Insuficiencia cardíaca crónica Comignani Pablo Jefe Unidad de Cuidados Críticos, Terapia Intensiva-Unidad Coronaria Hospital Alemán, Buenos Aires pcomignani@hospitalaleman.com.ar

CHF as a Mechanical Problem Normal Contractility Normal Contractility Depressed Contractility Depressed Contractility PRECHARGE POSTCHARGE The view of CHF as a mechanical problem might hipothesized that an improve in the charges conditions and an improvement in the inotropism state will translate in a improved survival

CHF as a Mechanical Problem VENOUS AND ARTERIAL VASODILATATION Normal Contractility Normal Contractility Depressed Contractility Depressed Contractility PRECHARGE POSTCHARGE

CHF as a Mechanical Problem Survival with adrenergic agonist % SURVIVAL Days

Incremento en el riesgo de muerte asociado a dobutamina en infusión ( 14 días ). FIRST Study

OPTIME CHF Study

OPTIME CHF Study

CHF as a Mechanical Problem Survival with Digoxin % SURVIVAL Months

FEY – DDVI – NYHA – EDAD & SEXO Diuretic treatment in contemporany care of CHF: An analysis of the VALHEFT Study Debido a que las características de los pacientes que reciben o no reciben diuréticos difieren sustancialmente la comparación entre los grupos se realizó utilizando un score de propensión que consideró: Cinco categorías (quintilos) de riesgo (progresivo) construidos en función de: FEY – DDVI – NYHA – EDAD & SEXO Y dentro de cada una de estas 5 categorías, los sujetos que recibian y no recibian diuréticos estaban “matcheados”.

Diuretic treatment in contemporany care of CHF: An analysis of the VALHEFT Study GROUP 1 GROUP 2 GROUP 3 GROUP 4 GROUP 5 P Matched variables Age (median) 59 63 64 65 67 <0.0001 Males 957 (95.6) 863 (86.1) 773 (77.1) 640 (63.9) LVEF (median) 35 28 22 21 LVIDD 3,27 3,54 3,68 3,56 3,86 NYHA II 1001 (100) 1002 (100) 882 (88.0) 205 (20.5) 8 (0.8) NYHA III 120 (12.0) 797 (79.5) 896 (89.5) NYHA IV 97 (9.7) NYHA III / IV 993 (99.2)

Diuretic treatment in contemporany care of CHF: An analysis of the VALHEFT Study

Diuretic treatment in contemporany care of CHF: An analysis of the VALHEFT Study

Diuretic treatment in contemporany care of CHF: An analysis of the VALHEFT Study HR 95% CI p Eventos PS = 1 (n=1001) 2.29 1.12 – 4.67 0.022 84 PS = 2 (n=1002) 1.98 1.10 – 3.37 0.036 121 PS = 3 (n=1002) 1.66 0.89 – 3.09 0.108 147 PS = 4 (n=1002) 1.14 0.63 – 2.07 0.665 186 PS = 5 (n=1001) 0.45 0.26– 0.77 0.004 249 Cox regression model adjusted by age, sex, NYHA class, HF etiology, HF duration, diabetes, body mass index (BMI), electrocardiographic rhythm, EF, LVDD, haemoglobin, WBC count, serum sodium, potassium, creatinine, uric acid, total cholesterol, BNP, plasma renin activity, aldosterone, norepinephrine, ACE inhibitors, beta blockers, amiodarone and digoxin.

