heart failure

1. Interventional Heart Failure
therapy
Kyaw Soe Win
AP/ Senior Consultant Cardiologist
Mandalay General Hospital
14th
Mandalay Myanmar Medical Conference 28 December
2014

2. Not feeling better with Medical therapy
What should we do ?

3. Heart Transplantation
 A good solution to the failing heart– get a
new heart
 Unfortunately we are limited by supply, not
demand
 Approximately 2200 transplants are performed
yearly in the US, and this number has been stable
for the past 20 years.

4. Christian Barnard
 Born in South Africa in 1922
 Studied heart surgery at the
University of Minnesota then
returned to set up a cardiac unit
in Cape Town.
 December 1967: transplanted
the heart of a road accident
victim into a 59 year old patient
 Patient only survived 18 days
due to infectious complications

5. Norm Shumway
 Stanford University
 1959: transplanted the heart of a
dog into a 2-year-old mongrel
 1968: performed the first heart
transplant in the US on a 54
year old steel worker who lived
14 days
 Pioneered immunosuppression
 1981: performed the world’s
first successful heart-lung
transplant

6. Outcomes
Survival:
 During the first year after transplantation, early
causes of death are graft failure, infection, and
rejection, with an overall 1-year survival rate of 87%.
 According to the 2009 update on heart disease and
stroke from the AHA and Stroke Statistics
Subcommittee, the 5-year survival after HHT is
72.3% for males and 67.4% for females
Functional Outcomes
 By the first year after transplantation surgery, 90%
of surviving patients report no functional
limitations, and approximately 35% return to work

7. Heart Transplant Waiting List
January 9th
2012
73 people Washington DC
metropolitan area
waiting for heart
transplant
3155 people In USA
waiting for heart
Transplant
2011, 1,760 patients on the heart wait
list received heart transplants. That
figure represents a decrease from
the 2,333 hearts transplanted in
2010 and the 2,211 in 2009.

8. Heart Transplant
• Despite success, heart transplant is limited by the
number of hearts available for transplant each year
• This limitation in resources reinforces the need for
the development of other interventional
therapies for the treatment of end-
stage heart failure.

9. Refractory Heart Failure - Definition
Persistence of symptoms that limit daily life
(functional class III or IV of the New York Heart
Association [NYHA]) despite optimal treatment with
drugs of proven efficacy for the condition, i.e. ACE
inhibitors, angiotensin II receptor antagonists (ARB),
diuretics, digoxin, beta-blockers and nitrate-
hydralazine (esp. in blacks)
Corresponds to stage D heart failure
[Nohria A, JAMA 2002;287:628-40 and D. Feldman, Clin. Cardiol. 2008;31, 7, 297–301]

10. Terminal Heart Failure
“Terminal HF is the last step in refractory HF,
where there is a very poor response to all forms of
treatment (by definition, heart transplantation is no
longer indicated), with serious deterioration of
quality of life - both physical and emotional,
frequent hospitalization and life expectancy less
than 6 months.”
[Rev Esp Cardiol 2004;57(9):869-83]

11. Stages of Heart Failure
• Designed to emphasize preventability of HF
• Designed to recognize the progressive
nature of LV dysfunction

12. Heart Failure as a Progressive
Disorder
Principal manifestation of progression
• change in the geometry and structure of
the LV
• chamber dilation and/or hypertrophy
• becomes more spherical
The collective process referred to as cardiac
remodeling

13. Outcomes of Cardiac Remodeling
• Patients die before developing symptoms
(in Stage A or B)
• Patients develop symptoms controlled by
treatment
• Patients die of progressive/refractory HF
*Sudden death can interrupt this course at any
time

14. ‘Interventional Heart Failure Therapy’
• Term coined by Daniel Burkhoff (2007)
• Vicious cycle of refractory HF -
- progressive cardiovascular remodeling
- deterioration of renal function
- decreased exercise tolerance
[Burkhoff D. SIS 2007 Yearbook;13:65-75]

15. Need for ‘Interventional HF Therapy’
• Even on maximal pharmacological therapy most
patients exhibit - disease progression
• - repeated hospitalizations
• - ultimately succumb to their disease
• Evidence indicates that additional neurohormonal
blockade may be detrimental
• The limit of neurohormonal and cytokine blockade in
CHF may be reached
• Heart transplantation as a final treatment option also
limited by the small number of donor hearts.
[Mann DL. (RENEWAL). Circulation 2004;109:1594-1602]

16. Basis of Interventional HF Therapies
• Strengthening of cardiac contraction with cardiac
contractility modulation
• Modification of heart rate with vagal nerve stimulation
• Reduction of ventricular size with surgical ventricular
restoration
• ↑ renal perfusion with targeted renal therapy
↓ fluid overload with ultrafiltration
• Improving cardiac output with continuous aortic flow
augmentation (orqis)
• Reverse remodeling with ventricular assist devices
[Burkhoff D. SIS 2007 Yearbook;13:65-75]

19. Treatment of Valvular Disease
• HF leads to enlargement of the mitral annulus,
displacement of the papillary muscles, and tethering of the
mitral valve
• Benefit of treating functional MR in HF is not well
established - class IIb recommendation according to the
ACC/AHA guideline
• Despite lack of evidence surgical correction of functional
MR is sometimes performed in patients with end-stage HF
• Minimally invasive tech for the treatment of MR have also
been developed (Mitra clip) & may provide additional
treatment options

