Clinical Aspects of Aconitum Preparations.

Aconite species have played an important role in human history. Aconitum species have been used worldwide as poisons as well as remedies. Their potential in targeting several ailments such as pain, rheumatism, and lethargy has been recognized by Western, Chinese, and Indian health care practitioners. Aconite use in herbal preparations has declined, especially in Europe and the United States, in the first half of the twentieth century due to several reported toxicity cases. The situation has changed with the application of new technologies for the accurate analysis of its toxic components and the development of efficient detoxification protocols. Some Asian countries started small clinical trials to evaluate the potency and safety of different marketed aconite preparations. The current review summarizes therapeutic uses of aconite preparations in China, Taiwan, India, and Japan. It also highlights clinical trial results with special emphasis on their limitations. Modern drugs and pharmacopoeial preparations derived from aconite are also discussed.

Electrolysed-reduced water dialysate improves T-cell damage in end-stage renal disease patients with chronic haemodialysis.

BACKGROUND: T-cell damage by increased oxidative stress in end-stage renal disease (ESRD) patients undergoing chronic haemodialysis (HD) led to the increased T-cell apoptosis and the alteration of surface markers and Th1/Th2 ratio in CD4(+) T lymphocytes. Antioxidant electrolysed-reduced water (ERW) was used as the dialysate in ESRD patients undergoing chronic HD to test for improved oxidative stress-related T-cell apoptosis, alterations of surface markers and intracellular cytokine profile. METHODS: We evaluated apoptosis formation by annexin V, CD25-related surface markers, and cytokine ratio of Th1/Th2 in CD4(+) T lymphocytes and Tc1/Tc2 in CD8(+) T lymphocytes of 42 ESRD patients haemodialysed with ERW for 1 year. RESULTS: In comparison to 12 healthy individuals, the ESRD patients had more T-cell apoptosis and less CD3(+), CD4(+) and CD8(+) T cells and CD25/CD69/CD94/CD3(+) phenotypes at baseline. Lower intracellular IL-2 and IFN-gamma levels in the Th1/CD4(+) and Tc1/CD8(+) cells and higher intracellular IL-4, IL-6 and IL-10 levels in the Th2/CD4(+) and Tc2/CD8(+) cells were also noted in the ESRD patients. After a 1-year ERW treatment, the patients had a decrease in T-cell apoptosis and increases in CD3(+), CD4(+) and CD8(+) cell numbers and CD25/CD69/CD94/CD3(+) phenotypes in the T cells. The intracellular IL-2 and IFN-gamma levels in the Th1/Tc1 cells significantly (P < 0.05) increased and the intracellular IL-4, IL-6 and IL-10 levels in the Th2/Tc2 cells decreased. Furthermore, the Th1/Th2 and Tc1/Tc2 cytokine ratios were improved toward a normal status. CONCLUSION: One-year ERW treatment effectively ameliorated T-cell apoptosis, altered CD25-related surface markers and intracellular cytokine profile in the HD patients.

Role of the right atrial substrate in different types of atrial arrhythmias.

BACKGROUND: The regional distribution of the low-voltage zones (LVZs) may relate to the maintenance of atrial arrhythmias in the right atrium (RA). OBJECTIVES: The purpose of this study was to investigate the RA substrate characteristics in different types of atrial arrhythmias originating from RA and left atrium (LA). METHODS: Forty-five patients (35 men, age = 62 +/- 15 years) with RA atypical atrial flutter (n = 15, group 1), RA atrial fibrillation (AF; n = 15, no PV initiating foci, group 2), and LA AF (n = 1 5, no RA arrhythmias, group 3) referred for three-dimensional EnSite mapping were included. Voltage and activation maps were visualized. RESULTS: The mean voltage of the RA was lower in group 2, and compared with group 3, a voltage reduction during atrial pacing was evident in groups 1 and 2. The fixed LVZs (independent of the rhythm) were mostly located along the lower crista terminalis (CT). A functional extension of the LVZ was located on the CT in 84% of patients, sinus venosa in 18%, and free-wall region in 27%, forming the borders of the slow conduction isthmus for the reentrant circuits. The number of slow conduction isthmuses was 1.3 +/- 0.9, 2.2 +/- 1.0, and 0.87 +/- 0.74, for the groups 1-3 patients, respectively (P <.05). Radiofrequency ablation connecting the LVZs successfully eliminated those isthmuses. The long-term follow-up revealed that 66% of the patients remained in sinus rhythm. CONCLUSIONS: Single and multiple slow conduction isthmuses bordered by the fixed and functional LVZs were critical for the reentrant circuits in the RA. The conduction isthmuses could be identified by their substrate characteristics and ablated successfully.

