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Role of CRT and CRTD in CHF
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Role of CRT and CRTD in CHF

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  • Main purpose: Show that a large number of patients have been studied in completed and ongoing randomized controlled studies of CRT. Use in conjunction with previous slide. Key messages: Over 3000 patients have been enrolled in randomized controlled clinical trials presented to date. When CARE-HF, another landmark trial assessing mortality and hospitalization, is reported, close to 4,000 patients will have been studied.
  • Main purpose: Show that a large number of patients have been studied in completed and ongoing randomized controlled studies of CRT. Use in conjunction with next slide. Key messages: Nearly 3000 patients have been enrolled in randomized controlled clinical trials presented to date. All studies have used a wide QRS in the presence of moderate to severe, systolic, dilated cardiomyopathy as inclusion criteria. Most included patients with normal sinus, and without a primary indication fro an ICD. All studies have reported favorable outcomes.
  • Key Message: CRT improves QOL as measured by NYHA functional class and the Minnesota Living with Heart Failure scores.
  • Key Message: CRT improves exercise capacity as measured by the 6 min. walk test and peak exercise oxygen consumption.
  • Odds ratio refers to odds of death from progressive heart failure among patients randomized to CRT or to no CRT. Odds ratio less than 1 favors CRT. Boxed area is proportional to the relative weight given to each trial in the statistical model.
  • Key Messages: The primary composite end-point (death or an unplanned hospitalization for a major cardiovascular event) was reduced substantially by CRT. There was no early hazard from device implantation. The curves began to separate within the first 90 days and remained separated during the follow up period. The absolute difference between the CRT and Medical Therapy arms in the percentage of patients reaching the primary endpoint during 29.5 months was 16%.
  • Key Messages: There was a striking reduction in mortality in the CRT group. The absolute difference between control and CRT was 10%. Again, there was no early hazard from device implantation and the curves begin to separate within 6 months. A reduction in both sudden deaths and deaths due to worsening heart failure was observed. However, in the CRT arm 29/82 deaths were sudden (35%). Mortality reduction in the CRT group was sustained over time. The benefits of CRT are in addition to those of optimal pharmacological therapy. Additional Information: Compared to controls, the hazard ratio of the effect of CRT in CARE-HF (0.64; 95% CI 0.48 to 0.85; p=0.0019) was similar to that of CRT-ICD in the COMPANION trial (0.64, 95% CI, 0.48 to 0.86; P=0.003) . The absolute estimated difference between CRT-ICD and control at 2 years in COMPANION was 8%. In CARE-HF the high mortality in controls could be explained by the long follow-up time. The absolute difference in mortality at 2 years was 7.1%. This compares to 5.2% with enalapril in the SOLVD-treatment study and is similar to the estimated two-year mortality difference between placebo and bisoprolol in the CIBIS-II study or the 8.8% difference between placebo and carvedilol in COPERNICUS (which using the method of trial duration used in our study had a duration of about 15 months).
  • Main purpose: Show that a large number of patients have been studied in completed and ongoing randomized controlled studies of CRT. Use in conjunction with previous slide. Key messages: Over 3000 patients have been enrolled in randomized controlled clinical trials presented to date. When CARE-HF, another landmark trial assessing mortality and hospitalization, is reported, close to 4,000 patients will have been studied.
  • Nearly 5000 mildly symptomatic patients have been enrolled in randomised controlled trials of cardiac resynchronisation therapy. Published studies to date have included approximately 3000 patients. Follow-up periods for the various studies ranged from 6 months in the initial pilot trials, to 2 years or more in pivotal trials. The MIRACLE ICD II and Contak CD studies were randomized pilot studies of the effect of cardiac resynchronisation in patients with NYHA Class II or I symptoms. MIRACLE ICD II prospectively enrolled NYHA Class II patients, and Contak CD NYHA Class III and IV patients who improved to NYHA Class I or II after randomization, are included here. A post-hoc analysis of CARE-HF patients reporting mild symptoms, but classified as NYHA Class II or IV by the physician are also included. Both the REVERSE and MADIT CRT studies are prospective and larger in scale. Along with RAFT (completed enrollment in March 2009, results expected in early 2011) these studies are considered pivotal. References: Contak CD: Higgins SL, et al. Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias J Am Coll Cardiol 2003 ; 42:1454-1459 MIRACLE ICD II: Abraham WT, et al. Effects of cardiac resynchronization on disease progression in patients with left ventricular systolic dysfunction, an indication for an implantable cardioverter defibrillator, and mildly symptomatic chronic heart failure. Circulation 2004; 110: 2864-2868. CARE-HF: Cleland JGF, et al. Long-term effect of cardiac resynchronisation in patients reporting mild symptoms of heart failure: a report from the CARE-HF study. Heart 2008;94(3):278-283. REVERSE: Linde C, et al. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol 2008;52(23):1834-43. AND: Daubert C, et al. J Am Coll Cardiol 2009;54(20):1837-46 MADIT CRT: Moss AJ, et al. Cardiac resynchronization therapy for the prevention of heart failure events. N Engl J Med 2009;361(14):1329-38 RAFT: Tang AS, et al. Resynchronization/defibrillation for ambulatory heart failure trial: rationale and trial design. Curr Opin Cardiol 2009;24(1):1-8
  • This slide summarizes the key inclusion criteria of the major prospective, randomised controlled studies of cardiac resynchronisation therapy in patients with milder symptoms. These studies have important commonalities, as well as subtle differences to note. All studies included New York Heart Association functional class II patients. Recall that these patients experience symptoms with ordinary exertion, but the symptoms are not limiting. All studies enrolled NYHA Class II patients regardless of etiology. Both REVERSE and MADIT CRT included NYHA Class I patients, those with symptoms only with greater than normal exertion. In REVERSE, NYHA Class I patients of any etiology needed to have been more symptomatic at some point, thereby classifying them as being in Stage C heart failure. MADIT CRT only included NYHA Class I patients who met guidelines for an ICD, that is they needed to have had a myocardial infarction at least 40 days prior to enrollment. RAFT initially NYHA Class III patients but did not include those with NYHA Class I symptoms. All patients in all studies had systolic heart failure, with a left ventricular ejection fraction of 30% or less in both MADIT CRT and RAFT, and a cut-off of no more than 40% in REVERSE. All patients in all studies had a prolonged QRS duration. Both REVERSE and RAFT required a QRS duration of at least 120 msec, while MADIT CRT limited inclusion to those patients with a QRS duration of 130 msec or more.
