This document summarizes a presentation on identifying predictors of super-response to cardiac resynchronization therapy (CRT). It discusses two problems with CRT response - an incompletely understood molecular mechanism and non-standard response criteria. The presentation aims to address these issues by identifying clinical predictors of a dramatic or "super-response" to CRT to help improve response rates. A study is summarized that found six predictors of left ventricular ejection fraction super-response to CRT, including female sex, no prior heart attack, longer QRS duration, left bundle branch block morphology, lower body mass index, and smaller left atrial volume. Super-responders experienced reduced risk of subsequent heart events.
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Presentation explaining how the PleuraFlow® ACT® System from ClearFlow,Inc.can Reduce Complications and Costs for your Cardiothoracic surgery patients.
Management of Takotsubo Syndrome: A Comprehensive ReviewNicolas Ugarte
Takotsubo syndrome (TTS), also known as Takotsubo cardiomyopathy, is a transient left
ventricular wall dysfunction that is often triggered by physical or emotional stressors. Although
TTS is a rare disease with a prevalence of only 0.5% to 0.9% in the general population, it is
often misdiagnosed as acute coronary syndrome. A diagnosis of TTS can be made using Mayo
diagnostic criteria. The initial management of TTS includes dual antiplatelet therapy,
anticoagulants, beta-blockers, angiotensin-converting enzyme inhibitors or aldosterone
receptor blockers, and statins. Treatment is usually provided for up to three months and has a
good safety profile. For TTS with complications such as cardiogenic shock, management
depends on left ventricular outflow tract obstruction (LVOTO). In patients without LVOTO,
inotropic agents can be used to maintain pressure, while inotropic agents are contraindicated
in patients with LVOTO. In TTS with thromboembolism, heparin should be started, and
patients should be bridged to warfarin for up to three months to prevent systemic emboli. Our
comprehensive review discussed the management in detail, derived from the most recent
literature from observational studies, systematic review, and meta-analyses.
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5. • Ventricular dyssynchrony can further
impair pump function of a failing
ventricle
• Resynchronization may improve pump
performance and reverse the
deleterious process of ventricular
remodeling
Rationale of CRT
6. • Presence of a bundle branch block /
intraventricular conduction delay
• May worsen systolic dysfunction by:
• Inducing regional loading disparities
• Reducing the efficiency of contraction
• Dyssynchrony by imaging not enough
• ASE consensus statement advises
dyssynchrony reports should NOT include a
recommendation as to whether a patient
should undergo CRT1
Rationale of CRT
1 Echocardiography for cardiac resynchronization therapy: recommendations for performance
and reporting--a report from the American Society of Echocardiography Dyssynchrony Writing
Group endorsed by the Heart Rhythm Society. Gorcsan J 3rd, et al. J Am Soc Echocardiogr.
2008;21(3):191.
8. • Clinical mechanisms of benefit:
• Improved contractile function
• Reverse ventricular remodeling
• The basic molecular basis for
mechanical changes affording
improvement in LVEF improvement
has not been completely elucidated
• May generate more homogeneous activation of
stress kinases and reduce apoptosis1
Mechanisms of Benefit
1Reversal of global apoptosis and regional stress kinase activation by cardiac
resynchronization. Chakir K, Daya, et al. Circulation. 2008;117(11):1369.
9. • Improved contractile function
• Improved coordination of global contraction
• In the CARE-HF trial1 (Median LVEF 25%):
• LVEF in the CRT compared to no CRT group increased by
3.7 percent at three months and 6.9 percent at 18 months
• CRT associated with a rise in systolic pressure of about 6
mmHg compared to no CRT (median baseline 110 mmHg)
and a reduction in NT-pro BNP of 225 pg/mL at three
months and 1122 pg/mL at 18 months
• MIRACLE trial2
• At six months, significantly greater increase in LVEF with
CRT than without (3.6 versus 0.4 percent).
Mechanisms of Benefit
1The effect of cardiac resynchronization on morbidity and mortality in heart failure. Cleland
JG, et al. N Engl J Med. 2005;352(15):1539.
