Seattle Heart Failure and Proportional Risk Models Predict Benefit From Implantable Cardioverter-Defibrillators

Abstract

Background: Recent clinical trials highlight the need for better models to identify patients at higher risk of sudden death.

Objectives: The authors hypothesized that the Seattle Heart Failure Model (SHFM) for overall survival and the Seattle Proportional Risk Model (SPRM) for proportional risk of sudden death, including death from ventricular arrhythmias, would predict the survival benefit with an implantable cardioverter-defibrillator (ICD).

Methods: Patients with primary prevention ICDs from the National Cardiovascular Data Registry (NCDR) were compared with control patients with heart failure (HF) without ICDs with respect to 5-year survival using multivariable Cox proportional hazards regression.

Results: Among 98,846 patients with HF (87,914 with ICDs and 10,932 without ICDs), the SHFM was strongly associated with all-cause mortality (p < 0.0001). The ICD-SPRM interaction was significant (p < 0.0001), such that SPRM quintile 5 patients had approximately twice the reduction in mortality with the ICD versus SPRM quintile 1 patients (adjusted hazard ratios [HR]: 0.602; 95% confidence interval [CI]: 0.537 to 0.675 vs. 0.793; 95% CI: 0.736 to 0.855, respectively). Among patients with SHFM-predicted annual mortality ≤5.7%, those with a SPRM-predicted risk of sudden death below the median had no reduction in mortality with the ICD (adjusted ICD HR: 0.921; 95% CI: 0.787 to 1.08; p = 0.31), whereas those with SPRM above the median derived the greatest benefit (adjusted HR: 0.599; 95% CI: 0.530 to 0.677; p < 0.0001).

Conclusions: The SHFM predicted all-cause mortality in a large cohort with and without ICDs, and the SPRM discriminated and calibrated the potential ICD benefit. Together, the models identified patients less likely to derive a survival benefit from primary prevention ICDs.

Keywords: heart failure; implantable cardioverter-defibrillator; risk models.

Figure 1. CONSORT Diagram

A flow diagram showing the derivation of the ICD and Control cohorts is shown. ICD = Implantable Cardioverter Defibrillator.

Figure 2. Overall Survival by SHFM Score in Control and ICD Cohorts

Kaplan-Meier curves demonstrate survival by SHFM in ICD (A) and control (B) cohorts. In both groups, an increase in the SHFM quintile is associated with decreased survival over 5 years. ICD = Implantable Cardioverter Defibrillator; SHFM = Seattle Heart Failure Model; SPRM = Seattle Proportional Risk Model.

Figure 3. Forest Plot for the Effect of the ICD on Survival in Subgroups of Interest

The hazard ratios for death with ICD implantation in subgroups of interests based on covariates of interest are plotted in the figure. Group interaction p-values are shown in addition to the p-value for ICD benefit in each subgroup of interest. ACE = Angiotensin Converting Enzyme; ARB = Angiotensin Receptor Blocker. ICD = Implantable Cardioverter Defibrillator; ICM = Ischemic Cardiomyopathy; LVEF = Left Ventricular Ejection Fraction; NICM = Nonischemic Cardiomyopathy; NYHA = New York Heart Association; SBP = Systolic Blood Pressure.

Figure 4. SPRM and the Improvement in Survival with ICDs

A fitted interaction from the Cox proportional hazards model of the ICD with the SPRM score as a continuous variable is shown with the ICD hazard ratio (solid line) and 95% upper and lower confidence bounds (dashed lines) plotted against the predicted proportional risk of sudden death based on the SPRM. As the SPRM-predicted proportional risk of sudden death increases, the ICD hazard ratio for death becomes more favorable. ICD = Implantable Cardioverter Defibrillator; SHFM = Seattle Heart Failure Model; SPRM = Seattle Proportional Risk Model.

Figure 5. Survival in ICD and Control Cohorts Stratified by SHFM and SPRM

Adjusted survival is shown in 4 groups based on whether SHFM and SPRM are above and below the median (A–D). Differences in life years gained with the ICD in these 4 groups (E) and the years needed to treat to add 1 year of life in the 4 groups (F) are also shown. ICD = Implantable Cardioverter Defibrillator; SHFM = Seattle Heart Failure Model; SPRM = Seattle Proportional Risk Model.

Figure 6. Adjusted Survival at 1 Year and 5 Years by Quintile of SPRM and SHFM

Adjusted 1-year survival with and without ICD implantation is shown for SPRM (A) and SHFM (B). Adjusted survival after 5 years of follow-up with and without ICD implantation is also provided for SPRM (C) and SHFM (D). ICD = Implantable Cardioverter Defibrillator; SHFM = Seattle Heart Failure Model; SPRM = Seattle Proportional Risk Model.

Central Illustration. Seattle Heart Failure Model, Seattle Proportional Risk Model, and ICD Benefit

These models together can be used to predict the survival benefit from the ICD. ICD = Implantable Cardioverter Defibrillator; SCA = Sudden Cardiac Arrest; SHFM = Seattle Heart Failure Model; SPRM = Seattle Proportional Risk Model.