  • In patients with mild symptoms and an indication for an implantable cardioverter defibrillator (ICD) for the primary prevention of sudden cardiac death, and a wide QRS, MADIT CRT was designed to determine whether cardiac resynchronisation therapy in combination with an ICD (CRT-D) and optimal medical therapy reduced all cause mortality and major heart failure events when compared with an ICD with optimal medical therapy. A nonfatal heart failure event included heart failure hospitalizations and outpatient administration of intravenous decongestive therapy. End point adjudication was made by independent, blinded committees. Key exclusion criteria included having an implanted pacemaker, a previous coronary artery bypass or percutaneous coronary intervention or myocardial infarction with 3 months, and atrial fibrillation within 1 month. Enrollment commenced in December 2004 and was completed in April 2008. Results were presented at the European Society of Cardiology meeting in September 2009, simultaneously with online publication in the New England Journal of Medicine.
  • In mildly symptomatic systolic heart failure patients, cardiac resynchronisation therapy in combination with an ICD and optimal medical therapy reduced the risk of death or a major heart failure event by 34% when compared with an ICD and optimal medical therapy alone. A total of 372 patients experienced the primary end point, 187 of 1089 patients in the CRT-D group (17.2%), and 185 of 731 patients in the ICD only group (25.3%). Of the 372 primary end point events, there were 54 deaths and 318 non-fatal heart failure events. Most of the heart failure events occurred in hospital, accounting for 276 or 87% of all non-fatal events. There were 127 deaths at any time during the study. With low annual rate of approximately 3% in each study group, there was no between group differences in mortality alone.
  • REVERSE enrollment started in September 2004 and was completed 2 years later in September 2006. Two minimum follow-up periods were pre-specified, 12 months for all enrolled patients, and 24 months for the European cohort only. The primary end point was the percent worsened in the clinical composite response. The clinical composite end point includes all randomised patients. Worsened patients have either died from any cause, been hospitalised for worsening heart failure, crossed over to the other arm because of worsening heart failure, worsened in their NYHA functional class, or were moderately of markedly worse on the patient global assessment. Change in left ventricular end systolic volume indexed to body surface area was a powered secondary end point. NYHA functional class criteria included all NYHA Class II patients as well as NYHA Class I patients who had been previously symptomatic, as well as NYHA Class I patients who had been previously symptomatic. Patients were excluded if they had NYHA Class III or IV symptoms, or were hospitalised fro heart failure in the previous 3 months. Other major exclusion criteria included indications for permanent pacing, or permanent or persistent atrial arrhythmias.
  • Chart on left are the primary end point results from the 12 month follow-up. It includes all patients randomized in the trial. 21% of the CRT Off group and 16% of the CRT On worsened in their clinical composite response. The P value is not significant at 0.1. When analysed conventionally by using the entire distribution of improved, unchanged, and worsened, a p-value of 0.004 n favor of CRT is achieved. The chart at right shows the results of the pre-specified 24 month cohort from European centers only. A higher proportion of CRT Off patients worsened (34%), compared with 19% of the CRT-On patients who worsened, P=0.01. When analysing the primary end point in the conventional manner, the P-value remains highly statistically significant at 0.0006. The clinical composite response score is calculated as follows: Worsened patients have either died from any cause, been hospitalised for worsening heart failure, crossed over to the other arm because of worsening heart failure, worsened in their NYHA functional class, or were moderately of markedly worse on the patient global assessment. Patients were classified as improved if they had not worsened, and they either improved in their NYHA functional class, or were moderately or markedly improved in their patient global assessment. If patients were neither worsened nor improved, then they were classified as unchanged.
  • For the three randomised trials including mildly symptomatic patients, this slide plots the hazard ratios with 95% confidence intervals of the risk of all cause mortality or adjudicated heart failure hospitalisation. Results from REVERSE at 24 months, and from the analysis of mildly symptomatic patients enrolled in CARE-HF are consistent with the primary end point of MADIT CRT.
  • Improvements with cardiac resynchronisation therapy were observed in all studies that reported this end point, with statistically significant increases in MIRCLE ICD II, REVERSE, and MADIT CRT. The magnitude of the difference in improvement in left ventricular ejection fraction was greatest in the MADIT CRT study.
  • In studies reporting data, cardiac resynchronisation therapy significantly reduced left ventricular volumes.
  • Cardiac resynchronisation therapy improves exercise capacity and quality of life for patients with moderate to severe symptoms, but does not improve these end points in less symptomatic patients.
  • June 2008
  • 1. Yu CM, et al. Predictors of response to cardiac resynchronization therapy (PROSPECT)—study design. Am Heart J 2005;149:600-5. 2. Packer M. Proposal for a new clinical end point to evaluate the efficacy of drugs and devices in the treatment of chronic heart failure. J Card Fail. 2001;7:176-182. 3. Pitzalis MV, et al . Cardiac resynchronization therapy tailored by echocardiographic evaluation of ventricular asynchrony. J Am Coll Cardiol. 2002; 40:1615-1622. 4. Yu CM, Fung WH, Lin H, Zhang Q, Sanderson JE, Lau CP et al. Predictors of left ventricular reverse remodeling after cardiac resynchronization therapy for heart failure secondary to idiopathic dilated or ischemic cardiomyopathy. Am J Cardiol. 2003; 91:684-688. The Clinical Composite Score (CCS) describes patients regardless of vital status at 6 months and includes both objective and subjective measures of clinical status. A patient’s CCS was classified as one of the following: Worsened —patient dies or has been hospitalized due to or associated with worsening heart failure; demonstrates worsening in NYHA class at last observation carried forward (LOCF); has moderate or marked worsening of patient global assessment score at last observation carried forward (LOCF); or permanently discontinues CRT due to or associated with worsening heart failure or Improved —patient has not worsened (as defined above) and demonstrates improvement in NYHA class at LOCF or has moderate or marked improvement in patient global assessment score at LOCF or Unchanged —patient is neither improved nor worsened. 1,2 A positive response to CRT was defined, in the case of CCS, as a designation of “improved,” and with LVESV, a reduction of 15% or more at 6 months compared with baseline (paired LVESV measurements) 1 . A reduction in LVESV of > 15% has been used in previous trials 3,4 and was used in PROSPECT as an objective measure of cardiac function.
