Seattle proportional risk model in GISSI-HF: Estimated benefit of ICD in patients with EF less than 50.

BACKGROUND: The Seattle Proportional Risk Model (SPRM) estimates the proportion of sudden cardiac death (SCD) in heart failure (HF) patients, identifying those most likely to benefit from implantable cardioverter-defibrillator (ICD) therapy (those with ≥50% estimated proportion of SCD). The GISSI-HF trial tested fish oil and rosuvastatin in HF patients. We used the SPRM to evaluate its accuracy in this cohort in predicting potential ICD benefit in patients with EF ≤50% and an SPRM-predicted proportion of SCD either ≥50% or <50%. METHODS: The SPRM was estimated in patients with EF ≤50% and in a logistic regression model comparing SCD with non-SCD. RESULTS: We evaluated 6,750 patients with EF ≤50%. There were 1,892 all-cause deaths, including 610 SCDs. Fifty percent of EF ≤35% patients and 43% with EF 36% to 50% had an SPRM of ≥50%. The SPRM (OR: 1.92, P < 0.0001) accurately predicted the risk of SCD vs non-SCD with an estimated proportion of SCD of 44% vs the observed proportion of 41% at 1 year. By traditional criteria for ICD implantation (EF ≤35%, NYHA class II or III), 64.5% of GISSI-HF patients would be eligible, with an estimated ICD benefit of 0.81. By SPRM >50%, 47.8% may be eligible, including 30.2% with EF >35%. GISSI-HF participants with EF ≤35% with SPRM ≥50% had an estimated ICD HR of 0.64, comparable to patients with EF 36% to 50% with SPRM ≥50% (HR: 0.65). CONCLUSIONS: The SPRM discriminated SCD vs non-SCD in GISSI-HF, both in patients with EF ≤35% and with EF 36% to 50%. The comparable estimated ICD benefit in patients with EF ≤35% and EF 36% to 50% supports the use of a proportional risk model for shared decision making with patients being considered for primary prevention ICD therapy.

Sudden Cardiac Death in Heart Failure: A 20-Year Perspective From a Mediterranean Cohort.

BACKGROUND: The prediction of sudden cardiac death (SCD) in heart failure (HF) remains an unmet need. The aim of our study was to assess the prevalence of SCD over 20 years in outpatients with HF managed in a Mediterranean multidisciplinary HF Clinic, and to compare the proportion of SCD (SCD/all-cause death) to the expected proportional occurrence based on the validated Seattle Proportional Risk Model (SPRM) score. METHODS AND RESULTS: This prospective observational registry study included 2772 outpatients with HF admitted between August 2001 and May 2021. Patients were included when the cause of death was known and SPRM score was available. Over the 20-year study period, 1351 patients (48.7%) died during a median follow-up period of 3.8 years (interquartile range 1.6-7.6). Among these patients, the proportion of SCD out of the total of deaths was 13.6%, whereas the predicted by SPRM was 39.6%. This lower proportion of SCD was observed independently of left ventricular ejection fraction, ischemic etiology, and the presence of an implantable cardiac defibrillator. CONCLUSIONS: In a Mediterranean cohort of outpatients with HF, the proportion of SCD was lower than expected based on the SPRM score. Future studies should investigate to what extend epidemiological and guideline-directed medical therapy patterns influence SCD.

An updated systematic review on heart failure treatments for patients with renal impairment: the tide is not turning.