20. Closure devices for ASD,VSD and PDA

21. Transcatheter MR Repair

22. Percutaneous Mitral annuoplasty

23. Percutaneous Mitral valve replacement

24. Percutaneous Aortic valve replacement

26. Targets of Electrical HF Therapy
• Increased risk of ventricular arrhythmias
• Sudden death
• Intraventricular dyssynchrony
• Impaired cardiac contractility
• Unregulated sympathetic tone

27. • Use of electrical pulse generators to deliver an
electric current to cardiac tissue
• ICDs & CRTs are the most important device-based
treatment currently FDA approved for use in CHF
• ICDs shown to reduce mortality
• CRT shown to reduce symptoms and mortality
• Newer types under investigation –
- Cardiac Contractility Modulators (CCM)
- Vagal Nerve Stimulation
Electrical HF Therapy

28. Implantable Cardiac Defribrillators

29. Implantable Cardiac Defribrillators
EBM Therapies Relative Risk
Reduction
Mortality
2 year
ACE-I 23% 27%
Β-Blockers 35% 12%
Aldosterone
Antagonists
30% 19%
ICD 31% 8.5%

30. Implantable Cardioverter Defibrillator
• Secondary prevention
– survivors of VF
- documented haemodynamically unstable VT
and/or VT with syncope, a LVEF of 40%, on
optimal medical therapy, and with an
expectation of survival with good functional
status for 1 yr
[ESC 2008, Class of recommendation I, level of evidence A]
[Meta-analysis of AVID, CASH and CIDS studies. Eur Heart J 2000;21:2071–2078]

31. Implantable Cardioverter Defibrillator
• Primary prevention is recommended to reduce
mortality in patients with non-ischemic dilated
cardiomyopathy or ischemic LV dysfunction due to
prior MI who are at least 40 days post-MI, have an
LVEF ≤35%, in NYHA functional class II or III,
receiving optimal medical therapy, and who have a
reasonable expectation of survival with good
functional status for 1 year
[ESC 2008, Class of recommendation I,
ICMP - level of evidence A
DCM - level of evidence B]

32. ICD – The Gender Bias!
• ICD therapy for the primary prevention of sudden
cardiac death may not provide a mortality benefit to
women with heart failure
• A recent meta-analysis of 5 large, RCTs including
934 women with HF revealed that primary
prophylaxis with ICDs did not significantly decrease
all-cause mortality (HR, 1.01; 95% CI, 0.76-1.33)
• Future guideline recommendations for the use of
ICDs in women is of ongoing interest
[Ghanbari H, Arch Intern Med.2009;169(16):1500-1506]

33. Cardiac Resynchronization Therapy

34. CRT or BiV Pacing

35. CRT or BiV Pacing

36. CRT - Recommendations

37. CRT - Issues
Impact on symptoms and exercise tolerance
•All RCTs have confirmed a significant alleviation of
symptoms and increase in exercise capacity conferred by
CRT.
•On average, NYHA function class decreased by 0.5–0.8
points
•The 6 min walk distance increased by 20%
•Peak oxygen consumption increased by 10–15%
•The functional benefits and quality of life improvements
were sustained
1. Cleland JG. The effect of cardiac resynchronization on morbidity and
mortality in heart failure. N Engl J Med 2005;352:1539–1549
2. Linde C, MUSTIC study. J Am Coll Cardiol 2002;40:111–118.
3. Cleland JG, The CArdiac REsynchronization-Heart Failure (CARE-HF) trial
extension phase. Eur Heart J 2006;27:1928–1932.

38. CRT - Issues
Impact of CRT on morbidity
•In the COMPANION trial, CRT with or without an ICD,
lowered the combined endpoint of all-cause mortality and
rehospitalization for HF by 35–40%, mainly driven by the 76%
lower rate of hospitalizations.
•In CARE-HF, CRT-P lowered the proportion of unplanned
hospitalizations for worsening HF by 52%, and of unplanned
hospitalizations for major cardiovascular events by 39%.
1. Bristow MR, Cardiac-resynchronization therapy with or without an implantable
defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140–2150.
2. Cleland JG, The effect of cardiac resynchronization on morbidity and mortality in
heart failure. N Engl J Med 2005;352:1539–1549.

39. CRT - Issues
Impact of CRT on mortality
•In COMPANION, CRT-D showed a significant decrease in all-
cause mortality (RR reduction: 36%; P = 0.003), while the
24% RR reduction with CRT-P was nearly significant (P
=0.059).
•In CARE-HF, (only CRT-P), a 36% RR reduction in the risk of
death (P , 0.002) was observed after a mean follow-up time of
29 months.
•In the CARE-HF extension study, a RR reduction of 40% (P
= 0.0001) was observed, mainly due to ↓ HF-related deaths
1. Bristow MR, Cardiac-resynchronization therapy with or without an implantable defibrillator in
advanced chronic heart failure. N Engl J Med 2004;350:2140–2150.
2. Cleland JG, The effect of cardiac resynchronization on morbidity and mortality in heart failure.
N Engl J Med 2005;352:1539–1549.
3. Cleland JG, The CArdiac REsynchronization-Heart Failure (CARE-HF) trial
extension phase. Eur Heart J 2006;27:1928–1932