  • Note: Results will be reported on the parameters with arrow only, in this presentation, all other parameters are reported in the results manuscript. To date, several echocardiographic methods are used to assess dyssynchrony, from conventional to advanced approaches including Tissue Doppler Imaging (TDI). The PROSPECT steering committee selected 12 echocardiographic paramaters identified from published and unpublished literature to evaluate which of these parameters provides optimal information on dyssynchrony and may prospectively identify responders to CRT. Pre-specified cutoff values for each echocardiographic parameter was tested against the response outcomes (CCS and LVESV). Some of these measures did not have a predictive cutoff value in the literature; in those cases the cutoff was defined as the median value. Results using the measures highlighted by the arrows will be reported in this presentation. For results on all of the measures please see the manuscript. These highlighted TDI measures were selected because they are the most reported in the literature. SPWMD is highlighted because it uses a standard parameter and has also been more widely reported. LPEI is selected because inter-observer variability analysis was performed on this parameter and is representative of the Doppler flow measures. Pitzalis MV. J Am Coll Cardiol. 2002; 40:1615-1622. Cazeau S. Pacing Clin Electrophysiol. 2003; 26(Pt II):137-143. Bax JJ . Am J Cardiol. 2003; 92:1238-40. Yu CM. Am J Cardiol. 2003; 91:684-688. Yu CM . Circulation. 2004; 110:66-73. Notabartolo D. Am J Cardiol . 2004; 94: 817-820. Søgaard P. Circulation. 2002; 106:2078-84. Søgaard P . J Am Coll Cardiol. 2002; 40:723-30
  • Chung, ES et al. Results of the Predictors of Response to CRT (PROSPECT) Trial. Circulation. 2008;117:2608-2616. During the 6-month Follow-Up Period: Deaths: 14 patients (3%) Hospitalized for worsening heart failure: 45 patients (11%) RESULTS: Patients were enrolled in line with current guideline practice. There were no statistically significant differences in CCS or LVESV responses between patients in the US and outside US (65.2% and 73.4% respectively, p=0.07 for CCS and 54.2% and 58.3%, respectively, p=0.55 for LVESV). The CCS response rate was higher among non-ischemic patients compared to those with ischemic etiology (75% vs. 64%, respectively, p=0.01); also, the LVESV response rate tended to be higher in the non-ischemic group compared with the ischemic group (63% vs. 50%, respectively, p=0.03). While the center reported mean LVEF was 23.6 ± 7% in PROSPECT, the core laboratory measured mean LVEF was 29.3 ± 10%; 20.2% of subjects had a core laboratory measured LVEF > 35%. In the subgroups defined by core laboratory measured LVEF < 35% (n=340, 79.8%) or LVEDD > 65 mm (n=265, 62.2%), there were no substantial differences in the predictive power of the echocardiographic parameters compared to all subjects.
  • The use of different echocardiographic platforms and equipment to collect and analyze images may have exacerbated variability in measurements. However, as a study evaluating methods across a wide spectrum of locations and medical practices, the steering committee sought to include the major vendors of these technologies to reflect current practice. Inter Core Lab Variability in Echo’s from 32 Randomly Selected Echo Recordings Inter-observer variability was low for LPEI, but high for both the Ts-SD (Yu index) and SPWMD (Pitzalis method) Inter-observer variability was measured between core laboratories using the echocardiographic parameters: LVESV, SPWMD, Ts-SD, LPEI, Ts-peak. LPEI, Ts-SD, and SPWMD are reported here. For this assessment a total of 12 recordings were exchanged by the US and Italian core laboratories, while the US and UK core laboratories exchanged 20 echocardiograms. The coefficient of variation is the ratio of the standard deviation to the mean. It is expressed as a percentage and is used to compare dispersions of different samples. [source: AMA Manual of Style. 9 th edition]. The Kappa coefficient is based on binary predictor variable that indicates echo measure is above or below cut-off. Results of the Intra-observer variability was similar in the 3 core-labs, with low variability for LVESV and LPEI (CV, 3.8% and 3.7%, respecively), moderate variability for Ts-SD and Ts-peak (CV, 11.4% and 15.8%, respectively) and high variability for SPWMD (CV, 24.3%). Interobserver variability was higher for each parameter than intraobserver variability, with high variability for Ts-peak, Ts-SD, and SPWMD (CV, 31.9%, 33.7%, and72.1%, respectively). Κ Interpretation < 0 No agreement 0.0 — 0.20 Slight agreement 0.21 — 0.40 Fair agreement 0.41 — 0.60 Moderate agreement 0.61 — 0.80 Substantial agreement 0.81 — 1.00 Almost perfect agreement
  • The main purpose of PROSPECT was to assess predictive abilities of 12 echocardiographic parameters, not to test whether the use of these parameters have a clinical impact. Relatively high levels of both inter- and intra-observer variability noted in this multi center, observational, nonrandomized study impairs the ability to conclusively assess the potential predictive capabilities of the echocardiographic parameters in an ideal setting. Despite promising preliminary data from prior single center studies, PROSPECT demonstrates that any method must be prospectively validated before being considered for routine clinical use. The results of PROSPECT do not support widespread use of echocardiographic measures of mechanical dyssynchrony in patient selection for CRT. Clinicians should continue to support the ACC/AHA/ESC and HFSA Heart Failure Guidelines for patients who meet indications for CRT + D therapies.
  • Main purpose: Show that a large number of patients have been studied in completed and ongoing randomized controlled studies of CRT. Use in conjunction with next slide. Key messages: Nearly 3000 patients have been enrolled in randomized controlled clinical trials presented to date. All studies have used a wide QRS in the presence of moderate to severe, systolic, dilated cardiomyopathy as inclusion criteria. Most included patients with normal sinus, and without a primary indication fro an ICD. All studies have reported favorable outcomes.
  • Main purpose: Show that a large number of patients have been studied in completed and ongoing randomized controlled studies of CRT. Use in conjunction with next slide. Key messages: Nearly 3000 patients have been enrolled in randomized controlled clinical trials presented to date. All studies have used a wide QRS in the presence of moderate to severe, systolic, dilated cardiomyopathy as inclusion criteria. Most included patients with normal sinus, and without a primary indication fro an ICD. All studies have reported favorable outcomes.
  • Defibrillator in Acute Myocardial Infarction Trial: a randomized, open-label comparison of ICD therapy (in 332 patients) and no ICD therapy (in 342 patients) 6 to 40 days after a myocardial infarction. Mean (±SD) follow-up period of 30±13 months In this randomized trial of high-risk patients who had recently had a myocardial infarction, overall survival was not improved by prophylactic implantation of an ICD.
  • MADIT I: Prior MI, EF  35%, Asymptomatic nsVT (3-30 beats), NYHA I-II-III, EPS (+). 54% reduction of mortality. P< 0.36 / abnormalities on SAECG . In total 1055 patients were enrolled, and randomly assigned 900 to therapy with an ICD (446 patients) or to the control group (454 patients). Overall mortality, HR 1.07 p=0.64. Negative study: no routine use of ICD MADIT II: Prior MI and LVEF<30%. 31% reduction of total mortality, p=0.016 DINAMIT: 6 to 40 days after MI, HRV(+). Mean (±SD) follow-up period of 30±13 months. HR 1.08. P=0.66. Negative study: no benefit in recent MI SCD-HeFT: ICM and NICM. NYHA II-III. 23% Reduction in All Cause Mortality For ICD Therapy .p-value 0.007
  • Primary prevention trial In patients with a Prior MI and LVD, the scarred tissue would serve as a trigger for malignant ventricular arrhythmias Hypothesis: prophylactic implantation in patients with Chronic CAD with prior MI EF < 30% significantly reduces mortality compared to conventionally managed patients Prophylactic implantation in the absence of EP testing to induce arrhythmias!