Advanced chronic kidney disease (CKD) frequently aggravates heart failure (HF). However, these patients have inherently been excluded from most HF trials. We aim to provide updated estimates of the representation of patients with advanced CKD and the provision of baseline renal function indices in HF trials with a focused interest on the landmark trials. Updated systematic review was performed from the inception of MEDLINE to 31 December 2019 to identify all chronic HF randomized trials published in the three major cardiology and medical journals, respectively, which included mortality endpoint. The included studies were analysed based on the representativeness of the advanced CKD population and the reporting of baseline renal function. A total of 187 eligible randomized trials with 322,374 participants were included in our analysis. One hundred and six trials (56.7%) had exclusion criteria related to renal function, which remained a continuing trend-55.1% (27/49) from inception-2000, 53.4% (39/73) from 2001-2010 and 61.5% (40/65) from 2011 (P = 0.64). The exclusion criteria, however, have become less restrictive. There was a temporal improvement in the likelihood of HF trials in providing baseline renal function indices (28.6% from inception-2000 versus 53.4% from 2001-2010 and 83.1% from 2011, P < 0.001). Concordant findings were observed in the landmark trials. Patients with advanced CKD remain underrepresented in HF trials in the contemporary era, even though the exclusion criteria have become less restrictive, and the quality of renal function monitoring has improved. The continued underrepresentation of patients with advanced CKD in HF trials merits measured broadening of eligibility in further trial studies.

Prognostic usefulness of planar 123I-MIBG scintigraphic images of myocardial sympathetic innervation in congestive heart failure: Follow-Up data from ADMIRE-HF.

BACKGROUND: To evaluate whether planar 123I-MIBG myocardial scintigraphy predicts risk of death in heart failure (HF) patients up to 5 years after imaging. METHODS AND RESULTS: Subjects from ADMIRE-HF were followed for approximately 5 years after imaging (964 subjects, median follow-up 62.7 months). Subjects were stratified according to the heart/mediastinum (H/M) ratio (< 1.60 vs ≥ 1.60) on planar 123I-MIBG scintigraphic images obtained at baseline in ADMIRE-HF. Cox proportional hazards models and Kaplan-Meier analyses were used to evaluate time to death, cardiac death, or arrhythmic events for subjects stratified by H/M ratio, baseline left ventricular ejection fraction (LVEF: < 25% and 25 to ≤ 35%), and by H/M strata within LVEF strata. All-cause mortality was 38.4% vs 20.9% and cardiac mortality was 16.8% vs 4.5%, in subjects with H/M < 1.60 vs ≥ 1.60, respectively (P < 0.05 for both comparisons). Subjects with preserved sympathetic innervation of the myocardium (H/M ≥ 1.60) were at significantly lower risk of all-cause and cardiac death, arrhythmic events, sudden cardiac death, or potentially life-threatening arrhythmias. Within LVEF strata, a trend toward a higher mortality for subjects with H/M < 1.60 was observed reaching significance for LVEF 25 to ≤ 35% only. CONCLUSIONS: During a median follow-up of 62.7 months, patients with H/M ≥ 1.60 were at significantly lower risk of death and arrhythmic events independently of LVEF values.

Time trends in sudden cardiac death risk in heart failure patients with cardiac resynchronization therapy: a systematic review.

AIMS: While data from randomized trials suggest a declining incidence of sudden cardiac death (SCD) among heart failure patients, the extent to which such a trend is present among patients with cardiac resynchronization therapy (CRT) has not been evaluated. We therefore assessed changes in SCD incidence, and associated factors, in CRT recipients over the last 20 years. METHODS AND RESULTS: Literature search from inception to 30 April 2018 for observational and randomized studies involving CRT patients, with or without defibrillator, providing specific cause-of-death data. Sudden cardiac death was the primary endpoint. For each study, rate of SCD per 1000 patient-years of follow-up was calculated. Trend line graphs were subsequently constructed to assess change in SCD rates over time, which were further analysed by device type, patient characteristics, and medical therapy. Fifty-three studies, comprising 22 351 patients with 60 879 patient-years of follow-up and a total of 585 SCD, were included. There was a gradual decrease in SCD rates since the early 2000s in both randomized and observational studies, with rates falling more than four-fold. The rate of decline in SCD was steeper than that of all-cause mortality, and accordingly, the proportion of deaths which were due to SCD declined over the years. The magnitude of absolute decline in SCD was more prominent among CRT-pacemaker (CRT-P) patients compared to those receiving CRT-defibrillator (CRT-D), with the difference in SCD rates between CRT-P and CRT-D decreasing considerably over time. There was a progressive increase in age, use of beta-blockers, and left ventricular ejection fraction, and conversely, a decrease in QRS duration and antiarrhythmic drug use. CONCLUSION: Sudden cardiac death rates have progressively declined in the CRT heart failure population over time, with the difference between CRT-D vs. CRT-P recipients narrowing considerably.