40. CRT - Issues
Impact of CRT on cardiac function & structure
•All RCTs have consistently shown up to 15% absolute
reduction in LVEDD and up to 6% increase in LVEF
following CRT
•The effect was significantly greater in patients with non-
ischaemic than in those with ischaemic heart disease.
•These observations provide consistent evidence of a
substantial, progressive, and sustained reverse
remodelling effect conferred by CRT.
1. Gervais R. Surface electrocardiogram to predict outcome in candidates for cardiac
resynchronization therapy: a subanalysis of the CARE-HF trial. Eur J Heart Fail
2009;11:699–705

41. CRT - Issues
Ambulatory patients in NYHA class IV
•COMPANION enrolled 217 NYHA class IV patients termed
‘ambulatory’ patients
•Patients with no scheduled or unscheduled admissions for
HF during the last month and with a life expectancy of 6
months.
•Time to all-cause mortality or first all-cause hospitalization
was significantly improved by both CRT-P and CRT-D vs
OMT
•No significant benefit was observed on all-cause mortality.
•Data support the use of CRT to improve morbidity (but not
mortality) in ambulatory class IV patients.
1. Lindenfeld J. Effects of cardiac resynchronization therapy with or without a defibrillator on survival
and hospitalizations in patients with New York Heart Association class IV heart failure. Circulation
2007;115:204–212

42. CRT - Issues
QRS morphology: LBBB vs RBBB
•‘Favourable outcome’ in CARE-HF was defined as
freedom from death or major cardiovascular event
•Baseline typical LBBB pattern predicted a favourable
outcome.
•By multivariable analysis, prolonged PR interval and
right bundle branch block (RBBB) were the only
predictors of non-favourable outcome.
1. Gervais R. Surface electrocardiogram to predict outcome in candidates for cardiac
resynchronization therapy: a subanalysis of the CARE-HF trial. Eur J Heart Fail 2009;11:699–
705.

43. CRT - Issues
CRT-D in patients with an indication for an ICD
•MIRACLE ICD and a large meta-analysis support the
choice of a CRT-D in patients in NYHA class III/IV, with
LVEF of ≤35%, QRS of ≥120 ms with a conventional
indication for an ICD
1. Abraham WT. 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.
2. Lam SK, Owen A. Combined resynchronisation and implantable defibrillator therapy in left
ventricular dysfunction: Bayesian network meta-analysis of randomised controlled trials. Br
Med J 2007;335:925

44. CRT - Beyond Current Guidelines
CRT in Patients With Narrow QRS Complex
•CONQUEST (Congestive Heart Failure and QRS Duration:
Establishing Prognosis) study, with 3,000 HF patients,
showed that 42% of the patients had a QRS duration < 120 ms
•Echo studies have shown that 40% - 50% of HF patients with
a narrow QRS complex may also exhibit LV dyssynchrony
•Echo predictors of response to CRT (small studies) –
- septal to lateral or opposing segment delay of 65 ms
- standard deviation of time to peak tissue velocity >32 ms
1. Abraham J. Is echocardiographic assessment of dyssynchrony useful to select candidates for cardiac
resynchronization therapy? Circulation: Cardiovascular Imaging. 2008; 1: 79-85.
2. Bommel V. CRT Beyond Current Guidelines . JACC; 56:10, 2010 Aug 31,754–62

45. CRT in Narrow QRS Complex
CRT in Patients With Narrow QRS Complex
•CONQUEST (Congestive Heart Failure and QRS Duration:
Establishing Prognosis) study, with 3,000 HF patients, showed
that 42% of the patients had a QRS duration < 120 ms
•Echo studies have shown that 40% - 50% of HF patients with a
narrow QRS complex may also exhibit LV dyssynchrony
•Echo predictors of response to CRT (small studies) –
- septal to lateral or opposing segment delay of 65 ms
- standard deviation of time to peak tissue velocity >32 ms
1̊
VO2
2̊
NYHA

46. CRT in Patients With Narrow QRS Complex
• ESTEEM-CRT & RethinQ Trials –
- no improvement in primary endpoints peak Vo2 or LVEF
- significant improvement in 2̊ endpoint of NYHA class
• Limitations of ESTEEM-CRT and RethinQ –
- included few patients with limited follow-up (up to 6
months)
- did not focus on rehospitalization and long-term survival
• Results from ESTEEM-CRT & RethinQ make the expansion
of CRT to HF pts with narrow QRS complex currently
unlikely
• Ongoing Echo-CRT trial with speckle tracking will
determine whether CRT is an effective Rx modality in this
specific group
1. Leon AR. Evaluation of CRT in Narrow QRS Patients With Mechanical Dyssynchrony From a Multicenter Study
(ESTEEM-CRT). Paper presented at Heart Rhythm Society Congress; May 15, 2008; SanFrancisco, CA
2. Beshai JF. RethinQ. N Engl J Med 2007;357:2461–71

47. CRT - Beyond Current Guidelines
CRT in patients with mild heart failure
•MIRACLE ICD II trial –
- 186 patients in NYHA class II with LVEF <35%, a
QRS width >130 ms and a Class I indication for an ICD
•At 6 months of follow-up, patients in the CRT-ON
group had a greater reduction in LV diastolic &
systolic volumes (p< 0.05) and significant
improvement in NYHA class (p=0.05)
•Similar results reported by the CONTAK-CD trial, with
significant reductions in LV dimensions

