Refractory heart failure - Diagnosis, Management, Device Therapy

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Refractory heart failure - Diagnosis, Management, Device Therapy

  1. 1. Dr. Imran Ahmed DM (Cardiology) Kolkata, India
  2. 2.  Prevalence and Incidence rates are alarmingly high - Increasing HF hospitalizations - Increasing HF-attributable deaths - Spiraling cost of HF-care  Worldwide 23 million people affected  Prevalence increases with age (6-10% in > 65 yrs)
  3. 3. Heart Failure in the U.S - A Growing Public Health Problem.  Approximately 5 million patients in this country have HF (1.5 – 2% of population)  Over 550,000 patients are diagnosed with HF for the first time each year  Primary reason for 12 to 15 million office visits and 6.5 million hospital days each year  In 2001, nearly 53,000 patients died of HF as a primary cause
  4. 4. “HF is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood” [ACC focused update 2009]
  5. 5. Stages of Heart Failure At Risk for Heart Failure: STAGE A High risk for developing HF STAGE B Asymptomatic LV dysfunction Heart Failure: STAGE C Past or current symptoms of HF STAGE D Refractory / End-stage HF
  6. 6. Stages of Heart Failure • Designed to emphasize preventability of HF • Designed to recognize the progressive nature of LV dysfunction
  7. 7. Stages of Heart Failure COMPLEMENT, DO NOT REPLACE NYHA CLASSES • NYHA Classes - shift back/forth in individual patient (in response to Rx and/or progression of disease) • Stages - progress in one direction due to cardiac remodeling
  8. 8. 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
  9. 9. 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
  10. 10. 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 previous 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) [Nohria A, JAMA 2002;287:628-40 and D. Feldman, Clin. Cardiol. 2008;31, 7, 297–301]
  11. 11. 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]
  12. 12. Refractory Heart Failure - Definition • Corresponds to stage D heart failure - refers to patients with advanced structural heart disease and severe signs of HF at rest who are candidates in the absence of contraindications for other specialized interventions such as – • heart transplantation • ventricular remodeling • implantation of mechanical assistance devices • intravenous inotropic drugs
  13. 13. ‘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]
  14. 14. Need for ‘Interventional HF Therapy’ • Even on max pharma 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]
  15. 15. Basis of Interventional HF Therapies • Strengthening of cardiac contraction with cardiac contractility modulation • Modification of ht rate with vagal nv 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]
  16. 16. • 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
  17. 17. Targets of Electrical HF Therapy • Increased risk of ventricular arrhythmias • Sudden death • Intraventricular dyssynchrony • Impaired cardiac contractility • Unregulated sympathetic tone
  18. 18. 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]
  19. 19. 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]
  20. 20. 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]
  21. 21. Cardiac Resynchronization Therapy
  22. 22. CRT - Recommendations
  23. 23. 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.
  24. 24. 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.
  25. 25. 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
  26. 26. 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
  27. 27. 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
  28. 28. 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.
  29. 29. 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
  30. 30. 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
  31. 31. 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
  32. 32. 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
  33. 33. 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
  34. 34. CRT - Beyond Current Guidelines CRT in patients with mild heart failure • Results of CONTAK-CD and MIRACLE ICD II showed that LV reverse remodeling was a better predictor of long-term survival than clinical improvement • Effect - 2 large clinical trials were conducted to investigate whether CRT could prevent or attenuate disease progression and induce LV reverse remodeling in mild heart failure – - The REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) [J Am Coll Cardiol 2009;54:1837–1846] - The MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) [Circulation 2010 10.1161/CIRCULATIONAHA.110.955039]
  35. 35. CRM6-4403-0810© 2010 Boston Scientific. All rights reserved. 40 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
  36. 36. CRM6-4403-0810© 2010 Boston Scientific. All rights reserved. 41 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 • 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%
  37. 37. CRM6-4403-0810© 2010 Boston Scientific. All rights reserved. MADIT-CRT Results of Minor Endpoints 42
  38. 38. 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]
  39. 39. • 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.
  40. 40. 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]
  41. 41. 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)
  42. 42. 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 25
  43. 43. 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 electrocardiogram, stimulation is adjusted to the patient’s desired heart rate • 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
  44. 44. 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 - 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
  45. 45. 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
  46. 46. 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 – - CorCap cardiac support device (CSD; Acorn CV Inc., Minn.) - Paracor HeartNet device (Paracor Medical, Sunnyvale, CA.)
  47. 47. 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
  48. 48. 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.
  49. 49. 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
  50. 50. STICH Trial • Patients with ICMP on OMT, randomized to undergo either CABG alone (499 patients) or CABG plus SVR (501 patients) • After a median follow-up of 48 months, there was no significant difference in death from any cause, death within 30 days of surgery, hospitalization for any cause, MI, stroke, anginal symptoms, NYHA class, or 6MWT between groups. • Given these findings, SVR should not be used in patients with ICMP who are amenable to CABG (debatable) 1. Jones R. Coronary bypass surgery with or without surgical ventricular reconstruction. N Engl J Med. 2009;360(17):1705-1717
