Cognitive dysfunction is common in patients with heart failure (HF). Despite the high prevalence and the adverse associations of cognitive dysfunction in HF, the prognostic implications remain poorly understood. We sought to determine the influence of cognitive dysfunction, identified using the Montreal Cognitive Assessment (MoCA), on 180-day cardiovascular events. We analyzed data on 246 participants in an observational cohort study of adults with HF. The interview-format MoCA was administered to all participants. Time to first cardiovascular event was assessed as a cumulative end point during the 180 days after enrollment. Cox proportional hazards model was used for analysis of time to first event. The MoCA score was <26 for 91 patients (37%). Patients with a MoCA score <26 were more likely to have a cardiovascular event at 180 days. MoCA score <26 remained an independent predictor of cardiovascular event risk at 180 days when adjusted for the Seattle Heart Failure Model Score and the Charlson comorbidity index (hazard ratio 1.7, 95% confidence interval 1.1 to 2.6, p = 0.03). In conclusion, in patients with HF, cognitive dysfunction identified with a MoCA score of <26 is associated with increased risk of cardiovascular events at 180 days.
More than 650,000 patients are diagnosed with heart failure (HF) each year in the United States. Despite advances in medical therapy and device technology over the decades, about 50% of patients with HF will die within 5 years of their diagnosis. As many as half of the 5 million patients living with HF in the United States experience cognitive dysfunction. When identified in patients with HF, cognitive dysfunction is associated with increased risk of hospitalization, progressive physical disability, and higher mortality rate. Despite the high prevalence and the adverse associations of cognitive dysfunction in HF, the prognostic implications remain poorly understood. We sought to determine the influence of cognitive dysfunction, identified using the Montreal Cognitive Assessment (MoCA), on 180-day cardiovascular events and to identify subsets of MoCA items that are associated with cardiovascular risk.
Methods
We analyzed data on 246 participants in an observational cohort study of symptoms in adults with HF. All patients were recruited from 2010 to 2013 through a single HF outpatient clinic in the Pacific Northwest. Participants were approached for study participation immediately after an HF clinic visit. Participants were aged ≥21 years with the ability to read and understand English at a fifth-grade level and were able to provide informed consent. All patients had symptomatic (New York Heart Association functional classes II to IV) HF and were either on optimal HF therapy or undergoing optimization of medical therapy by a treating HF cardiologist. Patients were ineligible for inclusion in the study if they had a diagnosis of cognitive dysfunction in the medial record, had a major uncorrected visual impairment, or were unable to complete the study requirements.
Written informed consent and Health Insurance Portability and Accountability Act authorization were obtained from all participants by study staff not directly involved in patient care. The study was reviewed and approved by the Institutional Review Board at Oregon Health and Science University. There was a 3% refusal rate for study participation and a 94% completion rate.
Sociodemographic characteristics were assessed using questionnaire. An HF cardiologist determined each participant’s NYHA functional class immediately before enrollment. Clinical and treatment characteristics were collected during an in-depth electronic medical record (EMR) review. Co-morbidities were assessed with the Charlson Comorbidity Index. A list of 17 co-morbid diseases were evaluated and weighted, with possible scores ranging from 0 to 30. Greater Charlson comorbidity index scores indicate greater risk of mortality. Seattle Heart Failure Scores were calculated for each participant using available clinical data. The Seattle Heart Failure Model is a commonly used HF risk prediction tool that uses routinely available clinical information to estimate 1- and 5-year survival. Depression was measured with the 9-item Patient Health Questionnaire (PHQ9). The PHQ9 has an 88% sensitivity and specificity for major depression using a cut-off score of ≥10.
Cognitive function was assessed using the MoCA. The MoCA is a 10-minute cognitive tool designed for use by clinicians to detect cognitive dysfunction. The MoCA has a sensitivity of 90% and a specificity of 87% to detect mild cognitive dysfunction, with a cut-off score of 26 in the general population. The MoCA has also been adjusted to improve diagnostic accuracy for patients with chronic cardiovascular disease. A cut-off score of 24 was demonstrated to be 100% sensitive to detect mild cognitive dysfunction in a sample for adults with chronic cardiovascular disease. The MoCA has also been validated in older patients living with HF. The MoCA assesses 6 cognitive domains: visualspatial ability, executive function, language, short-term memory, orientation and attention, and working memory and concentration. The cognitive domains defined in this study and the MoCA tasks comprising each domain are provided in Table 1 .
| Cognitive Domain (Total points) | MoCA Tasks Included (Individual points assigned) |
|---|---|
| Visualspatial ability (4 points) | Copy Cube (1 point) |
| Draw Clock (3 points) | |
| Executive function (4 points) | Trail making (1 point) |
| Phonetic fluency (1 point) | |
| Verbal abstraction (2 points) | |
| Short-term memory (5 points) | Delayed recall at 5 minutes (5 points) |
| Language (5 points) | Naming animals (3 points) |
| Sentences repeated (2 points) | |
| Phonetic fluency (1 point) | |
| Orientation (6 points) | Date (1 point) |
| Month (1 point) | |
| Year (1 point) | |
| Day (1 point) | |
| Place (1 point) | |
| City (1 point) | |
| Attention, working memory and concentration (6 points) | Tapping (1 point) |
| Serial subtraction (3 points) | |
| Forward/backward numbers (2 points) |
Time to first all-cause cardiovascular event (mortality, hospitalization, and emergency room visit) was assessed as a cumulative end point during the 180 days after enrollment. Clinical events and associated dates were extracted from the EMR and/or assessed by contacting participants by telephone. A second reviewer independently validated all clinical events, and 100% consensus was reached that the events were attributable to cardiovascular causes.