NEUROHORMORAL STATE Plasma norepinephrine CONTROL ASYMPTOMATIC SYMPTOMATIC HEART FAILURE

NEUROHORMORAL STATE Plasma norepinephrine Survival Probability Days

BETA BLOCKERS IN CHF CIBIS II ß-Adrenergic Blockers 1 Bisoprolol 11.8% 0.9 0.8 P< 0.00005 Survival Placebo 17.3% 0.7 ICCC NYHA III-IV n=2647 0.6 Annual Mortality: bisoprolol=8.2%; placebo=12% Mean Follow-up 1.4 years 0.5 200 400 600 800 CIBIS-II Lancet 1999;353:9 Days

BETA BLOCKERS IN CHF MERIT HF ß-Adrenergic Blockers Placebo 15 p=0.0062 Mortality % Metoprolol 10 5 Risk Reduction 34% NYHA II-IV N=3991 3 6 9 12 15 18 21 MERIT-HF Lancet 1999; 353: 2001 Months

BETA BLOCKERS IN CHF COPERNICUS ß-Adrenergic Blockers 100 90 80 Survival % Carvedilol 70 p=0.00014 35% RR 60 Placebo N = 2289 III-IV NYHA 50 4 8 12 16 20 24 28 COPERNICUS NEJM 2001;344:1651 Months

BETA BLOCKERS IN CHF CAPRICORN ß-Adrenergic Blockers 1 HR 0.77 (0.60 - 0.98) p<0.031 0.95 0.9 Carvedilol 116 / 975 (12%) Survival 0.85 0.8 LVD / HF Post AMI Placebo 151 / 984 (15%) 0.75 0.7 0.5 1 1.5 2 2.5 Years CAPRICORN Lancet 2001;357:1385

BETA BLOCKERS IN CHF A Metanalysis TRIAL Months of FU Mortality Placebo Beta Blockers RR IC 95 % P MDC 15 18 / 189 (10.1 %) 23 / 193 (11.9 %) 1.21 0.64 – 2.29 0.56 CIBIS I 21 67 / 321 (20.9 %) 53 / 320 (16.6 %) 0.75 0.51 – 1.12 0.16 ANZ 18 26 / 208 (12.5 %) 20 / 207 (9.7 %) 0.39 – 1.38 0.36 US Trial 6.5 31 / 398 (7.8 %) 22 / 696 (3.2 %) 0.37 0.21 – 0.65 0.0006 CIBIS II 15.6 228 / 1320 (17.3 %) 156 / 1327 (11.8 %) 0.64 0.52 – 0.80 0.0001 MERIT 12 217 / 2001 (10.8 %) 145 / 1990 (7.3 %) 0.65 0.52 – 0.81 BEST 24 449 / 1354 (33 %) 411 / 1354 (30 %) 0.88 0.75 – 1.03 0.1 COPERNICUS 10.4 190 / 1133 (16.8 %) 130 / 1156 (11.2 %) 0.63 0.49 – 0.80 CAPRICORN 13 151 / 984 (15 %) 116 / 975 (12 %) 0.74 0.57 – 0.97 0.03 TOTAL 1376 / 7908 (17.4 %) 1074 / 8218 (13.1 %) 0.72 0.66 – 0.79 < 0.0001

ALL BETA BLOCKERS ARE THE SAME ? Carvedilol Or Metoprolol European Trial 1511 1518 Age 61.6 ± 11.3 62.3 ± 11.4 Male (%) 1200 (79) 1217 (80) NYHA II/III/IV 48 / 48 / 3 49 / 47 / 1 ACE Previous (%) 92 91 ARB 6 7 Diuretics (%) 99 Digitalis (%) 72 75 Aldosterone antagonist 11 Ejection Fraction (%) 26.0 ± 7.0 26.0 ± 7 Systolic Pressure 126 ± 19.3 126 ± 19.7 Ischemic heart disease 51 54 Diabetes 24 Poole-Wilson PA et al.Lancet 2003;362:7-13

ALL BETA BLOCKERS ARE THE SAME ? Carvedilol Or Metoprolol European Trial HR IC 95 % P N 1511 1518 All Death (KM 5 years) 35.3 41.0 0.83 0.74-0.93 0.002 Yearly mortality rate 8.3 10.0 Cardiovascular Deaths 438 (29) 534 (35) 0.80 0.70-0.90 0.0004 Non Cardiovascular Deaths 74 (5) 66 (4) 1.08 0.77-1.50 All death and all cause admissions 1116 (74) 1160 (76) 0.94 0.86-1.02 0.122 Poole wilson PA et al.Lancet 2003;362:7-13

