Atrial fibrillation after DDDR pacemaker implantation

INTRODUCTION: Newer implantable pulse generators have data storage capabilities that permit detection of multiple episodes of atrial fibrillation (AF). This study evaluated the clinical predictors and time course of AF development in a general pacemaker population. METHODS AND RESULTS: Patients (n = 231) received DDDR pacemakers with features that permit detection and storage of information about the date, time of onset, and duration of multiple, sequential episodes of AF. Patients were followed for 718+/-383 days. Time to first occurrence of AF, interval between first and second episode of AF, and total AF burden were determined at each follow-up visit. AF occurred more often in patients (68%) with sinus node disease than in patients with AV block (37%; P < 0.001). Time to first occurrence of AF was 21.2 days (95% confidence interval [CI] 14.7 to 30.6 days) after pacemaker implantation. AF burden initially decreased significantly in patients (0.8 hours/day, 95% CI 0.7 to 0.9 at 8 weeks after implant vs 0.6 hours/day, 95% CI 0.4 to 0.8 at 12 months after implant; P = 0.005) but then increased significantly during long-term follow-up (2.0 hours/day, 95% CI 1.0 to 3.7 at 48 months after implant; P = 0.008). The long-term increase in AF burden was seen predominantly in patients with sinus node disease. A prior history of AF and the duration of follow-up were independent predictors of AF occurrence. CONCLUSION: AF develops frequently after dual-chamber pacemaker implantation. AF burden increases progressively over the long term.     

Burden of atrial fibrillation after cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) may diminish atrial fibrillation (AF) burden in patients with chronic heart failure (HF). Each of 27 patients without permanent AF in whom CRT implantation was unsuccessful was paired with 2 active CRT patients-1 responder and 1 nonresponder-based on age, gender, cause of HF, and history of paroxysmal AF. Device-documented high atrial rates and mode-switching episodes were tabulated during a median follow-up of 386 days. CRT responders had significantly improved left ventricular (LV) ejection fraction and New York Heart Association functional class compared with nonresponders and controls. Left atrial dimension change was similar among the groups (+0.03 +/- 0.92 cm controls; -0.18 +/- 0.80 cm responders; -0.11 +/- 1.01 cm nonresponders) despite a significant reduction in mitral regurgitation in responders compared with nonresponders. There was no significant difference in AF burden between controls and patients who underewent CRT when indexed over time. Median AF-free follow-up was significantly longer in patients who underwent CRT without a history of AF (log-rank p = 0.04), but no differences were seen in the overall cohorts. In conclusion, despite inducing LV reverse remodeling and clinical improvement, CRT does not appear to decrease AF burden in responders compared with nonresponders or matched controls in whom CRT implantation failed. CRT may, however, delay onset of new AF.     

Ventricular high-rate episodes in pacemaker diagnostics identify a high-risk subgroup of patients with tachy-brady syndrome.

OBJECTIVES: The purpose of this study was to evaluate the frequency and clinical significance of ventricular high-rate (VHR) episodes (ventricular rate >162 bpm) in patients with symptomatic bradycardia and paroxysmal atrial fibrillation (AF). BACKGROUND: Newer pacemakers have enhanced diagnostic features that permit detection and storage of detailed information about the frequency, duration, and time of onset of multiple episodes of AF, atrial tachycardia (AT), and ventricular tachycardia (VT). However, the prevalence and prognostic value of AF associated with rapid ventricular rates in the pacemaker population are unknown. METHODS: We prospectively followed 125 patients who received a Medtronic AT 500/501 pacemaker for symptomatic bradycardia and paroxysmal AF. RESULTS: AF recurred in 112 patients (90%) during 22 +/- 8 months of follow-up. A total of 1,324 VHR episodes occurred in 38 patients (30%). Episodes with available electrograms (n = 560) were reviewed and classified as AF (n = 279; 50%), AT (n = 266; 47%) or VT (n = 15; 3%). AF burden was higher in patients with VHR episodes (median 1.9 vs 0.2 hours/day; P < .001). After controlling for AT/AF burden and heart disease, VHR episodes were a significant independent predictor of hospitalization for cardiovascular symptoms (odds ratio 2.92, 95% confidence interval 1.33-6.38; P = .007). Heart rate control improved over time in the cohort, and the frequency of VHR episodes decreased during follow-up (P < .001). CONCLUSIONS: VHR episodes documented in the pacemaker diagnostics identify a high-risk subgroup of patients with AF. Monitoring VHR episodes may be useful for identifying pacemaker patients with AF who require more vigilant monitoring, additional investigations, and/or additional interventions.     

