title: Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome Comparative Reproducibility and Validity of Systems for Assessing Cardiovascular Functional Class: Advantages of a New Specific Activity Scale Effect of pacing mode on health-related quality of life in the Canadian Trial of Physiologic Pacing. Late complications following permanent pacemaker implantation or elective unit replacement Comparison of ventricular function in atrial rate adaptive versus dual chamber rate adaptive pacing during exercise. Complications of Dual Chamber Pacemaker Implantation in the Elderly Atrial High Rate Episodes Detected by Pacemaker Diagnostics Predict Death and Stroke: Report of the Atrial Diagnostics Ancillary Study of the MOde Selection Trial (MOST) High incidence of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based pacing in the Mode Selection Trial (MOST). Cost-Effectiveness of Dual-Chamber Pacing Compared With Ventricular Pacing for Sinus Node Dysfunction Adverse Effect of Ventricular Pacing on Heart Failure and Atrial Fibrillation Among Patients With Normal Baseline QRS Duration in a Clinical Trial of Pacemaker Therapy for Sinus Node Dysfunction 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. Pacemaker implantation and quality of life in the Mode Selection Trial (MOST). Early complications of permanent pacemaker implantation: no difference between dual and single chamber systems. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. Clinical and quality of life comparison of accelerometer, piezoelectric crystal, and blended sensors in DDDR-paced patients with sinus node dysfunction in the mode selection trial (MOST). Principles of good practice for decision analytic modeling in health-care evaluation: report of the ISPOR Task Force on Good Research Practices--Modeling Studies. Analysis of Cause-Specific Mortality in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome. Incidence of atrial fibrillation and thromboembolism in a randomised trial of atrial versus dual chamber pacing in 177 patients with sick sinus syndrome Heart failure in patients with sick sinus syndrome treated with single lead atrial or dual-chamber pacing: no association with pacing mode or right ventricular pacing site. A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome. AAIR versus DDDR pacing in the bradycardia tachycardia syndrome: a prospective, randomized, double-blind, crossover trial. Cost-effectiveness of physiologic pacing: results of the Canadian Health Economic Assessment of Physiologic Pacing. Routine follow-up after pacemaker implantation: frequency, pacemaker programming and professionals in charge. Incidence and predictors of in-hospital events after first implantation of pacemakers. Health values before and after pacemaker implantation. DDD(R)-pacing, but not AAI(R)-pacing induces left ventricular desynchronization in patients with sick sinus syndrome: tissue-Doppler and 3D echocardiographic evaluation in a randomized controlled comparison. Significant improvement of quality of life following atrioventricular synchronous pacing in patients with hypertrophic obstructive cardiomyopathy. Data from 1 year of follow-up. PIC study group. Pacing In Cardiomyopathy. Clinical characteristics of patients intolerant to VVIR pacing. Prospective randomised trial of atrial versus ventricular pacing in sick-sinus syndrome Atrial fibrillation and quality of life after pacemaker implantation for sick sinus syndrome: data from the Mode Selection Trial (MOST). Rate adaptive pacing in sick sinus syndrome: effects of pacing modes and intrinsic conduction on physiological responses, arrhythmias, symptomatology and quality of life. A comparison of rate control and rhythm control in patients with atrial fibrillation. Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. Pacemaker Selection in the Elderly Investigators. Progression to chronic atrial fibrillation after pacing: the Canadian Trial of Physiologic Pacing. CTOPP Investigators. Health economic evaluation of single-lead atrial pacing vs. dual-chamber pacing in sick sinus syndrome.
abstract: BACKGROUND In a previous study of 225 patients with sick-sinus syndrome r and omised to either single-chamber atrial pacing ( n=110 ) or single-chamber ventricular pacing ( n=115 ) , we found that after a mean follow-up of 3.3 years , atrial pacing was associated with significantly less atrial fibrillation and thromboembolism whereas there was no significant difference in mortality and heart failure between the two groups . We aim ed to find out whether this beneficial effect of atrial pacing is maintained during extended follow-up of up to 8 years . METHODS Follow-up visits for all patients were at 3 months , 12 months , then once a year at which patients had a physical examination , ECG recording , and pacemaker check-up . Endpoints were mortality , cardiovascular death , atrial fibrillation , thromboembolic events , heart failure , and atrioventricular block . Data was analysed on Dec 31 , 1996 . FINDINGS At long-term follow-up , 39 patients from the atrial group had died versus 57 from the ventricular group ( relative risk 0.66 [ 95 % CI 0.44 - 0.99 ] ; p=0.045 ) . 19 patients from the atrial group and 39 patients from the ventricular group died from a cardiovascular cause ( 0.47 [ 0.27 - 0.82 ] ; p=0.0065 ) . The cumulative incidences of atrial fibrillation and chronic atrial fibrillation were also significantly lower in the atrial group than in the ventricular group ( 0.54 [ 0.33 - 0.89 ] , p=0.012 and 0.35 [ 0.16 - 0.76 ] , p=0.004 , respectively ) . Thromboembolic events occurred in 13 patients in the atrial group and 26 in the ventricular group ( 0.47 [ 0.24 - 0.92 ] , p=0.023 ) . Heart failure was less severe in the atrial group than in the ventricular group ( p<0.05 ) . In multivariate analysis , atrial pacing was significantly associated with freedom from thromboembolic events ( 0.47 [ 0.24 - 0.92 ] , p=0.028 ) and survival from cardiovascular death ( 0.52 [ 0.30 - 0.91 ] , p=0.022 ) , but no longer with overall survival ( 0.71 [ 0.46 - 1.08 ] , p=0.11 ) or chronic atrial fibrillation ( 0.45 [ 0.20 - 1.05 ] , p=0.063 ) . Atrioventricular block occurred in four patients in the atrial group ( 0.6 % annual risk ) . INTERPRETATION The beneficial effect of atrial pacing found in our previous study is enhanced substantially over time . Patients with sick-sinus syndrome should be treated with an atrial rather than ventricular-pacing system because after long-term follow-up , atrial pacing is associated with a significantly higher survival , less atrial fibrillation , fewer thromboembolic complications , less heart failure , and a low-risk of atrioventricular block Reproducibility and validity are prerequisites for a useful clinical scale . We therefore prospect ively tested the reproducibility and validity of the New York Heart Association criteria and the Canadian Cardiovascular Society criteria for the assessment of cardiac functional class  and compared these criteria with a new Specific Activity Scale based on the metabolic costs of specific activities . The New York Heart Association estimates made by two physicians had a reproducibility of only 56 % , and only 51 % of the estimates agreed with treadmill exercise performance . Functional estimates based on the Canadian Cardiovascular Society criteria were significantly more reproducible ( 73 % ) , but not significantly more valid . The Specific Activity Scale was as reproducible as the Canadian Cardiovascular Society criteria , and its 68 % validity was significantly higher than the validities of the other systems . The easily administered Specific Activity Scale was equally reproducible and valid when used by a nonphysician . It was especially better than the other systems for the evaluation of true class II patients and was significantly less likely to underestimate treadmill performance . Although no set of questions can perfectly predict exercise tolerance , the Specific Activity Scale deserves wider prospect i ve testing BACKGROUND Both " physiologic " ( dual-chamber or atrial only ) or ventricular-pacing-only permanent pacemakers provide chronotropic competence , with unknown health-related quality of life ( QOL ) differences between these options . The QOL studies within the Canadian Trial of Physiologic Pacing were performed to assess whether QOL differences exist in patients r and omized to these 2 pacing modes . METHODS Two QOL protocol s were performed : 1 ) a sub study of 269 patients with detailed QOL measures ( The Medical Outcomes Study , Short-Form [ SF-36 ] , the Pacemaker Syndrome Scale , an activity scale , and a pacemaker-specific scale ) at baseline and 6 months after implantation ; and 2 ) a parent study assessment of QOL in 1721 patients with a 12-item QOL instrument package ( SF-6 , " ladder of life , " and pacemaker syndrome scale ) given 6 months after implantation only . RESULTS In the sub study , pacing was associated with an average significant ( P < .05 ) 0.36 SD unit improvement in QOL across all domains ( SF-36 : 38 + /- 9 to 41 + /- 11 for physical scores , 47 + /- 11 to 52 + /- 9 for mental health scores , both P < .001 ) . Similar improvements were seen with the pacemaker-specific scales . There were no significant differences in the absolute or relative improvement in QOL between assigned pacing modes . The parent study similarly showed no differences in QOL between pacing modalities . Presyncope occurred in 31 % of patients in the physiological pacing group , compared with 38 % of the patients in the ventricular pacing group ( P < .01 ) . No other symptoms were different between the 2 groups . Pacemaker dependency , defined as an escape heart rate < 50 beats per minute , did not influence the lack of difference in QOL scores between the 2 assigned pacing modes . CONCLUSION In this largest r and omized assessment of QOL in patients with pacemakers , with the instruments used , there was no significant health-related QOL difference seen between " physiologic " pacing and ventricular pacing Objective To determine the rate of late complications following first implantation or elective unit replacement of a permanent pacemaker system .  