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Jose Osorio, MD
www.theafcenter.com
CRT
 CRT Trials
 New Trials and Indications
◦ CRT in mildly symptomatic patients
 Non-Responders
New Devices
www.theafcenter.com
◦Reduces mortality and
hospitalization.
◦Improves functional capacity,
quality of life, exercise capacity.
◦Promotes reverse remodeling.
www.theafcenter.com
Yu C-M, Chau E, et al. Circulation 2002;105:438-445
Intraventricular
Synchrony
Atrioventricular
Synchrony
Interventricular
Synchrony
LA
Pressure
LV Diastolic
Filling
RV Stroke
Volume
LVESV LVEDV
Reverse Remodeling
Cardiac Resynchronization
MRdP/dt, EF, CO
( Pulse Pressure)
www.theafcenter.com
CRT Clinical Studies
www.theafcenter.com
 1995-1997: Mechanistic and longer-term
observational studies
 1998-1999: Randomized studies to assess
exercise capacity, functional capacity and
QoL
 2000-2002: Randomized trials to assess
combined mortality and hospitalization
NYHA III and ambulatory IV patients
www.theafcenter.com
• Mortality
benefit
• Reduced HF
hospitalizations• Mortality benefit
in LBBB population*
• Reduced HF
hospitalizations
• Improved cardiac
function*
• Improved CCR
• Improved
cardiac function
• Reduced HF
hospitalizations*
• Improved CCR*
• Improved cardiac
function
2003: CONTAK CD
6 mos; n = 263
2004: MICD II
6 mos; n = 186
2008: REVERSE
12 mos, n = 610;
24 mos, n = 262
2009: MADIT CRT
Average 29 mos, n = 1,820
2010: RAFT
Average 40 mos, n = 1,438
• Improved
cardiac function
www.theafcenter.com
34%
MADIT-CRT
www.theafcenter.com
57%
57% reduction (p < 0.001) in
the risk of a composite of
all-cause mortality or heart
failure events.
• 35% reduction (p = 0.048)
in the risk of all-cause
mortality
• 63% reduction (p < 0.001)
in the risk of heart failure
events
Moss AJ, et al. N Engl J Med. 2009;361:1329-1338.
www.theafcenter.com
Cecilia Linde JACC 2008
Resynchronization Reverses Remodeling
in
Systolic Left Ventricular Dysfunction
REVERSE)
www.theafcenter.com
Time to First Heart Failure Hospitalization
 Significant improvement in functional capacity
 Reverse remodeling
 Decrease in mortality and hospitalization
 Alters disease progression
CRT
NYHA I-II Patients
REVERSE: Linde C, et al. JACC. 2008;52:1834-1843.
RAFT: Tang A, et al. N Engl J Med. 2010;363: 2385-2395.
MADIT-CRT: Moss A, et al. N Engl J Med. 2009;361:1329-1338. www.theafcenter.com
www.theafcenter.com
 How do you classify your patient
 Why some patients do not respond
 What do you do
www.theafcenter.com
 How do you classify your patient
 Why some patients do not respond
 What do you do
www.theafcenter.com
 Responder
◦ Super-responders
◦ Delayed Progression
 Non-Responder
 Negatively affected
Clinical or Echo parameters
www.theafcenter.com
Ypenburg JACC 2008
CRT
Response and Prognosis
6 months post CRT
www.theafcenter.com
CRT
Response and Prognosis
www.theafcenter.com
www.theafcenter.com
 How do you classify your patient
 Why some patients do not respond
 What do you do
www.theafcenter.com
Mullens W, et al. JACC 2009; 53:765
Response to CRT
Causes for “Non-response”
www.theafcenter.com
Response to CRT
Causes for “Non-response”
 Lack of electrical dysynchrony
 Lack of Mechanical dysynchrony
 Myocardial scar
 RV failure
www.theafcenter.com
 We aim to correct mechanical dyssynchrony with
CRT
 The amount of baseline mechanical dyssynchrony
is currently the best predictor of response to CRT
 A wide QRS (electrical dyssynchrony) is a
screening tool for mechanical dyssynchrony
1 Yu et al., PACE 2000;23-II:9
2 Nelson et al., Circulation 2001;101:2703-9
3 Yu et a., PACE 2000;23-II:148
4 Breithardt et al., PACE 2001;24-II:736
5. Sassara et al., Eurpace 2 SB, 2001
www.theafcenter.com
 ~30% of patients with a wide QRS do not
show LV mechanical dyssynchrony:
◦ 50% may have induced dyssynchrony with CRT
 Worse outcomes
Auger et al. Eur H J 2012; 33:913www.theafcenter.com
Auger et al. Eur H J 2012; 33:913www.theafcenter.com
Response to CRT
Pace Away From Scar
Van Deursen C, et al. Circ Arrhythm Electrophysiol 2009; 2:580
• Speckle Tracking Echo
• Target the most delayed
actively contracting site in
patients with ICMP