Means and standard deviations and proportions were used to describe the sample. Cox proportional hazards model was used for analysis of time to first event. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to quantify the influence of the overall MoCA score and individual MoCA domains on 180-day event risk. The proportional hazards assumption was justified on the basis of Schoenfeld residuals. Model fit was assessed using the overall model chi-square test and by calculating Harrell’s C statistic. The influence of the overall MoCA score and individual MoCA domains on 180-day event-free survival was adjusted for the Seattle Heart Failure Score and the Charlson comorbidity index. Multiple other factors including body mass index, moderate or severe depression, and education were considered in Cox model but did not improve the model fit or remain independently associated with cardiovascular events when the Seattle Heart Failure Score and Charlson comorbidity index were included. All analyses were performed with Stata IC 13.0 (Stata Corp, College Station, Texas).
Results
The baseline characteristics of the study population are described in Table 2 .
| Patient Demographics | ||
|---|---|---|
| Female | 92 (37.8%) | |
| Male | 153 (62.2%) | |
| White/Caucasian | 196 (88.4%) | |
| Ischemic cardiomyopathy | 81 (32.9%) | |
| Non-ischemic cardiomyopathy | 165 (67.1%) | |
| NYHA Class II | 98 (39.8%) | |
| NYHA Class III | 135 (54.9%) | |
| NYHA Class IV | 13 (5.3%) | |
| Ejection fraction < 40% | 196 (80.3%) | |
| Ejection fraction >= 40% | 48 (19.7%) | |
| Medication Use | Diuretic | 210 (85.4%) |
| ACE Inhibitor or ARB | 202 (82.1%) | |
| Beta blocker | 220 (89.4%) | |
| Aldosterone Antagonist | 114 (46.3%) | |
| Statin | 140 (56.9%) | |
| Digoxin | 59 (24.0%) | |
| Antiplatelet or anticoagulation | 197 (80.1%) | |
| Married or Partnered | 145 (62.8%) | |
| Single, divorced, widowed, separated | 86 (37.2%) | |
| High school or less education | 74 (32.0%) | |
| Some college or higher education | 157 (68.0%) | |
| Moderate or severe depression | 59 (25.8%) | |
| Charlson Comorbidity Index | 1 | 90 (36.6%) |
| 2 | 72 (29.3%) | |
| 3 | 53 (21.5%) | |
| 4 | 19 (7.7%) | |
| >= 5 | 12 (4.9%) | |
| Age (years) | 56.6 +/- 13.1 | |
| Body Mass Index (kg/m 2 ) | 31.4 +/- 7.7 | |
| Seattle Heart Failure Survival Model predicted 1-year survival (%) | 75.1 +/- 0.2 | |
| Seattle Heart Failure Survival Model predicted 5- year survival (%) | 32.1 +/-0.2 | |
The mean MoCA score was 25.9 ± 2.6. Additional information regarding MoCA scores including scores for the individual MoCA domains is provided in Table 3 . With more than 35,000 follow-up days (mean 145.9 ± 60.8 days), the cardiovascular event risk was 45.6%. At 180 days, 163 patients were alive without cardiovascular events and 6 patients were lost to follow-up. There were 4 deaths at 180 days, 14 emergency room visits for cardiovascular causes, and 59 cardiovascular hospitalizations. Patients with a MoCA score <26 were more likely to have a cardiovascular event at 180 days ( Figure 1 ). MoCA score <26 remained an independent predictor of cardiovascular event risk at 180 days when adjusted for the Seattle Heart Failure Score and the Charlson comorbidity index (HR 1.7, 95% CI 1.1 to 2.6, p = 0.03, Harrell’s C = 0.65).
| MoCA standard cutoff | < 26 | 91 (37.0%) |
| >= 26 | 155 (63.0%) | |
| MoCA cardiovascular cutoff | < 24 | 38 (15.4%) |
| >=24 | 208 (84.6%) | |
| Visualspatial domain (4 points) | 4 | 153 (62.2%) |
| < 4 | 93 (37.8%) | |
| Executive domain (4 points) | 4 | 124 (50.4%) |
| < 4 | 122 (49.6%) | |
| Short-term memory domain (5 points) | >=3 | 162 (65.9%) |
| <3 | 84 (34.1%) | |
| Language domain (5 points) | 5 | 168 (68.3%) |
| < 5 | 78 (31.7%) | |
| Orientation domain (6 points) | 6 | 232 (94.3%) |
| <6 | 14 (5.7%) | |
| Attention, working memory and concentration domain (6 points) | 6 | 151 (61.4%) |
| <6 | 78 (38.6%) |
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