  • MADIT I: Prior MI, EF  35%, Asymptomatic nsVT (3-30 beats), NYHA I-II-III, EPS (+). 54% reduction of mortality. P< 0.36 / abnormalities on SAECG . In total 1055 patients were enrolled, and randomly assigned 900 to therapy with an ICD (446 patients) or to the control group (454 patients). Overall mortality, HR 1.07 p=0.64. Negative study: no routine use of ICD MADIT II: Prior MI and LVEF<30%. 31% reduction of total mortality, p=0.016 DINAMIT: 6 to 40 days after MI, HRV(+). Mean (±SD) follow-up period of 30±13 months. HR 1.08. P=0.66. Negative study: no benefit in recent MI SCD-HeFT: ICM and NICM. NYHA II-III. 23% Reduction in All Cause Mortality For ICD Therapy .p-value 0.007
  • The Kaplan-Meier curves for total mortality show the ICD sub-group with a hazard ratio of 0.49; i.e, 51% lower mortality than the control group, p < 0.001. The AARx group appears slightly worse than the control group, but not statistically significant. It is evident from this (and previous slide) that the EP-guided limb is made up of the good results with ICD, diluted by the poor results with AARx, yielding a total result for the EP-guided limb which is only moderately better than the control group. Note: analysis of the patient characteristics of the three subgroups demonstrates that the clinical risk factors placed the ICD group at higher risk compared to the other two groups (AHA 1999 abstracts; Circulation 1999; vol. 100).
  • MADIT I: Prior MI, EF  35%, Asymptomatic nsVT (3-30 beats), NYHA I-II-III, EPS (+). 54% reduction of mortality. P< 0.36 / abnormalities on SAECG . In total 1055 patients were enrolled, and randomly assigned 900 to therapy with an ICD (446 patients) or to the control group (454 patients). Overall mortality, HR 1.07 p=0.64. Negative study: no routine use of ICD MADIT II: Prior MI and LVEF<30%. 31% reduction of total mortality, p=0.016 DINAMIT: 6 to 40 days after MI, HRV(+). Mean (±SD) follow-up period of 30±13 months. HR 1.08. P=0.66. Negative study: no benefit in recent MI SCD-HeFT: ICM and NICM. NYHA II-III. 23% Reduction in All Cause Mortality For ICD Therapy .p-value 0.007
  • The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial was a prospective, randomized, investigator-initiated study based on observational data and was funded by St. Jude Medical. Follow-up lasted a mean (±SD) of 29.0±14.4 months.
  • SCD-HeFT: ICM and NICM. NYHA II-III. 23% Reduction in All Cause Mortality For ICD Therapy .p-value 0.007 The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial was a prospective, randomized, investigator-initiated study based on observational data and was funded by St. Jude Medical. Follow-up lasted a mean (±SD) of 29.0±14.4 months.
  • Lead location? Single, two, triple leads? Settings: AV, VV delay

Role of CRT and CRTD in CHF Role of CRT and CRTD in CHF Presentation Transcript

  • Role of CRT/CRT-D in Chronic Heart Failure 游治節 2010/10/05 台大醫院內科心臟電生理教學演講系列 (2010) 時間:每週二,下午 17:30-18:30 地點: 14C 教室 ( 錫琴講堂 )
  • Cumulative Enrollment in Cardiac Resynchronization Randomized Trials
  • Randomized Controlled Trials on CRT * RV paced QRS ¶ Primary endpoint not met; key secondary endpoints reached LVEF  35% for all trials CRT Improves: NYHA Class, Quality of life score, Exercise Capacity: 6 MW, Peak VO2 LV function: EF, MR Reverse remodeling: LVEDV Hospitalization Mortality + ¶ Published Yes Normal  130 II MIRACLE ICD II (186) + Published Both Normal  120 III, IV PATH CHF II (89) + Published Yes Normal  130 III, IV MIRACLE ICD (369) + + Published Yes Normal  120 III, IV COMPANION (1520) + ¶ + + + + Results Published No Normal  120 III, IV CARE HF (814) Published Yes Normal  120 II -IV CONTAK CD (490) Published No Normal  120 III, IV PATH CHF (41) Published No AF  200 * III MUSTIC AF (43) Published No Normal  150 III MUSTIC SR (58) Published No Normal  130 III, IV MIRACLE (453) Status ICD? Sinus QRS NYHA Study (n randomized)
  • CRT Improves QoL and NYHA * P < 0.05 Abraham et al., 2003
  • CRT Improves Exercise Capacity * P < 0.05 Abraham et al., 2003
  • Progressive Heart Failure Mortality 51% Relative Reduction with CRT Bradley DJ, et al. JAMA 2003;289:730-740 Overall odds ratio (95% CI) of 0.49 (0.25 - 0.93) Favors CRT Favors No CRT Overall (n=1634) MUSTIC (n=58) MIRACLE (n=532) MIRACLE ICD (n=554) CONTAK CD (n=490)
  • CARE-HF: Primary Endpoint (All-cause Mortality or HF Hosp.) CRT : 159 pts (39%) 3 48 118 232 292 404 Medical Therapy 7 68 166 273 323 409 CRT Number at risk 0 500 1000 1500 0.00 0.25 0.50 0.75 1.00 HR 0.63 (95% CI 0.51 to 0.77) Event-free Survival Days P < .0001 Medical : 224 pts Therapy (55 %)
  • CARE HF: All-Cause Mortality 5 71 192 321 365 404 Medical Therapy 8 89 213 351 376 409 CRT Number at risk 0 500 1000 1500 0.00 0.25 0.50 0.75 1.00 Event-free Survival Days Medical 120 pts Therapy (30%) HR 0.64 (95% CI 0.48 to 0.85) P = .0019 CRT : 82pts (20%)
  • Cumulative Enrollment in Cardiac Resynchronization Randomized Trials
    • EF <35%
    • QRS>120ms
    • sinus rhythm
    • NYHA III~IV (ambulatory)
    • on optimal recommended medical therapy.
    CRT for severe HF I IIa IIa
    • EF <35%
    • QRS>120ms
    • Atrial fibrillation
    • NYHA III~IV (ambulatory)
    • on optimal recommended medical therapy.
    • EF <35%
    • Ventricular pacing dependant
    • NYHA III~IV (ambulatory)
    • on optimal recommended medical therapy.
