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POST OPERATIVE CLINICAL IMPROVEMENT IN THE ABSENCE OF REVERSE REMODELING. CLINICAL MANAGEMENT AND QUALITY OF LIFE WITH THE COMPROMISED VENTRICLE Ernesto E Salcedo, MD Professor of Medicine University of Colorado School of Medicine Director of Echocardiography University of Colorado Hospital Key Concepts • Ventricular adaptation to Pressure and Volume Overload • Determinants of Remodeling and Reverse Remodeling • Determinants of Post Operative Clinical Improvement • Clinical Management and Quality of Life in patients with Compromised Ventricle The cardiac myocyte • The most physically energetic cell in the body • Contracting constantly, (without tiring), 3 billion times or more in an average human lifespan • Coordinating its beating activity with that of its 3 billion neighbors in the main pump of the human heart • Over 7,000 litres of blood are pumped per day, along 100,000 miles of blood vessels Nicholas J. SeversBioEssays 22:188–199, 2000 Walker A J Thorac Cardiovasc Surg 1999;118:375-82 Ventricular adaptation to Pressure and Volume Overload • Aortic Stenosis: pure pressure overload • Mitral Regurgitation: pure volume overload • Aortic regurgitation: combined pressure and volume overload • Mitral stenosis: volume underload • Hypertrophy means an increase in mass whereas • Remodeling indicates a change in geometry and/or volume AORTIC STENOSIS Pressure Overload LV Remodeling Patterns Based on LVH and LV M-C Ratio Rodriguez C J Am Coll Cardiol 2010;55:234–42 CMR definitions of the six patterns of left ventricular hypertrophy and remodeling in aortic stenosis Normal ventricular structure: characterized by a normal LV mass index, indexed LVEDV, and a normal M/V. Concentric remodeling: characterised by an increased M/V and normal LV mass index. Asymmetric remodeling: similar to concentric remodeling except that in addition there is evidence of asymmetric wall thickening. Concentric Hypertrophy: characterised by an increased M/V and LV mass index. Asymmetric hypertrophy: similar to concentric hypertrophy except that in addition there is evidence of asymmetric wall thickening. Left Ventricular Decompensation: characterised by a dilated left ventricle and normal M/V. The LV mass index may be increased primarily due to LV dilatation. Dweck et al. Journal of Cardiovascular Magnetic Resonance 2012, 14:50 Patterns of LVH Khouri M Circ Cardiovasc Imaging 2010;3;164-171 Types of hypertrophy and remodeling that occur in valvular heart disease A, Normal. B, Concentric left ventricular hypertrophy (LVH). C, Concentric remodeling. D, Eccentric LVH. E, Eccentric remodeling. Mass Index (g/m2) r/h m/v NL 86 3.05 (88) 1.25 (225) MR 158 4.03 (64) 0.87 (117) AR 230 3.52 (31) 1.00 (141) AS 178 2.35 (93) 1.55 (296) Carabelo B J Heart Valve Dis 1995 (Suppl 2):S132-S138 LV volume, mass, and geometry, stress, and systolic shortening in various cardiac disorders Aurigemma GP, Gaasch WH, Villegas B, Meyer TE: Curr Probl Cardiol 20:385, 1995 Lack of correlation between aortic valve area and left ventricular mass index A. Total population. B. Population after excluding patients with hypertension. C. Males. D. Females. Left Ventricular Reverse Remodeling After Surgical Therapy for Aortic Stenosis Left ventricular mass index (LVMI, in g/m2), maximum aortic pressure gradient (Pmax, in mm Hg), and myocardial fiber index (in m/m2) at baseline (A), after development of left ventricular hypertrophy (B), and after corrective surgical therapy (C). Walther T Circulation. 2002;106[suppl I]:I-23-I-26.) Correlation to Renin-Angiotensin System Gene Expression The association between left ventricular mass index (LVMI) and gene expression for angiotensin-converting enzyme (ACE) as well as angiotensin receptor subtype 1 and 2 (AT1-R, AT2-R) is shown according to the different time intervals using the symbols as indicated in the figure. On the left side, baseline (A) vs. left ventricular hypertrophy (B) is shown and on the right side, (B) vs. regression of LVH (C). Prevalence and characteristics of patients with clinical improvement but not significant left ventricular reverse remodeling after cardiac resynchronization therapy Auger D Am Heart J. 2010 Oct;160(4):737-43 Normalization of diastolic dysfunction in aortic stenosis late after valve replacement Villari B, Circulation. 1995;91:2353-8. Yarbrough WJ Thorac Cardiovasc Surg. 2012 March; 143(3): 656–664 Transcatheter aortic-valve replacement for inoperable severe aortic stenosis Two-year mortality stratified according to the Society of Thoracic Surgeons (STS) risk score. In patients with an STS score of ≥ 15%, transcatheter aortic valve replacement (TAVR) is no longer superior over standard therapy R.R. Makkar N Engl J Med, 366 (2012), pp. 1696–1704 Health-Related Quality of Life After TAVR PARTNER trial Kansas City Cardiomyopathy Questionnaire (23 Questions) 5 health domains pertaining to heart failure: symptoms, physical limitation, social limitation, self-efficacy, and quality of life. NYHA KCCQ Class I Increased in KCCQ 75-100 Clinical Improvement Class II 60-74 Small 5 Class III 45-59 Moderate 10 Class IV 0-44 Large 20 Reynolds, M Circulation. 