NEUROHORMORAL STATE Renin activity CONTROL ASYMPTOMATIC SYMPTOMATIC HEART FAILURE

NEUROHUMORAL CHANGES AFTER 6 W TREATMENT NEUROHORMORAL STATE Renin activity NEUROHUMORAL CHANGES AFTER 6 W TREATMENT Angiotensin Aldosterone PNA Norepinephrine

NEUROHORMORAL STATE Renin activity SURVIVAL SURVIVAL % MORTALITY % Months Months

Asymptomatic dysfunction post AMI NEUROHORMORAL STATE Renin activity SURVIVAL Asymptomatic dysfunction post AMI MORTALITY % N 2231 3 –16 days post AMI EF < 41% YEARS

NEUROHORMORAL STATE Renin activity Placebo Better Enalapril Better EJECTION FRACTION % SOLVD TREATMENT % DEATH RISK REDUCTION

NEUROHORMORAL STATE Post Trial Benefits SOLVD PREVENTION ENALAPRIL N 2111 PLACEBO N 2117 HR IC 95 % P ALL CAUSE MORTALITY 1074 (50.9) 1195 (56.4) 0.86 0.79-0.93 0.001 SOLVD TREATMENT ENALAPRIL N 1285 PLACEBO N 1284 HR IC 95 % P ALL CAUSE MORTALITY 1025 (79.8) 1038 (80.8) 0.93 0.85-1.01 0.01 Jong P. Lancet 2003;361:1843-48

Which Dose should we use ? ATLAS Study Low dose High dose Hazard Ratio P All cause mortality 717 (44.9) 666 (42.5) 0.92 (0.82-1.03) 0.128 Cardiovascular mortality 641 (40.2) 583 (37.2) 0.90 (0.81-1.01) 0.073 All cause mortality + Hospitalization any reason 1338 (83.8) 1250 (79.7) 0.88 (0.82-0.96) 0.002 Hospitalization CV reason 1182 (74.1) 1115 (71.1) 0.92 (0.84-0.99) 0.036 Hospitalization CHF 964 (60.4) 864 (55.1) 0.85 (0.78-0.93) < 0.001

NEUROHORMORAL STATE Angiotensin Receptor Antagonism SURVIVAL Days

Angiotensin Receptor Antagonism ELITE II ELEGILIBILITY CRITERIA Age > 60 years with 85 % > 65 New York Heart association II - IV Ejection Fraction < 40 % 298 Centers in 46 Countries Median Follow up 1.5 years Event-driven superiority trial designed with 90 % power to detect a relative 25 % difference in total mortality beetween treatments. Assumption of annual mortality rate of 9.4 %.

Angiotensin Receptor Antagonism ELITE II LOSARTAN CAPTOPRIL HR IC 95 % P N 1578 1574 TOTAL MORTALITY 280 (17.7) 250 (15.9) 1.13 0.95 – 1.35 0.16 Sudden death 130 (8.2) 101 (6.4) 1.30 1 – 1.69 Progresive HF 46 (2.9) 53 (3.4) 0.88 0.59 – 1.3 TOTAL MORTALITY OR READMISSION 752 (47.7) 707 (44.9) 1.07 0.97 – 1.19 0.18 ANY CAUSE HOSPITAL READMISSION 659 (41.8) 638 (40.5) 1.04 0.94 – 1.16 0.45 HF HOSPITAL READMISSION 270 (17.1) 293 (18.6) 0.92 0.78 – 1.08 0.32

Angiotensin Receptor Antagonism Val-HeFT ELEGILIBILITY CRITERIA RCT, DB, PC, Paralel Groups. 302 Centers in 16 Countries. Age > 18 years AND 3 months with signs and symptoms of HF New york heart Association II – IV. Ejection fraction < 40 % and Left ventricle > 2.9 cm /m2 2 – 4 weeks RUN IN and thenafter Valsartan 40 mg twice up to 160 mg twice. Follow up planned at 2 – 4 – 6 months and then after 3 months Primary end point : TOTAL MORTALITY and MORTALITY + MORBIDITY (Sudden death-HF Hospitalization-Inotropic drugs > 4 hs Cohn J. N Engl J Med 2001;345:1667-75