48. 49
MADIT-CRT
Main Inclusion Criteria
Ischemic heart disease (NYHA Class I or II) or non-
ischemic heart disease (NYHA Class II) for at least
three months prior to entry
Optimal pharmacologic therapy
 Beta blockers, ACE/ARB, and statins (ischemic
patients) unless not tolerated or contraindicated
Left ventricular ejection fraction ≤ 30%
QRS duration ≥ 130 ms
Sinus rhythm

49. 50
MADIT-CRT Results
 The primary endpoint was a composite
of death from any cause and non-fatal
HF-related adverse events.
 Mean follow-up of 2.4 years
 Results showed that CRT-D was
associated with a 34% reduction in the
relative risk of the primary endpoint
 Benefit attributable primarily to a 41%
decrease in HF-related adverse events
• It was subsequently discovered and
validated that in the LBBB subgroup,
patients received substantial benefit from
CRT-D. Non-LBBB patients did not show
evidence of benefit. The LBBB sub-group
made up approximately 70% of the total
MADIT-CRT population.
• 3% mortality in both groups
34% 57%

50. REVERSE Trial
• Inclusion criteria (N =610)
- patients treated with an optimal medical regimen
- NYHA function class I or II and NSR
- LVEF ≤40%, QRS duration ≥120 ms, LVEDD≥55 mm
- All patients had a history of HF symptoms
• Method - implantation of a CRT-D (85%) or CRT-P
(15%) and compared between activated (CRT-ON) vs
CRT-OFF
• Primary endpoint was the percentage of clinically
worsened patients, ascertained by the use of a
composite endpoint.
• Secondary endpoint was echocardiographic change in
LV end-systolic volume index
[Linde C. REVERSE trial. J Am Coll Cardiol 2008;52:1834–1843]

51. • After 12 months, no significant difference observed in the primary endpoint
• However, a significant degree of reverse LV remodelling was observed
among patients on CRT, manifested by decreases in the LVESVi (p <
0.0001) and LVEDV, and an increase in LVEF (p < 0.0001)
• Significant reverse remodelling linked to reduced HF morbidity indicates
that CRT may potentially modify disease progression in mild HF patients.
MADIT-CRT Results of Minor Endpoints

52. Inferences from MADIT-CRT & REVERSE
• MADIT-CRT & REVERSE demonstrated reduced
morbidity
• No significant improvement seen in NYHA I class
pts at baseline (18% of pts in REVERSE & 15% pts in
MADIT-CRT)
• Improvement primarily in pts with QRS ≥150 ms
and/or typical LBBB.
• In MADIT-CRT, women with LBBB demonstrated a
particularly favourable response.
• Survival advantage is not established.
• In MADIT-CRT the extent of reverse remodelling was
concordant with & predictive of improved clinical
outcomes
[ESC guidelines . Focussed update. European Heart Journal (2010) 31, 2677–87]

54. CRT in Heart Failure patients with AF

55. Electrical Therapy for CHF
Cardiac Contractility Modulation (CCM) Therapy
•Mech. - To enhance the strength of cardiac muscular
contraction, non-excitatory electrical signals are
delivered during the absolute refractory period of the
cardiac cycle
•The CCM signals delivered by OPTIMIZER™device is
via 3 cardiac leads (1 right atrial and 2 right ventricular
septal)

56. Cardiac Contractility Modulation Therapy
• The OPTIMIZER system was studied in the FIX-CHF-4 trial
- enrolled 164 subjects; ineligible for CRT; EF <35%; NYHA
class II or III symptoms despite optimal medical therapy
• Significant improvements were found in peak VO2,
Minnesota Heart Failure scores, and the 6-minute walk
test (6MW)
• A trend toward fewer deaths and hospitalizations
• CCM signals improve the strength of muscle contraction,
it is postulated to work equally well in patients with
normal and abnormal QRS duration and also in
combination with CRT
1. Gottlieb SS. Scientific Sessions of the Heart Failure Society of America: Seattle,
Washington, September 10-13, 2006. J Am Coll Cardiol 2007;49:608-15.
2. Butter C. First use of CCM in a patient failing CRT therapy: clinical and technical
aspects of combined therapies. Eur J Heart Fail 2007 Jun 25aa

57. Vagal Nerve Stimulation
 Aim – to counteract the maladaptive increase in SNS
activation
 CardioFit system device is implanted in chest wall and
the electrode is positioned around the vagus nerve in
the neck. By continuously monitoring an ECG,
stimulation is adjusted to the patient’s desired HR
 It will be of interest to see if heart rate modulation
beyond that of β-blockers can provide additional
clinical benefit.
 The device is presently in early studies for treatment
of class II and III heart failure patients.
1. Schwartz PJ. Long term vagal stimulation in patients with advanced heart failure - first
experience in man. Eur J Heart Fail. 2008;10(9):884-891
2. De Ferrari GM. Chronic vagal stimulation in patients with congestive heart failure. Conf
Proc IEEE Eng Med Biol Soc. 2009;2009:2037-2039

59. Interventional Medical Therapy
Continous Inotropic Support
•Long-term inotropes in refractory HF has remained
controversial
•Associated with ventricular arrhythmias, sudden cardiac
death, and increased mortality
•More recent studies evaluating long-term use of inotropes in
patients who have ICDs and are awaiting heart transplant have
demonstrated promising results
•Several groups of heart failure specialists have reevaluated
long-term inotropic therapy and are using it with increasing
frequency, especially in patients with end-stage disease,
where alternative treatment options are limited
1. O’Connor CM. Continuous iv dobutamine is associated with an increased risk of death in pts with advanced heart
failure: insights from the Flolan International Randomized Survival Trial (FIRST). Am Heart J. 1999;138(1 pt 1):78-86
2. Jimenez J. Long-term (>8weeks) home inotropic therapy as destination therapy in patients of advanced heart
failure or as BTT. Int J Cardiol. 2005;99(1):47-50.