www.theafcenter.com
 Apex in 14%
 Apical lead placement
◦ Primary end point - up 64%
◦ Mortality – rose 2.6 times
◦ Resynchronization less effective
www.theafcenter.com
 How do you classify your patient
 Why some patients do not respond
 What do you do
www.theafcenter.com
 Clinical and Laboratory evaluation
 Device parameters
 LV lead position
 ECHO guided AV optimitzation
 Protocol evaluation
www.theafcenter.com
Mullens, et al. JACC 2009www.theafcenter.com
www.theafcenter.com
www.theafcenter.com
www.theafcenter.com
CRT
 CRT Trials
 New Trials and Indications
◦ CRT in mildly symptomatic patients
 Non-Responders
New Devices
www.theafcenter.com
www.theafcenter.com
 ICD without issues associated with
transvenous leads
◦ Lead not exposed to heart stresses
◦ Infection
 Patients without pacing indications
www.theafcenter.com
www.theafcenter.com
 CRT is a well established treatment option for
patients with HF and wide QRS
◦ NYHA Class I to IV
 Non-responders
◦ Important to identify the cause
◦ Favorable intervention often possible
 Advances in CRMD
www.theafcenter.com

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Cardiac resynchronization therapy

  • 2. CRT  CRT Trials  New Trials and Indications ◦ CRT in mildly symptomatic patients  Non-Responders New Devices www.theafcenter.com
  • 3. ◦Reduces mortality and hospitalization. ◦Improves functional capacity, quality of life, exercise capacity. ◦Promotes reverse remodeling. www.theafcenter.com
  • 4. Yu C-M, Chau E, et al. Circulation 2002;105:438-445 Intraventricular Synchrony Atrioventricular Synchrony Interventricular Synchrony LA Pressure LV Diastolic Filling RV Stroke Volume LVESV LVEDV Reverse Remodeling Cardiac Resynchronization MRdP/dt, EF, CO ( Pulse Pressure) www.theafcenter.com
  • 6.  1995-1997: Mechanistic and longer-term observational studies  1998-1999: Randomized studies to assess exercise capacity, functional capacity and QoL  2000-2002: Randomized trials to assess combined mortality and hospitalization NYHA III and ambulatory IV patients www.theafcenter.com
  • 7. • Mortality benefit • Reduced HF hospitalizations• Mortality benefit in LBBB population* • Reduced HF hospitalizations • Improved cardiac function* • Improved CCR • Improved cardiac function • Reduced HF hospitalizations* • Improved CCR* • Improved cardiac function 2003: CONTAK CD 6 mos; n = 263 2004: MICD II 6 mos; n = 186 2008: REVERSE 12 mos, n = 610; 24 mos, n = 262 2009: MADIT CRT Average 29 mos, n = 1,820 2010: RAFT Average 40 mos, n = 1,438 • Improved cardiac function www.theafcenter.com
  • 9. 57% 57% reduction (p < 0.001) in the risk of a composite of all-cause mortality or heart failure events. • 35% reduction (p = 0.048) in the risk of all-cause mortality • 63% reduction (p < 0.001) in the risk of heart failure events Moss AJ, et al. N Engl J Med. 2009;361:1329-1338. www.theafcenter.com
  • 10. Cecilia Linde JACC 2008 Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction REVERSE) www.theafcenter.com
  • 11. Time to First Heart Failure Hospitalization
  • 12.  Significant improvement in functional capacity  Reverse remodeling  Decrease in mortality and hospitalization  Alters disease progression CRT NYHA I-II Patients REVERSE: Linde C, et al. JACC. 2008;52:1834-1843. RAFT: Tang A, et al. N Engl J Med. 2010;363: 2385-2395. MADIT-CRT: Moss A, et al. N Engl J Med. 2009;361:1329-1338. www.theafcenter.com
  • 14.  How do you classify your patient  Why some patients do not respond  What do you do www.theafcenter.com
  • 15.  How do you classify your patient  Why some patients do not respond  What do you do www.theafcenter.com
  • 16.  Responder ◦ Super-responders ◦ Delayed Progression  Non-Responder  Negatively affected Clinical or Echo parameters www.theafcenter.com
  • 17. Ypenburg JACC 2008 CRT Response and Prognosis 6 months post CRT www.theafcenter.com
  • 20.  How do you classify your patient  Why some patients do not respond  What do you do www.theafcenter.com
  • 21. Mullens W, et al. JACC 2009; 53:765 Response to CRT Causes for “Non-response” www.theafcenter.com