Results of the multicenter RENEWAL 3 AVT clinical study of cardiac resynchronization defibrillator therapy in patients with paroxysmal atrial fibrillation

INTRODUCTION: Atrial fibrillation impacts the clinical course of up to 50% of patients with advanced heart failure (HF) who are eligible for cardiac resynchronization therapy with a defibrillator (CRT-D). While RV-based defibrillators are available with advanced atrial diagnostics and therapies that provide rapid diagnosis and treatment of spontaneously occurring atrial tachycardia/fibrillation (AT/AF) episodes, there is no CRT-D device that combines atrial/ventricular and CRT therapies. PURPOSE: The purpose of the prospective multicenter RENEWAL 3 AVT study is to assess the performance of atrial diagnostics and therapies used in combination with a CRT-D device. METHODS: Enrolled patients were required to have indications for a CRT-D device and a documented episode of AT/AF within 12 months of enrollment. A total of 170 patients were enrolled over 9 months (85% male; mean age 72 +/- 10 years; NYHA classification: 88% III, 12% IV; left ventricular ejection fraction [LVEF] mean 23 +/- 6%; mean QRS duration 150 +/- 25 msec; 78% ischemic etiology). The documented atrial arrhythmia was AF in 77% of patients. A total of 60% of patients had the CRT-D device placed for primary prevention of sudden death and 40% of patients had a history of ventricular arrhythmia in addition to HF. The device operates in the biventricular (BiV) triggered mode for sensed ventricular events associated with AF. RESULTS: A total of 159 patients (95%) had a successful CRT-D implant. Over a mean follow-up of 5.7 +/- 2.3 months, there were a total of 152 atrial shocks delivered in 108 patients for induced (93%) or spontaneous (7%) occurring episodes of AF. Spontaneously occurring AF was observed in 40 patients (25%). The rate of first shock conversion was 118/152 (78%, mean energy 11.6 +/- 5.9 J). Overall shock therapy conversion rate was 138/152 (91%). The number of shock conversions resulting in sinus rhythm maintained for at least 2 minutes postshock was 87% for induced episodes. Therapy was delivered for spontaneous ventricular tachycardia/fibrillation in nine patients (6%). There was no instance of ventricular proarrhythmia associated with atrial shock therapies, undersensing of ventricular arrhythmias, or interruption of CRT therapy associated with the combined device. CONCLUSIONS: In CRT-D candidates with a history of AF, 25% experience recurrent AF within 6 months of implant. Atrial detection and ventricular detection, shock, and resynchronization therapies are not compromised by the addition of atrial therapies to a CRT-D device.     

心脏再同步治疗术后新发心房颤动与窦性心律的对比分析

目的 分析心脏再同步治疗（CRT）术后1年内慢性心力衰竭（CHF）患者出现新发心房颤动（房颤）与保持窦性心律的疗效对比情况.方法 接受CRT治疗CHF患者54例,所有患者术前均无房颤病史,于术前和术后6、12个月进行程控随访及临床、超声心动图检查.结果 1年随访结束时,54例患者中有12例（22.2%）出现新发房颤,其余42例保持窦性心律.窦性心律组术后临床及超声心动图指标均较术前明显改善（P＜0.001）.新发房颤组术后心功能、左心室射血分数（LVEF）、左心室舒张末内径也较术前有明显改善（P＜0.05）,但左心房内径及二尖瓣反流无明显变化.两组间比较,左心房内径在窦性心律组较新发房颤组有明显缩小的趋势（P=0.057）.亚组分析,阵发性房颤患者术后心功能、LVEF较术前改善（P＜0.05）,而持续性房颤患者术后各指标较术前均无明显变化.CRT术后新发房颤危险因素经Logistic回归显示为术前二尖瓣反流程度（P=0.046,OR=3.729）和新发房颤发生前的心房起搏比例（P=0.010,OR=1.050）.结论 CRT术后新发房颤与二尖瓣反流程度加重和心房起搏比例增高明显相关.新发阵发性房颤一般不影响CRT疗效,新发持续性房颤CRT术后疗效较差.     