60. Continous Inotropic Support
• Continuous intravenous infusion of a positive inotropic
agent may be considered for palliation of symptoms in
patients with refractory end-stage HF (ACC Class IIb / Level
of Evidence: C)
• The use of continuous IV support to allow hospital
discharge should be distinguished from the intermittent
administration of infusions of such agents to patients who
have been successfully weaned from inotropic support
• Intermittent outpatient infusions of vasoactive drugs such
as nesiritide or positive inotropic drugs have not shown to
improve symptoms or survival in patients with advanced
HF
1. Jessup M. 2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in
Adults: Developed in Collaboration With the International Society of Heart and Lung Transplantation. Circulation.
2009;119(14):1977-2016..

62. Mechanical Circulatory Assist Devices
• Aim - assist failing ventricle, alter hemodynamics,
improve CO
• Percutaneous therapies, for short-term use in
- acutely decompensated heart failure
- cardiogenic shock
- support during PCI
- perioperatively
Eg: intraaortic balloon pumps (IABPs)
continuous aortic flow augmentation (CAFA)
catheter-based pumps
• Surgical therapies, intended for long-term CHF
treatment Eg: VADs and TAHs.

63. Intraaortic Balloon Pump (IABP)

64. Intraaortic Balloon Pumps
• IABP rapidly improves hemodynamics in
cardiogenic shock
• Technique - a percutaneous balloon catheter is
inserted into the femoral artery and advanced into
the descending aorta distal to the left subclavian
artery
• Balloon is inflated during diastole and deflated
during systole
• Effects - decreased mean systolic arterial pressures
- decreased ventricular outflow resistance
- increased diastolic pressure & coronary
blood flow
- increased cardiac index.
1. Jones R. Coronary bypass surgery with or without surgical ventricular reconstruction. N Engl J
Med. 2009;360(17):1705-1717

65. Continuous Aortic Flow Augmentation (CAFA)
• Investigational approach for acute
CHF exacerbations in patients who
are inotrope dependent or refractory
• The CANCION® System (Orquis
Medical) consists of an
extracorporeal, magnetically levitated
centrifugal pump that withdraws
blood from both femoral arteries and
returns it to the descending thoracic
aorta in a continuous, nonpulsatile
manner at rates between 1.1 and 1.5
L/min

66. Continuous Aortic Flow Augmentation (CAFA)
• MOMENTUM trial (Multicenter Trial of the Orqis
Medical CRS for the Enhanced Treatment of CHF,
Unresponsive to Medical Therapy) assessed the
Cancion system in 109 patients
• CAFA has been associated with improvements in
cardiac index, clinical benefits have not been
demonstrated and safety (increased bleeding)
remains a concern
• CAFA has not been approved for commercial use
and is currently only available for investigational
purposes
1. Greenberg B. Results of the multicenter trial of the Orqis Medical Cancion System for the
enhanced treatment of heart failure unresponsive to medical therapy (MOMENTUM). Circulation.
2008;118(12):1241-1249

67. Catheter-Based Pumps
• Percutaneous catheter-based pumps designed for short-
term hemodynamic support in patients with cardiogenic
shock
• Available devices –
Hemopump (Medtronic), which is no longer in use
The Impella device (Abiomed, Danvers, Massachusetts)
Tandem Heart
Percutaneous Transseptal Ventricular Assist (PTVA)
system (CardiacAssist, Inc, Pittsburgh, Pennsylvania)
• The Impella and the Tandem Heart are FDA approved to
provide partial circulatory support for up to 6 hours

68. The Impella device
• The Impella 2.5 is a minimally invasive catheter-based cardiac
assist device that can be inserted into the left ventricle via
femoral arterial access in the cath lab. An in-line microaxial
pump continuously pumps blood from the left ventricle into
the ascending aorta at a maximum rate of 2.5 L per minute.
• A small RCT comparing the Impella 2.5
system and IABP in 25 patients with
cardiogenic shock due to MI
demonstrated a more significant increase
in cardiac index in the Impella group
• 30-day mortality (46%) was not different
between groups
1. Seyfarth M. A randomized clinical trial to evaluate the
safety and efficacy of a percutaneous left ventricular
assist device versus IABP for treatment of cardiogenic
shock caused by myocardial infarction. JACC.
2008;52(19):1584-1588.