The role of left atrial muscular bundles in catheter ablation of atrial fibrillation.

OBJECTIVES: We sought to investigate the imaging of the left atrial (LA) muscular bundle and the relationship between the bundle and inducibility of tachyarrhythmia after pulmonary vein isolation (PVI). BACKGROUND: Noninducibility is used as a clinical end point of atrial substrate ablation after PVI. However, little is known about the role of the LA muscular bundles in tachyarrhythmia after PVI. METHODS: Forty-three consecutive patients with paroxysmal atrial fibrillation who underwent catheter ablation were included. Bi-atrial isochronal mapping was performed with the NavX system (St. Jude Medical Inc., St. Paul, Minnesota) during sinus rhythm. After 4 PVI, inducible organized LA flutter with or without transforming to atrial fibrillation (AF) (LA flutter/AF) was ablated with additional lines at the roof and/or mitral isthmus. RESULTS: The existence of bilateral muscular bundles was an independent predictor of LA flutter/AF after PVI (p = 0.02). Patients with LA flutter/AF after PVI had a greater index of the double potentials (5.4 +/- 3.4% vs. 2.8 +/- 1.8%, p = 0.006) and interpotential interval (33 +/- 5 ms vs. 29 +/- 4 ms, p = 0.02) than without LA flutter/AF. The muscular bundles were identified in 28% patients using 16-slice multidetector computed tomography, which were identical to the isochrone map. Patients with noninducible LA flutter/AF after PVI plus the additional linear ablation had a lower recurrence rate as compared with the patients without it (19% vs. 75%, p = 0.02). CONCLUSIONS: Left atrial muscular bundles may provide a conduction block line and barrier, which is important for the formation of LA flutter/AF after PVI. The noninducibility of LA flutter/AF achieved after additional linear ablation may contribute to a better outcome in RF ablation of paroxysmal atrial fibrillation.

Effects of heart rate on brachial-ankle pulse wave velocity and ankle-brachial pressure index in patients without significant organic heart disease.

This study evaluated the effects of heart rate (HR) on brachial-ankle pulse wave velocity (baPWV) and ankle-brachial pressure index (ABI). Thirty-two patients without significant organic heart disease underwent elective cardiac catheterization or electrophysiologic study, and were then enrolled in right atrial pacing (RAP; 11 men, 9 women; aged 48 -/+ 15 years) or right ventricular pacing (RVP; 6 men, 6 women, aged 45 -/+ 13 years) studies. Three different HR levels (90, 100, and 110 beats per minute) were paced in random order. By stepwise, multiple linear regression analysis, age, systolic blood pressure (SBP), and pulse pressure (PP) correlated positively with baseline baPWV. In the RAP group, as HR increased, baPWV and left brachial diastolic blood pressure increased significantly (p < or = 0.015), while ABI, left ankle SBP, left brachial PP, and left ankle PP decreased significantly (p < or = 0.013). In the RVP group, as HR increased, baPWV also increased significantly (p = 0.001), while ABI, left ankle SBP, and PP decreased significantly (p < or = 0.034). Values of baPWV and ABI may be influenced by HR in young and middle-aged patients without significant organic heart disease. When these values are used to evaluate and follow up cardiovascular risk in patients, HR changes should be considered.

Noncontact three-dimensional mapping guides catheter ablation of difficult atrioventricular nodal reentrant tachycardia.

BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common supraventricular tachycardia in adulthood. Although selective ablation of the slow AV nodal pathway can cure AVNRT, accidental AV block may occur. The details on the electrophysiologic characteristics, quantitative data on the voltage inside Koch's triangle, and the use of three-dimensional noncontact mapping to facilitate the catheter ablation of AVNRT associated with a high-risk for AV block or other arrhythmias have been limited. METHODS AND RESULTS: Nine patients (M/F=5/4, 34+/-23 years, range 17-76) with clinically documented AVNRT were included. All patients had undergone previous sessions for slow AV nodal pathway ablation but they had failed, because of repetitive episodes of complete AV block during the RF energy applications. Further, one patient had a complex anatomy and 4 patients were associated with other tachycardias, respectively. The electrophysiologic studies revealed that 4 patients had the slow-fast, 4 the slow-intermediate and one the fast-intermediate form of AVNRT. Noncontact mapping demonstrated two types of antegrade AV nodal conduction, markedly differing sites of the earliest atrial activation during retrograde VA conduction, and a lower range of voltage within Koch's triangle. The lowest border of the retrograde conduction region was defined on the map, and the application of the RF energy was delivered below that border to prevent the occurrence of AV block. The distance between the successful ablation lesions and the lowest border of the retrograde conduction region was significantly shorter in the patients with the slow-intermediate form of AVNRT than in those with the slow-fast form (5.5+/-3.4 vs. 15+/-7.6 mm; p<0.05). After the ablation procedure, either rapid pacing or extrastimulation could not induce any tachycardia, and there was no recurrence during the follow-up (10.3+/-5.4, 2 to 22 months). CONCLUSIONS: Noncontact mapping could effectively demonstrate the antegrade and retrograde atrionodal conduction patterns, electrophysiologic characteristics of Koch's triangle, and guide the successful catheter ablation in difficult AVNRT cases.

The electrophysiologic characteristics of atrioventricular nodal reentry tachycardia with eccentric retrograde activation.

BACKGROUND: The occurrence of eccentric retrograde atrial activation has been demonstrated to be from 6 to 8% in patients with atrioventricular nodal reentrant tachycardia (AVNRT) by several previous reports. However, most of those reports were limited by the absence of coronary sinus venography to confirm if the retrograde activation was truly left sided. The purposes of this study were to 1) determine the incidence of left sided retrograde atrial activation in our center, 2) determine the specific electrophysiologic characteristics of eccentric and concentric atrial activation and 3) determine the outcome of radiofrequency catheter ablation for AVNRT with eccentric retrograde atrial activation. METHODS: From November 2001 to July 2004, 290 consecutive patients with AVNRT who underwent an electrophysiologic study and radiofrequency ablation were included. Group 1 consisted of AVNRT patients with eccentric retrograde atrial activation; group 2 consisted of AVNRT patients with concentric retrograde atrial activation. The electrophysiologic characteristics of the group 1 and group 2 patients were then compared. RESULTS: The incidence of AVNRT with eccentric retrograde activation confirmed by CS venography was 6.5%. There were more females and atypical AVNRT in patients with retrograde eccentric conduction. There was more VA block after ablation and tachycardia induction by right ventricular pacing/extrastimuli in eccentric rather than concentric retrograde atrial activation. A shorter antegrade fast functional refractory period of the AV node was demonstrated in the atypical eccentric group as compared to the atypical concentric group. CONCLUSION: This study demonstrated the different electrophysiologic characteristics between the AVNRT patients with eccentric and concentric retrograde atrial activation. Successful ablation sites were similar to the standard RA ablation sites in patients with retrograde eccentric conduction.

Substrate mapping to detect abnormal atrial endocardium with slow conduction in patients with atypical right atrial flutter.

