypothesized that left atrial (LA) dysfunction persisted even after successful maintenance of sinus rhythm for > 3 months. METHODS: A total of 93 patients with AF and satisfactory rhythm control for > 3 months were included. Satisfactory rhythm control was defined as being free of AF based on patient-reported symptoms, monthly ECG follow-up, and ambulatory Holter ECG if needed. Among the 93 patients, 25 patients had sustained AF that was terminated by electrical or pharmacologic cardioversion, while 68 patients had paroxysmal AF under good medical control. Clinical data were obtained, and transthoracic and transesophageal echocardiography were performed after satisfactory rhythm control for > 3 months. RESULTS: Among the 93 patients, 34 patients (37%) had LA dysfunction, defined as LA appendage (LAA) peak emptying velocity < 40 cm/s or spontaneous echo contrast and/or thrombus in the LA or LAA. When compared to the other 59 patients without LA dysfunction, they had larger LA dimension (40 +/- 6 mm vs 36 +/- 8 mm [+/- SD], p = 0.018) but did not differ significantly regarding the left ventricular (LV) chamber size, LV ejection fraction, mitral or tricuspid inflow, and ratio of the amplitude of the waves created by early diastolic filling and atrial contraction. We also analyzed the relationship between LA function and clinical risk factors for stroke, including hypertension, diabetes mellitus, coronary artery disease, age > 65 years, and prior cerebral vascular accident. LA dysfunction was found in 10 of 17 patients (59%) with three or more risk factors. The odds ratio for having LA dysfunction was 3.1 (p = 0.04; 95% confidence interval, 1.1 to 9.1) when compared with patients with less than three risk factors. CONCLUSIONS: LA dysfunction was present in more than one third of AF patients after satisfactory rhythm control for > 3 months. Patients with higher burden (three or more) of clinical risk factors were more likely to have impaired LA function.

Aged↗

PubMed2005

Low frequency of target organ damage in Taiwanese with white coat hypertension.

BACKGROUND AND PURPOSE: The clinical importance of white coat hypertension (WCH) remains to be clarified. This study investigated the target organ damage in Taiwanese with WCH. METHODS: A total of 188 consecutive Taiwanese (88 men and 100 women), aged 26 to 75 years who had an abnormal office casual blood pressure (systolic blood pressure >/= 140 mm Hg or diastolic blood pressure >/= 90 mm Hg or both) and a normal ambulatory blood pressure (ABP) average (systolic ABP average < 140 mm Hg and diastolic ABP average < 90 mm Hg) at the outpatient clinic or from a mass survey were enrolled. Office casual blood pressure measurements were obtained by standard sphygmomanometric methods. Twenty-four-hour blood pressures were recorded by a commercial ambulatory pressure recorder (Del Mar Avionics, Model 1990 Pressurometer IV System). Hypertension-related target organ complications were assessed by electrocardiogram, chest X-ray, urinalysis and eye fundus examinations. RESULTS: Target organ damage was found in 6.4% of subjects with WCH. Roentgenographic left ventricular hypertrophy (LVH) was found in 1.1% of subjects and electrocardiographic LVH in 2.7%. Proteinuria was found in 1.6% of subjects and retinopathy in 1.1%. The frequencies of various target organ damage were not significantly associated with age, gender and the definition of normal ABP average as 135/85 mm Hg or 140/90 mm Hg. CONCLUSIONS: WCH represents a low-risk stratum for target organ damage in Taiwanese. These subjects should be identified and followed up regularly. The factors responsible for the low frequency of target organ damage in Taiwanese with WCH need further study.

Adult↗

PubMed2005

Proximal common pathway in the circuit of atrioventricular nodal reentrant tachycardia.

Whether atrium tissue is involved in the reentrant circuit of atrioventricular nodal reentrant tachycardia (AVNRT) has been debated for decades. Animal models, clinical electrophysiological studies, surgery and catheter ablation have all documented that the perinodal tissue forms part of the tachycardia circuit. However, the occasional clinical finding of AVNRT with ventriculoatrial block suggests the presence of a proximal common pathway. We describe a 43-year-old woman who developed recurrent AVNRT with new onset of complete ventriculoatrial block after an attempted radiofrequency ablation at the posterior septal area. This case demonstrates the anatomical existence of a proximal common pathway and the topological location of such a pathway for typical AVNRT. This case also demonstrates the isolated nature of the AVNRT circuit and the delicate nature of the responsible reentrant substrate.

Adult↗

PubMed2004

Usefulness of single-bolus adenosine test for confirming sinus node dysfunction and correlation with atrial overdrive suppression test.

We prospectively studied 42 consecutive patients who had symptomatic sinus node dysfunction and 17 age-matched controls by measuring maximal and corrected maximal sinus node recovery times with an atrial overdrive suppression test and single-bolus adenosine administration (0.15 mg/kg). We found a positive correlation between the 2 methods, with reasonably good sensitivity, specificity, and predictive accuracy.