70. The Tandem Heart
• The Tandem Heart unloads the LV
and pumps blood from the LA to the
peripheral arterial circulation
• Consists of a percutaneous venous
inflow catheter that is inserted into
the LA via transseptal puncture, a
percutaneous outflow catheter in the
descending aorta, an extracorporeal
pump with a max flow rate of 5.0
L/min, and a controller unit

71. The Tandem Heart
• TandemHeart PTVA vs IABP has demonstrated
- significant improvement in CO & cardiac index
- significant reduction in PCWP and serum lactate
- no significant difference in 30-day mortality
• Adverse effects - risk of severe bleeding and limb
ischemia.
1. Thiele H. Randomized comparison of intra-aortic balloon support with a percutaneous left ventricular assist
device in patients with revascularized acute myocardial infarction complicated by cardiogenic shock. Eur
Heart J. 2005;26(13):1276-1283

73. Tissue Transplantation
• Tissue transplantation uses living cells or tissue to
restore cardiac pump function
• It includes
- cellular therapy
- stem cell therapy
• - heart transplant

74. Cellular Cardiomyoplasty & Stem Cells
• Cellular cardiomyoplasty remains a promising
interventional approach for the treatment of ischemic
cardiomyopathy and has been associated with modest
improvements in LV function in several human studies
• Future research is necessary to optimize selection of cell
source, cell culture technique, method of cell delivery, and
also to determine the long-term clinical benefit of therapy
• Stem cell therapy is also promising; however, their use is
currently limited by scientific (increased arrhythmia) and
ethical concerns (MAGIC trial, 2009)

75. Cellular Cardiomyoplasty
• Cellular therapy or cellular cardiomyoplasty is an investigational
approach to the treatment of ischemic cardiomyopathy
• Transplanted cell include –
fetal and neonatal cardiomyocytes;
skeletal myoblasts
vascular endothelial cells;
bone marrow-derived stem cells
cardiac-derived stem cells;
embryonic stem cells
• Methods of delivering stem include
- injection during an invasive procedure (CABG / VAD)
- injection directly into the coronary arteries
- injection directly into the myocardium with the use of
transcutaneous endoventricular catheters such as MyoCath

77. Interventional Fluid Removal
• Decompensated HF is complicated by sodium and fluid
retention
• Limitations of loop diuretics have led to the development
of interventional approaches to fluid removal such as
- Interventional vasodilatation
- Ultrafiltration

78. Interventional Vasodilatation
• A novel technique that aims to target the kidneys directly, with
drugs administered directly into the renal arteries
• One approach called Targeted Renal Therapy (TRT) can be
achieved with the Benephit Renal Infusion System
• A bifurcated femoral catheter that can be advanced through
the ascending aorta and into the renal arteries
• This catheter can then be used to deliver vasodilators directly
into the renal arteries in attempts to improve renal perfusion &
GFR thus limiting the systemic effects of the medication

79. Interventional Ultrafiltration
• Ultrafiltration is currently a class IIa recommendation by
the ACC/AHA guidelines and is indicated for patients
with refractory congestion not responding to medical
therapy
• One type of ultrafiltration device, the Aquadex system
consists of a peripheral venous access catheter, a
disposable 0.12 m2
polysulphone filter circuit and a
console unit

81. The Aquadex Ultrafiltration System
• Can be used by a trained cardiologist, does not require a
nephrologist or use of a dialysis unit
• Can remove fluid at a max rate of 500 mL/h for up to 8 hrs
• Compared to intravenous diuretic therapy, the Aquadex
system resulted in greater weight loss, net fluid loss,
decreased frequency of hypokalemia at 48 hours, and with
reduced heart failure rehospitalizations at 90 days
1. Wertman B. Ultrafiltration for the management of acute decompensated heart failure. J Cardiac
Fail. 2008;14(9):754-759

83. Self Care
• Self-care is defined as a naturalistic decision-making process
involving the choice of behaviors that maintain
- physiologic stability (self-care maintenance)
- response to symptoms when it occurs (self-care management)
• Self-care maintenance includes adhering to LSMs such as taking
prescribed medications, eating a low-sodium diet, restricting fluid
intake, exercising and by recognizing signs of worsening HF
• Self-care management includes - reducing sodium or fluid intake,
taking an extra dose of diuretic, or seeking medical help Chronicle
(Medtronic), an implantable continuous hemodynamic
monitor (ICHM) measures & stores information for outpatient
monitoring
1. Bourge RC. Randomized controlled trial of an implantable continuous hemodynamic monitor in
patients with advanced heart failure: the COMPASS-HF study. J Am Coll Cardiol. 2008;51(11):1073-
1079

84. Intrathoracic Impedance for Heart Failure

88. Palliative Care
• Palliative care describes a multidisciplinary approach to
patient care that targets both the symptomatic and
psychosocial issues associated with a disease
• Being recognized as an essential aspect of HF therapy
because of the extreme physical and emotional symptoms
that patients with HF experience
• Although the ultimate goal of interventional heart failure
therapy is to prolong life and reduce symptoms, many of
these therapies are associated with unique emotional
complications that should be addressed with the
principals of palliative care described by Goodlin in his
state-of-the-art review article
1. Goodlin SJ. Palliative care in congestive heart failure. J Am Coll Cardiol. 2009;54(5):386-396

89. Conclusions and Future…
• The treatment options for patients with refractory end-
stage heart failure are currently limited
• At this advanced stage, the goals of treatment frequently
change from prolonging life to hospice / end-of-life care
• The role of interventional therapy promises additional
treatment options to these patients
• Currently available interventional options include heart
transplant, interventional medical therapy, VADs, TAHs.
• Future treatment options include the interventional
treatment of mitral valve disease, cellular and stem cell
therapy, and use of next generation VADs or TAHs &
ambulatory monitoring devices

90. Surgical options
 Coronary artery revascularization
 Valve surgery
 Left ventricular reconstruction
 Passive cardiac support devices
 Assist devices
 Cardiac transplantation

91. Coronary artery revascularization
Ischemic cardiomyopathy:
 myocardial dysfunction that arises secondary to
occlusive or obstructive coronary artery disease
 The most important determinant, however, is the
extent of jeopardized but still viable myocardium.
 Current studies have suggest at least 25% of the
myocardium should be viable