Design Analysis of pacemaker data and complications prospect ively acquired on a computerised data base . Complications were studied over an 11 year period from January 1984 to December 1994 . Setting Tertiary referral cardiothoracic centre . Patients Records of 2621 patients were analysed retrospectively . Main outcome measures Complications requiring repeat procedures occurring more than six weeks after pacemaker implantation or elective unit replacement . Results The overall rate of late complications was significantly lower after first implantation of a permanent pacemaker ( 34 cases , complication rate 1.4 % , 95 % confidence interval 0.9 % to 1.9 % ) than after elective unit replacement ( 16 cases , complication rate 6.5 % ( 3.3 % to 9.7 % ) . There were 20 cases of erosion , 18 infections , five electrode problems , and seven miscellaneous problems . Complications were more common with inexperienced operators ( 18.9 % ( 6.0 % to 31.8 % ) ) than with experienced operators ( 0.9 % ( 0.3 % to 1.5 % ) ) . Conclusions The incidence of late complications following pacemaker implantation is low and compares favourably with early complication rates . The majority are caused by erosion and infection . Patients who have undergone elective unit replacement are at particular risk The hemodynamic effects of two different pacing modes -- rate adaptive atrial ( AAIR ) versus dual chamber ( DDDR ) pacing -- were assessed in 12 patients with DDDR pacemakers during upright bicycle exercise first-pass radionuclide angiography using a multiwire gamma camera with tantalum-178 as a tracer . All patients had sinus node disease with intact AV conduction . Patients exercised to the same heart rate in r and om order in these two different pacing modes , AAIR and DDDR with AV delay ( of 100 msec ) selected to maintain 100 % ventricular capture . Cardiac output increased significantly above baseline values during exercise in both pacing modes : 154 + /- 41 % ( mean + /- SEM , P = 0.002 ) with AAIR , versus 95 + /- 24 % ( P = 0.004 ) with DDDR ( P = NS between the two modes ) . The peak filling rate , likewise , increased in both pacing modes ( 2.3 + /- 0.21 end-diastolic volumes/sec to 3.8 + /- 0.31 end-diastolic volumes/sec in AAIR [ P = 0.0004 ] and 2.2 + /- 0.18 end-diastolic volumes/sec to 3.4 + /- 0.27 end-diastolic volumes/sec in DDDR [ P = 0.0008 ] ) . LV ejection fraction was normal at rest ( 60 + /- 4 % , SEM ) and did not significantly change with submaximal exercise in either pacing mode ( both 56 % , P = NS ) . No significant changes in end-diastolic volume or stroke volume indexes occurred with exercise in either pacing mode . Our study demonstrates that in patients with normal resting LV function , AAIR and DDDR pacing are equally effective in attaining appropriate increases in cardiac output and LV filling during exercise Pacemakers are frequently implanted , yet accurate prospect i ve data on implant complications are limited . Elderly patients may be at increased risk of implant complications and are increasingly being referred for pacemaker implantation . The purpose of the present analysis was to define the incidence and possible predictors of serious complications of dual chamber permanent pacemaker implantation  in the elderly . Therefore , we sought to prospect ively identify the incidence and predictors of pacemaker implant complications in a large multicenter trial involving patients receiving a dual chamber pacemaker .  The Pacemaker Selection in the Elderly ( PASE ) study was a prospect i ve trial design ed to evaluate quality of life in  dual chamber pacemaker recipients age 65 years or older r and omized to DDDR versus VVIR programming . In addition to being age 65 years or older , patients enrolled in this study were in normal sinus rhythm , and had st and ard indications for permanent pacemaker implantation . All patients received dual chamber pacemakers and were r and omized to DDDR versus VVIR pacing . Pacemaker implant complications were collected on st and ardized forms which were completed at pacemaker implantation and during follow-up appointments . In this study of 407 patients , there were 26 complications occurring in 25 patients ( 6.1 % ) . The most frequent complication was lead dislodgment which occurred in 9 patients . This was followed by pneumothorax ( 8 patients ) and cardiac perforations ( 4 patients ) . In 18 patients ( 4.4 % ) repeat surgical procedures ( including chest tubes ) were required . Complications were noted prior to discharge in only 18 patients . There were no significant predictors of overall complications . Pneumothorax was more frequent in patients ≤75 years old , and was observed only in patients with subclavian venous access . In conclusion , complications from pacemaker implantation in the elderly are seen in 6.1 % of patients and 4.4 % of patients require a repeat surgical procedure . Other than advanced age and lower weight predicting for pneumothorax , there are no significant clinical predictors of Background —Some current pacing systems can automatically detect and record atrial tachyarrhythmias that may be asymptomatic . We prospect ively studied a 312-patient ( pt ) subgroup of MOST ( MOde Selection Trial ) , a 2010-patient , 6-year r and omized trial of DDDR versus VVIR pacing in sinus node dysfunction ( SND ) . The purpose of the study was to correlate atrial high rate events ( AHREs ) detected by pacemaker diagnostics with clinical outcomes . Methods and Results —Pacemakers were programmed to log an AHRE when the atrial rate was > 220 bpm for 10 consecutive beats . Analysis was confined to patients with at least 1 AHRE duration exceeding 5 minutes . The 312 patients were median age 74 years , 55 % female , and 60 % had a history of SVT . 160 of 312 ( 51.3 % ) patients enrolled had at least 1 AHRE > 5 minutes duration over median follow-up of 27 months . Cox proportional hazards analysis assessed the relationship of AHREs with clinical events , adjusting for prognostic variables and baseline covariates . The presence of any AHRE was an independent predictor of the following : total mortality ( hazard ratio AHRE versus no AHRE and 95 % confidence intervals=2.48 [ 1.25 , 4.91 ] , P = 0.0092 ) ; death or nonfatal stroke ( 2.79 [ 1.51 , 5.15 ] , P = 0.0011 ) ; and atrial fibrillation ( 5.93 [ 2.88 , 12.2 ] , P = 0.0001 ) . There was no significant effect of pacing mode on the presence or absence of AHREs . Conclusions —AHRE detected by pacemakers in patients with SND identify patients that are more than twice as likely to die or have a stroke , and 6 times as likely to develop atrial fibrillation as similar patients without AHRE OBJECTIVES We evaluated the incidence , predictors , and treatment of  pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based ( VVIR ) pacing in the Mode Selection Trial ( MOST ) . BACKGROUND Pacemaker syndrome , or intolerance to VVIR pacing , consists of cardiovascular signs and symptoms induced by VVIR pacing . METHODS The definition of pacemaker syndrome required that a patient with single-chamber VVIR pacing develop either congestive signs and symptoms associated with retro grade conduction during VVIR pacing or a > or=20 mm Hg reduction of systolic blood pressure during VVIR pacing , associated with reproducible symptoms of weakness , lightheadedness , or syncope . RESULTS Of 996 patients r and omized to VVIR pacing , 182 ( 18.3 % ) met criteria for pacemaker syndrome in follow-up . Pacemaker syndrome occurred early in most patients ( 13.8 % at 6 months , 16.0 % at 1 year , increasing to 19.7 % at 4 years ) . Baseline univariate predictors of pacemaker syndrome included a lower sinus rate and higher programmed pacemaker rate . Previous heart failure , ejection fraction , and drop in systolic blood pressure with VVIR pacing at implantation did not predict the development of pacemaker syndrome . Post-implantation predictors of pacemaker syndrome were a higher percentage of paced beats , higher programmed low rate , and slower underlying spontaneous sinus rate . Quality of life decreased at the time of diagnosis of pacemaker syndrome and improved with reprogramming to atrial-based pacing . CONCLUSIONS Severe pacemaker syndrome developed in nearly 20 % of VVIR-paced patients and improved with reprogramming to the dual-chamber pacing mode . Because prediction of pacemaker syndrome is difficult , the only way to prevent pacemaker syndrome is to implant atrial-based pacemakers in all patients Background —Compared with single-chamber ventricular pacing , dual-chamber pacing can reduce adverse events and , as a result , improve quality of life in patients paced for sick sinus syndrome . It is not clear , however , how these benefits compare with the increased cost of dual-chamber pacemakers . Methods and Results —We used 4-year data from a 2010-patient , r and omized trial to estimate the incremental cost-effectiveness of dual-chamber pacing compared with ventricular pacing and then projected these findings over the patients ’ lifetimes by using a Markov model that was calibrated to the first 5 years of in-trial data . To assess the stability of the findings , we performed 1000 bootstrap analyses and multiple sensitivity analyses . During the first 4 years of the trial , dual-chamber pacemakers  increased quality -adjusted life expectancy by 0.013 year