    ACC / AHA / HRS 2008 Guideline +LBBB
  • Case 1
    • 65 y/o 吳 OO
    • DCM
    • EF 25%
    • Normal daily life
    • Dyspnea while slightly chasing the bus (NYHA II)
    • QRS 160ms
  • Randomised Controlled Trials of CRT in Less Symptomatic, Wide QRS Heart Failure
    • Nearly 5000 mildly symptomatic patients have been enrolled in randomised controlled trials to date
    Follow-up (Months) * NYHA Class I and II during run-in period. Contak CD* CARE-HF* REVERSE (Europe) MIRACLE ICD II REVERSE MADIT CRT Contak CD* MIRACLE ICD II REVERSE MADIT CRT RAFT ‘ 03 ‘ 04 ‘ 05 ‘ 06 ‘ 07 ‘ 08 ‘ 09 ‘ 10 Actual Forecasted CARE-HF*
  • Comparison of Prospective, Pivotal Trials MADIT CRT ( M ulticenter A utomatic D efibrillator I mplantation T rial – C ardiac R esynchronization T herapy: Moss AJ, et al. N Engl J Med 2009;36:1329-38 REVERSE ( Re synchronization Re ve rses R emodeling in S ystolic Left V e ntricular Dysfunction): Linde C, et al. J Am Coll Cardiol 2008;52:1834-43. RAFT ( R esynchronization/defibrillation for A mbulatory Heart F ailure T rial): Tang AS, et al. Curr Opin Cardiol 2009;24:1-8 Total mortality & heart failure hospitalisation Heart failure clinical composite (proportion worsened) Total mortality & major heart failure events Primary Endpoint ≥ 120 msec ≥ 120 msec ≥ 130 msec QRS ≤ 30% ≤ 40% ≤ 30% LVEF Class II or III Class I or II (ACC/AHA stage C) Class I or II ischemic; Class II non-ischemic NYHA Minimum 18 months 12 months (all subjects) 24 months (Europe only) Average follow-up 28 months Duration N=1800 Canada, Europe N=610 US, Europe, Canada N=1820 US, Europe, Canada Size Randomised (CRTD:ICD - 1:1) Double-blinded Parallel Controlled Randomised (CRT ± D On:Off - 2:1) Double-blinded Parallel Controlled Randomised (CRTD:ICD – 3:2) Unblinded Parallel Controlled Study Design RAFT REVERSE MADIT CRT
  • MADIT CRT Design Baseline Evaluation Randomisation 3:2 Unblinded ICD Only (N = 731) CRT-D (N = 1089) Follow-up 2.4 year average Stopped after 9 th of 20 planned analyses, per DSMB recommendation Moss AJ, et al. N Engl J Med . 2009;361(14):1329-38. Boston Scientific Research grant: University of Rochester (New York) Coordination & Data Center: ≥ 130 msec QRS Duration: ≤ 30% LVEF: Any aetiology NYHA II; Post-MI NYHA I NYHA Class: Key inclusion criteria 110 centres: US (88); Europe (20); Canada (2) Study Locations: Death, any cause, or nonfatal heart failure event Primary endpoint:
  • MADIT CRT: 34% Relative Risk Reduction in Mortality or Heart Failure Event, Whichever Came First Moss AJ, et al. N Engl J Med . 2009;361(14):1329-38.
  • REVERSE Design Baseline Evaluation Randomisation 2:1 Blinded CRT Off (n = 191) CRT On (N = 419) Linde C, et al. J Am Coll Cardiol . 2008;52:1834-43. Daubert C, et al. J Am Coll Cardiol 2009;54(20):1837-46. CRT Off (n = 82) CRT On (N = 180) 12 Months 24 Months (Europe) 73 centres: US (37); Canada (1); Europe (35) Study Locations: Left Ventricular Volume Indexed (LVESVi) Powered secondary endpoint: Medtronic Sponsor: ≥ 120 msec QRS Duration: ≤ 40% LVEF: NYHA II or Previously Symptomatic NYHA I NYHA Class: Key inclusion criteria Clinical Composite % Worsened Primary endpoint:
  • REVERSE Primary Endpoint: Clinical Composite Score (% Worsened) 1 Linde C, et al. J Am Coll Cardiol . 2008;52:1834-43. 2 Daubert C, et al. J Am Coll Cardiol 2009;54(20):1837-46. 24 Months 2 P=0.01 P=0.0006 P=0.10 12 Months 1 P=0.004
  • CRT Reduces the Risk of Death or Heart Failure Hospitalisation in Mildly Symptomatic Patients 1 Moss AJ, et al. N Engl J Med 2009; 36(14):1329-38 [HF hospitalisation includes major heart failure event.] 2 Daubert C, et al. J Am Coll Cardiol 2009;54(20):1837-46. And Available at http://assets.cardiosource.com/REVERSE_Daubert.ppt 3 Cleland JGF, et al. Heart 2008;94:278–283 Study Events/ Patients MADIT CRT 1 REVERSE (24 mo.) 2 318/1820 41/262 Favours CRT CARE-HF (Mild HF) 3 75/610 0.38 0.69 Hazard Ratio 0.1 1 10
  • Cardiac Resynchronisation Increases Absolute LVEF in Mildly Symptomatic Patients 1 Higgins SL, et al. J Am Coll Cardiol . 2003; 42:1454-9. 2 Abraham WT, et al. Circulation . 2004; 110:2864-8. 3 Linde C, et al. J Am Coll Cardiol . 2008;52:1834-43. 4 Daubert C, et al. J Am Coll Cardiol 2009;54(20):1837-46. 5 Moss AJ, et al. N Engl J Med . 2009;361(14):1329-38. p=0.16 p=0.02 p<0.0001 p<0.001 Duration EF Inclusion 6 mo. ≤ 35% 6 mo. ≤ 35% 12 mo. ≤ 40% 12 mo. ≤ 30% 24 mo. ≤ 40% 1 2 3 4 5 p<0.0001
  • Cardiac Resynchronisation Reduces Left Ventricular Volumes in Mildly Symptomatic Patients MIRACLE ICD II: Abraham WT, et al. Circulation . 2004; 110:2864-8. REVERSE: Linde C, et al. J Am Coll Cardiol. 2008;52:1834-43. MADIT CRT: Moss AJ, et al. N Engl J Med . 2009; 361; published online September 1, 2009. P=0.01 P<0.001 P<0.0001 P=0.01 P<0.001 P<0.0001 No CRT CRT
  • No Changes with CRT in Exercise Capacity or Quality of Life in Mildly Symptomatic Patients Improved ↑ MIRACLE ICD II: Abraham WT, et al. Circulation . 2004; 110:2864-8. REVERSE (12 mo.): Linde C, et al. J Am Coll Cardiol. 2008;52:1834-43. REVERSE (24 mo.): Daubert C, et al. J Am Coll Cardiol 2009;54(20):1837-46. P=0.57 P=0.52 P=0.59 P=0.26 P=0.62 P=0.49
  • IIb
    • EF <35%
    • Anticipated ventricular pacing
    • NYHA I~II
    • on optimal recommended medical therapy.
    III III
    • EF <35%
    • NYHA I
    • on optimal recommended medical therapy.
    • EF <35%
    • QRS>120ms
    • sinus rhythm
    • NYHA III~IV (ambulatory)
    • on optimal recommended medical therapy.
    • functional status and life expectancy are limited predominantly by chronic noncardiac conditions .
    CRT for severe HF ACC / AHA / HRS 2008 Guideline
  • Case 2
    • 58 y/o woman
    • DCM
    • EF 25%
    • Dyspnea while walking to second floor (NYHA III)
    • QRS 105ms
    • UCG (TDI): septal to lateral wall delay 90ms
  • Concept of Dyssynchrony Mechanical dyssynchrony Electrical dyssynchrony ?