Modeling defibrillation benefit for survival among cardiac resynchronization therapy defibrillator recipients.

BACKGROUND: Patients with heart failure having a low expected probability of arrhythmic death may not benefit from implantable cardioverter defibrillators (ICDs). OBJECTIVE: The objective was to validate models to identify cardiac resynchronization therapy (CRT) candidates who may not require CRT devices with ICD functionality. METHODS: Heart failure (HF) patients with CRT-Ds and non-CRT ICDs from the National Cardiovascular Data Registry and others with no device from 3 separate registries and 3 heart failure trials were analyzed using multivariable Cox proportional hazards regression for survival with the Seattle Heart Failure Model (SHFM; estimates overall mortality) and the Seattle Proportional Risk Model (SPRM; estimates proportional risk of arrhythmic death). RESULTS: Among 60,185 patients (age 68.6 ±â€¯11.3 years, 31.9% female) meeting CRT-D criteria, 38,348 had CRT-Ds, 11,389 had non-CRT ICDs, and 10,448 had no device. CRT-D patients had a prominent adjusted survival benefit (HR 0.52, 95% CI 0.50-0.55, P < .0001 versus no device). CRT-D patients with SHFM-predicted 4-year survival ≥81% (median) and a low SPRM-predicted probability of an arrhythmic mode of death ≤42% (median) had an absolute adjusted risk reduction attributable to ICD functionality of just 0.95%/year with the majority of survival benefit (70%) attributable to CRT pacing. In contrast, CRT-D patients with SHFM-predicted survival median had substantially more ICD-attributable benefit (absolute risk reduction of 2.6%/year combined; P < .0001). CONCLUSIONS: The SPRM and SHFM identified a quarter of real-world, primary prevention CRT-D patients with minimal benefit from ICD functionality. Further studies to evaluate CRT pacemakers in these low-risk CRT candidates are indicated.

Prediction of sudden cardiac death in Japanese heart failure patients: international validation of the Seattle Proportional Risk Model.

AIMS: Heart failure (HF) is associated with an increased risk of sudden cardiac death (SCD). This study sought to demonstrate the incidence of SCD within a multicentre Japanese registry of HF patients hospitalized for acute decompensation, and externally validate the Seattle Proportional Risk Model (SPRM). METHODS AND RESULTS: We consecutively registered 2240 acute HF patients from academic institutions in Tokyo, Japan. The discrimination and calibration of the SPRM were assessed by the c-statistic, Hosmer-Lemeshow statistic, and visual plotting among non-survivors. Patient-level SPRM predictions and implantable cardioverter-defibrillator (ICD) benefit [ICD estimated hazard ratio (HR), derived from the Cox proportional hazards model in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)] was calculated. During the 2-year follow-up, 356 deaths (15.9%) occurred, which included 76 adjudicated SCDs (3.4%) and 280 non-SCDs (12.5%). The SPRM showed acceptable discrimination [c-index = 0.63; 95% confidence interval (CI) 0.56-0.70], similar to that of original SPRM-derivation cohort. The calibration plot showed reasonable conformance. Among HF patients with reduced ejection fraction (EF; < 40%), SPRM showed improved discrimination compared with the ICD eligibility criteria (e.g. New York Heart Association functional Class II-III with EF ≤ 35%): c-index = 0.53 (95% CI 0.42-0.63) vs. 0.65 (95% CI 0.55-0.75) for SPRM. Finally, in the subgroup of 246 patients with both EF ≤ 35% and SPRM-predicted risk of ≥ 42.0% (SCD-HeFT defined ICD benefit threshold), mean ICD estimated HR was 0.70 (30% reduction of all-cause mortality by ICD). CONCLUSION: The cumulative incidence of SCD was 3.4% in Japanese HF registry. The SPRM performed reasonably well in Japanese patients and may aid in improving SCD prediction.

Validation and Recalibration of Seattle Heart Failure Model in Japanese Acute Heart Failure Patients.