per subject at an incremental cost-effectiveness ratio of $ 53 000 per quality -adjusted year of life gained . Over a lifetime , dual-chamber pacing was projected to increase quality -adjusted life expectancy by 0.14 year with an incremental cost-effectiveness ratio of ≈$6800 per quality -adjusted year of life gained . In bootstrap analyses , dual-chamber pacing was cost-effective in 91.9 % of simulations at a threshold of $ 50 000 per quality -adjusted year of life and in 93.2 % of simulations at a threshold of $ 100 000 . Its cost-effectiveness ratio was also below this threshold in numerous sensitivity analyses that varied key estimates . Conclusions —For patients with sick sinus syndrome requiring pacing  , dual-chamber pacing  increases quality -adjusted life expectancy at a cost that is generally considered acceptable Background Dual‐chamber ( DDDR ) pacing preserves AV synchrony and may reduce heart failure ( HF ) and atrial fibrillation ( AF ) compared with ventricular ( VVIR ) pacing in sinus node dysfunction ( SND ) . However , DDDR pacing often results in prolonged QRS duration s ( QRSd ) as the result of right ventricular stimulation , and ventricular desynchronization may result . The effect of pacing‐induced ventricular desynchronization in patients with normal baseline QRSd is unknown . Methods and Results Baseline QRSd was obtained from 12‐lead ECGs before pacemaker implantation in MOST , a 2010‐patient , 6‐year , r and omized trial of DDDR versus VVIR pacing in SND .  Cumulative percent ventricular paced ( Cum%VP ) was determined from stored pacemaker data . Baseline QRSd < 120 ms was observed in 1339 patients ( 707 DDDR , 632 VVIR ) . Cum%VP was greater in DDDR versus VVIR ( 90 % versus 58 % , P=0.001 ) . Cox models demonstrated that the time‐dependent covariate Cum%VP was a strong predictor of HF hospitalization in DDDR ( hazard ratio [ HR ] , 2.99 [ 95 % CI , 1.15 to 7.75 ] for Cum%VP > 40 % ) and VVIR ( HR 2.56 [ 95 % CI , 1.48 to 4.43 ] for Cum%VP > 80 % ) . The risk of AF increased linearly with Cum%VP from 0 % to 85 % in both groups ( DDDR , HR 1.36 [ 95 % CI , 1.09 , 1.69 ] ; VVIR , HR 1.21 [ 95 % CI 1.02 , 1.43 ] , for each 25 % increase in Cum%VP ) . Model results were unaffected by adjustment for known baseline predictors of HF hospitalization and AF . Conclusions Ventricular desynchronization imposed by ventricular pacing even when AV synchrony is preserved increases the risk of HF hospitalization and AF in SND with normal baseline QRSd . ( Circulation . 2003;107:2932‐2937 . ACCF : American College of Cardiology Foundation ACCP : American College of Chest Physicians ACS : acute coronary syndrome ACT : Atrial arrhythmia Conversion Trial ADONIS : American – Australian – African trial with DronedarONe In atrial fibrillation or flutter for the maintenance of Sinus rhythm AF : atrial fibrillation AHA : American Heart Association AND ROMEDA : ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity DecreAse APHRS : Asia Pacific Heart Rhythm Society aPTT : activated partial thromboplastin time ARB : angiotensin-receptor blocker ARISTOTLE : Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fibrillation ATHENA : A placebo-controlled , double-blind , parallel arm Trial to assess the efficacy of dronedarone 400 mg b.i.d . for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter ATRIA : AnTicoagulation and Risk factors In Atrial fibrillation AVERROES : Apixaban VErsus acetylsalicylic acid ( ASA ) to Reduce the Rate Of Embolic Stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment AVRO : A prospect i ve , r and omized , double-blind , Active-controlled , superiority study of Vernakalant vs. amiodarone in Recent Onset atrial fibrillation b.i.d : bis in die ( twice daily ) b.p.m . : beats per minute CABANA : Catheter ABlation vs . ANtiarrhythmic drug therapy for Atrial fibrillation CABG : coronary artery bypass graft CAP : Continued Access to Protect AF CHA2DS2-VASc : Congestive heart failure or left ventricular dysfunction Hypertension , Age ≥75 ( doubled ) , Diabetes , Stroke (doubled)-Vascular disease , Age 65–74 , Sex category ( female ) CHADS2 : Congestive heart failure , Hypertension , Age ≥75 , Diabetes , Stroke ( doubled ) CI : confidence interval CRAFT : Controlled R and omized Atrial Fibrillation Trial CrCl : creatinine clearance DAFNE : Dronedarone Atrial FibrillatioN study after Electrical cardioversion DIONYSOS : R and omized Double blind trIal to evaluate efficacy and safety of drOnedarone ( 400 mg b.i.d . ) vs . amiodaroNe ( 600 mg q.d . for 28 daYS , then 200 mg qd thereafter ) for at least 6 mOnths for the maintenance of Sinus rhythm in patients with atrial fibrillation EAST : Early treatment of Atrial fibrillation for Stroke prevention Trial EHRA : European Heart Rhythm Association ECG : electrocardiogram EMA : European Medicines Agency ERATO : Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation EURIDIS : EURopean trial In atrial fibrillation or flutter patients receiving Dronedarone for the maIntenance of Sinus rhythm FAST : atrial Fibrillation catheter Ablation vs . Surgical ablation Treatment FDA : Food and Drug Administration Flec-SL : Flecainide Short-Long trial HAS-BLED : Hypertension , Abnormal renal/liver function , Stroke , Bleeding history or predisposition , Labile INR , Elderly , Drugs/alcohol concomitantly HF-PEF : heart failure with preserved ejection fraction HF-REF : heart failure with reduced ejection fraction HR : hazard ratio HRS : Heart Rhythm Society ICH : intracranial haemorrhage INR : international normalized ratio i.v . : intravenous J-RHYTHM : Japanese RHYTHM management trial for atrial fibrillation LAA : left atrial appendage LoE : level of evidence LVEF : left ventricular ejection fraction MANTRA-PAF : Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation NICE : National Institute for Health and Clinical Excellence NOAC : novel oral anticoagulant NSAID : non-steroidal anti-inflammatory drug NYHA : New York Heart Association OAC : oral anticoagulant or oral anticoagulation o.d . : omni die ( every day ) PALLAS : Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of st and ard therapy PCI : percutaneous coronary intervention PREVAIL : Prospect i ve R and omized EVAluation of the LAA closure device In patients with atrial fibrillation v s. Long-term warfarin therapy PROTECT AF : WATCHMAN LAA system for embolic PROTECTion in patients with Atrial Fibrillation PT : prothrombin time RAAFT : Radio frequency Ablation Atrial Fibrillation Trial RE-LY : R and omized Evaluation of Long-term anticoagulant therapY with dabigatran etexilate ROCKET-AF : Rivaroxaban Once daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in atrial fibrillation RRR : relative risk reduction TE : thromboembolism TIA : transient ischaemic attack t.i.d . : ter in die ( three times daily ) TOE : transoesophageal echocardiogram TTR : time in therapeutic range VKA : vitamin K antagonist Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition , taking into account the impact on BACKGROUND Evidence suggests that physiologic pacing ( dual-chamber or atrial ) may be superior to single-chamber ( ventricular ) pacing because it is associated with lower risks of atrial fibrillation , stroke , and death . These benefits have not been evaluated in a large , r and omized , controlled trial . METHODS At 32 Canadian centers , patients without chronic atrial fibrillation who were scheduled for a first implantation of a pacemaker to treat symptomatic bradycardia were eligible for enrollment . We r and omly assigned patients to receive either a ventricular pacemaker or a physiologic pacemaker and followed them for an average of three years . The primary outcome was stroke or death due to cardiovascular causes . Secondary outcomes were death from any cause , atrial fibrillation , and hospitalization for heart failure . RESULTS A total of 1474 patients were r and omly assigned to receive a ventricular pacemaker and 1094 to receive a physiologic pacemaker .  The annual rate of stroke or death due to cardiovascular causes was 5.5 percent with ventricular pacing , as compared with 4.9 percent with physiologic pacing ( reduction in relative risk , 9.4 percent ; 95 percent confidence interval , -10.5 to 25.7 percent [ the negative value indicates an increase in risk ] ; P=0.33 ) . The annual rate of atrial fibrillation was significantly lower among the patients in the physiologic-pacing group ( 5.3 percent ) than among those in the ventricular-pacing group ( 6.6 percent ) , for a reduction in relative risk of 18.0 percent ( 95 percent confidence interval , 0.3 to 32.6 percent ; P=0.05 ) . The effect on the rate of atrial fibrillation was not apparent until two years after implantation . The observed annual rates of death from all causes and of hospitalization for heart failure were lower among the patients with a physiologic pacemaker than among those with a ventricular pacemaker , but not significantly so ( annual rates of death , 6.6 percent with ventricular pacing and 6.3 percent with physiologic pacing ; annual rates of hospitalization for heart failure , 3.5 percent and 3.1 percent , respectively ) . There were significantly more perioperative complications with physiologic pacing than with ventricular pacing ( 9.0 percent vs. 3.8 percent , P<0.001 ) . CONCLUSIONS Physiologic pacing provides little benefit over ventricular pacing for the prevention of stroke or death due to cardiovascular causes BACKGROUND Dual-chamber pacemakers restore AV synchrony compared with ventricular pacemakers , but the effects on health-related quality of life ( QOL ) are uncertain . OBJECTIVES The purpose of this study was to assess the effect of pacemaker implantation , clinical factors , and pacing mode on QOL . METHODS The Mode Selection Trial ( MOST ) r and omized 2,010 patients with sinus node dysfunction to rate-modulated right ventricular ( VVIR ) or dual-chamber ( DDDR ) pacing .  