  • Dyssynchrony
    • Electrical dyssynchrony
      • QRS duration
      • Intracardiac electrogram
    • Mechanical dyssynchrony
      • UCG
      • MRI
      • Nuclear medicine
  • Mechanical Dyssynchrony
    • Echocardiography
      • Mmode
      • Tissue velocity imaging:
        • Velocity, time to peak velocity
        • Strain, time to peak strain
      • Speckle tracking
  • Results of the Pr edictors o f Re sp ons e to C R T ( PROSPECT) Trial Chung ES, Leon AR, Tavazzi L, Sun J-P, Nihoyannopoulos P, Merlino J, Abraham WT, Ghio S, Leclercq C, Bax JJ, Yu C-M, Gorcsan J 3rd, St John Sutton M, De Sutter J, Murillo J, Circulation. 2008;117:2608-2616.
    • Purpose:
      • Prospective, multi-center study designed to evaluate the ability of selected, pre-defined baseline echocardiographic parameters to predict clinical or echocardiographic response to CRT in a prospective, multi center study
  • PROSPECT Study
    • Primary Endpoints at 6 months:
      • Clinical Composite Score
        • Subjective and objective measures of clinical status include: Survival, heart failure hospitalization, change in NYHA Class and change in Patient Global Assessment Score
        • Definition of Improved: Has not Worsened (death, HF hospitalization, worsening NYHA Class) and demonstrates improvement in NYHA Class and/or improvement in patient global assessment score
      • Left Ventricular End-Systolic Volume
        • Definition of Improved: Reduction of ≥ 15%
    Chung, E. Circulation. 2008;117:2608-2616.
  • 12 Predefined Echo Measures of Dyssynchrony
    • Standard Echo
      •  SPWMD Septal to posterior wall motion delay (≥ 130 ms)
      • IVMD Interventricular mechanical delay (≥ 40 ms)
      •  LPEI LV pre-ejection interval (≥ 140 ms)
      • LVFT/RR LV filling time as % of cardiac cycle length (R-R interval) (≤40%)
      • LLWC Left lateral wall contraction (any overlap)
    • Tissue Doppler Imaging
      •  Ts- (lateral-septal) Time Δ between basal lateral and septal peak (≥60 ms)
      •  Ts-SD Standard deviation of time to peak systolic velocity (≥ 32 ms)
      • PVD Peak velocity difference (≥ 110 ms)
      •  DLC Delayed longitudinal contraction (≥ 2 segments)
      • TD Maximum difference in time to peak displacement (median)
      • Ts-peak Maximum Δ in time to peak systolic velocity (median)
      • Ts-onset Maximum Δ in time to onset of systolic velocity (median)
    Chung, E. Circulation. 2008;117:2608-2616.
  • Primary Endpoint Results for All Patients at 6 Months Chung, E. Circulation. 2008;117:2608-2616. ≥ 15% Reduction ≥ 15% Increase Other Clinical Composite Response N = 426 Change in LVESV N = 286 Percent of Patients Improved Un- changed Worsened P = 0.01 75% 64% Non-Ischemic Ischemic % Improved P = 0.03 63% 50% Non-Ischemic Ischemic % with ≥ 15% Reduction
  • Primary Endpoint Results Selected Echo Measures 0.44 0.013 0.27 0.79 P-value Clinical Composite Response % Improved 0.021 0.016 0.33 0.68 P-value LVESV % with ≥ 15% Reduction ■ Cut-off Met ■ Cut-off Not Met 1.00 0.005 Chung, E. Circulation. 2008;117:2608-2616.
  • Inter-observer Variability Coef. of Variation: 6.5% Kappa Coefficient: 0.67 LPEI Coef. of Variation: 33.7% Kappa Coefficient: 0.15 Ts-SD (Yu) SPWMD (Pitzalis) Coef. of Variation: 72.1% (not displayed) Kappa Coefficient: 0.35 Chung, E. Circulation. 2008;117:2608-2616. Atlanta US London UK Pavia Italy 10 10 6 6 Philips GE
  • Conclusions
    • The results of the PROSPECT study indicate that no single echocardiographic measure of dyssynchrony, as applied in this multi-center study, may be recommended to further improve patient selection among the CRT candidates.
    • Current clinical criteria including electrocardiogram, remain the standard for CRT patient selection.
    Chung, E. Circulation. 2008;117:2608-2616.
  • Randomized Controlled Trials on CRT * RV paced QRS ¶ Primary endpoint not met; key secondary endpoints reached LVEF  35% for all trials + ¶ Published Yes Normal  130 II MIRACLE ICD II (186) + Published Both Normal  120 III, IV PATH CHF II (89) + Published Yes Normal  130 III, IV MIRACLE ICD (369) + + Published Yes Normal  120 III, IV COMPANION (1520) + ¶ + + + + Results Published No Normal  120 III, IV CARE HF (814) Published Yes Normal  120 II -IV CONTAK CD (490) Published No Normal  120 III, IV PATH CHF (41) Published No AF  200* III MUSTIC AF (43) Published No Normal  150 III MUSTIC SR (58) Published No Normal  130 III, IV MIRACLE (453) Status ICD? Sinus QRS NYHA Study (n randomized)
  • Case 3
    • 58 y/o woman
    • DCM
    • EF 25%
    • Dyspnea while walking to second floor (NYHA III)
    • QRS 160ms, but a trial fibrillation
  • Randomized Controlled Trials on CRT * RV paced QRS ¶ Primary endpoint not met; key secondary endpoints reached LVEF  35% for all trials + ¶ Published Yes Normal  130 II MIRACLE ICD II (186) + Published Both Normal  120 III, IV PATH CHF II (89) + Published Yes Normal  130 III, IV MIRACLE ICD (369) + + Published Yes Normal  120 III, IV COMPANION (1520) + ¶ + + + + Results Published No Normal  120 III, IV CARE HF (814) Published Yes Normal  120 II -IV CONTAK CD (490) Published No Normal  120 III, IV PATH CHF (41) Published No AF  200 * III MUSTIC AF (43) Published No Normal  150 III MUSTIC SR (58) Published No Normal  130 III, IV MIRACLE (453) Status ICD? Sinus QRS NYHA Study (n randomized)
    • EF <35%
    • QRS>120ms
    • sinus rhythm
    • NYHA III~IV (ambulatory)
    • on optimal recommended medical therapy.
    CRT for severe HF I IIa IIa
    • EF <35%
    • QRS>120ms
    • Atrial fibrillation
    • NYHA III~IV (ambulatory)
    • on optimal recommended medical therapy.
    • EF <35%
    • Ventricular pacing dependant
    • NYHA III~IV (ambulatory)
    • on optimal recommended medical therapy.