Spontaneous episodes of atrial fibrillation after implantation of the Metrix Atrioverter: observations on treated and nontreated episodes. Metrix Investigators

OBJECTIVES: We sought to evaluate the number and duration of device-treated and self-terminating, nontreated episodes of atrial fibrillation (AF) after implantation of the Metrix Atrioverter. BACKGROUND: A recent study has shown that the Atrioverter can rapidly restore sinus rhythm in patients with AF; however, the effect of the device on the clinical course of the arrhythmia in these patients is unknown. METHODS: The Atrioverter was implanted in 51 patients with symptomatic, recurrent, drug-refractory AF. The device was programmed to periodically monitor the cardiac rhythm. Defibrillation of AF episodes was performed under physician observation. RESULTS: During a mean follow-up of 260 +/- 144 days, 1,161 episodes of AF were observed during valid monitoring periods in 45 of 51 patients. Forty-one patients experienced 231 episodes for which they sought defibrillation therapy. The average duration of the treated episodes during valid monitoring periods (190 of 231 episodes in 39 of 41 patients) was significantly longer than that of the nontreated episodes (38 +/- 44 vs. 10 +/- 8 h; p < 0.05). The time between episodes requiring Atrioverter therapy increased, and the risk of having an episode requiring treatment decreased. No changes were observed in the number and duration of the short-lasting, nontreated episodes as time since implantation of the device increased. CONCLUSIONS: In patients with symptomatic, recurrent, drug-refractory AF, the frequency of long-lasting episodes, which were treated under observation with repeated defibrillation using the Atrioverter, decreased. The number and duration of short-lasting, nontreated episodes did not change during the 20-month study period. The effect of ambulatory use of the device on the recurrence of short-lasting episodes needs to be evaluated.     

Decrease in plasma B-type natriuretic peptide early after initiation of cardiac resynchronization therapy predicts clinical improvement at 12 months

BACKGROUND: Decrease in neurohormonal activation during pharmacotherapy for chronic heart failure (CHF) is associated with haemodynamic and clinical improvement. We tested the hypothesis that changes in neurohormonal activation after initiation of cardiac resynchronization therapy (CRT) predict its long-term clinical effect. METHODS: The study group included 43 patients with CHF (37 males, mean age 62+/-9 years, NYHA class 3.2+/-0.4, QRS duration 195+/-24 ms) who underwent successful implantation of a CRT system. Pharmacotherapy remained stable during the first 3 months of follow-up. Plasma levels of B-type natriuretic peptide (BNP) and big endothelin-1 (big ET-1) were evaluated before and 3 months after implantation. Clinical, echocardiographic and exercise parameters were monitored for a mean period of 25.8+/-6.7 months. RESULTS: At 12 months of follow-up 13 non-responders were identified (no improvement in NYHA class (n=10), urgent heart transplantation (n=2) and death due to progressive heart failure (n=1)). CRT resulted in a significant reduction in neurohormone levels (BNP 345.4+/-346 vs. 267.7+/-320.8 pg/ml, p<0.01, big ET-1 3.11+/-1.50 vs. 2.50+/-1.56 fmol/ml p<0.05), especially in responders. Percentage change in BNP level was a stronger predictor of long-term clinical improvement than clinical, echocardiographic and exercise parameters at 3 months of follow-up. CONCLUSIONS: Percentage change in plasma BNP levels from baseline to 3 months was the strongest predictor of long-term response to CRT and may have potential to predict outcome.     

Incremental programming of atrial anti-tachycardia pacing therapies in bradycardia-indicated patients: effects on therapy efficacy and atrial tachyarrhythmia burden.

AIMS: Efficacy of pace-termination of atrial arrhythmias (ATP) may depend on atrial cycle length and regularity. Whether device programming of ATP therapies can improve ATP efficacy and alter atrial tachyarrhythmia burden is unknown. METHODS AND RESULTS: ATP efficacy was evaluated in 61 patients (39 males; 66 +/- 10 years) with a standard indication for pacing, 95% with a history of AT/AF. Each patient was implanted with a novel DDDRP pacemaker capable of delivering ATP therapy. ATP efficacy and AT/AF frequency and burden were compared within each patient during a period of nominal ATP programming (NP) followed by a period of aggressive incremental programming (IP). Adjusted ATP-termination efficacy was higher during IP than during NP (54.8% vs 37.9%, P < 0.05). No differences in AT/AF frequency (3.3 +/- 5.9 vs 3.2 +/- 6.9 day(-1)) or burden (18 +/- 28% vs 18 +/- 29%) were observed comparing NP with IP. The majority of episodes during both the NP (81%) and IP (77%) periods terminated within 10 min. Episodes lasting 24 h or more accounted for only 0.4% of the episodes in both groups. but accounted for 38% of the average burden during NP and 51% during IP. CONCLUSIONS: Device programming of ATP therapies can influence the number of treated episodes and the efficacy of ATP therapies although arrhythmic frequency and burden may not change. Total atrial arrhythmia burden is disproportionately influenced by long (>24 h) episodes.     