A longitudinal analysis of serial QOL measures ( Short Form-36 [ SF-36 ] , Specific Activity Scale , and time trade-off utility ) was performed . In patients who crossed over from VVIR to DDDR because of severe pacemaker syndrome , the last known QOL prior to crossover was carried forward . RESULTS Pacemaker implantation result ed in substantial improvement in almost all QOL measures .  Subjects 75 years or older experienced significantly less improvement in functional status and physical component summary scores than did younger subjects . In longitudinal analyses of the effect of pacing mode on QOL , significant improvement in three SF-36 subscales was observed with DDDR pacing compared with VVIR pacing : role physical [ 62.8 points ( 95 % confidence interval [ CI ] 60.2 , 65.5 ) vs 56.4 ( 95 % CI 53.7 , 59.1 ) ] , role emotional [ 85.0 ( 95 % CI 82.9 , 87.0 ) vs 81.9 ( 95 % CI 79.9 , 84.0 ) ] , and vitality [ 51.8 ( 95 % CI 50.3 , 53.3 ) vs 49.3 ( 95 % CI 47.8 , 50.7 ) ] , but not in other SF-36 subscales , the Specific Activity Scale , or utilities . The gains in QOL were larger than the declines associated with 1 year of aging but smaller than those associated with heart failure . CONCLUSION Pacemaker implantation improved health-related QOL . The mode selected was associated with much smaller , but significant , improvements in several domains , particularly role physical function OBJECTIVE --To evaluate the incidence of intraoperative and early postoperative complications ( up to two months after implant ) of endocardial permanent pacemaker insertion in all patients under-going a first implant at a referral centre . METHODS -- Prospect i ve evaluation of all  endocardial pacemaker implantation procedures performed from April 1992 to January 1994 carried out by completion of st and ard audit form at implant . Patients ' demographic data , medical history , details of pacemaker hardware used , and any complications were noted . Follow up information was also collected prospect ively onto st and ard forms at pacemaker outpatient clinic . SETTING --United Kingdom tertiary referral cardiothoracic centre . PATIENTS --1088 consecutive patients underwent implantation of their first endocardial permanent pacemaker from April 1992 to January 1994 . Implant and follow up data were available for 1059 ( 97.3 % ) patients at analysis . The median ( range ) age was 77 years ( 16 - 99 ) ; 51.2 % were male . RESULTS --Dual chamber units were implanted in 54.1 % of patients , single chamber atrial in 5.2 % , and ventricular in 40.7 % . A temporary pacing lead was present at implant in 22.9 % of patients . Most ( 93.6 % ) implants were performed via the subclavian vein . Immediate complications were rare : eight ( 0.8 % ) patients developed pneumothorax requiring medical treatment and 11 ( 1.0 % ) an insignificant pneumothorax . There was no significant difference in the pneumothorax rate for dual chamber ( DDD ) compared with single chamber systems . Arterial puncture without sequelae was documented in 2.7 % of attempts at subclavian vein cannulation . A total of 35 patients ( 3.3 % ) required reoperation ; the reoperation rate for dual chamber ( 3.5 % ) was similar to that for single chamber ( 3.1 % ) systems . Electrode displacement ( n = 15 , 1.4 % ) was the most common reason for reoperation . Atrial lead displacement ( n = 10 , 1.6 % of atrial leads ) was significantly more common than ventricular lead displacement ( n = 5 , 0.5 % of ventricular leads , P = 0.047 ) . There was no difference in electrode displacement rates for dual ( 1.6 % ) compared with single ( 1.2 % ) chamber systems . Pacemaker pocket infection led to reoperation in 10 patients ( six dual , four single chamber , P = not significant ) and was significantly more common in patients who had a temporary pacing lead in place at implant ( 2.9 % ) than in those who did not ( 0.4 % , P = 0.0014 ) . Five patients ( 0.5 % ) required reoperation for generator erosion ( two dual , three single chamber , P = not significant ) . and a further five for drainage of haematoma or a serous fluid collection ( three dual , two single chamber , P = not significant ) . Complications that did not require reoperation were also rare . Undersensing occurred in 10 patients ( 0.9 % ) . Atrial undersensing ( n = 8) was significantly more common than ventricular undersensing ( n = 2 , P = 0.017 ) . All patients were successfully treated by reprogramming of sensitivity . Superficial wound infection was treated successfully with antibiotics in nine patients ( six dual , three single chamber , P = not significant ) . Three patients with DDD generators developed sustained atrial fibrillation : two required reprogramming to VVI mode and one required cardioversion . CONCLUSIONS --Permanent pacing in a large tertiary referral centre with experienced operators carries a low risk . Infection rates are low , < 1 % overall but significantly higher in patients who undergo temporary pacing before implantation . Lead displacement and undersensing are more likely to occur with atrial than ventricular leads . The overall complication rate for dual chamber pacing , however , is no higher than for single chamber pacing BACKGROUND Dual-chamber ( atrioventricular ) and single-chamber ( ventricular ) pacing are alternative treatment approaches for sinus-node dysfunction that causes clinical ly significant bradycardia . However , it is unknown which type of pacing results in the better outcome . METHODS We r and omly assigned a total of 2010 patients with sinus-node dysfunction to dual-chamber pacing ( 1014 patients ) or ventricular pacing ( 996 patients ) and followed them for a median of 33.1 months . The primary end point was death from any cause or nonfatal stroke . Secondary end points included the composite of death , stroke , or hospitalization for heart failure ; atrial fibrillation ; heart-failure score ; the pacemaker syndrome ; and the quality of life . RESULTS The incidence of the primary end point did not differ significantly between the dual-chamber group ( 21.5 percent ) and the ventricular-paced group ( 23.0 percent , P=0.48 ) . In patients assigned to dual-chamber pacing , the risk of atrial fibrillation was lower ( hazard ratio , 0.79 ; 95 percent confidence interval , 0.66 to 0.94 ; P=0.008 ) , and heart-failure scores were better ( P<0.001 ) . The differences in the rates of hospitalization for heart failure and of death , stroke , or hospitalization for heart failure were not significant in unadjusted analyses but became marginally significant in adjusted analyses . Dual-chamber pacing result ed in a small but measurable increase in the quality of life , as compared with ventricular pacing . CONCLUSIONS In sinus-node dysfunction , dual-chamber pacing does not improve stroke-free survival , as compared with ventricular pacing . However , dual-chamber pacing reduces the risk of atrial fibrillation , reduces signs and symptoms of heart failure , and slightly improves the quality of life . Overall , dual-chamber pacing offers significant improvement as compared with ventricular pacing INTRODUCTION Permanent pacemakers are capable of increasing heart rate in response to physical activity by a variety of sensors including accelerometers , piezoelectric crystals , or blended sensors . The impact of these different physiologic sensors on cardiovascular events and quality of life is not known . METHODS Of 2,010 patients r and omized in the Mode Selection Trial , 1,245 patients were selected with the most commonly used pacemakers with these three sensors .  Clinical characteristics and quality of life were compared between groups at baseline , 3 months , and then yearly . RESULTS There were 449 patients with an accelerometer sensor device  , 682 with a piezoelectric sensor  , and 114 with a blended sensor . The groups were similar in terms of age ( mean 74 years ) , gender , and cardiac risk factors but differences existed in weight , heart rate , mitral regurgitation , revascularization history , and drug therapy . The median ventricular pacing frequency was 80 % ( 25th , 75th percentiles 42 , 97 ) . After a median follow-up of 33.1 months , the risk of death , heart failure hospitalization , atrial fibrillation , and the combined endpoint of mortality and stroke was not significantly different between the sensor types , after adjustment for baseline differences . Quality of life analyses demonstrated that patients with blended sensors had significantly worse ( P < 0.01 ) physical function than did patients with the other two sensor systems . Moreover , patients receiving blended sensors had the poorest absolute scores , without reaching statistical significance , on 9 of 13 quality of life measures after adjusting for differences in the groups . CONCLUSION We found no significant differences among the three most utilized sensors in clinical endpoints . Those patients who received blended sensors had worse physical function quality of life scores . However , clinical selection of the most sophisticated sensor for the most ill patients can not be excluded as an explanation of these results OBJECTIVES Mathematical modeling is used widely in economic evaluations of pharmaceuticals and other health-care technologies . Users of models in government and the private sector need to be able to evaluate the quality of models according to scientific criteria of good practice . This report describes the consensus of a task force convened to provide modelers with guidelines for conducting and reporting modeling studies . METHODS The task force was appointed with the advice and