OBJECTIVES: The purpose of this study was to investigate the relationship between the abnormal substrate and peak negative voltage (PNV) in the right atrium (RA) with atypical flutter. BACKGROUND: The impact of a local abnormally low voltage electrogram on the local activation pattern and velocity of atrial flutter (AFL) remains unclear. METHODS: Twelve patients with clinically documented AFL were included to undergo noncontact mapping of the RA. The atrial substrate was characterized by the: 1) activation mapping; 2) high-density voltage mapping; and 3) conduction velocity along the flutter re-entrant circuit. The normalized PNV (i.e., the relative ratio to the maximal PNV) in each virtual electrode recording was used to produce the voltage maps of the entire chamber. The protected isthmus was bordered by low voltage zones. RESULTS: Atypical AFL of the RA was induced by atrial pacing in 12 patients, including 10 upper loop re-entry and 2 RA free wall re-entry flutter. These protected isthmuses were located near the crista terminalis. The mean width of the protected isthmus was 1.7 +/- 0.3 cm and mean voltage at the isthmus was -0.91 +/- 0.39 mV. The conduction velocities within these paths were significantly slower than outside the path (0.30 +/- 0.18 m/s vs. 1.14 +/- 0.41 m/s, respectively; p = 0.004). The ratiometric PNV of 37.6% of the maximal PNV had the best cut-off value to predict slow conduction, with a high sensitivity (92.3%) and specificity (85.7%). CONCLUSIONS: Characterization of the RA substrate in terms of the unipolar PNV is an effective predictor of the slow conduction path within the critical isthmus of the re-entrant circuit.

Coronary sinus morphology in different types of supraventricular tachycardias.

BACKGROUND: Atrioventricular nodal reentry tachycardia (AVNRT) is based on the concept of dual AV node pathways that are functionally and anatomically distinct. The bigger coronary sinus ostium (CSO) in patients with AVNRT compared to other supraventricular tachycardias (SVTs) may produce separation of atrial inputs into the AV node or create anisotropic conduction, thus giving rise to a different AV nodal physiology. Previous studies measuring the size of the CSO using CS angiography between patients with AVNRT and other SVTs showed conflicting results. Besides, no previous studies have compared the CS morphology of the different forms of AVNRT. OBJECTIVES: This study compares the size and morphology of the CS among patients with typical AVNRT, atypical AVNRT and accessory pathways mediated reentrant tachycardia (AVRT). METHODS: Ninety-six patients with clinically documented SVTs were divided into three groups. The diameter of the CS was measured in LAO projection during end ventricular systole (by choosing the last ventricular inward motion). The CSO as well as 5, 10 and 15 mm inside the CS were measured. CS morphology is defined as either wind-sock shape or tubular shape. RESULTS: The size of the CS ostium was 13.58 +/- 3.98, 15.93 +/- 4.86 and 12.50 +/- 2.83 mm for the atypical AVNRT, typical AVNRT and AVRT, respectively (p = 0.03). There was significant difference in the size of the CS from the ostium until 15 mm into the CS between 1) typical AVNRT and AVRT, 2) typical AVNRT and atypical AVNRT. Typical and atypical AVNRT patients had more windsock morphology CS (13/32, 40.6% and 10/32, 31.2%) compared to AVRT which had only one (1/32, 3.1%) windsock morphology (p = 0.002). CONCLUSION: The easier CS cannulation in patients with typical AVNRT could be due to a bigger CS size and to a more windsock morphology. The CS size and morphology may be a very important substrate of tachycardia in patients with AVNRT.

The different mechanisms between late and very late recurrences of atrial fibrillation in patients undergoing a repeated catheter ablation.

INTRODUCTION: The mechanisms of late (<1 year after the ablation) and very late (>1 year after the ablation) recurrences of paroxysmal atrial fibrillation (AF) after catheter ablation have not been reported. METHODS AND RESULTS: Fifty consecutive patients undergoing a repeated electrophysiologic study to investigate the recurrence of paroxysmal AF after the first ablation were included. Group 1 consisted of 12 patients with very late (26 +/- 13 months) and group 2 consisted of 38 patients with late (3 +/- 3 months) recurrence of paroxysmal AF. In the baseline study, group 1 had a lower incidence of AF foci from the pulmonary veins (PVs) (67% vs 92%, P = 0.048) and a higher incidence of AF foci from the right atrium (50% vs 13%, P = 0.014) than group 2. In the repeated study, group 1 had a higher incidence of AF foci from the right atrium (67% vs 3%, P < 0.001) and a lower incidence of AF foci from the left atrium (50% vs 97%, P < 0.001), including a lower incidence of AF foci from the PVs (50% vs 79%, P = 0.07) and from the left atrial free wall (0% vs 29%, P = 0.046) than group 2. Furthermore, most of these AF foci (64% of group 1, 65% of group 2) were from the previously targeted foci. CONCLUSION: The right atrial foci played an important role in the very late recurrence of AF, whereas the left atrial foci (the majority were PVs) were the major origin of the late recurrence of AF after the catheter ablation of paroxysmal AF.