BACKGROUND: Precise risk stratification in heart failure (HF) patients enables clinicians to tailor the intensity of their management. The Seattle Heart Failure Model (SHFM), which uses conventional clinical variables for its prediction, is widely used. We aimed to externally validate SHFM in Japanese HF patients with a recent episode of acute decompensation requiring hospital admission. METHODS AND RESULTS: SHFM was applied to 2470 HF patients registered in the West Tokyo Heart Failure and National Cerebral And Cardiovascular Center Acute Decompensated Heart Failure databases from 2006 to 2016. Discrimination and calibration were assessed with the use of the c-statistic and calibration plots, respectively, in HF patients with reduced ejection fraction (HFrEF; <40%) and preserved ejection fraction (HFpEF; ≥40%). In a perfectly calibrated model, the slope and intercept would be 1.0 and 0.0, respectively. The method of intercept recalibration was used to update the model. The registered patients (mean age 74 ± 13 y) were predominantly men (62%). Overall, 572 patients (23.2%) died during a mean follow-up of 2.1 years. Among HFrEF patients, SHFM showed good discrimination (c-statistic = 0.75) but miscalibration, tending to overestimate 1-year survival (slope = 0.78; intercept = -0.22). Among HFpEF patients, SHFM showed modest discrimination (c-statistic = 0.69) and calibration, tending to underestimate 1-year survival (slope = 1.18; intercept = 0.16). Intercept recalibration (replacing the baseline survival function) successfully updated the model for HFrEF (slope = 1.03; intercept = -0.04) but not for HFpEF patients. CONCLUSIONS: In Japanese acute HF patients, SHFM showed adequate performance after recalibration among HFrEF patients. Using prediction models to tailor the care for HF patients may improve the allocation of medical resources.

Predicting Survival in Patients With Heart Failure With an Implantable Cardioverter Defibrillator: The Heart Failure Meta-Score.

BACKGROUND: Prognostic evaluation in heart failure (HF) is important to predict future events and decide timely management. Many HF patients are treated with the use of an implantable cardioverter-defibrillator (ICD). This study aimed to validate a meta-analytically derived prognostic score to predict survival in ICD-HF patients. METHODS AND RESULTS: The HF Meta-score includes 14 independent mortality predictors identified in a meta-analysis, including age, sex, ethnicity, diabetes, chronic obstructive pulmonary disease, peripheral vascular disease, atrial fibrillation, ischemic cardiomyopathy, history of HF admission, New York Heart Association functional class, left ventricular ejection fraction, renal function, QRS duration, secondary prevention indication, and ICD shocks. The HF Meta-score performance was evaluated in comparison with the Seattle Heart Failure Model (SHFM) and the SHOCKED predictors in a cohort of 9860 ambulatory ICD patients from the Ontario provincial database for 2007-2011. During 3-year follow-up, 1816 patients died. The HF Meta-score showed excellent calibration, very good discrimination (c-statistic 0.74) and enhanced risk classification compared with the SHOCKED predictors, with better reclassifying in 19% and 56% of patients for 1- and 3-year survival, respectively. HF Meta-score performance was similar to the SHFM. CONCLUSIONS: The HF Meta-score is an evidence-based derived model that provides an accurate prognosis assessment in HF patients with ICDs. Its development strategy permits further incorporation of new predictors when evidence becomes available.

Adverse Effects of Delayed Transplant Listing Among Patients With Implantable Left Ventricular Assist Devices.

BACKGROUND: The timing of transplant listing after implantation of a left ventricular assist device (LVAD) remains uncertain, given high device complication rates and apparent stability of some LVAD-supported patients. This investigation quantifies the effect of delayed transplant listing and transplantation rates on medium-term survival and LVAD complications. METHODS AND RESULTS: A Markov model was used to simulate the effects of delaying initial transplant listing after LVAD implantation. Modeled parameters were derived from the Standard Transplant Analysis and Research file. When transplant listing was delayed and 5-year results were examined, fewer persons underwent transplantation (53% in base model vs 51% in 180-day-delay model) and the fraction of deaths while waiting increased (17% in base model vs 21% in 180-day delay model). Life expectancy changed minimally from the base model (3.50 y) when initial listing was delayed by 180 days (3.51 y). CONCLUSIONS: Delaying initial transplant listing increased the likelihood of death while waiting for a transplant and decreased the likelihood of transplantation. In aggregate, life expectancy was unchanged by delays in listing. This study suggests that delaying transplant listing with the expectation of providing additional life expectancy is not likely with current LVAD technology.