    ACC / AHA / HRS 2008 Guideline +LBBB
  • Case 4
    • 58 y/o woman
    • DCM
    • EF 25%
    • Dyspnea while walking to second floor (NYHA III)
    • QRS 160ms, but not LBBB pattern
  • COMPANION Subgroup Analysis
    • COMPANION study
      • 1 year duration
      • Randomized CRT-P, CRT-D, OMT in 2:2:1 ratio
    • Subgroup analysis
      • LBBB: 215 OMT and 426 CRT-P patients
      • Other includes RBBB and IVCD: 93 OMT and 190 CRT-P patients
    LBBB Other Favors CRT Bristow M, et al. N Engl J Med 2004; 350:2140-50. [COMPANION sponsored by Guidant]
  • Sub-analyses of RBBB from Other Randomized Controlled Studies
    • MIRACLE 1
      • 313 patients with LBBB, 43 with RBBB
      • With CRT, RBBB patients improved NYHA class compared to control
      • With CRT, RBBB patients’ improvements in exercise time and peak VO 2 did not reach statistical significance
    • Pooled data from MIRACLE and Contak CD studies 2
      • 61 patients with RBBB (34 CRT, 27 Control)
      • CRT improved NYHA Class compared to control
      • Trends toward improved QoL, 6 minute walk distance, norepinephrine (NE) with CRT compared to baseline, but with no difference compared to control
    1. Aranda J, et al. Clin Cardiol 2004;27: 678–82. [MIRACLE was sponsored by Medtronic] 2. Egoavil CA, et al. Heart Rhythm 2005;2:611–615. [Contak CD was sponsored by Guidant]
  • Do RBBB patients benefit from CRT?
    • Small number of RBBB patients in randomized controlled trials precludes definitive conclusions about efficacy of CRT. 1
    • Masked LBBB may be present in significant proportion of patients identified as having RBBB. 2,3
    • Not sufficient evidence to withhold therapy from this group
    1. J Am Coll Cardiol, 2008; 51:2085-2105 2. Fantoni C, et al. J Cardiovasc Electrophysiol 200516:112-119 3. Aranda J, et al. Clin Cardiol 2004;27: 678–82.
  • Case 4
    • 90 y/o man
    • DCM
    • EF 25%
    • Dyspnea while walking to second floor (NYHA III)
    • QRS 160ms
  • Yancy C et al. J Cardiac Fail 2007;13(suppl):S158. Abstract 290. Findings from IMPROVE HF: Underutilization of CRT in Elderly
    • Underutilization of CRT is exaggerated in eligible elderly HF patients
    Patients Receiving Recommended HF Therapies by Age Tertiles at Baseline (All Patients)
  • CARE-HF: Reductions in morbidity and mortality in elderly CRT patients
    • CARE-HF sub-population of patients aged ≥70 years
    • CRT reduced mortality and morbidity versus medical treatment alone (MT) in elderly patients
    Mabo P et al. Circulation 2008;118:S949 (Abstract 8450). [CARE-HF, a Medtronic sponsored study] 54.5% 39.3% 58.6% Control N=145 <0.001 0.55 (0.36-0.84) 22.9% All cause mortality 0.0001 0.51 (0.36-0.73) 32.5% All cause mortality or un-planned HF hospitalization 0.015 0.67 (0.48-0.92) 43.3% All cause mortality or un-planned CV hospitalization P-value Hazard ratio (95% CI) CRT N=157
  • CARE-HF: CRT improves QoL and cardiac function/status in the elderly P=0.50 P<0.001 P=0.001 ■ CRT On ■ CRT Off P<0.001 P=0.53 P=0.40 P<0.001 1 2 2
    • CARE-HF sub-population of patients aged ≥70 years
    • Presented at AHA 2008
    • 1. Laviolle et al. Circulation 2008;118:S950b (Abstract 48540).
    • 2. Leclercq C, et al. Circulation 2008;118:S619b (Abstract 826 )
  • MIRACLE study program demonstrates CRT benefit in elderly patients Absolute LVEF Change Kron et al.J Interv Card Electrophysiol:2009 Jan 19. [Epub ahead of print Jan 19] ■ CRT On ■ CRT Off P<0.001 P=0.002 P=0.004 P=0.008 P<0.001 P=0.002 P<0.001 P<0.001 P=0.06
    • MIRACLE + MIRACLE ICD
    • Mean change at 6 months
    • 839 patients: 368 < 65 years; 297 65 – 75 years; 174 > 75 years
    • No evidence of increased adverse event rates in most elderly group
  • Cost-benefit
  • Number Needed to Treat To Save A Life NNT x years = 100 / (% Mortality in Control Group – % Mortality in Treatment Group) CRT CRT-D CRT ICD Drugs CRT Adapted from Auricchio A, Abraham W. Circulation 2004; 109; 300-307. (1Yr) (3Yr) (5Yr) (2.4Yr) (3Yr) (3Yr) (4Yr) (0.8Yr) (3.5Yr) (1Yr) (1Yr) (1.5Yr) (2Yr) (4 Yr) COMPANION COPER-NICUS CAP-RICORN
  • COMPANION: CRT-D and CRT-P Incremental Cost-Effectiveness Ratios
    • 2-year analysis of COMPANION study
    • CRT-P ICER = $19,600 per Quality-Adjusted Life-Year (QALY)
    • CRT-D ICER = $43,000 per QALY
      • Essentially getting two therapies for one price
    • Well below generally accepted benchmarks for therapeutic interventions of $50,000 - $100,000 per QALY
    Feldman AM, et al. J Am Coll Cardiol 2005; 46: 2311 – 2321. [COMPANION sponsored by Guidant] Benchmark $50,000/QALY Incremental Cost-Effectiveness Ratios of CRT-P/CRT-D ($/QALY)
  • CARE-HF: CRT-P Incremental Cost-Effectiveness Ratio
    • 5-year analysis of CARE-HF 1
    • CRT-P Incremental Cost-Effectiveness Ratio (ICER) = $21,700 per Quality-Adjusted Life-Year (QALY)
    • Below benchmark of $28,500 considered reasonable in UK (Converted from £ to today’s $)
    • Model predicted a 26% reduction in mortality and 22% reduction in hospitalization for CRT compared to optimal medical therapy
    • 2005 analysis yielded similar results 2
      • CRT-P ICER = $24,400 per QALY
      • Below benchmark of $37,000 (Converted from € to today’s $)
    1. Caro JJ et al. Curr Med Res Opin 2006; 22: 1171 – 9. 2. Calvert MJ, et al. Eur Heart J. 2005;26:2681-8. [CARE-HF sponsored by Medtronic] Benchmark $28,500/QALY Incremental Cost-Effectiveness Ratios of CRT-P ( $ /QALY)
  • CRT Cost Effectiveness
    • Cost-effectiveness of CRT has been evaluated extensively 1,2,3,4
    • Initial investment in implantation and ongoing device management is substantial
    • However, cost effectiveness measures have been positive
      • Reduced hospitalization plus
      • Improved quality of life plus
      • Improved survival yields
      • Favorable incremental cost-effectiveness ratios (ICERS) per Quality Adjusted Life Year (QALY)
    1. Fox M, et al. Health Technol Assess 2007;11(47):1-248 [Meta-analysis] 2. Calvert MJ, et al. Eur Heart J. 2005;26:2681-8. [CARE-HF sponsored by Medtronic] 3. Caro JJ et al. Curr Med Res Opin 2006; 22: 1171 – 9. 4. Feldman AM, et al. J Am Coll Cardiol 2005;46:2311–21. [COMPANION sponsored by Guidant]
  • ICD ( Only primary prevention covered )
  • MERIT - HF CHF 12% SD 64% SD 59% CHF 26% SD 33% Mode of Death by NYHA Class No. of deaths n=103 No. of deaths n=232 No. of deaths n=27 NYHA II NYHA III NYHA IV CHF 56% Other 24% Other 15% Other 11% The MERIT-HF Study Group, Lancet 1999;353:2001-07
  • Case 5
    • 36 y/o man, smoking
    • Admitted due to AMI
    • s/p primary PTCA
    • Exertional dyspnea (NYHA II)
    • One months later, EF 34% at OPD follow up
    • Q: Will I get sudden death? Do I need ICD?