Combined efficacy of atrial septal lead placement and atrial pacing algorithms for prevention of paroxysmal atrial tachyarrhythmia

INTRODUCTION: The combined role of atrial septal lead location and atrial pacing algorithms in the prevention of atrial tachyarrhythmias (AT/AF), including both atrial fibrillation and flutter, is unknown. We tested the hypothesis that atrial prevention pacing algorithms could decrease AT/AF frequency in patients with atrial septal leads, bradycardia, and paroxysmal AT/AF. METHODS AND RESULTS: A total of 298 patients (age 70 +/- 10 years; 61% male) from 35 centers were implanted with a DDDRP pacing system including three AT/AF prevention pacing algorithms. Lead site was randomized at implant to right atrial septal or nonseptal. Patients were randomized 1 month postimplant to AT/AF prevention ON or OFF for 3 months and then crossed over for 3 months. Patients logged symptomatic AT/AF episodes via a manual activator. Prevention efficacy was evaluated based on intention-to-treat in 277 patients (138 septal) with complete follow-up. No changes in device-recorded AT/AF frequency or burden were observed with algorithms OFF versus ON or between patients randomized to septal versus nonseptal lead location. Analysis of other secondary outcomes revealed that AT/AF prevention pacing resulted in decreased atrial premature contractions in both the septal (1.9 [0.2-8.7] vs 3.3 [0.3-10.6]x 103/day; P < 0.01) and nonseptal groups (0.9 [0.2-3.3] vs 1.3 [0.3-5.5]x 103/day; P < 0.001). Patients with septal leads had fewer symptomatic AT/AF episodes ON versus OFF (1.4 +/- 3.0 vs 2.5 +/- 5.2/month, P = 0.01). CONCLUSION: The combination of three atrial prevention pacing algorithms did not decrease device classified atrial tachyarrhythmia frequency or burden during a 3-month cross-over period in bradycardic patients and septal or nonseptal atrial pacing leads. Prevention pacing was associated with decreased frequency of premature atrial contractions and with decreased symptomatic atrial tachyarrhythmia frequency in patients with atrial septal leads.     

New insights into long-term follow-up of atrial fibrillation ablation: full disclosure by an implantable pacemaker device

Introduction : Long-term outcome of radiofrequency ablation (RFA) for atrial fibrillation (AF) is difficult to assess. This study sought to evaluate various aspects of very long-term follow-up (FU) by the properties of an implantable device.
Methods : Fourteen patients with an implanted pacemaker device (Medtronic AT500) were selected for RFA, due to drug-refractory and highly symptomatic AF despite antibradycardic pacing.
Results : With a mean FU of 41.4 ± 15.1 months, we could achieve continuous monitoring for more than 400,000 hours after RFA. Based on symptomatic episodes, simulated 24-hour, 48-hour, or 7-day Holter, 57% to 71% of the patients were classified as RFA responders. With permanent FU provided by the implanted device, 43% of the patients exhibited a positive treatment effect and only 21% had no tachyarrhythmic episode at all in long-term FU. With a mean of 1.7 ± 0.7 RFA per subject, atrial tachyarrhythmia burden (ATB) was significantly reduced from a median of 3.6 to 0.3 hours per day (P < 0.001). Two out of 14 patients developed AF recurrences after a tachyarrhythmia-free period of more than 12 months.
Conclusion : Continuous monitoring provided by an implantable device is able to detect significantly more AF episodes than routine FU. ATB is decreased significantly by (repeated) RFA over a very long-term FU. AF may reoccur very late after long-lasting (>1 year) episode-free intervals. A subgroup of patients with drug-aggravated bradycardia in brady-tachy syndrome might be considered for PV isolation rather than pacemaker implantation.     

Impact of upgrade to cardiac resynchronization therapy on ventricular arrhythmia frequency in patients with implantable cardioverter-defibrillators.