Adenosine↗

PubMed2004

Three single-nucleotide polymorphisms of the angiotensinogen gene and susceptibility to hypertension: single locus genotype vs. haplotype analysis.

Although some single polymorphism analyses of the angiotensinogen (AGT) gene have been found to be associated with hypertension, the results are still inconsistent. The objectives of this study are to evaluate the association of the genotype and haplotype distributions of three single-nucleotide polymorphisms (SNPs) (G-217A, A-6G, and M235T) in the AGT gene with hypertension. In a sample of 461 hypertensive and 327 normotensive patients in Taiwan, we found that -217AA and -6GG homozygotes conferred independently an increased risk to hypertension (P = 0.008 and P = 0.037, respectively), as illustrated by their significant associations with hypertension in both single SNP and pair-wise SNPs analyses. Meanwhile, a very weak linkage disequilibrium was found between the G-217A and the A-6G polymorphisms in terms of r2 (<0.05). On the basis of likelihood ratio test, only the set of haplotypes that constituted the A-6G and the M235T polymorphisms was associated with hypertension (chi2 = 20.91, P = 0.0008), which was mainly due to the increased frequency of the recombinant haplotypes (-6A identical with 235M and -6G identical with 235T), and a pathophysiological role in the predisposition to hypertension was hence indicated. In functional assays, the promoter activities of the haplotypes -217A identical with -6A and -217G identical with -6G were significantly higher than the most common haplotype -217G identical with -6A. These results highlight the necessity of a thorough analysis of all reported variants of a candidate gene in the elucidation of genetic susceptibility to a complex disease like hypertension, even when the variants are in the same haplotype block.

Angiotensinogen↗

PubMed2004

Renin-angiotensin system gene polymorphisms and atrial fibrillation.

BACKGROUND: The activated local atrial renin-angiotensin system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation (AF). We hypothesized that RAS genes might be among the susceptibility genes of nonfamilial structural AF and conducted a genetic case-control study to demonstrate this. METHODS AND RESULTS: A total of 250 patients with documented nonfamilial structural AF and 250 controls were selected. The controls were matched to cases on a 1-to-1 basis with regard to age, gender, presence of left ventricular dysfunction, and presence of significant valvular heart disease. The ACE gene insertion/deletion polymorphism, the T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen gene, and the A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In multilocus haplotype analysis, the angiotensinogen gene haplotype profile was significantly different between cases and controls (chi2=62.5, P=0.0002). In single-locus analysis, M235T, G-6A, and G-217A were significantly associated with AF. Frequencies of the M235, G-6, and G-217 alleles were significantly higher in cases than in controls (P=0.000, 0.005, and 0.002, respectively). The odds ratios for AF were 2.5 (95% CI 1.7 to 3.3) with M235/M235 plus M235/T235 genotype, 3.3 (95% CI 1.3 to 10.0) with G-6/G-6 genotype, and 2.0 (95% CI 1.3 to 2.5) with G-217/G-217 genotype. Furthermore, significant gene-gene interactions were detected by the multifactor-dimensionality reduction method and multilocus linkage disequilibrium tests. CONCLUSIONS: This study demonstrates the association of RAS gene polymorphisms with nonfamilial structural AF and may provide the rationale for clinical trials to investigate the use of ACE inhibitor or angiotensin II antagonist in the treatment of structural AF.

Aged↗

PubMed2004

Restoration of heart rate turbulence by titrated beta-blocker therapy in patients with advanced congestive heart failure: positive correlation with enhanced vagal modulation of heart rate.

INTRODUCTION: Heart rate turbulence (HRT) is a powerful novel predictor for cardiovascular mortality. Chronic congestive heart failure is associated with abnormal HRT. Whether antiadrenergic beta-blocker therapy can restore control of HRT in patients with chronic congestive heart failure is unknown. METHODS AND RESULTS: A 24-hour Holter ECG recording was obtained before and 1 and 3 months after titrated addition of atenolol therapy in 10 consecutive patients with advanced congestive heart failure. Two parameters derived from HRT, turbulence slope (TS) and turbulence onset (TO), and time- and frequency-domain heart rate variability (HRV) parameters (SDNN, RMSSD, VLF, LF, HF) from 24-hour ECG were compared before and after beta-blocker therapy, together with the same parameters in age-matched normal control. Results showed that TS (3.1 +/- 2.2 vs 6.2 +/- 3.0; P = 0.001) and all HRV parameters were increased after 3 months of atenolol treatment. No changes in TO were evident (0.6 +/- 0.5 vs -0.2 +/- 1.3; P = 0.13). The improvement of TS and the vagally mediated parameters of mean R-R interval, RMSSD, and the HF component of HRV were positively correlated. CONCLUSION: Abnormal HRT caused by chronic congestive heart failure can be restored by beta-blocker therapy. The evolution of TS was positively correlated with measures of vagal modulation of heart rate.

Adrenergic beta-Antagonists↗