  51. 51. Mechanical Circulatory Assist Devices • Aim - assist failing ventricle, alter hemodynamics, improve CO • Percutaneous therapies, indicated 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.
  52. 52. 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
  53. 53. Intraaortic Balloon Pumps • Associated with a 2.8% rate of significant complications and a 0.05% rate of IABP-related in-hospital mortality • The ACC/AHA guidelines on STEMI recommend IABP as a class I recommendation in patients with - hypotension who do not respond to other interventions - low-output state, - cardiogenic shock not quickly reversed with treatment - recurrent ischemic chest discomfort with unstable hemodynamics - poor left ventricular function - large area of myocardium at risk
  54. 54. 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
  55. 55. 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
  56. 56. 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) - TandemHeart 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
  57. 57. 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.
  58. 58. 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
  59. 59. 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
  60. 60. 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)
  61. 61. Indications 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
  62. 62. 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)
  63. 63. VAD -Classification • First Generation - uses volume displacement to invoke pulsatility - large in profile - preload dependent - decreased durability HeartMate VE/XVE Novacor LVAS
  64. 64. VAD -Classification • Second Generation - Continuous-flow pumps (axial) - smaller - similar degrees of pumping support (10 liters/min) - more durable - functionally dependent on both preload and afterload
  65. 65. 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
  66. 66. • Intra-Pericardial Implant • BBT and D • 10 L Flow
  67. 67. Third Generation VAD
  68. 68. 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
  69. 69. 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
  70. 70. 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.
  71. 71. Prognostic Categorization of Stage D HF Modifiers for Profiles Possible Profiles to Modify TCS (temporary circ support) 1,2,3 A (arrhythmia) Any profile FF (frequent flyer) – only opd 3(at home),4,5,6
  72. 72. INTERMACS Profile Profile 1 • Profile 1 are in cardiogenic shock, often called “crash and burn” • Hemodynamics have “crashed” and many end organs start “burning” • Often seen after large myocardial infarction by left main trunk occlusion or with fulminant myocarditis • Marked ↑ in liver enzymes & ↑total bilirubin may occur • Treated with multiple intravenous catecholamines, intra-aortic balloon pump (IABP), percutaneous cardiopulmonary support (PCPS) or a ventilator
  73. 73. INTERMACS Profile Profile 2 • Represents the second sickest status and is called “sliding on inotropes” • In these patients, end-organ damage is worsening despite high- dose intravenous catecholamines.
  74. 74. INTERMACS Profile Profile 3 • Is a stable condition on intravenous catecholamines without progression of end-organ damage • Referred to as “dependent stability”, requiring only a single low-dose administration of an inotrope (2–3 μg · kg–1 ·min–1) usually dobutamine in most cases • To determine the dependency on catecholamines, tapering of intravenous catecholamines should be tried several times, but patients with Profile 3 must have significant symptoms or hemodynamic deterioration at withdrawal or very low dose
  75. 75. INTERMACS Profile Profile 4-7 • Profile 4 is defined as resting symptoms that do not necessarily require intravenous inotropes. In order to maintain euvolemic status, patients usually need high-dose diuretics, resulting in their deteriorating renal function. • The less sick Profile 5 is called “house-bound”, because the patient’s daily life is limited to inside the house • Profile 6 represents “walking wounded” status, and patients with this profile can barely walk 1 block • Patients with Profiles 5–6, easily fall into Profile 4, depending on comorbidities • Profile 7 represent advanced NYHA class III, and not currently been considered as candidates for transplantation or VAD implantation in any country.
  76. 76. INTERMACS & VADs - Summary • The prognosis of stage D HF varies with each patient’s clinical status, now widely known as INTERMACS profiles • The best indication of implantable VADs is Profiles 2–4 • Extracorporeal VADs still play a crucial role as an emergency device in Profile 1 patients or during a VT storm • Patients with modifier A can be candidates for implantable VADs even if their profile is 5 or 6.
  77. 77. INTERMACS & VADs - Summary • Continuous flow VADs are state-of-the-art and have numerous superiorities over pulsatile VADs • But some complications specific to continuous flow VADs – - (1) de novo aortic insufficiency - (2) decreased level of high-molecular weight vWF - (3) gastrointestinal bleeding from arteriovenous malformation 1. Hatano M. Less frequent opening of the aortic valve and a continuous flow pump are risk factors for postoperative onset of aortic insufficiency in patients with a left ventricular assist device. Circ J 2011; 75: 1147 – 1155 2. Demirozu ZT. Arteriovenous malformation and gastrointestinal bleeding in patients with HeartMate II LVAD. J Heart Lung Transplant 2011; 30: 849 – 85
  78. 78. 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.
  79. 79. 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..
  80. 80. Interventional Fluid Removal • Decompensated HF is comlicated 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
  81. 81. 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
  82. 82. 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
  83. 83. 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 hours • 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
  84. 84. 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
  85. 85. Tissue Transplantation • Tissue transplantation uses living cells or tissue to restore cardiac pump function • It includes - cellular therapy - stem cell therapy • - heart transplant
  86. 86. 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
  87. 87. 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)
  88. 88. Human Heart Transplant (HHT) • Allogeneic HHT is a therapeutic option for patients with refractory end-stage HF, who have failed other options • 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 • 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.
  89. 89. 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
  90. 90. 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
  91. 91. 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

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