92.  Clinical factors for selection of suitable heart failure
patients
 the presence of angina,
 severity of heart failure symptoms,
 LV dimensions,
 degree of hemodynamic compromise, and
 comorbidities
 Other major technical issues to be considered are
 adequacy of target vessels for revascularization &
 adequate conduit strategy.
Coronary artery revascularization

93. Benefits of Coronary Artery Bypass Grafting
 The beneficial effect of revascularization should,
theoretically, result from improved blood flow to
hypoperfused but viable myocardium, with a
subsequent improvement in LV function and clinical
outcomes.
 Alleviation of ischemia may also lessen the tendency
toward proarrhythmias, thereby reducing the incidence
of sudden cardiac death.
 Accordingly, coronary artery revascularization has the
potential to improve symptoms of heart failure, LV
function, and survival.

94. Improvement in LV function

96. VALVE SURGERY
MITRAL REGURGITATION:
 Progressive LV remodeling
progressive LV dilation
more spherical shape
Functional MR
• annular dilation,
• papillary muscle displacement
• chordal tethering.

97. Consequences:
 increased preload,
 increased wall tension,
 increased LV workload,
Significance:
 independent risk factor of poor outcome, in
both nonischemic and ischemic causes
Heart
failure

98. the reduction of the annulus by a small ring
reduces a radius of curvature of the LV at the
base equatorial and apical levels
restore a more elliptical ventricular shape
reverse remodelling

100. Ventricular support and restoration
• Surgical interventions aimed at altering left ventricular
shape, size, or contractility
• In ventricular support, the heart is wrapped with
materials that provide structural reinforcement to the
cardiac muscle
• In ventricular restoration, the left ventricle is
surgically modified to a more natural shape and size
• Specific techniques include
- cardiomyoplasty,
- passive ventricular restraint (PVR)
- surgical ventricular restoration (SVR)
1. Schwartz PJ. Long term vagal stimulation in patients with advanced heart failure - first experience
in man. Eur J Heart Fail. 2008;10(9):884-891
2. De Ferrari GM. Chronic vagal stimulation in patients with congestive heart failure. Conf Proc IEEE
Eng Med Biol Soc. 2009;2009:2037-2039

101. Cardiomyoplasty (active ventricular restraint)
• Surgical intervention for end-stage heart failure in which
skeletal muscle, traditionally latissimus dorsi, is wrapped
around the heart and stimulated to contract during
systole, via use of a pacemaker - assisting ventricular
contractile force
• Results in improvements in NYHA class, ejection fraction,
quality of life, and in reduced hospitalizations
• A mortality benefit has never been established.
• Despite these benefits, postop mortality ranges from 3%-
31% & surgical risks are thought to be too high for NYHA
IV pts
• Due to recruitment difficulties for large trials, the use of
cardiomyoplasty in the United States has almost ended
1. Leier CV. Cardiomyoplasty: is it time to wrap it up? J Am Coll Cardiol. 1996;28(5):1101-1102

103. Passive Ventricular Restraint
• The benefit of Cardiomyoplasty may be due to a girdling
effect on ventricle than a squeezing one as initially thought
• This theory forms the basis for PVR - in which a
supporting mesh is wrapped around the heart to reinforce
the ventricles.
• In dog models, passive ventricular support shown to
- prevent progressive left ventricular dilation
- improve ejection fraction
- promote reverse remodeling & reduce systolic wall
stress
- reverse chronic molecular and cellular abnormalities
• Two devices developed –
The CorCap Cardiac Support Device
Paracor HeartNet device

105. The CorCap Cardiac Support Device
• Corcap was evaluated in a RCT - 300 patients with DCM,
ejection fraction < 35%, NYHA III-IV symptoms and OMT
• Compared with controls, those received a CSD had greater
reduction in LVEDV, LVESV and improved MLWHFQ and
clinical composite scores
1. Starling RC. Three years follow-up results from the
ACORN trial. Ann Thoracic Surg 2007;84:1236
• No difference in mortality
or rehospitalization rates
• Benefits additive to MVR /
OMT
• Not yet approved by FDA

106. Paracor HeartNet device
• Data on the Paracor HeartNet device are available on 51
patients with heart failure, its use was associated with
- significant improvement in 6-minute walk test (P = 0.002)
- MLWHFQ score (P =0.002)
- improvement in echocardiographic findings
• A multicenter RCT, the PEERLESS-HF trial (Prospective
Evaluation of Elastic Restraint to Lessen the Effects of Heart
Failure) to evaluate efficacy of the HeartNet device is ongoing
1. Klodell CT Jr. Worldwide surgical experience with the paracor
HeartNet cardiac restraint device.
J Thorac Cardiovasc Surg. 2008;135(1):188-195.

