Defining End Stage CMP

Guillermo Torre-Amione MD, PhD

Defining what is End-Stage CMP

1. What is not end-stage

2. What is clearly end-stage

3. Dissecting the ambulatory high risk

1. What is not End stage

Heart Failure and Progression

Heart Failure and Progression

Circulation. 1993;88:2277-2283Circulation. 1992;86:431-438

Mortality rates in Heart Failure

Mortality rates in Heart Failure

LVEF 25%

LVEF 29%

Circulation. 1993;88:2277-2283

Modern Era Mortlity

Primary Endpoint: CV death or HF Hospitalization

N Engl J Med 2014; 371:993-1004

Mortality in asymptomatic untreated patients with LVD

20% at 4 years

SOLVD Prevention

Levy W C et al. Circulation 2006;113:1424-1433

The Seattle Heart Failure Model

2. What is clearly end-stage

Actuarial survival DT vs REMATCH

NEJM 2009;361(23):2241-51. NEJM 2001;345(20):1435-43.

Inotrope dependent patient

VAD

3. Dissecting the high risk ambulatory patient

Where do we draw the line?

INTERMACS PROFILES AND OTHER CLASSIFICATION SYSTEMS

Profile # Description NYHA Class Time to MCS therapyAHA/ACC

Stage

INTERMACS 1 Crashing and burning IV Within hours D

INTERMACS 2 Progressive decline on inotropic support IV Within a few days D

INTERMACS 3 Stable but inotrope dependent IV Within a few weeks D

INTERMACS 4Recurrent advanced heart failure;

resting symptoms at home on oral therapyAmbulatory IV Within weeks to months D

INTERMACS 5 Exertion intolerant Ambulatory IV Variable D

INTERMACS 6 Exertion limited or walking wounded Ambulatory IV Variable C-D

INTERMACS 7 Advanced NYHA III IIIB Variable C

16

Class IIB-IVIntermacs 4-6

Biomarkers

• Cathecolamine levels

• Peristent BNP elevations

• Sodium

• Hemoglobin

• Uric Acid

Prognosis and Peak VO2

Patients were subdivided into quartiles according to peak VO2 (P1:<13.0 ml/kg/min, P2:13.0-16.5 ml/kg/min, P3:16.6-21.6 ml/kg/min, P4: >21.6 ml/kg/min). Their respective Kaplan-Meier survival curves were significantly different ( p<0.0001). Mortalities at 24 months were 48%, 32%, 12%, and 4% respectively.

Francis DP, Shamim W, Davies LC, Ponikowski P, Anker SD, Coats AJS.European Heart Journal 2000 21: 154-161

VE/VCO2 (rate of increase ventilation per carbon dioxide production

Patients were separately subdivided in quartiles according to VE/VCO2 slope (V1:<27.7, V2:27.7-34.5, V3:34.6-42.1, V4: >42.1), whose Kaplan-Meier Survival curves were again distinct from each other (Figure 3, p<0.0001). Mortalities at 24 months were 3%, 17%, 26% and 49% respectively.

Francis DP, Shamim W, Davies LC, Ponikowski P, Anker SD, Coats AJS.European Heart Journal 2000 21: 154-161

Evidence of end-organ damage

• Pulmonary Hypertension

• Liver fibrosis/Cirrhosis

• Renal Failure

Pulmonary Hypertension

Combined Post and Pre Capillary PH

• DPG > 7 mm/h

• PVR > 3 W

European Heart Journal doi:10.1093/eurheartj/ehv317

“Fixed PAH”

• TPG >15 mmHg

• DPG (defined as diastolic PAP − mean PAWP) appears to best approach the characteristics required to determine pulmonary vascular disease. (ESC 2015 guidelines)

European Heart Journal doi:10.1093/eurheartj/ehv317

Anatomy of the Portal System

U Penn

Summary

• Ambulatory low EF: Long life

• Critically ill and needing Inotropes: Poor

• Ambulatory High risk: pulmonary hypertension, portal hypertension, renal dysfunction

• Ongoing registry studies will further define