An Appraisal of Biomarker-Based Risk-Scoring Models in Chronic Heart Failure: Which One Is Best?

PURPOSE OF REVIEW: While prediction models incorporating biomarkers are used in heart failure, these have shown wide-ranging discrimination and calibration. This review will discuss externally validated biomarker-based risk models in chronic heart failure patients assessing their quality and relevance to clinical practice. RECENT FINDINGS: Biomarkers may help in determining prognosis in chronic heart failure patients as they reflect early pathologic processes, even before symptoms or worsening disease. We present the characteristics and describe the performance of 10 externally validated prediction models including at least one biomarker among their predictive factors. Very few models report adequate discrimination and calibration. Some studies evaluated the additional predictive value of adding a biomarker to a model. However, these have not been routinely assessed in subsequent validation studies. New and existing prediction models should include biomarkers, which improve model performance. Ongoing research is needed to assess the performance of models in contemporary patients.

Application and comparison of the FADES, MADIT, and SHFM-D risk models for risk stratification of prophylactic implantable cardioverter-defibrillator treatment.

AIMS: Implantable cardioverter-defibrillator (ICD) treatment is beneficial in selected patients. However, it remains difficult to accurately predict which patients benefit most from ICD implantation. For this purpose, different risk models have been developed. The aim was to validate and compare the FADES, MADIT, and SHFM-D models. METHODS AND RESULTS: All patients receiving a prophylactic ICD at the Leiden University Medical Center were evaluated. Individual model performance was evaluated by C-statistics. Model performances were compared using net reclassification improvement (NRI) and integrated differentiation improvement (IDI). The primary endpoint was non-benefit of ICD treatment, defined as mortality without prior ventricular arrhythmias requiring ICD intervention. A total of 1969 patients were included (age 63 ± 11 years; 79% male). During a median follow-up of 4.5 ± 3.9 years, 318 (16%) patients died without prior ICD intervention. All three risk models were predictive for event-free mortality (all: P < 0.001). The C-statistics were 0.66, 0.69, and 0.75, respectively, for FADES, MADIT, and SHFM-D (all: P < 0.001). Application of the SHFM-D resulted in an improved IDI of 4% and NRI of 26% compared with MADIT; IDI improved 11% with the use of SHFM-D instead of FADES (all: P < 0.001), but NRI remained unchanged (P = 0.71). Patients in the highest-risk category of the MADIT and SHFM-D models had 1.7 times higher risk to experience ICD non-benefit than receive appropriate ICD interventions [MADIT: mean difference (MD) 20% (95% CI: 7-33%), P = 0.001; SHFM-D: MD 16% (95% CI: 5-27%), P = 0.005]. Patients in the highest-risk category of FADES were as likely to experience ICD intervention as ICD non-benefit [MD 3% (95% CI: -8 to 14%), P = 0.60]. CONCLUSION: The predictive and discriminatory value of SHFM-D to predict non-benefit of ICD treatment is superior to FADES and MADIT in patients receiving prophylactic ICD treatment.

Improved outcome with repeated intracoronary injection of bone marrow-derived cells within a registry: rationale for the randomized outcome trial REPEAT.