OBJECTIVES: This study compared cardiac resynchronization therapy's (CRT) impact on ventricular tachyarrhythmia susceptibility in patients who, due to worsening heart failure (HF) symptoms, underwent a replacement of a conventional implantable cardioverter-defibrillator (ICD) with a CRT-ICD. BACKGROUND: Cardiac resynchronization therapy is an effective addition to conventional treatment of HF in many patients with left ventricular systolic dysfunction. However, whether CRT-induced improvements in HF status also reduce susceptibility to life-threatening arrhythmias is less certain. METHODS: Clinical and ICD electrogram data were evaluated in 18 consecutive ICD patients who underwent an upgrade to CRT-ICD. Pharmacologic HF therapy was not altered during follow-up. The definition of ventricular tachycardia (VT) and ventricular fibrillation (VF) for each patient was as determined by device programming. Statistical comparisons used paired t tests. RESULTS: Findings were recorded during two time periods: 47 +/- 21 months (range 24 to 70 months) before and 14 +/- 2 months (range 9 to 18 months) after CRT upgrade. At time of upgrade, patient age was 69 +/- 11 years and ejection fraction was 21 +/- 8%. Before CRT the frequency of VT, VF, and appropriate ICD shocks was 0.31 +/- 1.23, 0.047 +/- 0.083, and 0.048 +/- 0.085 episodes/month/patient, respectively. After CRT-ICD, VT and VF arrhythmia burdens and frequency of shocks were respectively 0.13 +/- 0.56, 0.001 +/- 0.004, and 0.003 +/- 0.016 episodes/month/patient (p = 0.59, 0.03, and 0.05 vs. pre-CRT). CONCLUSIONS: Arrhythmia frequency and number of appropriate ICD treatments were reduced after upgrade to CRT-ICD for HF treatment. Thus, apart from hemodynamic benefits, CRT may also ameliorate ventricular tachyarrhythmia susceptibility in HF patients.     

Intrathoracic impedance monitoring to detect chronic heart failure deterioration: relationship to changes in NT-proBNP

BACKGROUND: An alert algorithm, based on intrathoracic impedance monitoring, has been incorporated into a cardiac resynchronisation device (CRT) to detect pulmonary fluid accumulation, and to audibly alert patients to decompensating chronic heart failure (CHF). AIMS: To evaluate this algorithm, alert events were correlated with changes in NT-proBNP concentration and CHF status. METHODS AND RESULTS: In a prospective observational study of 62 patients (89% male, aged 67+/-1 year), NT-proBNP plasma concentrations, clinical CHF status, and device data were collected at enrolment, during regular follow-up and at device alerts. Over a mean follow-up of 27+/-2 weeks, pooled data indicated a weak, but significant inverse relationship between relative changes in intrathoracic impedance and NT-proBNP (r=-0.3; p<0.001). In 52 device alerts from 35 patients, NT-proBNP increased by 66+/-19% from 2039+/-331 pg/ml (p<0.001). The increase in NT-proBNP was higher in alerts with clinical signs of CHF deterioration (n=30, 89+/-25%; p<0.001) than in alert events without clinical signs (n=22, 25+/-15%; p=n.s.). CONCLUSION: Intrathoracic impedance based alert events are associated with a significant increase in NT-proBNP concentration. These data indicate that intrathoracic impedance monitoring might facilitate the outpatient management of CHF patients with implanted CRT devices.     

Cardiac resynchronization therapy increases plasma levels of the endogenous inotrope apelin

BACKGROUND: Cardiac resynchronization therapy (CRT) has been introduced to treat drug refractory chronic heart failure (CHF). Apelin, the endogenous ligand of the APJ receptor, is under evaluation for its potential role in human CHF pathophysiology. This study aims to assess whether biventricular pacing affects plasma apelin levels in patients with severe CHF. METHODS AND RESULTS: Fourteen patients (9 men, 5 women, mean age 68+/-13 years) undergoing biventricular pace-maker/ICD implantation were studied. Patients underwent baseline clinical and echocardiographic evaluation, and assessment of plasma apelin and NT-proBNP levels. The evaluation was repeated 48 h and 9+/-2 months after device implantation to assess the acute and chronic effects of CRT on apelin and NT-proBNP levels. Eight healthy age- and sex-matched subjects served as controls. In CHF patients, baseline apelin levels were reduced and NT-proBNP increased compared to control subjects (apelin: 0.47+/-0.2 vs. 0.97+/-0.3 ng/mL, p<0.001; NT-proBNP: 2007+/-114 vs. 229+/-72 pmol/L, p<0.001). Short-term evaluation did not reveal any effect of CRT on apelin or NT-proBNP levels. By contrast, at 9+/-2 months follow-up, CRT responders showed left ventricular reverse remodelling and an increase in ejection fraction, together with a significant increase in plasma apelin levels (0.99+/-0.1 vs. 0.47+/-0.2 ng/mL, p<0.001) and decrease in NT-proBNP (938+/-591 vs. 2007+/-114 pmol/L, p<0.05). CONCLUSIONS: Long-term CRT increases plasma levels of the endogenous inotrope apelin in patients with CHF.     

