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Precision Medicine for Cardiac Resynchronization: Predicting Quality of Life Benefits for Individual Patients-An Analysis From 5 Clinical Trials.

ABSTRACT: Clinical trials have established the average benefit of cardiac resynchronization therapy (CRT), but estimating benefit for individual patients remains difficult because of the heterogeneity in treatment response. Accordingly, we created a multivariable model to predict changes in quality of life (QoL) with and without CRT. Patient-level data from 5 randomized trials comparing CRT with no CRT were used to create a prediction model of change in QoL at 3 months using a partial proportional odds model for no change, small, moderate, and large improvement, or deterioration of any magnitude. The C statistics for not worsening or obtaining at least a small, moderate, and large improvement were calculated. Among the 3614 patients, regardless of assigned treatment, 33.3% had a deterioration in QoL, 9.2% had no change, 9.2% had a small improvement, 13.5% had a moderate improvement, and the remaining 34.9% had a large improvement. Patients undergoing CRT were less likely to have a decrement in their QoL (28.2% versus 38.9%; P<0.001) and more likely to have a large QoL improvement (38.7% versus 30.6%; P<0.001). A partial proportional odds model identified baseline QoL, age, and an interaction of CRT with QRS duration as predictors of QoL benefits 3 months after randomization. C statistics of 0.65 for not worsening, 0.68 for at least a small improvement, 0.69 for at least a moderate improvement, and 0.73 for predicting a large improvement were observed. There is marked heterogeneity of treatment benefit of CRT that can be predicted based on baseline QoL, age, and QRS duration.

SUBMITTER: Nassif ME

PROVIDER: S-EPMC5724761 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Precision Medicine for Cardiac Resynchronization: Predicting Quality of Life Benefits for Individual Patients-An Analysis From 5 Clinical Trials.

Nassif Michael E ME Tang Yuanyuan Y Cleland John G JG Abraham William T WT Linde Cecilia C Gold Michael R MR Young James B JB Daubert J Claude JC Sherfesee Lou L Schaber Dan D Tang Anthony S L ASL Jones Philip G PG Arnold Suzanne V SV Spertus John A JA

Circulation. Heart failure 20171001 10

<h4>Background</h4>Clinical trials have established the average benefit of cardiac resynchronization therapy (CRT), but estimating benefit for individual patients remains difficult because of the heterogeneity in treatment response. Accordingly, we created a multivariable model to predict changes in quality of life (QoL) with and without CRT.<h4>Methods and results</h4>Patient-level data from 5 randomized trials comparing CRT with no CRT were used to create a prediction model of change in QoL at ...[more]

PMID: 29038172

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Project description:Background: Cardiac resynchronization therapy (CRT) improves quality of life (QOL) in heart failure (HF) patients with reduced ejection fraction. Clinicians may have difficulty choosing between CRT with a pacemaker (CRT-P) or a defibrillator (CRT-D) for older patients. CRT-P devices are smaller, have more battery longevity, are less prone to erosions or recalls, and do not deliver shocks. These factors may impact patients' QOL, but data on such comparisons are lacking. Objectives: We examined the impact of CRT-P versus CRT-D on the QOL of older (≥75 years) HF patients who qualified for implantable cardioverter defibrillator therapy. Settings/Subjects/Measurements: We enrolled 101 CRT recipients and assessed QOL at baseline and at six-month post-implant using the Short Form Health Survey (SF-36) and the Minnesota living with heart failure (MLHF) questionnaires. Results: The average age of enrolled patients was 81 years, 27% were women, and 40 received a CRT-P device. After adjusting for baseline QOL score, age, sex, HF functional class, and the occurrence of adverse events, we found no significant differences in QOL outcomes between CRT-P and CRT-D recipients based on either the subscales or the composite scores for the SF-36 or MLHF questionnaires at six-months post-implantation. Conclusions: Older CRT-P and CRT-D recipients report comparable QOL scores six months after device implantation. Larger cohort studies with longer follow-up are needed to accurately assess potential QOL differences between CRT-D and CRT-P recipients to guide clinical decision making and ensure the right balance of risk versus benefit in these patients. Appropriate goals-of-care discussions are the corner stone of clinical decision making regarding defibrillator therapy. As such, even as the data stand at present, there is a need for more deliberate referral of older patients with HF to Palliative Care Specialists, or to Cardiologists trained in Palliative Care Medicine. clinicaltrials.gov listing: NCT03031847.