consent of the Board of Directors of ISPOR . Members were experienced developers or users of models , worked in academia and industry , and came from several countries in North America and Europe . The task force met on three occasions , conducted frequent correspondence and exchanges of drafts by electronic mail , and solicited comments on three drafts from a core group of external review ers and more broadly from the membership of ISPOR . RESULTS Criteria for assessing the quality of models fell into three areas : model structure , data used as inputs to models , and model validation . Several major themes cut across these areas . Models and their results should be represented as aids to decision making , not as statements of scientific fact ; therefore , it is inappropriate to dem and that models be vali date d prospect ively before use . However , model assumptions regarding causal structure and parameter estimates should be continually assessed against data , and models should be revised accordingly . Structural assumptions and parameter estimates should be reported clearly and explicitly , and opportunities for users to appreciate the conditional relationship between inputs and outputs should be provided through sensitivity analyses . CONCLUSIONS Model-based evaluations are a valuable re source for health-care decision makers . It is the responsibility of model developers to conduct modeling studies according to the best practicable st and ards of quality and to communicate results with adequate disclosure of assumptions and with the caveat that conclusions are conditional upon the assumptions and data on which the model is built Background —Expectations that reestablishing and maintaining sinus rhythm in patients with atrial fibrillation might improve survival were disproved in the Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study . This report describes the cause-specific modes of death in the AFFIRM treatment groups . Methods and Results —All deaths in patients enrolled in AFFIRM underwent blinded review by the AFFIRM Events Committee , and a mode of death was assigned . In AFFIRM , 2033 patients were r and omized to a rhythm-control strategy and 2027 patients to a rate-control strategy .  During a mean follow-up of 3.5 years , there were 356 deaths in the rhythm-control patients and 310 deaths in the rate-control patients ( P = 0.07 ) . In the rhythm-control group , 129 patients ( 9 % ) died of a cardiac cause , and in the rate-control group , 130 patients ( 10 % ) died ( P = 0.95 ) . Both groups had similar rates of arrhythmic and nonarrhythmic cardiac deaths . The numbers of vascular deaths were similar in the 2 groups : 35 ( 3 % ) in the rhythm-control group and 37 ( 3 % ) in the rate-control group ( P = 0.82 ) . There were no differences in the rates of ischemic stroke and central nervous system hemorrhage . In the rhythm-control group , there were 169 noncardiovascular deaths ( 47.5 % of the total number of deaths ) , whereas in the rate-control arm , there were 113 noncardiovascular deaths ( 36.5 % of the total number of deaths ) ( P = 0.0008 ) . Differences in noncardiovascular death rates were due to pulmonary and cancer-related deaths . Conclusions —Management of atrial fibrillation with a rhythm-control strategy conferred no advantage over a rate-control strategy in cardiac or vascular mortality and may be associated with an increased noncardiovascular death rate AIMS In patients with sick sinus syndrome , bradycardia can be treated with a single-lead pacemaker or a dual-chamber pacemaker . Previous trials have revealed that pacing modes preserving atrio-ventricular synchrony are superior to single-lead ventricular pacing , but it remains unclear if there is any difference between single-lead atrial pacing ( AAIR ) and dual-chamber pacing ( DDDR ) . METHODS AND RESULTS We r and omly assigned 1415 patients referred for first pacemaker implantation to AAIR ( n = 707 ) or DDDR ( n = 708 ) pacing and followed them for a mean of 5.4 ± 2.6 years . The primary outcome was death from any cause . Secondary outcomes included paroxysmal and chronic atrial fibrillation , stroke , heart failure , and need for pacemaker reoperation . In the AAIR group , 209 patients ( 29.6 % ) died during follow-up vs. 193 patients ( 27.3 % ) in the DDDR group , hazard ratio ( HR ) 1.06 , 95 % confidence interval ( CI ) 0.88 - 1.29 , P = 0.53 . Paroxysmal atrial fibrillation was observed in 201 patients ( 28.4 % ) in the AAIR group vs. 163 patients ( 23.0 % ) in the DDDR group , HR 1.27 , 95 % CI 1.03 - 1.56 , P = 0.024 . A total of 240 patients underwent one or more pacemaker reoperations during follow-up , 156 ( 22.1 % ) in the AAIR group vs. 84 ( 11.9 % ) in the DDDR group ( HR 1.99 , 95 % CI 1.53 - 2.59 , P < 0.001 ) . The incidence of chronic atrial fibrillation , stroke , and heart failure did not differ between treatment groups . CONCLUSION In patients with sick sinus syndrome , there is no statistically significant difference in death from any cause between AAIR pacing and DDDR pacing . AAIR pacing is associated with a higher incidence of paroxysmal atrial fibrillation and a two-fold increased risk of pacemaker reoperation . These findings support the routine use of DDDR pacing in these patients . CLINICAL TRIAL REGISTRATION URL http://www . clinical trials.gov . Unique identifier : NCT00236158 Objective : To analyse the occurrence of atrial fibrillation ( AF ) and thromboembolism in a r and omised comparison of rate adaptive single chamber atrial pacing ( AAIR ) and dual chamber pacing ( DDDR ) in patients with sick sinus syndrome and normal atrioventricular ( AV ) conduction , in which left atrial dilatation and decreased left ventricular fractional shortening had been observed in the DDDR group . Methods : 177 consecutive patients with sick sinus syndrome ( mean ( SD ) age 74 ( 9 ) years , 104 women ) were r and omly assigned to treatment with one of three pacemakers : AAIR ( n = 54 ) , DDDR with a short rate adaptive AV delay ( n = 60 ) ( DDDR-s ) ; or DDDR with a fixed long AV delay ( n = 63 ) ( DDDR-l ) . Analysis was intention to treat . Results : Mean follow up was 2.9 ( 1.1 ) years . AF at one or more ambulatory visits was significantly less common in the AAIR group ( 4 ( 7.4 % ) v 14 ( 23.3 % ) in the DDDR-s group v 11 ( 17.5 % ) in the DDDR-l group ; p = 0.03 , log rank test ) . The risk of developing AF in the AAIR group compared with the DDDR-s group was significantly decreased after adjustment for brady-tachy syndrome in a Cox regression analysis ( relative risk 0.27 , 95 % confidence interval ( CI ) 0.09 to 0.83 , p = 0.02 ) . The benefit of AAIR was highest among patients with brady-tachy syndrome . Brady-tachy syndrome and a thromboembolic event before pacemaker implantation were independent predictors of thromboembolism during follow up ( relative risk 7.5 , 95 % CI 1.6 to 36.2 , p = 0.01 , and relative risk 4.7 , 95 % CI 1.2 to 17.9 , p = 0.02 , respectively ) . Conclusions : During a mean follow up of 2.9 years AAIR was associated with significantly less AF . The beneficial effect of AAIR was still significant after adjustment for brady-tachy syndrome . Brady-tachy syndrome was associated with an increased risk of thromboembolism AIMS Previous studies indicate that ventricular pacing may precipitate heart failure ( HF ) . We investigated occurrence of HF during long-term follow-up among patients with sick sinus syndrome ( SSS ) r and omized to AAIR or DDDR pacing . Furthermore , we investigated effects of percentage of ventricular pacing ( % VP ) and pacing site in the ventricle . METHODS AND RESULTS We analysed data from 1415 patients r and omized to AAIR ( n = 707 ) or DDDR pacing ( n = 708 ) . Ventricular pacing leads were recorded as located in either an apical or a non-apical position . The % VP and HF hospitalizations were recorded during follow-up . Patients were classified with new HF , if in New York Heart Association ( NYHA ) functional class IV or if presence of ≥2 of : oedema ; dyspnoea ; NYHA functional class III . Mean follow-up was 5.4 ± 2.4 years . Heart failure hospitalizations did not differ between groups . In the AAIR group , 170 of the 707 ( 26 % ) patients developed HF vs. 169 of the 708 ( 26 % ) patients in the DDDR group , hazard rate ratio ( HR ) 1.00 , 95 % confidence interval ( CI ) 0.79 - 1.22 , P = 0.87 . In DDDR patients , 146 of the 512 patients ( 29 % ) with ventricular leads in an apical position developed HF vs. 28 of the 161 patients ( 17 % ) with the leads in a non-apical position , HR 0.67 , CI 0.45 - 1.00 , P = 0.05 . After adjustments this difference was non-significant . The incidence of HF was not associated with % VP ( P = 0.57 ) . CONCLUSION In patients with SSS , HF was not associated with pacing mode , % VP , or ventricular lead localization . This suggests that DDDR pacing is safe in patients with SSS without precipitating HF OBJECTIVES A r and omized trial was done to compare single-chamber atrial ( AAI ) and dual-chamber ( DDD ) pacing in patients with sick sinus syndrome ( SSS ) . Primary end points were changes in left atrial ( LA ) size and left ventricular ( LV ) size and function as measured by M-mode echocardiography . BACKGROUND In patients with SSS and normal atrioventricular conduction , it is still not clear whether the optimal pacing mode is AAI or DDD pacing . METHODS A total of 177 consecutive patients ( mean age 74 + /- 9 years , 73 men ) were r and omized to treatment with one of three rate-adaptive ( R ) pacemakers  : AAIR ( n = 54 ) , DDDR with a short atrioventricular delay ( n = 60 ) ( DDDR-s ) , or DDDR with a fixed long atrioventricular delay ( n = 63 ) ( DDDR-l ) . Before pacemaker implantation and at each follow-up , M-mode echocardiography was done to measure LA and LV diameters . Left ventricular fractional shortening ( LVFS ) was calculated . Analysis was on an intention-to-treat basis . RESULTS Mean follow-up was 2.9 + /- 1.1 years . In the AAIR group , no significant changes were observed in LA or LV diameters or LVFS from baseline to last follow-up . In both DDDR groups , LA diameter increased significantly ( p < 0.05 ) , and in the DDDR-s group , LVFS decreased significantly ( p < 0.01 ) . Atrial fibrillation was significantly less common in the AAIR group , 7.4 % versus 23.3 % in the DDDR-s group versus 17.5 % in the DDDR-l group ( p = 0.03 , log-rank test ) . Mortality , thromboembolism , and congestive heart failure did not differ between groups . CONCLUSIONS During a mean follow-up of 2.9 + /- 1.1 years , DDDR pacing causes increased LA diameter , and DDDR pacing with a short atrioventricular delay also causes decreased LVFS . No changes occur in LA or LV diameters or LVFS during AAIR pacing . Atrial fibrillation is significantly less common during AAIR pacing In 19 patients paced and medicated for bradycardia tachycardia syndrome ( BTS ) , AAIR and DDDR pacing were compared with regard to quality of life ( QoL ) , atrial tachyarrhythmia ( AFib ) , exercise tolerance , and left ventricular (LV)function .  