具有一键优化功能的起搏器心脏再同步化治疗慢性心力衰竭的临床观察

目的:观察具有一键优化功能的起搏器心脏再同步化(CRT)治疗慢性心力衰竭(CHF)的临床疗效.方法:16例CHF患者接受起搏器CRT治疗,并分别于植入起搏器术后1周、3个月、6个月、12个月行一键优化,同时行超声心动图及组织多普勒检查.评价具有一键优化功能的起搏器CRT治疗的临床疗效.结果:最佳一键优化AV间期在110-180(159.33±19.50)ms之间,最佳VV间期在0～28(15.73 ±7.55)ms之间.16例患者一键优化起搏器植入术后1周、3个月、6个月、12个月行一键优化后QRS时限、室间隔和左心室后壁收缩时间差(SPWMD)、左心室射血前时间与右心室射血前时间差值(TQ-AV-TQ-PV)、二尖瓣反流面积、左心室舒张末内径(植入术后1周除外)、血浆脑钠素均较植入前降低,并且术后随时间延长逐渐降低,差异均有统计学意义(P均<0.05);主动脉前向血流速度时间积分(VTI)、左心室射血分数、6分钟步行距离均较植入前增加,并且术后随时间延长逐渐增加(血浆脑钠素植入术后12个月与6个月比较除外),差异均有统计学意义(P均<0.05).结论:具有一键优化功能的起搏器CRT治疗能改善CHF患者的血流动力学、临床症状,提高其疗效.     

Comparison of trimetazidine plus sildenafil to chronic nitrates in the control of myocardial ischemia during sexual activity in patients with coronary artery disease

A large proportion of patients who have erectile dysfunction also have coronary artery disease (CAD). In these patients, nitrate therapy is a contraindication to the use of sildenafil. To assess whether the metabolic anti-ischemic agent, trimetazidine, is effective in controlling episodes of myocardial ischemia during sexual activity in patients who have CAD and use long-term nitrate therapy, we studied 38 men (57 +/- 6 years of age) who had proved CAD. Patients underwent 24-hour ambulatory electrocardiographic monitoring at baseline, after 1 week of oral nitrate therapy (20 mg 3 times a day), and after 1 week of trimetazidine (20 mg 3 times a day). Patients were asked to engage in >/=1 session of sexual intercourse during each session of ambulatory electrocardiographic monitoring. They were instructed to take sildenafil (100 mg) 1 hour before sexual intercourse performed at baseline and during therapy with trimetazidine and sildenafil or placebo (blinded) during therapy with nitrates. A decrease in total ischemic burden was observed with nitrates and trimetazidine compared with baseline (-3 +/- 1.2 episodes/patient/24 hours vs -5 +/- 1.3 episodes/patient/24 hours and -6 +/- 5 min/patient/24 hours vs -8 +/- 3 min/patient/24 hours, p <0.01 for nitrates and trimetazidine vs baseline). Trimetazidine plus sildenafil was more effective in controlling episodes of myocardial ischemia during sexual activity than nitrates alone (-45 +/- 11% vs -18 +/- 7%, p <0.04). In conclusion, in patients who have CAD, combination therapy with sildenafil and trimetazidine is more effective than nitrate therapy in the control of ischemic episodes during sexual activity, suggesting that long-term nitrate therapy may be safely switched to trimetazidine therapy when therapy for erectile dysfunction is required.     

Total atrioventricular nodal ablation increases atrial fibrillation burden in patients with paroxysmal atrial fibrillation despite continuation of antiarrhythmic drug therapy

INTRODUCTION: Total atrioventricular nodal (TAVN) ablation and pacing is an accepted and safe treatment for patients with drug-refractory paroxysmal atrial fibrillation (AF). Many patients develop permanent AF within the first 6 months after TAVN ablation. This usually is ascribed to the cessation of antiarrhythmic drug therapy. We hypothesized that TAVN ablation itself creates an atrial substrate prone to AF. METHODS AND RESULTS: Patients participating in the Atrial Pacing Periablation for Paroxysmal Atrial Fibrillation (PA3) study who remained on stable antiarrhythmic drug therapy throughout follow-up were included in this analysis. AF burden and the development of persistent AF in the preablation period were compared to two consecutive postablation periods. Echocardiographic changes also were evaluated. Twenty-two patients remained on stable drug therapy (9 men and 13 women, age 59 +/- 3 years). One patient developed persistent AF preablation compared to 10 postablation (P < 0.05). AF burden preablation was 3.0 +/- 1.2 hours/day and increased to 10.4 +/- 2.2 hours/day and 11.8 +/- 2.3 hours/day in the two postablation follow-up periods (P < 0.05). In patients with fractional shortening (FS) >30% prior to ablation, FS decreased significantly from 39.4% +/- 1.3% to 36.4%+/- 1.7% (P < 0.05). In contrast, in patients with a FS < or =30% prior to ablation, FS increased from 27% +/- 0.8% to 33.6 +/- 1.7% (P < 0.05). CONCLUSION: TAVN ablation increases AF burden and facilitates the development of persistent AF in patients with paroxysmal AF despite the continuation of antiarrhythmic drugs. Loss of AV and/or interventricular synchrony may lead to altered cardiac hemodynamics resulting in atrial stretch and increasing AF burden.     