A new electrocardiographic algorithm to differentiate upper loop re-entry from reverse typical atrial flutter.

OBJECTIVES: This study was performed to differentiate upper loop re-entry (ULR) from reverse typical atrial flutter (AFL). BACKGROUND: Right atrial ULR and reverse typical AFL have different mechanisms and ablation strategies, but similar electrocardiographic characteristics. METHODS: This study included 26 patients with reverse typical AFL and 20 patients with ULR. The noncontact mapping system (EnSite-3000, Endocardial Solutions, St. Paul, Minnesota) was used to confirm diagnosis and guide successful radiofrequency ablation. Flutter wave polarity and amplitude in the 12-lead surface electrocardiogram were determined by two independent electrophysiologists. RESULTS: The flutter wave polarity in leads I and aVL was significantly different between the reverse typical AFL and ULR groups (p < or = 0.001). Voltage measurement revealed significant differences between reverse typical AFL and ULR in leads I, II, aVR, aVF, V1, and V2 (p < 0.001). A new diagnostic algorithm based on negative or isoelectric/flat flutter wave polarity and amplitude < or =0.07 mV in lead I was useful for diagnosis of ULR, with an accuracy of 90% to 97%, a sensitivity of 82% to 100%, and a specificity of 95%. CONCLUSIONS: Polarity and voltage measurement of flutter wave in lead I can differentiate reverse typical AFL from ULR.

Effects of right bundle branch block during atrioventricular nodal reentrant tachycardia.

BACKGROUND: The significant role of bundle branch block during atrioventricular nodal reentrant tachycardia (AVNRT) is not clear. The purposes of this study were to study the effects of complete right bundle branch block (RBBB) on electrophysiological parameters during AVNRT and to define the significance of complete RBBB during AVNRT. METHODS AND RESULTS: According to characteristics of electrocardiogram during sinus rhythm and AVNRT, 50 patients who underwent catheter ablation for slow-fast AVNRT were divided into three groups. Group I included 20 patients who had narrow QRS (< or = 110 ms) during sinus rhythm and AVNRT. Group II included 18 patients who had persistent RBBB (< or = 120 ms) during sinus rhythm and AVNRT. Group III included 12 patients who had narrow QRS during sinus rhythm, but they had narrow QRS and transient RBBB during AVNRT. The atrio-His (AH) interval (296+/-60 vs. 288+/-75 ms), His-ventricular (HV) interval (36+/-11 vs. 35+/-11 ms), His-atrial (HA) interval (72+/-24 vs. 71+/-28 ms), VA(HRA) interval (defined as the interval between the onset of ventricular depolarization and the onset of atrial activity of right high atrium; 34+/-24 vs. 37+/-25 ms), VA(CSO) interval (defined as the interval between the onset of ventricular depolarization and the onset of atrial activity of coronary sinus ostium; 13+/-28 vs. 26+/-23 ms) and tachycardia cycle length (TCL; 368+/-67 vs. 359+/-73 ms) during AVNRT were similar between group I and group II (all P > 0.05). In group III, the AH interval (255+/-81 vs. 246+/-83 ms), HV interval (44+/-5 vs. 42+/-11 ms), HA interval (66+/-19 vs. 70+/-15 ms), VA(HRA) interval (27+/-15 vs. 29+/-16 ms), VA(CSO) interval (23+/-25 vs. 21+/-25 ms) and TCL (322+/-76 vs. 316+/-77 ms) were not significantly different between AVNRT with narrow QRS and those with transient RBBB (all P > 0.05). CONCLUSIONS: Persistent RBBB and transient RBBB have no significant effects on the electrophysiological parameters during AVNRT. These findings suggest that RBBB might not influence the conduction of lower common pathway or the circuit of AVNRT.

The electrophysiologic characteristics in patients with only ventricular-pacing inducible slow-fast form atrioventricular nodal reentrant tachycardia.

BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) can be usually induced by atrial pacing or extrastimulation. However, it is less commonly induced only by ventricular pacing or extrastimulation. OBJECTIVE: The purpose of this retrospective study was to investigate the electrophysiologic characteristics in patients with slow-fast form AVNRT that could be induced only by ventricular pacing or extrastimulation. METHODS: The total population was 1497 patients associated with AVNRT. There were 1373 (91.7%) patients who had slow-fast form AVNRT included in our study. Group 1 (n = 45) could be induced only by ventricular pacing or extrastimulation, and Group 2 (n = 1328) could be induced by only atrial stimulation or both atrial and ventricular stimulation. The electrophysiologic characteristics of the group 1 and group 2 patients were compared. RESULTS: Group 1 patients had a significantly lower incidence of both antegrade and retrograde dual AV nodal pathways. The pacing cycle length (CL) of the antegrade 1:1 fast pathway (FP) and antegrade ERP of the FP were both significantly shorter in Group 1 patients. Mean antegrade FRP of the fast and slow pathways were significantly shorter in Group 1 patients. The differences of pacing CL of 1:1 antegrade conduction, antegrade ERP and FRP were much longer in Group 2 patients. CONCLUSION: This study demonstrated the patients with slow-fast form AVNRT that could be induced only by ventricular stimulation had a lower incidence of dual AV nodal pathways and the different electrophysiologic characteristics (shorter pacing CL of the antegrade 1:1 FP, antegrade ERP of the FP and the differences of pacing CL of 1:1 antegrade conduction, antegrade ERP and FRP) from the other patients. The specific electrophysiologic characteristics in such patients could be the reason that could be induced only by ventricular stimulation.

Electrophysiological mechanisms and catheter ablation of complex atrial arrhythmias from crista terminalis:.

Paroxysmal atrial fibrillation (PAF) can be initiated by ectopic activation from the crista terminalis. The crista terminalis conduction gap is also a critical isthmus in atrial reentrant arrhythmias like upper and lower loop reentry. The aim of this study was to investigate the mechanism and results of catheter ablation for complex atrial arrhythmias originating from the crista terminalis using the noncontact mapping system (NCM). The study population consisted of six patients (5 men, 1 woman; 70 +/- 9 years) with drug refractory PAF and typical/atypical atrial flutter. NCM identified the earliest ectopic activation originating from the crista terminalis in these six patients. The reentry circuit of atypical atrial flutter propagated around the upper crista terminalis in five patients, and lower crista terminalis in one patient. The reentry circuit of atypical atrial flutter and the initial reentry circuit of AF conducted through the crista terminalis gap in all patients. Radiofrequency applications were delivered on the sites of ectopy, which initiated AF. Substrate modification was also performed over the crista terminalis gap (six patients) and cavotricuspid isthmus (three patients) responsible for the reentry. During a mean follow-up of 9 +/- 5 months (range 5-18 months), five patients were free of AF without antiarrhythmic drugs, and one patient did not have AF or atrial flutter using propafenone. NCM demonstrated the mechanism of crista terminalis ectopy-initiating AF and associated typical/atypical atrial flutter. Catheter ablation of crista terminalis ectopy and substrate for the reentry guided by NCM successfully eliminated these atrial arrhythmias.

Effect of electrophysiologic character of ventricular premature beat on heart rate turbulence.

Heart rate turbulence (HRT) has been described as a predictor of high-risk patients with cardiac diseases. The purpose of this study is to determine how the degree of prematurity of a ventricular premature beat (VPB%) and retrograde ventriculoatrial (VA) conduction of VPBs affect HRT. We studied 30 patients without organic heart disease. We calculated turbulent slope (TS) and turbulent onset (TO) from VPBs induced by programmed stimulation from the right ventricular apex. TS was inversely and TO was positively correlated to VPB%. Without retrograde VA conduction of VPBs, TS was inversely and TO was positively correlated to VPB%. In VPBs with retrograde VA conduction, there were no significant correlations between TO and TS with VPB%. In conclusion, TS and TO calculated from VPBs with different degrees of prematurity varied widely. Both VPB% and characteristics of retrograde VA conduction may affect HRT.