Val-HeFT All Cause Mortality Months of FU (Time from randomization) 1.0 P = 0.8 0.9 % Survival 0.8 VALSARTAN PLACEBO 0.7 3 6 9 12 15 18 21 24 27 Months of FU (Time from randomization)

Val-HeFT Morbidity & Mortality Months of FU (Time from randomization) 1.0 Risk Reduction: 13,3 % p = 0.009 0.9 0.8 % Survival 0.7 0.6 VALSARTAN PLACEBO 3 6 9 12 15 18 21 24 27 Months of FU (Time from randomization)

Val-HeFT Heart Failure Hospitalization 1.0 Risk Reduction: 27,5 % p = 0.00001 0.9 % Survival 0.8 VALSARTAN PLACEBO 0.7 3 6 9 12 15 18 21 24 27 Months of FU (Time from randomization)

CHARM OVERALL Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity

SPIRONOLACTONE Randomized ALdactone Evaluation Study PLACEBO SPIRONOLACTONE N 841 822 Age 65 ± 12 Male / Female 73 / 27 NYHA II/III/IV 0.4 / 69 / 31 0.5 / 72 / 27 ACE Previous (%) 94 95 Beta Blockers (%) 10 11 Diuretics (%) 100 Digitalis (%) 72 75 Ejection Fraction (%) 25.2 ± 6.8 25.6 ± 6.7 Systolic Pressure 122 ± 20 123 ± 21 Diastolic Pressure 75 ± 11 75 ± 12

SPIRONOLACTONE Randomized ALdactone Evaluation Study RELATIVE RISK OF DEATH PLACEBO SPIRONOLACTONE HR IC 95 % P N 841 822 TOTAL MORTALITY 386 284 0.70 0.60 – 0.82 <0.001 CARDIAC CAUSES Progression of HF Sudden death AMI 314 189 110 15 226 127 82 17 0.69 0.64 0.71 0.58 – 0.82 0.51 – 0.80 0.54 – 0.95 OTHER CV CAUSES 13 12 STROKE 11 8 NON CV CAUSES 41 29 UNKNOWN 7 9

SPIRONOLACTONE Randomized ALdactone Evaluation Study RELATIVE RISK OF HOSPITALIZATION PLACEBO SPIRONOLACTONE HR IC 95 % P N 841 822 CARDIAC CAUSES Worsening HF Angina Ventricular arrhytmia AMI 336 / 753 330 / 663 35 / 44 24 / 31 14 / 15 260 / 515 215 / 413 43 / 66 23 / 25 10 / 11 0.70 0.65 0.59-0.82 0.54-0.77 <0.001 OTHER CV CAUSES 112 / 163 117 / 169 STROKE 20 / 24 NON CV CAUSES 232 / 377 223 / 361

SPIRONOLACTONE Randomized ALdactone Evaluation Study 1.0 0.9 0.8 0.7 0.6 0.5 Annual Mortality Aldactone 18%; Placebo 23% Survival Aldactone N = 1663 NYHA III-IV Mean follow-up 2 y p < 0.0001 RALES NEJM 1999;341:709 months Placebo 6 12 18 24 30 36

Una historia de éxitos Masoudi FA, Havranek EP, Wolfe P, et al. Aunque no para todos…. ARTICLES Most hospitalized older persons do not meet the enrollment criteria for clinical trials in heart failure. Masoudi FA, Havranek EP, Wolfe P, et al. Masoudi FA. Am Heart J 2003;146:250-7

Insuficiencia Cardíaca / Ancianidad / Comorbilidad 20,338 “Pacientes mundo real” (VA) SOLVD 18 % MERIT HF 13 % RALES 25 % Masoudi FA. Am Heart J 2003;146:250-7