2Effect of cardiac resynchronization therapy on left ventricular size and function in chronic
heart failure. St John Sutton MG, et al. Circulation. 2003;107(15):1985.
10. • Reverse ventricular remodeling
• Significant reductions in LV end-systolic and
end-diastolic dimensions, mitral regurgitant jet
area
• CARE-HF trial1
• MIRACLE trial2
• Significant reductions in LV mass
• MIRACLE trial2
• All signs of beneficial remodeling
Mechanisms of Benefit
1The effect of cardiac resynchronization on morbidity and mortality in heart failure. Cleland
JG, et al. N Engl J Med. 2005;352(15):1539.
2Effect of cardiac resynchronization therapy on left ventricular size and function in chronic
heart failure. St John Sutton MG, et al. Circulation. 2003;107(15):1985.
12. • Difficult comparing response to CRT
across trials due to disparity of
response criteria
• A review identified 17 different primary
response criteria (clinical and imaging) in the
26 most cited CRT publications1
• Agreement among 15 of these criteria was
assessed in 426 patients from the PROSPECT
study
• 75 percent of comparisons showed poor agreement and
only 4 percent showed strong agreement
Criteria for CRT Response
1Agreement is Poor Amongst Current Criteria Used to Define Response to Cardiac
Resynchronization Therapy. Fornwalt BK, et al. Circulation. 2010; 121(18):1985-9.
13.
14.
15. Foreseeing super-response to cardiac resynchronization therapy: a perspective for clinicians.
Ellenbogen KA, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2374-7.
16. Results of the Predictors of Response to CRT (PROSPECT)
Trial. Circulation.2008; 117: 2608-2616
Evaluating Response:
Symptoms and Echo
18. A Solution?
Identify predictors of super-response in order to elucidate
mechanisms of response and improve CRT response rates
and subsequent hard clinical endpoints
19. Hsu, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2366-73.
20. Background
• Wide variability in the extent of LV
remodeling and improvement in LVEF
with CRT
• “Super-responders” may derive
dramatic improvements, including near
normalization of LVEF
Hsu, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2366-73.
21. Methods
• Included only patients randomized to CRT-D
with paired echocardiograms at baseline and
at 12 months (n=752).
• Super-response defined by the top quartile of
LVEF change
• Best-subset regression analysis identified
predictors of LVEF super-response
• Kaplan-Meier survival analysis and Cox
proportional hazards regression
• Investigate associations of response category with
development of nonfatal HF event or all-cause death.
Hsu, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2366-73.
22. Results
• All 191 super-responders experienced
an LVEF increase of at least 14.5%
(mean LVEF increase 17.5 ±2.7%)
Hsu, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2366-73.
23. Hsu, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2366-73.
24. Hsu, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2366-73.
25. Results
• In multivariable analysis, six predictors
were associated with LVEF super-
response to CRT-D therapy
Hsu, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2366-73.
26. Hsu, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2366-73.
27. Hsu, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2366-73.
28. Hsu, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2366-73.
29. Implications
• Clinical predictors may help the
clinician to characterize who may have
a dramatic response to CRT
• Importance of followup (12 month
echo in this study)
• Prognosis
• Counseling
Hsu, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2366-73.
30. Conclusions
• Six baseline factors predicted LVEF
super-response in CRT-D–treated patients
with mild HF:
• Female sex
• No prior myocardial infarction
• QRS duration > 150 msec
• LBBB
• Body mass index <30 kg/m2
• Smaller baseline left atrial volume index
• Super-response was associated with
reduced risk of subsequent cardiac events
Hsu, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2366-73.
31. Foreseeing super-response to cardiac resynchronization therapy: a perspective for clinicians.
Ellenbogen KA, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2374-7.
32. Foreseeing super-response to cardiac resynchronization therapy: a perspective for clinicians.
Ellenbogen KA, et al. J Am Coll Cardiol. 2012 Jun 19;59(25):2374-7.
33. • Mechanisms of CRT response and
formalized criteria for response require
further efforts for clarification
• Established clinical predictors of CRT
super-response may help guide
strategies aimed at further improving
CRT response rates
Summary