Impact of cardiac resynchronisation therapy on adaptation of circulatory and respiratory systems to exercise assessed by cardiopulmonary exercise test in patients with chronic heart failure

BACKGROUND: Cardiac resynchronisation therapy (CRT) has become a valuable therapeutic tool in patients with advanced chronic heart failure (CHF). The search for optimal methods for the assessment of CRT efficacy is still underway. AIM: To evaluate the impact of implantation of CRT devices in patients with CHF on adaptation of circulatory and respiratory systems to maximal exercise assessed by cardiopulmonary exercise tests (CPX) and 6-minute walking tests (6MWT). METHODS: We investigated 27 patients (22 males, 5 females, 61.2+/-9.1 years) with a CRT device implanted due to advanced CHF, which resulted from ischaemic or dilated cardiomyopathy. All patients before implantation underwent echocardiography, CPX with expired gas analysis and 6MWT. Investigations were repeated at 3-6 months after CRT implantation. In CPX we evaluated peak oxygen uptake (peak VO2), oxygen pulse, maximal minute ventilation-carbon dioxide production (VE/VCO2 (max)), and its slope (VE/VCO2 slope) and VE/VO2 slope, VO2 in anaerobic threshold (AT), and cardiac and respiratory reserve. In 6MWT we evaluated walking distance and heart rate and blood pressure response to exercise. RESULTS: We noted statistically higher mean peak VO2 after CRT implantation in the studied group: 11.34+/-3.38 vs. 14.56+/-3.99 ml/kg/min (p<0.0001) and 1.01 +/-0.44 vs. 1.4+/-0.55 l/min (p=0.003) and higher values of expired CO2: 1.00+/-0.43 vs. 1.43+/-0.67 l/min (p=0.004). The O2 pulse rose from 9.65+/-3.39 to 13.23+/-5.43 ml/beat (p=0.015). We also observed a significant reduction of VE/VCO2 slope from 42.34+/-13.35 before CRT to 34.77+/-6.04 after CRT (p=0.0196) and a significant decrease of VE/VO2 slope from 41.32 +/-15.46 to 34.01+/-6.27 (p=0.037). VE/VCO2 (max) fell from 58.02+/-15.86 to 50.1+/-13.14 (p=0.009). Patients estimated their dyspnoea on the Borg scale at peak exercise at 4.75+/-0.75 points before CRT and at 3.67+/-1.15 points (p=0.002) after CRT. Patients could walk a longer distance during 6MWT than before CRT (367+/-154.9 vs. 231.1+/-170.3 m, p<0.001). CONCLUSIONS: Cardiac resynchronisation therapy improves exercise tolerance measured by means of CPX and 6MWT, improves respiratory system efficiency and restores its adaptive mechanisms during exercise in patients with advanced CHF. Better exercise adaptation after CRT may be objectively measured with CPX parameters, and correlates with improvement of clinical symptoms. CPX seems to be a very helpful tool in assessing the results of CRT.     

Reduced atrial tachyarrhythmia susceptibility after upgrade of conventional implanted pulse generator to cardiac resynchronization therapy in patients with heart failure.