2011;124:1964-1972 Health-Related Quality of Life After TAVR PARTNER trial Medical Outcomes Study Short-Form 12 (SF-12) Health Survey • Generic health status was evaluated with the Medical Outcomes Study Short-Form 12 (SF-12) Health Survey • The SF-12 was derived from the original SF-36 health survey by selecting those items having the greatest explanatory power. • Higher scores are better • Multiple groups have agreed that the minimal clinically important changes in the mental and physical summary scores are roughly 2 to 2.5 points Reynolds, M Circulation. 2011;124:1964-1972 Health-Related Quality of Life After TAVR PARTNER trial Reynolds, M Circulation. 2011;124:1964-1972 Health-Related Quality of Life Twelve Months After TAVR -PARTNER trial Medical Therapy in Aortic Stenosis with Heart Failure • Statin therapy should therefore not be used in AS patients • • • • where their only purpose is to slow progression. Patients who are unsuitable candidates for surgery or TAVI—or who are currently awaiting a surgical or TAVI procedure—may be treated with digoxin, diuretics, ACE inhibitors, or ARBs if they experience HF symptoms. Co-existing hypertension should be treated. Treatment should be carefully titrated to avoid hypotension and patients should be re-evaluated frequently. Maintenance of sinus rhythm is important. MITRAL REGURGITATION Volume Overload Percutaneous Mitral Valve Repair Feldman T Curr Probl Cardiol 2012;37:42-68. LV Response to Mitral Regurgitation Carabello BA Curr Probl Cardiol 28:553, 2003 LV Structure and Function in the 3 Stages of Chronic MR Stage 1 Stage 2 Stage 3 Chronic compensated MR with LV enlargement, eccentric hypertrophy, and normal systolic function Transitional phase with mild LV dysfunction that is reversible after surgical correction of the regurgitant lesion Decompensated MR with progressive and irreversible structural and functional changes in the ventricle Gash W Circulation 2008 vol. 118 no. 22 2298-2303 Chronic MR Mitral valve surgery in heart failure: Insights from the Acorn Clinical Trial Acker, M J Thorac Cardiovasc Surg 2006;132:568-77 Mitral valve surgery in heart failure: Insights from the Acorn Clinical Trial Mitral valve surgery in heart failure: Insights from the Acorn Clinical Trial Minnesota Living with Heart Failure Questionnaire. Medical Therapy in Patients with Severe Mitral Regurgitation and Heart Failure • In acute MR, reduction of filling pressures can be obtained with nitrates and diuretics. Sodium nitroprusside reduces afterload and regurgitant fraction, as does an intra-aortic balloon pump. Inotropic agents and intra-aortic balloon pump should be added in case of hypotension. • There is no evidence to support the use of vasodilators, including ACE inhibitors, in chronic MR without HF. • However, when HF has developed, ACE inhibitors are beneficial and should be considered in patients with advanced MR and severe symptoms, who are not suitable for surgery or when there are still residual symptoms following surgery AORTIC REGURGITATION Mixed Pressure and Volume Overload Exercise echocardiography predicts development of left ventricular dysfunction in medically and surgically treated patients with asymptomatic severe aortic regurgitation Change in left ventricular end systolic volume (ESV) with exercise (Ex) and on follow up (F/U) compared with baseline at rest (R), in patients with maintained left ventricular function (A) and latent dysfunction (B). Wahi S Heart. 2000 December; 84(6): 606–614 Different Stages of Aortic Regurgitation Medical Management in Aortic Regurgitation with Heart Failure • Vasodilators [angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)] are useful in the presence of hypertension when surgery is contraindicated, or LV dysfunction persists postoperatively. • A positive effect of these agents, or dihydropyridine calcium channel blockers, in asymptomatic patients without hypertension in order to delay surgery is unproven Vahanian A European Heart Journal (2012) 33, 2451–2496 Conclusions • Ventricular remodeling results from pressure or volume • • • • overload of the left ventricle Reverse remodeling may occur when the overload is corrected Symptomatic improvement usually follows reverse remodeling…but not always Quality of life improvement is an important marker of therapeutic success Severe valvular heart disease usually requires a mechanical solution since medical therapies are limited.