AIMS: Regenerative therapies have evolved as a promising new option in the treatment of post-infarction heart failure. A major limitation of intracoronary application of autologous bone marrow-derived mononuclear cells (BM-MNCs) is that homing of the applied cells is profoundly reduced in patients with post-infarction heart failure compared with patients with acute myocardial infarction. However, early pilot and also randomized controlled trials have demonstrated significant improvements in overall cardiac function. The aim of the present analysis was to quantify a potential mortality risk reduction and reduced hospitalization in order to provide data for a prospective outcome trial. METHODS AND RESULTS: The results of an ongoing single-centre registry including 297 post-infarction heart failure patients suggest that repeated intracoronary application of autologous bone marrow-derived cells is associated with a significant better 2-year survival compared with a single BM-MNC application (2-year survival 93.6 vs. 84.0%, P = 0.03). Likewise, mortality is significantly lower at 2-year follow-up compared with the mortality estimated by the use of the Seattle Heart Failure Model (SHFM) in patients receiving repeated BM-MNC application (observed mortality 6.4%, predicted mortality 16.2%, P = 0.02). Although the trend persisted at 3-year follow-up, the mortality reduction was no longer statistically significant between single and repeated treatment (mortality 21.9 vs. 13.7%, P = 0.06). CONCLUSION: Repeated intracoronary administration of BM-MNC appears to be associated with improved clinical outcome compared with single treatment at 2 years. This registry provides the rationale for the design of the multicentre randomized, controlled, open-label REPEAT trial, which prospectively compares the effects of single vs. repeated intracoronary application of autologous BM-MNC on total and SHFM-predicted mortality in patients with chronic post-infarction heart failure.

Prognostic Impact of Implementation of QRS Characteristics in the Seattle Heart Failure Model in ICD and CRT-D Recipients.

BACKGROUND: The Seattle Heart Failure Model (SHFM) provides accurate estimates of survival in heart failure (HF) patients. The model is, however, not developed for HF patients with cardiac resynchronization therapy (CRT). The aim of this study was to assess the prognostic value of SHFM combined with QRS morphology and CRT-related change in QRS duration in implantable cardioverter defibrillator (ICD) and CRT defibrillator (CRT-D) recipients. METHODS: All patients who underwent prophylactic ICD implantation at the Leiden University Medical Center since 1996 were included. Baseline SHFM, QRS morphology, and duration before and after device implantation were determined. The regression coefficients of the QRS characteristics derived from a Cox regression analysis were implemented in the SHFM. SHFM-estimated survival was compared with Kaplan-Meier observed survival. RESULTS: The current study includes 1,834 defibrillator recipients (63 ± 11 years; 79% male; 53% CRT-D). In 585 (60%) CRT-D recipients a left bundle branch block was present, the mean QRS duration was 147 ± 31 ms before and 151 ± 27 ms after device implantation. After a median follow-up of 4.4 years (25(th) -75(th) percentile 2.7-6.4 years), 285 (29%) CRT-D recipients had died. CRT-related decrease in QRS duration adjusted for QRS morphology was associated with improved survival (hazard ratio 1.05/10 ms; 95% confidence interval [CI]: 1.01-1.09; P = 0.02). The estimated 5-year survival of CRT-D recipients after implementation of the QRS characteristic was 70%, and comparable with the observed 5-year survival of 68% (95% CI: 65-72). CONCLUSION: Implementation of native QRS morphology and change in QRS duration due to CRT in the SHFM improves the prognostic value of this model in HF patients with CRT-D.

The effect of duration of follow-up and presence of competing risk on lifespan-gain from implantable cardioverter defibrillator therapy: who benefits the most?

BACKGROUND: In at-risk patients with left ventricular dysfunction, implantable cardioverter defibrillators (ICDs) prolong life. Implantable cardioverter defibrillators are increasingly implanted for primary prevention and therefore into lower risk patients. Trial data have demonstrated the benefit of these devices but does not provide an estimate of potential lifespan-gain over longer time periods, e.g. a patient's lifespan. METHODS: Using data from landmark ICD trials, lifespan-gain was plotted against baseline annual mortality in the individual trials. Lifespan-gain was then extrapolated to a time-horizon of >20 years while adjusting for increasing 'competing' risk from ageing and non-sudden cardiac death (pump failure). RESULTS: At 3 years, directly observed lifespan-gain was strongly dependent on baseline event rate (r = 0.94, P < 0.001). However, projecting beyond the duration of the trial, lifespan-gain increases rapidly and non-linearly with time. At 3 years, it averages 1.7 months, but by 10 years up to 9-fold more. Lifespan-gain over time horizons >20 years were greatest in lower risk patients (∼5 life-years for 5% baseline mortality, ∼2 life-years for 15% baseline mortality). Increased competing risks significantly reduce lifespan-gain from ICD implantation. CONCLUSION: While high-risk patients may show the greatest short-term gain, the dramatic growth of lifespan-gain over time means that it is the lower risk patients, e.g. primary prevention ICD implantation, who gain the most life-years over their lifetime. Benefit is underestimated when only trial data are assessed as trials can only maintain randomization over limited periods. Lifespan-gain may be further increased through advances in ICD device programming.