Patients had a PQ interval < or = 240 ms during sinus rhythm , no second or third degree AV block , no bundle branch block , or bifascicular block . In DDDR mode , AV delay was optimized using the aortic time velocity integral . After 3 months , QoL was assessed by question naires , patients were investigated by 24-hour Holter , cardiopulmonary exercise testing ( CPX ) was performed , and LV function was determined by echocardiography .  QoL was similar in all dimensions , except dizziness , showing a significantly lower prevalence in AAIR mode . The incidence of AFib was 12 episodes in 2 patients with AAIR versus 22 episodes in 7 patients with DDDR pacing ( P = 0.072 ) . In AAIR mode , 164 events of second and third degree AV block were detected in 7 patients ( 37 % ) with pauses between 1 and 4 seconds . During CPX , exercise duration and work load were higher in AAIR than in DDDR mode ( 423+/-127 vs 402+/-102 s and 103+/-31 vs 96+/-27 Watt , P < 0.05 ) . Oxygen consumption ( VO2 ) , was similar in both modes . During echocardiography , only deceleration of early diastolic flow velocity and early diastolic closure rate of the anterior mitral valve leaflet were higher in DDD than in AAI pacing ( 5.16+/-1.35 vs 3.56+/-0.95 m/s2 and 69.2+/-23 vs 54.1+/-26 mm/s , P < 0.05 ) . As preferred pacing mode , 11 patients chose DDDR , 8 patients chose AAIR . Hence , AAIR and DDDR pacing seem to be equally effective in  BTS patients . In view of a considerable rate of high degree AV block during AAIR pacing , DDDR mode should be preferred for safety reasons OBJECTIVES The purpose of this study was to determine the cost-effectiveness of physiologic pacemakers . BACKGROUND The Canadian Trial of Physiologic Pacing ( CTOPP ) was a large r and omized trial that evaluated the efficacy of physiologic pacing compared with ventricular pacing . CTOPP also included a prospect i ve cost-effectiveness sub study . METHODS Re source usage and costs were collected from a subset of 472 patients ( of 1,094 ) who received a physiologic pacemaker and 586 ( of 1,474 ) who received a ventricular pacemaker .  Costs included initial pacemaker implantation and all health care follow-up costs over a follow-up of 5.2 years . Costs are reported in 2004 Canadian dollars ( 1 Canadian dollar = 0.76 US dollars ) , with adjustments for censoring . Incremental cost-effectiveness was estimated as the ratio of the difference ( treatment-control ) in mean cost to the difference in life expectancy ( mean survival ) , with costs and effects discounted at 3 % per year . RESULTS Over a mean follow-up of 3.1 years , physiologic pacing was associated with a gain of 0.01 life-years . This benefit increases to 0.25 life-years in the subgroup of patients with an intrinsic ( unpaced ) heart rate < or = 60 bpm . Physiologic pacing was more expensive than ventricular ( 16,833 Canadian dollars vs 13,857 US dollars ) , largely because of the increased cost of dual-chamber devices . Among all sub study patients , the incremental cost-effectiveness of physiologic pacing is 297,600 Canadian dollars per life-year gained ; however , this value falls to 16,343 Canadian dollars in patients with an intrinsic heart rate > 60 . CONCLUSIONS In the short term , a strategy of routine implantation of physiologic pacemakers is not cost-effective by currently accepted st and ards . The selective use of these devices in patients likely to be pacemaker dependent appears to be cost-effective . Further studies with longer follow-up and which consider the benefit of reducing nonfatal cardiac events would be valuable AIMS To describe current evidence of the frequency , contents , and involved professionals of the routine follow-up visits in patients who have received a pacemaker ( PM ) .  METHODS AND RESULTS The multicentre FOLLOWPACE study prospect ively collected data during implantation and follow-up of 1526 patients who received a PM for the first time . A total of 4914 follow-up visits were studied . Mean follow-up was 394 days with a mean of 3.2 visits per patient . At all follow-up visits , the battery condition was tested in > 93 % , the stimulation threshold in > 91 % , and sensing in > 87 % . The pacemaker parameters as stimulation and sensing thresholds , lead impedances , and percentages of pacing remained stable over time , but these values did depend on the lead location , lead fixation , and pulse duration . The majority of  PM (re-)programming  was performed during implantation and /or shortly before hospital discharge ( 50 % ) .  PM re-programming  during follow-up was most frequently performed by the PM technician alone ( 95 % ) . CONCLUSION Crucial PM parameters are regularly checked . Re-programming of PM parameters declined during the first year after PM implantation . The majority of PM checks were carried out by the PM technician , indicating the major influence of the allied professional on the quality and safety of the pacing therapy AIMS Despite an annual rise in the numbers of patients receiving their first pacemaker ( PM )  , the risks of the implantation procedure remains unclear . The purpose of this prospect i ve study is to estimate the incidence of in-hospital events after first PM implantation  and to determine the predictors of these events . METHODS AND RESULTS Patients with conventional pacing diagnosis were included in the Dutch multicentre FOLLOWPACE PM registry that prospect ively documented patients ' prognosis and quality of life , and PM events after first implantation . From these registry characteristics , implantation data and in-hospital findings were analysed as potential predictors for events in a sample of 1198 patients . In 111 patients studied , at least one serious in-hospital event occurred ( incidence 10.1 % , 95%CI : 8.9 - 12.3 ) . Six variables , i.e. a lower body mass index , presence of heart failure in medical history , main indication for implantation , vena subclavia use for venous access , active atrial lead fixation , and the implantation of a dual chamber system , were found to be independent predictors of events after first PM implantation . The overall multivariable model yielded an ROC area of 0.65 ( 95%CI : 0.60 - 0.70 ) . CONCLUSION This large prospect i ve multicentre study identified six variables as independent predictors for serious in-hospital events after first implantation . This may assist the implanting cardiologist and surgeon to identify patients at higher risk , during and immediately after PM implantation BACKGROUND Health value or utility is the abstract ed magnitude of a person 's preference for quality and quantity of life . It reflects how much lifetime with the patient 's current health condition a patient is willing to exchange for a life in excellent health . Health values are used in cost-effectiveness analysis as a means of calculating quality -adjusted years of life . OBJECTIVE This study assessed the health values of elderly patients before and after pacemaker implantation . METHODS We prospect ively examined 398 patients from the Pacemaker Selection in the Elderly study , in which patients were r and omized to either VVIR or DDDR mode .  Health values were estimated with the  time tradeoff method  before implantation and at 3 , 9 , and 18 months after implantation . RESULTS The mean age of patients was 76 + /- 6 years ; 234 patients ( 59 % ) were male . At baseline , patients were , on average , willing to exchange 5 years of current health for approximately 4 years in perfect health ( value 0.76 + /- 0.06 ) . There was no difference in baseline health values with implant diagnosis ( sinus node dysfunction n = 172 , 0.72 , atrioventricular block n = 227 , 0.75 , other diagnoses n = 39 , 0.78 , P = not significant ) . The overall improvement in health values at 3 months after pacemaker implantation was 0.165 + /- 0.4 ( P = .0001 ) . The improvement in health values was independent of pacing mode ( P = .6 ) . The time tradeoff score was modestly correlated with other measurements of health-related quality of life . The change in time tradeoff score with time was not influenced by demographic characteristics such as age and sex , diagnoses , pacing mode , employment status , or history of angina . Patients with a lower functional class at enrollment ( III or IV on the Specific Activity Scale ) demonstrated an absolute improvement of 23 % in their health values , whereas patients in class I or II improved only by 12 % , ( P = .03 ) . CONCLUSIONS Permanent pacemaker implantation for st and ard indications improves health values and descriptive health status measures . The values reported here may be used as a means of calculating the cost-effectiveness of different pacing modalities AIMS Increasing evidence from r and omized trials and experimental studies indicates that right ventricular ( RV ) pacing may induce congestive heart failure . We studied regional left ventricular ( LV ) dyssynchrony and global LV function in 50 consecutive patients with sick sinus syndrome ( SSS ) r and omized to either atrial pacing [ AAI(R ) ] or dual chamber RV-pacing [ DDD(R ) ] .  