Insuficiencia Cardíaca / Ancianidad / Comorbilidad TODOS 65-69 70-74 75-79 80-84 85 p IECA (SOLVD) Todos 18 32 30 27 <0.001 Hombres 23 38 35 Mujeres 13 25  Bloqueantes (MERIT HF) 21 22 0.02 17 26 24 NS 11 19 Espironolactona (RALES) 31 29 37 28 20 16 Masoudi FA. Am Heart J 2003;146:250-7

The EVEREST Outcome Trial. ARTICLES Effects of Oral Tolvaptan in Patients Hospitalized for Worsening Heart Failure. The EVEREST Outcome Trial. Konstan M JAMA March 28 2007, 297,12:1319

ANEMIA AND CONGESTIVE HEART FAILURE A staircase to construct knowledge Time to enroll patients in big RCT Small RCT demonstrate benefits Clear association between anemia & mortality / morbidity and quality of life Prevalence of anemia is related to HF severity Anemia is highly prevalent in HF

ANEMIA AND CONGESTIVE HEART FAILURE A staircase to construct knowledge Time to enroll patients in big RCT Small RCT demonstrate benefits Clear association between anemia & mortality / morbidity and quality of life Prevalence of anemia is related to HF severity Anemia is highly prevalent in HF

ANEMIA AND CONGESTIVE HEART FAILURE Prevalence of anemia in CHF patients The prevalence of anemia in heart failure patients is approximately: 30% for In-patients 20% for Out-patients Atencion: El dato del valheft (10%) es de un abstract a un europeo con 11 y 12 g de hb como cuttpoints. En circulation despues se publica 23% porque usan 13g para hombres y 12 para mujeres… OPTIME-CHF (Hb<13 -<12 g/dl) STAMINA-CHF (Hb<13 -<12 g/dl) McClellan (Hct<40%) Androne (Hct<41% - 38%) Silverberg (Hb<12 g/dl) Euro HF survey (Hb<11g/dl) RENAISSANCE (Hb<11g/dl COPERNICUS (Hb<12.5 g/dl) Val-HeFT (Hb<12 -<11 g/dl) Wexler (Hb<12 g/dl) Wisniacki (Hb<12 g/dl) Kosiborod (Hct<37%) Horwich (Hb<13 -<12 g/dl) Herzog (ICD-9 Codes) PRAISE (Hct<37.6%) ELITE II (Hb<12.5 g/dl) Szachniewicz (Hb<11g/dl) Ezekowitz (ICD-9 Codes) IN-CHF (Hb<12 -<11 g/dl) Tanner (Hb<12 g/dl) Cromie (Hb<11g/dl)

ANEMIA AND CONGESTIVE HEART FAILURE A staircase to construct knowledge Time to enroll patients in big RCT Small RCT demonstrate benefits Clear association between anemia & mortality / morbidity and quality of life Prevalence of anemia is related to HF severity Anemia is highly prevalent in HF

ANEMIA AND CONGESTIVE HEART FAILURE Prevalence and CHF severity NYHA I NYHA II NYHA III NYHA IV Hb <10g/dl Hb <11g/dl Hb <11.5g/dl Hb <12.0g/dl Hb <12.5g/dl (N=32) (N=97) (N=165) (N=244) (N=337) Source: STAMINA Registry – 45 General Cardiologist sites, n=673, 12 Academic sites (incl. HF Specialists), n=337

ANEMIA AND CONGESTIVE HEART FAILURE A staircase to construct knowledge Time to enroll patients in big RCT Small RCT demonstrate benefits Clear association between anemia & mortality / morbidity and quality of life Prevalence of anemia is related to HF severity Anemia is highly prevalent in HF

ANEMIA AND CONGESTIVE HEART FAILURE Anemia and all-cause mortality IN CHF HR = 1.54 (1.20 - 1.97) HR = 1.26 (1.04 - 1.52) ANNUALIZED MORTALITY Maggioni AP. J Card Fail 2005;11:91-8