Mortality prediction using a modified Seattle Heart Failure Model may improve patient selection for ventricular tachycardia ablation.

BACKGROUND: Catheter ablation is frequently used as a palliative option to reduce shock burden in patients with ventricular tachycardia (VT). A risk prediction tool that accurately predicts short-term survival could improve patient selection for VT ablation. OBJECTIVE: The objective of the study is to assess utility of the Seattle Heart Failure Model (SHFM) to predict 6-month mortality in patients undergoing VT ablation. METHODS: Data on patients who underwent VT ablation at 2 tertiary institutions were retrospectively compiled. The SHFM score at the time of ablation, including 2 added VT variables, was used to predict 6-month mortality. The predicted number of deaths was compared to the observed number to assess model calibration. Model discrimination of those who died within 6 months was assessed by both K- and C-statistics. RESULTS: Mean age of the 243 patients was 63 ± 12 years; 89% were male. Mean SHFM score for the cohort was 1.3 ± 1.3. The Kaplan-Meier probability of death within 6 months was 14% (34 patients). The number of deaths estimated by the SHFM at 6 months was 31 (13%) giving a predicted to observed ratio of 0.91 (95% CI 0.64-1.30). The K-statistic for 6-month mortality predictions was 0.77 (95% CI 0.73-0.81), whereas the C-statistic was 0.84 (95% CI 0.78-0.92). Patients with an SHFM score ≥4.0 had an estimated positive predictive value of 80% (95% CI 28%-99%) for dying within 6 months of VT ablation. CONCLUSION: The SHFM was well calibrated to a sample of patients who underwent VT ablation and provided good discrimination of short-term deaths. This model could be useful as a prognostic tool to improve patient selection for VT ablation.

Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model: A Web-based program designed to evaluate the cost-effectiveness of disease management programs in heart failure.

BACKGROUND: Heart failure disease management programs can influence medical resource use and quality-adjusted survival. Because projecting long-term costs and survival is challenging, a consistent and valid approach to extrapolating short-term outcomes would be valuable. METHODS: We developed the Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model, a Web-based simulation tool designed to integrate data on demographic, clinical, and laboratory characteristics; use of evidence-based medications; and costs to generate predicted outcomes. Survival projections are based on a modified Seattle Heart Failure Model. Projections of resource use and quality of life are modeled using relationships with time-varying Seattle Heart Failure Model scores. The model can be used to evaluate parallel-group and single-cohort study designs and hypothetical programs. Simulations consist of 10,000 pairs of virtual cohorts used to generate estimates of resource use, costs, survival, and incremental cost-effectiveness ratios from user inputs. RESULTS: The model demonstrated acceptable internal and external validity in replicating resource use, costs, and survival estimates from 3 clinical trials. Simulations to evaluate the cost-effectiveness of heart failure disease management programs across 3 scenarios demonstrate how the model can be used to design a program in which short-term improvements in functioning and use of evidence-based treatments are sufficient to demonstrate good long-term value to the health care system. CONCLUSION: The Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model provides researchers and providers with a tool for conducting long-term cost-effectiveness analyses of disease management programs in heart failure.

Predictors of clinical outcomes in acute decompensated heart failure: Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure outcome models.