Project description:BackgroundStudies of cardiac resynchronization therapy in addition to an implantable cardioverter defibrillator in patients with mild to moderate congestive heart failure had not been shown to reduce mortality until the recent RAFT trial (Resynchronization/Defibrillation for Ambulatory Heart Failure Trial). We performed a meta-analysis including the RAFT trial to determine the effect of cardiac resynchronization therapy with or without an implantable defibrillator on mortality.MethodsWe searched electronic databases and other sources for reports of randomized trials using a parallel or crossover design. We included studies involving patients with heart failure receiving optimal medical therapy that compared cardiac resynchronization therapy with optimal medical therapy alone, or cardiac resynchronization therapy plus an implantable defibrillator with a standard implantable defibrillator. The primary outcome was mortality. The optimum information size was considered to assess the minimum amount of information required in the literature to reach reliable conclusions about cardiac resynchronization therapy.ResultsOf 3071 reports identified, 12 studies (n = 7538) were included in our meta-analysis. Compared with optimal medical therapy alone, cardiac resynchronization therapy plus optimal medical therapy significantly reduced mortality (relative risk [RR] 0.73, 95% confidence interval [CI] 0.62-0.85). Compared with an implantable defibrillator alone, cardiac resynchronization therapy plus an implantable defibrillator significantly reduced mortality (RR 0.83, 95% CI 0.72-0.96). This last finding remained significant among patients with New York Heart Association (NYHA) class I or II disease (RR 0.80, 95% CI 0.67-0.96) but not among those with class III or IV disease (RR 0.84, 95% CI 0.69-1.07). Analysis of the optimum information size showed that the sequential monitoring boundary was crossed, which suggests no need for further clinical trials.InterpretationThe cumulative evidence is now conclusive that the addition of cardiac resynchronization to optimal medical therapy or defibrillator therapy significantly reduces mortality among patients with heart failure.

Project description:BackgroundOne component of precision medicine is to construct prediction models with their predicitve ability as high as possible, e.g. to enable individual risk prediction. In genetic epidemiology, complex diseases like coronary artery disease, rheumatoid arthritis, and type 2 diabetes, have a polygenic basis and a common assumption is that biological and genetic features affect the outcome under consideration via interactions. In the case of omics data, the use of standard approaches such as generalized linear models may be suboptimal and machine learning methods are appealing to make individual predictions. However, most of these algorithms focus mostly on main or marginal effects of the single features in a dataset. On the other hand, the detection of interacting features is an active area of research in the realm of genetic epidemiology. One big class of algorithms to detect interacting features is based on the multifactor dimensionality reduction (MDR). Here, we further develop the model-based MDR (MB-MDR), a powerful extension of the original MDR algorithm, to enable interaction empowered individual prediction.ResultsUsing a comprehensive simulation study we show that our new algorithm (median AUC: 0.66) can use information hidden in interactions and outperforms two other state-of-the-art algorithms, namely the Random Forest (median AUC: 0.54) and Elastic Net (median AUC: 0.50), if interactions are present in a scenario of two pairs of two features having small effects. The performance of these algorithms is comparable if no interactions are present. Further, we show that our new algorithm is applicable to real data by comparing the performance of the three algorithms on a dataset of rheumatoid arthritis cases and healthy controls. As our new algorithm is not only applicable to biological/genetic data but to all datasets with discrete features, it may have practical implications in other research fields where interactions between features have to be considered as well, and we made our method available as an R package ( https://github.com/imbs-hl/MBMDRClassifieR ).ConclusionsThe explicit use of interactions between features can improve the prediction performance and thus should be included in further attempts to move precision medicine forward.

Dataset Information

Precision Medicine for Cardiac Resynchronization: Predicting Quality of Life Benefits for Individual Patients-An Analysis From 5 Clinical Trials.

Publications

Precision Medicine for Cardiac Resynchronization: Predicting Quality of Life Benefits for Individual Patients-An Analysis From 5 Clinical Trials.

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