  • 22. Response to CRT Causes for “Non-response”  Lack of electrical dysynchrony  Lack of Mechanical dysynchrony  Myocardial scar  RV failure www.theafcenter.com
  • 23.  We aim to correct mechanical dyssynchrony with CRT  The amount of baseline mechanical dyssynchrony is currently the best predictor of response to CRT  A wide QRS (electrical dyssynchrony) is a screening tool for mechanical dyssynchrony 1 Yu et al., PACE 2000;23-II:9 2 Nelson et al., Circulation 2001;101:2703-9 3 Yu et a., PACE 2000;23-II:148 4 Breithardt et al., PACE 2001;24-II:736 5. Sassara et al., Eurpace 2 SB, 2001 www.theafcenter.com
  • 24.  ~30% of patients with a wide QRS do not show LV mechanical dyssynchrony: ◦ 50% may have induced dyssynchrony with CRT  Worse outcomes Auger et al. Eur H J 2012; 33:913www.theafcenter.com
  • 25. Auger et al. Eur H J 2012; 33:913www.theafcenter.com
  • 26. Response to CRT Pace Away From Scar Van Deursen C, et al. Circ Arrhythm Electrophysiol 2009; 2:580 • Speckle Tracking Echo • Target the most delayed actively contracting site in patients with ICMP www.theafcenter.com
  • 27.  Apex in 14%  Apical lead placement ◦ Primary end point - up 64% ◦ Mortality – rose 2.6 times ◦ Resynchronization less effective www.theafcenter.com
  • 28.  How do you classify your patient  Why some patients do not respond  What do you do www.theafcenter.com
  • 29.  Clinical and Laboratory evaluation  Device parameters  LV lead position  ECHO guided AV optimitzation  Protocol evaluation www.theafcenter.com
  • 30. Mullens, et al. JACC 2009www.theafcenter.com
  • 34. CRT  CRT Trials  New Trials and Indications ◦ CRT in mildly symptomatic patients  Non-Responders New Devices www.theafcenter.com
  • 36.
  • 37.  ICD without issues associated with transvenous leads ◦ Lead not exposed to heart stresses ◦ Infection  Patients without pacing indications www.theafcenter.com
  • 39.
  • 40.  CRT is a well established treatment option for patients with HF and wide QRS ◦ NYHA Class I to IV  Non-responders ◦ Important to identify the cause ◦ Favorable intervention often possible  Advances in CRMD www.theafcenter.com

Editor's Notes

  1. Finally, the 4 trials (MADIT CRT, REVERSE, Miracle ICD II, and Contak CD) that evaluated cardiac structure and/or function all showed that, in the mildly symptomatic HF population, there was improved cardiac function and/or cardiac structure over time with CRT therapy.
  2. The aim of the current study was to evaluate the relation between the extent of left ventricular (LV) reverse re- modeling and clinical/echocardiographic improvement after 6 months of cardiac resynchronization therapy (CRT) as well as long-term outcome. Background Despite the current selection criteria, individual response to CRT varies significantly. Furthermore, it has been suggested that reduction in left ventricular end-systolic volume (LVESV) after CRT is related to outcome. Methods A total of 302 CRT candidates were included. Clinical status and echocardiographic evaluation were performed before implantation and after 6 months of CRT. Long-term follow-up included all-cause mortality and hospitaliza- tions for heart failure. Results Based on different extents of LV reverse remodeling, 22% of patients were classified as super-responders (de- crease in LVESV 􏰁30%), 35% as responders (decrease in LVESV 15% to 29%), 21% as nonresponders (decrease in LVESV 0% to 14%), and 22% negative responders (increase in LVESV). More extensive LV reverse remodeling resulted in more clinical improvement, with a larger increase in LV function and more reduction in mitral regurgi- tation. In addition, more LV reverse remodeling resulted in less heart failure hospitalizations and lower mortality during long-term follow-up (22 􏰃 11 months); 1- and 2-year hospitalization-free survival rates were 90% and 70% in the negative responder group compared with 98% and 96% in the super-responder group (log-rank p value 􏰆0.001). Conclusions The extent of LV reverse remodeling at midterm follow-up is predictive for long-term outcome in CRT patients. (J Am Coll Cardiol 2009;53:483–90) © 2009 by the American College of Cardiology Foundation