ANEMIA AND CONGESTIVE HEART FAILURE Anemia and death/hospitalization 1.7 1.56 1.6 1.5 1.40 1.4 Relative Risk 1.3 1.2 1.1 1.00 1.02 0.83 At baseline, 15.9% of patients had anaemia according to WHO criteria (males 16.0%; females 15.2%)—3.3% of patients had severe anaemia (Group 1: males 3.6%; females 2.0%) and 12.6% had moderate anaemia (Group 2: males 12.4%; females 13.2%). 0.94 1 0.9 <11.5 11.5 -13.0 13.0-14.0 14.0-15.0 15.0-16.5 >16.5 Hb (g/dL) HR for Death adjusted for age, SBP, NYHA, BMI, EF, Cr, Na, Diabetes, HF duration, Gender and Carvedilol vs Metoprolol Komajda M. Eur Heart J 2006. 27:1440-6.

ANEMIA AND CONGESTIVE HEART FAILURE A staircase to construct knowledge Time to enroll patients in big RCT Small RCT demonstrate benefits Clear association between anemia & mortality / morbidity and quality of life Prevalence of anemia is related to HF severity Anemia is highly prevalent in HF

ANEMIA AND CONGESTIVE HEART FAILURE Small clinical trials results Mean Change in Exercise Duration Mean Change in 6-Minute Walk Distance 6-Minute Walk Distance (feet) Exercise Duration (seconds) P=NS P<0.004 P<0.05 Randomized, placebo-controlled, single-blinded study; N=23 (n=8 for placebo group, n=15 for EPO group) Mancini D. Circulation. 2003;107:294-299.

ANEMIA AND CONGESTIVE HEART FAILURE Anemia is likely to be multifactorial Anemia of Chronic Disease Pharmaco therapy Renal Dysfunction Malnutrition Decreased Cardiac Output Inflammation Bone marrow dysfunction Abnormal iron homeostasis (uptake, release, utilization) Intravascular fluid imbalance (hemodilution) EPO deficiency or resistance

ANEMIA AND CONGESTIVE HEART FAILURE The cardio-renal-anemia syndrome  Cardiac output RAS activation Sympathetic tone  ACE inhibitor therapy Heart Failure Kidney  EPO (relative) Ischemia Apoptosis LVH  Perfusion Malnutrition  TNF alpha Vasoconstriction Hemodilution Bone Marrow Anemia EPO resistance  RBC Production Felker MG. J Am Coll Cardiol 2004;44:959-66

Prevención Primaria MADIT CABG-Patch MUST MADIT II DEFINITE DINAMIT SCD-HeFT MUST MADIT II

Disminución significativa de la mortalidad en el grupo CDI MADIT CDI vs. Tratamiento médico (75% amiodarona) 196 pacientes, > de 3 semanas post IAM Con registro de TVNS asintomática CF I, II o III FEY < 35% Arritmia inducida en EEF que no responde a procainamida EP 1°: Mortalidad por todas las causas Disminución significativa de la mortalidad en el grupo CDI NEJM 1996; 335: 1933-40

CABG-Patch 900 pacientes. CRM programada. FEY < 36%, ateraciones en el ECG de señales promediadas. 82% con antecedente de IAM y 50% con antecedente de IC CDI Vs Tratamiento médico EP 1°: Mortalidad por todas las causas NO hubo diferencia significativa

Sin diferencias en el tratamiento con drogas Vs placebo MUST 704 pacientes con antecedente de enfermedad coronaria, FEY< 40%, TVNS asintomática Arritmia inducida en el EEF. No tratamiento Tratamiento CDI Antiarritmicos Se hizo para ver si la terapia guiada poe EEF tenia beneficio, en elgrupo drogas Vs CDI no fue distribución aleatorizada ni ciega. Reducción significativa del riesgo de paro cardíaco ó muerte arrítmica del 27% con CDI a 5 años Sin diferencias en el tratamiento con drogas Vs placebo