METHODS AND RESULTS Fifty consecutive patients were r and omized to AAI(R ) or DDD(R)-pacing .  Tissue-Doppler imaging was used to quantify LV dyssynchrony in terms of number of segments with delayed longitudinal contraction ( DLC ) . Left ventricular ejection fraction ( LVEF ) was measured using three-dimensional echocardiography . Dyssynchrony was more pronounced in the DDD(R)-group than in the AAI(R)-group at the 12 months follow-up ( P < 0.05 ) . This reflected a significant increase of dyssynchrony in the DDD(R)-group from baseline to the 12 months follow-up ( 1.3 + /- 1 to 2.1 + /- 1 segments displaying DLC per patient ) , P < 0.05 . No change was observed in the AAI(R)-group ( 1.6 + /- 2 to 1.3 + /- 2 segments displaying DLC per patient , NS ) . No difference in LVEF , NYHA or NT-proBNP was observed between AAI(R)- and DDD(R)-mode after 12 months of pacing although LVEF decreased significantly in the DDD(R)-group from baseline ( 63.1 + /- 8 % ) to the 12 months follow-up ( 59.3 + /- 8 % , P < 0.05 ) , while LVEF remained unchanged in the AAI(R)-group ( 61.5 + /- 11 % at baseline vs. 62.3 + /- 7 % after 12 months , NS . CONCLUSION In patients with SSS , DDD(R)-pacing but not AAI(R)-pacing induces significant LV desynchronization and reduction of LVEF AIMS Atrioventricular synchronous pacing exerts beneficial effects , including reduction of left ventricular outflow tract gradients , in patients with hypertrophic obstructive cardiomyopathy . The Pacing in Cardiomyopathy study was initiated to explore the effects of pacing in a double-blind r and omized crossover fashion . The aims were to ascertain the beneficial effects of pacing in a controlled study and to rule out a placebo effect by pacing . This paper deals with the outcome of pacing on quality of life during 1 year of follow-up . METHODS Quality of life was evaluated with the Karolinska question naire , vali date d for patients paced for bradyarrhythmias and ischaemic heart disease . Drug-refractory patients with hypertrophic obstructive cardiomyopathy were recruited for the study and after a temporary pacing procedure implanted with permanent pacemakers . Patients were r and omized to two study arms defining the sequence of pacemaker programming . In one arm the pacemaker was inactive , in the other active . After 3 months the pacemaker was reprogrammed to the alternate mode and a further 3 months followed . After this period subsequent pacemaker programming corresponded to the mode preferred by the patient . A last assessment was made 1 year after baseline examinations . RESULTS Eighty patients completed the first crossover period and 75 completed the full 1 year of follow-up . Active pacing induced significant quality of life improvements , in the order of 9 - 44 % , regardless of programming sequence . Discontinuation of pacing after a first active period result ed in the return of symptoms . Fourteen patients requested early reprogramming after having been programmed to inactive pacing after a first period of active pacing .  Seventy-six patients preferred active pacing after the crossover period . A further 6 months of pacing induced progressive improvement in symptoms already favourably influenced . CONCLUSION Atrioventricular synchronous pacing has a profound beneficial effect on most domains of quality of life in patients with hypertrophic obstructive cardiomyopathy refractory to drug treatment The incidence and clinical predictors of the development of intolerance to VVIR pacing have not been extensively studied in prospect i ve long-term r and omized trials comparing different pacing modes . The frequency and clinical factors predicting intolerance to ventricular pacing are controversial . The Pacemaker Selection in the Elderly ( PASE ) Trial enrolled 407 patients aged > /=65 years in a 30-month , single-blind , r and omized , controlled comparison of quality of life and clinical outcomes with ventricular pacing and dual-chamber pacing in patients undergoing dual-chamber pacemaker implantation for st and ard clinical ly accepted indications . We review ed the clinical , hemodynamic , and electrophysiologic variables at the time of pacemaker implantation  in 204 patients enrolled in the PASE trial and r and omized to the VVIR mode , some of whom subsequently required crossover ( reprogramming ) to DDDR pacing . During a median follow-up of 555 days , 53 patients ( 26 % ) crossed over from VVIR to DDDR pacing . A decrease in systolic blood pressure during ventricular pacing at the time of pacemaker implantation ( p = 0.001 ) , use of beta blockers at the time of r and omization ( p = 0.01 ) , and nonischemic cardiomyopathy ( p = 0.04 ) were the only variables that predicted crossover in the Cox multivariate regression model . After reprogramming to the dual-chamber mode , patients showed improvement in all aspects of quality of life , with significant improvements in physical and emotional role . The high incidence of crossover from VVIR to DDDR pacing along with significant improvements in quality of life after crossover to DDDR pacing strongly favors dual-chamber pacing compared with single-chamber ventricular pacing in elderly patients requiring permanent pacing In patients with sick-sinus syndrome , single-chamber atrial pacing has been reported , in retrospective studies , to be associated with lower frequencies of atrial fibrillation , thromboembolism , heart failure , and mortality than ventricular pacing ; although single-chamber ventricular pacing is most commonly used . We did a prospect i ve r and omised trial in 225 consecutive patients ( 142 women , 83 men ; mean age 76 years ) with the sick-sinus syndrome , r and omised to atrial ( n = 110 ) or ventricular ( n = 115 ) pacing and followed for up to 5 years ( mean 40 [ SD 18 ] months ) . During follow-up , the frequency of atrial fibrillation was higher in the ventricular group , except at the first follow-up at 3 months . Thromboembolic events ( stroke or peripheral arterial embolus ) occurred in 20 patients in the ventricular group and in 6 patients in the atrial group ( p = 0.0083 ) . 25 patients died in the ventricular group compared with 21 in the atrial group ( p = 0.74 ) . Heart failure estimated by the New York Heart Association classification and by the daily doses of diuretics did not differ between the two groups . Atrioventricular block occurred in 2 patients in the atrial group . Patients with sick-sinus syndrome should be treated with atrial pacing rather than ventricular pacing because atrial pacing is associated with lower frequencies of atrial fibrillation , thromboembolic complications , and a low risk of atrioventricular block BACKGROUND In the Mode Selection Trial ( MOST ) of 2,010 patients with sinus node dysfunction , dual-chamber-paced patients had less atrial fibrillation ( AF ) and heart failure and had slightly improved health-related quality of life ( QOL ) compared with rate modulated right ventricular-paced patients . Our objective was to assess the impact of AF on QOL within MOST . METHODS We analyzed serial QOL measures ( Short Form-36 , Specific Activity Scale , time trade-off ) in 3 groups : ( 1 ) those without AF ; ( 2 ) those with paroxysmal AF ( PAF ) , but not chronic AF ( CAF ) ; and ( 3 ) those with CAF . We carried forward the last known QOL before crossover for all subsequent time points in patients r and omized to rate modulated right ventricular pacing who crossed over to dual-chamber pacing for severe pacemaker syndrome . RESULTS Three hundred seventeen patients ( 15.8 % ) had AF in the year after implantation , 206 patients within 3 months ( 191 PAF , 15 CAF ) , and another 159 ( 124 PAF , 35 CAF ) between 3 and 12 months . There were no significant differences among groups in individual Short Form-36 subscales or time trade-off scores at 12 months as compared with baseline or 3 months . Cardiovascular health status was better at 12 months as compared with baseline or 3 months in those without AF . CONCLUSIONS Atrial fibrillation after pacemaker implantation in elderly patients with sick sinus syndrome was not a major determinant of QOL . However , there was a trend toward better cardiovascular functional status in patients without AF An atrial-based pacing mode is superior to ventricular constant rate dem and pacing ( VVI ) mode in patients with sick sinus syndrome ( SSS ) by providing both rate adaptation and atrioventricular ( AV ) synchrony . The use of a non-atrial sensor to overcome chronotropic incompetence and preserve normal intrinsic AV conduction in pacemaker therapy for SSS was investigated in 15 consecutive patients ( mean age 66 + /- 2 years ) . All had intact AV conduction ( ante grade conduction capacity > 100 beats.min-1 and an atrial paced to intrinsic R interval of < or = 220 ms ) .  