  • SCD-HeFT ( NYHA II~III, EF<35%) N Engl. J Med. 2005; 352:225-237. 23% Reduction in All Cause Mortality For ICD Therapy (p-value 0.007) 7%
  • DINAMIT
    • 6 – 40 days post MI, LVEF ≤ 35%
    NEJM 2004;351,24 p = 0.66
  • Primary prevention should be
    • Ischemic cardiomyopathy (post-MI 40days DYNAMIT )
      • NYHA II~III, EF<35% SCD-HeF
    I ACC / AHA / HRS 2008 Guideline
  • Case 6
    • 36 y/o man, smoking
    • Admitted due to AMI
    • s/p primary PTCA
    • Totally asymptomatic (NYHA I)
    • One months later, EF 34% at OPD follow up
    • Q: Will I get sudden death? Do I need ICD?
  • MADIT II NEJM 2002;346
    • Post MI and LVD (EF<30%)
    31% mortality reduction p = 0.007
  • Primary prevention should be
    • Ischemic cardiomyopathy (post-MI 40days DYNAMIT )
      • NYHA II~III, EF<35% SCD-HeF
      • NYHA I, EF<30% MADIT II
    I
  • Case 6
    • 36 y/o man, smoking
    • Admitted due to AMI
    • s/p primary PTCA
    • Totally asymptomatic (NYHA I)
    • One months later, EF 38% at OPD follow up
    • Q: Will I get sudden death? Do I need ICD?
  • MUSTT: All-cause Mortality Buxton A. NEJM 1999
  • Primary prevention should be
    • Ischemic cardiomyopathy (post-MI 40days DYNAMIT )
      • NYHA II~III, EF<35% SCD-HeF
      • NYHA I, EF<30% MADIT II
      • EF<35~40%, nsVT
        • EPS(+) MUSTT
    I
  • Case 7
    • 36 y/o man, smoking
    • DCM
    • Exertional dyspnea(NYHA II)
    • EF 34%
    • Q: Will I get sudden death? Do I need ICD?
  • SCD-HeF
    • Ischemic CHF
    • Nonischemic CHF
    6.5% 7.3%
  • DEFINITE
    • NIDCM, LVEF <36% and premature ventricular complexes or nsVT
    NEJM 2004;350:2151-8 35% Reduction in All Cause Mortality 20% Reduction in SCD from arrhythmia
  • Primary prevention should be
    • Non-ischemic DCM
      • EF<35%, NYHA II~III SCD-HeF
      • EF<35%, NYHA I DEFINIT
    I IIb
  • NHI indication for ICD 95.11.1 生效
    • 嚴重心室頻脈、心室顫動導致猝死可能或昏迷。
    • 反覆發作之持續性心室頻脈
    • 高危險性心臟血管疾病或遺傳性疾病,如:曾經心肌梗塞併左心室射出分率≦ 40% , long QT syndrome , short QT syndrome , Brugada syndrome , idiopathic ventricular fibrillation , arrhythmogenic right ventricle dysplasia , catecholaminergic polymorphic ventricular tachycardia ,肥厚性心肌症,擴張性心肌症等,且臨床合併心室快速不整脈或合併猝死症之家族史者。
  • Other technical issues
  • Technical issues
    • Lead location?
    • Single, two, triple leads?
    • Settings: AV, VV delay
  •  
  • Comments
  • Case X
    • 65 y/o 吳 OO
    • CAD, 3vd, Ischemic cardiomyopathy
    • EF 33%
    • Dyspnea while slightly chasing the bus (NYHA II)
    • QRS 160ms
  • CARE-HF: Ischemic patients benefit from CRT
    • Despite poorer prognosis, ischemic patients benefit as much from CRT as non-ischemic patients
      • Mortality
      • Mortality or CV hospitalization
      • NYHA Class
    • With CRT, ischemic patients improve cardiac function and status, but to lesser degree than non-ischemic patients
    Non-ischemic Ischemic Mortality or CV hospitalization Non-ischemic Ischemic Mortality Hazard Ratio Favors CRT Wikstrom E, et al. Eur Heart J. e-published January 24, 2009 [CARE HF study sponsored by Medtronic].
  • MIRACLE: CRT Improves Cardiac Status in Ischemic Patients, but to Lesser Degree LVEDV LVEF MR Jet Area Paired, Median Changes from Baseline at 6 Months St. John Sutton M, et al. Circulation 2003;107:1985-1990. [MIRACLE sponsored by Medtronic] * p<0.05, CRT vs. CRT between subgroup  Control  CRT
  • Ischemic Patients: Better Outcomes with CRT
    • CRT patients with ischemic etiology have poorer prognosis and less improvement in cardiac function and status than non-ischemic patients
    • Ischemic patients have comparable survival benefit
    Wikstrom E, et al. Eur Heart J. e-published January 24, 2009 [CARE HF sponsored by Medtronic].
  •  
  • AV Delay Optimization
    • Trans-mitral Flow Duration
      • Iterative method. Assess filling patterns at various AV delays.
      • “ Ritter” method. 1 Formula derived optimum from a short AV delay and a long AV delay.
    • Trans-mitral Flow Volume
      • Select maximum mitral VTI from tested AV delays
      • Concordant with invasively measured maximum dP/dt 2
    Too short AV delay. E and A waves separated, but A wave is truncated. Too long AV delay. E and A waves fused, filling time reduced. “ Just Right” AV delay. BiV pacing sustained, active filling maintained.
  • VV Delay Optimization: Aortic VTI
    • Conflicting results from RCTs
    • Select the setting yielding the largest VTI as the optimal paced interval
    LV first by 4 ms LV first by 20 ms RV first by 40 ms