MADIT II 1232 pacientes, > de 1 mes post- IAM Fey < 30% Sin EEF previo CDI Vs Tratamiento médico EP 1°: Mortalidad por todas las causas Reducción significativa del riesgo relativo del 28% con CDI a 2 años HR 0,69 IC 95% (0.51-0.93) p<0.016

MADIT II p<0.016

CDI Vs Tratamiento médico DEFINITE 458 pacientes con miocardiopatía no isquémica, antecedentes de IC Fey < 35%, EV ó TVNS. CDI Vs Tratamiento médico HR 0,2 IC 0,06-0,75 HR 0,65 IC 0,40-1,06

EP 1°: Mortalitada por todas las causas SCD-HeFT 2521 pacientes con IC CF II/III, Fey < 35% 85% antecedentes de cardiopatía isquémica. Grupo control Tratamiento con amiodarona CDI EP 1°: Mortalitada por todas las causas

SCD-HeFT

Indicaciones CDI Disfunción del VI post IAM Cardiopatías congénitas Miocarditis Miocardiopatías infiltrativas/endócrinas Miocardiopatía dilatada Miocardiopatía hipertrófica Displasia arritmogénica del VD Insuficiencia cardíaca Sme. QT largo Sme de brugada TV polimórficas catecolaminnérgicas Arritmias en corazones estructuralmente normales

Resincronización Ventricular 35% de los pacientes con IC presentan trastornos de la conducción intraventricular (25% BRI) La estimulación ventricular sincronizada mejora ó revierte la contracción asincrónica Mejora el perfil hemodinámico a corto plazo Previene el remodelado reverso a largo plazo

Resincronización Ventricular COMPANION CARE - HeFT MUSTIC AF MIRACLE MUSTIC Retin Q PROSPECT Miracle , Mustic y Mustic AF : estudios mas pequeños comparando resincro con tratamiento médico, que dieron beneficios para el resincro en EP subrrogadoos de test de caminata, calidad de vida y consumo de O2.

EP 1°: Muerte ú hospitalización COMPANION 1520 pacientes, IC CF III / IV, Fey < 35%, QRS > 120 mseg Ritmo sinusal Seguimiento al año Tratamiento médico Resincro Resincro + CDI EP 1°: Muerte ú hospitalización

Mortalidad ú hospitalización Mortalidad por todas las causas

CARE HF 830 pacientes con IC CF III / IV, Fey < 35% QRS > 120 mseg Si QRS e/ 120 y 149: criterios ecocardiográficos de disincronía Tratamiento médico óptimo Resincronización ventricular EP 1°: Muerte ú hospitalización de causa cardiovascular

CARE HF Muerte por todas las causas ó reinternación por eventos cardiovasculares Mortalidad por todas las causas

Prospect Especificidad y Sensibilidad de 12 parámetros ecocardiográficos para predecir el EP combinado: muerte por todas las causas, IC, CF y mejoría en la calidad de vida.

INDICACIONES RESINCRO Clase I A Pacientes con IC, Que permanecen sintomáticos a pesar del tratamiento médico óptimo, Ritmo sinusal En CF III / IV QRS > 120 mseg Clase II A Con FA Con dependencia frecuente de MCP Clase II B CF I, II a los que se les implantará MCP ó CDI

1820 pacientes , entre el 2004 y 2008. Antecedentes de cardiopatía isquémica (CF I ó II) ó miocardiopatía NO isquémica (CF II). RS Fey<30% QRS > 130 mseg

Criterios de exclusión Indicaciones para CRT Implante previo de MCP ó CDI CD III / IV CRM previa IAM ó PTCA 3 meses previos FA 1 mes previo

EP 1°: Mortalidad por todas las causas, ó IC Randomización 3:2 CDI Vs CDI + Resincro ECG, Ecocardiograma, examen físico y Test de caminata de 6 minutos pre-randomización Ecocardiograma al año de seguimiento EP 1°: Mortalidad por todas las causas, ó IC