OBJECTIVES: We sought to identify the impact of cardiac resynchronization therapy (CRT) on atrial tachyarrhythmia (AT) susceptibility in patients with left ventricular (LV) systolic dysfunction in whom worsening heart failure (HF) resulted in upgrade from conventional dual-chamber pulse generator to cardiac resynchronization therapy-defibrillator (CRT-D). BACKGROUND: Cardiac resynchronization therapy with a defibrillator improves survival rates and symptoms in patients with LV systolic dysfunction but little is known about its effects on AT incidence in the same patient population. METHODS: Twenty-eight consecutive HF patients who underwent device upgrade to CRT-D were included. Patients had > or =2 device interrogations in the 1 year before upgrade and > or =3 interrogations in the 18- to 24-month follow-up after upgrade. Echocardiographic parameters were assessed before and at 3 to 6 months after CRT-D. Additional observations included number of hospital stays, HF clinical status, and concomitant pharmacological therapy. By virtue of this study design, each patient served as his/her own control. Statistical analysis was performed by 2-tailed paired t test and with nonparametric tests where appropriate. RESULTS: Within 3 months after CRT, the number of HF patients with documented AT decreased significantly from the immediate pre-CRT value and tended to decline with time. At 1-year follow-up, 90% of patients were AT-free compared with 14% of patients 3 months before CRT (p < 0.001). Furthermore, the number of AT episodes/year and their maximum duration decreased after CRT (mean +/- SD; 181 +/- 50 vs. 50 +/- 20.2, p < 0.05, and 220.8 +/- 87 s vs. 28 +/- 21 s, p < 0.05, respectively). Finally, CRT was associated with improved LV ejection fraction (mean +/- SD; from 26 +/- 5.3% to 31 +/- 7%, p < 0.001) and reduced number of HF or arrhythmia hospital stays (p < 0.05). CONCLUSIONS: Our findings support the view that CRT might decrease AT susceptibility in HF patients with LV systolic dysfunction.     

Comparison of continuous versus intermittent monitoring of atrial arrhythmias

BACKGROUND: The ability of intermittent or symptom-based monitoring to accurately identify patients with atrial tachycardia/atrial fibrillation (AT/AF) and to quantify AT/AF burden is not well established. OBJECTIVES: The purpose of this study was to compare intermittent and symptom-based monitoring to continuous monitoring for (1) identification of patients with any AT/AF, (2) identification of patients with long-duration AT/AF, and (3) assessment of AT/AF burden. METHODS: Data from 574 pacemaker (AT500, Medtronic) patients were analyzed retrospectively over 1 year. The device recorded the amount of AT/AF detected each day. Intermittent monitoring (annual, quarterly, and monthly 24-hour Holter; 7-day and 30-day annual long-term recordings) was simulated by analyzing data from randomly selected days within a prescribed monitoring window. Symptom-based monitoring was approximated by analyzing days when patients indicated symptoms with an external activator. RESULTS: All intermittent and symptom-based monitoring resulted in significantly lower sensitivity (range 31%-71%) and negative predictive value (range 21%-39%) for identification of patients with any AT/AF (P <.001) and underestimated AT/AF burden (P <.001) compared with continuous monitoring. Sensitivity for identifying patients with long-duration episodes ranged from 23% to 58% (P <.001 vs continuous monitoring). Identification of patients with AT/AF and assessment of AT/AF burden with intermittent monitoring depended on the patient's actual AT/AF burden and improved with increasing frequency or duration of intermittent monitoring. CONCLUSION: Intermittent and symptom-based monitoring is highly inaccurate for identifying patients with any or long-duration AT/AF and for assessing AT/AF burden. Further investigation is required to determine if full AT/AF disclosure with implantable devices is effective in reducing stroke risk and facilitating maintenance of sinus rhythm.     

Clinical and electrocardiographic predictors of a positive response to cardiac resynchronization therapy in advanced heart failure.

AIMS: Cardiac resynchronization therapy (CRT) is an effective treatment for refractory congestive heart failure (CHF). However, up to 30% of patients do not respond to CRT. The aim of this study was to identify clinical and electrocardiographic (ECG) predictors of a positive response to CRT. METHODS AND RESULTS: This retrospective study included 139 consecutive patients successfully implanted with a CRT device (mean age, 68+/-9 years, 113 men). At baseline, 69% of patients were in New York Heart Association (NYHA) functional class III, and 31% in class IV, mean left ventricular ejection fraction was 21+/-6%, and mean QRS duration was 188+/-28 ms. In each patient, left and right ventricular leads were placed to attain the shortest QRS duration during biventricular stimulation. Patients were classified at 6 months as responders to CRT (n=100) if they were alive, they had not been re-hospitalized for management of CHF, and the NYHA class had decreased by 1 point, and/or peak VO(2) or 6 min hall-walk increased by >10%. All others were classified as non-responders (n=38; one patient was lost to follow-up). Uni- and multivariate logistic regression analyses were performed to detect a pre- or intra-operative predictor of a positive response to CRT. Among multiple demographic, clinical, and ECG variables, the amount of QRS shortening (DeltaQRS) associated with biventricular stimulation was the only independent predictor of a positive (37+/-23 ms) vs. negative (11+/-23 ms) response to CRT (P<0.001). CONCLUSION: A positive response to CRT was observed in 73% of patients at 6 months and predicted only by DeltaQRS.