BACKGROUND: Patients hospitalized for acute decompensated heart failure (ADHF) are at high risk for early mortality and rehospitalization. Risk stratification of ADHF using clinically available data on admission is increasingly important to integrate with clinical pathways. Our goal was to create a simple method of screening patients upon admission to identify those with increased risk of future adverse events. METHODS: Using ASCEND-HF, a pragmatic clinical trial conducted in 398 sites globally, we developed and validated logistic regression risk models for (a) 30-day mortality/HF rehospitalization, (b) 30-day mortality/all-cause rehospitalization, (c) 30-day all-cause mortality, and (d) 180-day all-cause mortality. Fifty-one candidate variables were evaluated based on prior publications and clinical review. Final models were selected based on stepwise selection with entry and a staying criterion of P < .01. The 30-day mortality model was externally validated, and coefficients were converted to an additive risk score. RESULTS: Among 7,141 patients, the median age was 67 years, 34% were female, and 80% had a left ventricular ejection fraction <40%. The models had between 5 and 12 risk factors with c-indices ranging from 0.68 to 0.75. A simplified score, including age, systolic blood pressure, sodium, blood urea nitrogen, and dyspnea at rest, discriminated 30-day mortality risk from 0.5% (score 0) to 53% (score 10). CONCLUSIONS: Commonly available clinical variables provide simple risk stratification for clinical outcomes among patients with ADHF, and these models may be considered for integration into routine clinical care.

Associations between seattle heart failure model scores and medical resource use and costs: findings from HF-ACTION.

BACKGROUND: Prognostic models, such as the Seattle Heart Failure Model (SHFM), have been developed to predict patient survival. The extent to which they predict medical resource use and costs has not been explored. In this study, we evaluated relationships between baseline SHFM scores and 1-year resource use and costs using data from a clinical trial. METHODS AND RESULTS: We applied generalized linear models to examine the relative impact of a 1-unit increase in SHFM scores on counts of medical resource use and direct medical costs at 1 year of follow-up. Of 2331 randomized patients, 2288 (98%) had a rounded integer SHFM score between -1 and 2, consistent with predicted 1-year survival of 98% and 74%, respectively. At baseline, median age was 59 years, 28% of patients were women, and nearly two-thirds of the cohort had New York Heart Association class II heart failure and one-third had class III heart failure. Higher SHFM scores were associated with more hospitalizations (rate ratio per 1-unit increase, 1.86; P < .001), more inpatient days (2.30; P < .001), and higher inpatient costs (2.28; P < .001), outpatient costs (1.54; P < .001), and total medical costs (2.13; P < .001). CONCLUSION: Although developed to predict all-cause mortality, SHFM scores also predict medical resource use and costs.

Safety and efficacy of the MitraClip® system for severe mitral regurgitation: a systematic review.

BACKGROUND: The MitraClip® system is a newer percutaneous device that has shown promising results but data on its safety and efficacy in low- and high-surgical risk populations continues to evolve. We performed a systematic review of the published studies reporting the safety and efficacy of MitraClip® implantation for treatment of moderate to severe and severe mitral regurgitation (MR). METHODS: Reviewers independently searched for relevant articles in Medline and abstracted clinical information based on pre-defined criteria and end-points. Patients were classified as low- or high-surgical risk for conventional mitral valve (MV) surgery based on Society of Thoracic Surgeons score, EuroSCORE, or surgeon discretion. Primary safety outcome was 30-day mortality and primary efficacy outcomes were freedom from death, ≥3+ MR, and requirement for MV surgery during follow-up. RESULTS: Immediate and long-term outcomes of 16 studies, including 2980 patients (age 73.7 ± 0.6 years; 63.3% males) receiving the MitraClip®, were analyzed. Acute procedural success rate was 91.4% with a procedural mortality of 0.1%. Mortality at 30 days and long-term (310 days) follow-up was 4.2 and 15.8%, respectively and was significantly higher in the high-risk group (P = 0.003 and 0.019, respectively). Incidence of major procedural adverse outcomes was relatively low with blood transfusion accounting for most events. At follow-up, the number of patients with ≥3+ MR reduced from 96.3% to 14.7% (P < 0.001), and those with NYHA class III/IV reduced from 83.2% to 23.4% (P < 0.001). CONCLUSION: MitraClip® implantation for moderate to severe or severe MR appears to be safe with a very low procedural mortality. There is significant improvement in functional outcomes although long-term mortality is high, especially in high surgical risk patients.