DDDR pacemakers capable of being programmed into atrial rate adaptive ( AAIR ) , dual chamber rate adaptive ( DDDR ) and ventricular rate adaptive ( VVIR ) modes were used . Beginning with an acute study , arterial pressure was invasively assessed in each pacing mode during physiological stresses and low level exercise . In the ambulatory phase , the incidence of ventricular pacing and arrhythmias ( Holter recording ) , diurnal blood pressure changes ( ambulatory blood pressure recording ) , and symptom and quality of life level ( question naires and interviews ) were compared . Despite similar heart rate changes during acute physiological stresses , a higher blood pressure was recorded during AAIR or DDDR pacing compared with VVIR pacing . Systolic blood pressure over 24 h was lower in the VVIR mode ( 122 + /- 5 mmHg ) than AAIR/DDDR pacing ( 129 + /- 6/128 + /- 6 mmHg , P < 0.05 ) . VVIR pacing was associated with a higher frequency of atrial and ventricular ectopics , with two patients developing paroxysmal atrial fibrillation . Ventricular pacing was used in a higher percentage in the DDDR compared with the VVIR mode ( 64 + /- 11 and 39 + /- 7 % , P < 0.03 ) . VVIR pacing was associated with more palpitations , a lower level of general well being and depression . Despite the use of a sensor to overcome chronotropic incompetence , VVIR pacing is a less satisfactory pacing mode for SSS . Although AAIR/DDDR pacing may achieve similar haemodynamic and clinical status , in patients with intact AV conduction , AAIR pacing may be preferable by avoiding an abnormal ventricular activation pattern BACKGROUND There are two approaches to the treatment of atrial fibrillation : one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm , and the other is the use of rate-controlling drugs , allowing atrial fibrillation to persist . In both approaches , the use of anticoagulant drugs is recommended . METHODS We conducted a r and omized , multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death . The primary end point was overall mortality . RESULTS A total of 4060 patients ( mean [ + /-SD ] age , 69.7+/-9.0 years ) were enrolled in the study ; 70.8 percent had a history of hypertension , and 38.2 percent had coronary artery disease . Of the 3311 patients with echocardiograms , the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent . There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy ( mortality at five years , 23.8 percent and 21.3 percent , respectively ; hazard ratio , 1.15 [ 95 percent confidence interval , 0.99 to 1.34 ] ; P=0.08 ) . More patients in the rhythm-control group than in the rate-control group were hospitalized , and there were more adverse drug effects in the rhythm-control group as well . In both groups , the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic . CONCLUSIONS Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy , and there are potential advantages , such as a lower risk of adverse drug effects , with the rate-control strategy . Anticoagulation should be continued in this group of high-risk patients BACKGROUND St and ard clinical practice permits the use of either single-chamber ventricular pacemakers or dual-chamber pacemakers for most patients who require cardiac pacing .  Ventricular pacemakers are less expensive , but dual-chamber pacemakers are believed to be more physiologic . However , it is not known whether either type of pacemaker results in superior clinical outcomes . METHODS The Pacemaker Selection in the Elderly study was a 30-month , single-blind , r and omized , controlled comparison of ventricular pacing and dual-chamber pacing in 407 patients 65 years of age or older in 29 centers . Patients received a dual-chamber pacemaker that had been r and omly programmed to either ventricular pacing or dual-chamber pacing . The primary end point was health-related quality of life as measured by the 36-item Medical Outcomes Study Short-Form General Health Survey . RESULT The average age of the patients was 76 years ( range , 65 to 96 ) , and 60 percent were men .  Quality of life improved significantly after pacemaker implantation ( P<0.001 ) , but there were no differences between the two pacing modes in either the quality of life or prespecified clinical outcomes ( including cardiovascular events or death ) . However , 53 patients assigned to ventricular pacing ( 26 percent ) were crossed over to dual-chamber pacing because of symptoms related to the pacemaker syndrome . Patients with sinus-node dysfunction , but not those with atrioventricular block , had moderately better quality of life and cardiovascular functional status with dual-chamber pacing than with ventricular pacing . Trends of borderline statistical significance in clinical end points favoring dual-chamber pacing were observed in patients with sinus-node dysfunction , but not in those with atrioventricular block . CONCLUSION The implantation of a permanent pacemaker improves health-related quality of life . However , the quality -of-life benefits associated with dual-chamber pacing as compared with ventricular pacing are observed principally in the subgroup of patients with sinus-node dysfunction OBJECTIVES This study examined the effect of physiologic pacing on the development of  chronic atrial fibrillation ( CAF ) in the Canadian Trial Of Physiologic Pacing ( CTOPP ) . BACKGROUND The role of physiologic pacing to prevent CAF remains unclear . Small r and omized studies have suggested a benefit for patients with sick sinus syndrome . No data from a large r and omized trial are available . METHODS The CTOPP r and omized patients undergoing first pacemaker implant to ventricular-based or physiologic pacing ( AAI or DDD ) . Patients who were prospect ively found to have persistent atrial fibrillation ( AF ) lasting greater than or equal to one week were defined as having CAF . Kaplan-Meier plots for the development of CAF were compared by log-rank test . The effect of baseline variables on the benefit of physiologic pacing was evaluated by Cox proportional hazards modeling . RESULTS Physiologic pacing reduced the development of CAF by 27.1 % , from 3.84 % per year to 2.8 % per year ( p = 0.016 ) . Three clinical factors predicted the development of CAF : age > or = 74 years ( p = 0.057 ) , sinoatrial ( SA ) node disease ( p < 0.001 ) and prior AF ( p < 0.001 ) . Subgroup analysis demonstrated a trend for patients with no history of myocardial infa rct ion or coronary disease ( p = 0.09 ) as well as apparently normal left ventricular function ( p = 0.11 ) to derive greatest benefit . CONCLUSIONS Physiologic pacing reduces the annual rate of development of chronic AF in patients undergoing first pacemaker implant . Age > or = 74 years , SA node disease and prior AF predicted the development of CAF . Patients with structurally normal hearts appear to derive greatest benefits AIMS The recent Danish Multicentre R and omized Trial on Single-Lead Atrial ( AAIR ) Pacing versus Dual-Chamber ( DDDR ) Pacing in Sick Sinus Syndrome ( DANPACE ) suggested DDDR pacing as st and ard care . However , previous findings supported the routine use of AAIR pacing . This study investigated the cost-effectiveness of DDDR pacing compared with AAIR pacing for sick sinus syndrome . METHODS AND RESULTS A decision-analytical model based on patient-level data from three r and omized trials was design ed from the Danish healthcare system 's perspective . The main outcomes were lifetime costs , quality -adjusted lifeyears ( QALYs ) , and net monetary benefit . Quality -adjusted lifeyears were calculated by utilizing community-based preferences . Costs were calculated by utilizing the extensive data on re source consumption , from the DANPACE trial . Data were pooled and adjusted for baseline differences . Dual-chamber pacing was shown to be cost-effective in all the analyses using a willingness-to-pay ( WTP ) threshold of £ 20,000/QALY , and most analyses using a WTP of £ 30,000/QALY . When pooling the data and adjusting for baseline differences , Monte Carlo simulations revealed a 51 - 71 % probability of DDDR pacing being cost-effective at a WTP of £ 20,000/QALY , and a 42 - 58 % probability at a WTP of £ 30,000/QALY . Dual-chamber pacing was most likely to be cost-effective among elderly patients with comorbidity . The expected value of perfect information was low and initiation of additional publicly funded Danish trials was discouraged . CONCLUSION Dual-chamber pacing is likely to be a cost-effective treatment for sick sinus syndrome patients
target: No statistically significant difference was found between the pacing modes for mortality , heart failure , stroke , chronic atrial fibrillation or quality of life .
  However , the risk of developing heart failure may vary with age and device .
  The risk of heart failure may have an impact on the decision to use dual-chamber or single-chamber atrial pacemakers .
  Results from an analysis based on age ( > 75 years or ≤ 75 years ) and risk of heart failure indicate that dual-chamber pacemakers dominate single-chamber atrial pacemakers ( i.e. are less expensive and more effective ) in older patients , whereas dual-chamber pacemakers are dominated by ( i.e. more expensive and less effective ) single-chamber atrial pacemakers in younger patients .
  In patients with SSS without evidence of impaired AV conduction , dual-chamber pacemakers appear to be cost-effective compared with single-chamber atrial pacemakers .
background: BACKGROUND Bradycardia [ resting heart rate below 60 beats per minute ( b.p.m . ) ]
  can be caused by conditions affecting the natural pacemakers of the heart , such as sick sinus syndrome ( SSS ) and atrioventricular ( AV ) blocks .
  People suffering from bradycardia may present with palpitations , exercise intolerance and fainting .
  The only effective treatment for patients suffering from symptomatic bradycardia is implantation of a permanent pacemaker .
  OBJECTIVE To appraise the clinical effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber atrial pacemakers for treating symptomatic bradycardia in people with SSS and no evidence of AV block .