107. Surgical Ventricular Restoration
• SVR describes invasive surgical procedures aimed at
reducing LV size and remodelling, creating a more
natural, elliptical LV
• Dyskinetic scar (aneurysm) removal -
aneurysmomorphy, is already a clinically accepted
procedure.
• Akinetic scar removal - Dor procedure, used in STICH
trial
• Initial clinical data of SVR in humans showed
improved ejection fraction, NYHA class, reduced
LVESV index, and improved long-term survival
• STICH trial, a large RCT had less promising results

108. Left ventricular reconstruction
The goals of ventricular reconstruction are
 to remove or to exclude the infarcted segment
 to restore an elliptical ventricular chamber
 to diminish remote wall stress
 to promote helical fiber orientation and
 to increase thickening of the akinetic or dyskinetic
portion of the chamber
 to reduce end-systolic volume
 to diminish mitral insufficiency, and
 to eliminate residual ischemia

109. The goal is to reduce ESV by at least 30% while ensuring
that the ventricle is not too small.

110. Ventricular Assist Devices (VAD)
• VADs are surgically implanted mechanical pumps used to
support the failing ventricles in patients with refractory end-
stage heart failure
• Basic Principle -
- Improve arterial flow (end organ perfusion)
- Improve ventricular unloading
• Due to limited availability of donor
organs and urgency of cardiac
support in severe CHF – VADs
have the potential to play an
important role as a bridge-to-transplantation(BTT)
or even as destination therapy (DT)

112. Indications for VADIndications for VAD
 Bridge to transplant
(BTT)
 most common
 allow rehab from
severe CHF while
awaiting donor
 Bridge to recovery (BTR)
 unload heart, allow
“reverse remodeling”
 can be short- or long-
term
 “Destination” therapy (DT)
 permanent device, instead of
transplant
 currently only in transplant-
ineligible patients
 Bridge to candidacy (BTC)
 when eligibility unclear at
implant
 Bridge to decision (BTD)
 Potential for transplant or
recovery unclear

113. VAD -Classification
• Based on location of pump –
- Extracorporeal (outside the body)
- Intracorporeal (contained within the body)
• Based on ventricle supported –
- LVAD
- RVAD
- BiVAD
• Based on pump characteristics –
- pulsatile
- continous flow pumps (axial / centrifugal)

116. VAD -Classification
• First Generation
- uses volume displacement to invoke pulsatility
- large in profile
- preload dependent
- decreased durability
HeartMate VE/XVE Novacor LVAS

117. VAD -Classification
• Second Generation
- Continuous-flow pumps (axial)
- smaller
- similar degrees of pumping support (10 l/min)
- more durable
- functionally dependent on both preload and
afterload

118. VAD -Classification
• Third Generation
- Continuous-flow pumps (axial / centrifugal)
- use an impeller pump that is either magnetically
or hydrodynamically levitated
- smaller profile
- lower weight
- potential for greater durability
- early evidence suggests improvements in RV
failure and infection rates

119. • Intra-Pericardial Implant
• BBT and D
• 10 L Flow
No abdominal surgery
No pump pocket
Shorter pump implantation time

122. VAD – Selection of Patients
• If a risk reduction rate of ACE inhibitor alone is 25%, and
spironolactone was 30% and carvedilol was 35%, the calculated
1-year mortality after combination therapy in ambulatory NYHA
class IV patients is approximately 11%
• CRT-D reduced the 1-year mortality to 30%, and 2-yr to 55% in
NYHA class IV HF (COMPANION)
• If the calculated 1- and 2-year mortality rates of patient exceed
38% and 61%, LVAD becomes a future treatment option
1. Kinugawa K. How to Treat Stage D Heart Failure? – When to Implant LVADs in the Era of
Continuous Flow Pumps? Circ J 2011; 75: 2038 – 2045

123. VAD – Selection of Patients
Calculation of mortality rates -
•Heart Failure Survival Score (HFSS) and Seattle Heart Failure
Model (SHFM) are widely used
•SHFM is a more convenient index and is available on the
internet, where patient data can be input and the mortality
rate is immediately calculated
•Age, sex, NYHA class, body weight, LVEF, SBP, medication
(including dose of diuretics), hemoglobin, %lymphocytes,
uric acid, total cholesterol, sodium, and CRT-D treatment, if
any, can be input and the model produces a graph of
mortality with information on how future interventions, such
as additive medication, CRT-D or LVAD, can modify the
prognosis

124. Prognostic Categorization of Stage D HF
• Stage D HF can be further divided, based on the
INTERMACS (Interagency Registry for Mechanically
Assisted Circulatory classification) registry classification
• INTERMACS is a comprehensive VAD registry in USA that
was started in March 2006, and approximately 4,800 VADs
have been enrolled from 130 hospitals as of June 2011
• There are 7 major categories called Profiles and 3
modifiers
• Profile 1 represents the most severe status, and the least
sick profile is 7
1. Kirklin JK. Second INTERMACS annual report: More than 1,000 primary left ventricular assist
device implants. J Heart Lung Transplant 2010; 29: 1 – 10.

125. strategies to re-power the failing heart:
Electrical:
– cardiac resynchronisation therapy (CRT), CCM, VS
Mechanical:
– ventricular assist devices : left (LVAS), right (RVAS), bi- (BiVAS)
Biological:
– dynamic cardiac myoplasty
– heart transplantation
– cell transplantation
– gene therapy
– up-regulation of natural pathways
Interventional medical therapy
Specific treatment of heart failure: revascularization, valve surgery and intervention
Short term circulatory support : IABP, Impella, Tandem heart
Prevention of sudden death: AICD
Total Artificial heart

126. Total Artificial Heart

127. Artificial Hearts

128. William DeVries
 Born in 1943
 Trained at the University of
Utah and Duke University
 Worked with Kolff to implant
artificial heart in animals
 1982: Implanted first artificial
heart into Seattle dentist
Barney Clark
 1985: Implanted 2nd Jarvik
into Bill Schroeder in
Louisville KY