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Abstract: Background: Hypokalemia is common in heart failure (HF) and is associated with increased mortality. Potassium supplements are commonly used to treat hypokalemia and maintain normokalemia. However, their long-term effects on outcomes in chronic HF are unknown. We used a public-use copy of the Digitalis Investigation Group (DIG) trial dataset to determine the associations of potassium supplement use with outcomes using a propensity-matched design. Methods: Of the 7788 DIG participants with chronic HF, 2199 were using oral potassium supplements at baseline. We estimated propensity scores for potassium supplement use for each patient and used them to match 2131 pairs of patients receiving and not receiving potassium supplements. Matched Cox regression models were used to estimate associations of potassium supplement use with mortality and hospitalization during 40 months of median follow-up. Results: All-cause mortality occurred in 818 (rate, 1327/10,000 person-years) and 802 (rate, 1313/10,000 person-years) patients respectively receiving and not receiving potassium supplements (hazard ratio {HR} when potassium supplement use was compared with nonuse, 1.05; 95% confidence interval {CI}, 0.94–1.18; P =0.390). All-cause hospitalizations occurred in 1516 (rate, 4777/10,000 person-years) and 1445 (rate, 4120/10,000 person-years) patients respectively receiving and not receiving potassium supplements (HR, 1.15; 95% CI, 1.05–1.26; P =0.004). HRs (95% CI) for hospitalizations due to cardiovascular causes and worsening HF were respectively 1.19 (95% CI, 1.08–1.32; P =0.001) and 1.27 (1.12–1.43; P <0.0001). Conclusion: The use of potassium supplements in chronic HF was not associated with mortality. However, their use was associated with increased hospitalization due to cardiovascular causes and progressive HF. [Copyright &y& Elsevier]

Abstract: Background: Low serum magnesium levels may cause fatal ventricular arrhythmias. However, their long-term effects on mortality and morbidity in chronic heart failure patients are relatively unknown. Methods: We studied 1569 chronic systolic and diastolic heart failure patients with normal sinus rhythm who participated in the Digitalis Investigation Group trial and had serum magnesium data available at one month. Of these, 741 patients had normal (>2 mEq/L) and 828 had low (≤2 mEq/L) serum magnesium levels. Propensity scores for having low serum magnesium levels were calculated for each patient using a non-parsimonious multivariable logistic regression model, and were used to match 560 (76%) low-magnesium patients with 560 normal-magnesium patients. Effects of low-magnesium on mortality and hospitalization during a mean follow-up of 36 months were assessed using matched Cox regression analyses. Results: All-cause mortality occurred in 156 (rate, 915/10,000 person-years) normal- magnesium and 171 (rate, 1034/10,000 person-years) low-magnesium patients, respectively, during 1704 and 1653 years of follow-up (hazard ratio, 1.23; 95% confidence interval, 0.97–1.57; p =0.089). Cardiovascular mortality occurred in 110 (rate, 646/10,000 person-years) normal-magnesium and 133 (rate, 805/10,000 person-years) low-magnesium patients (hazard ratio, 1.38, 95% confidence interval, 1.04–1.83, p =0.024). Hazard ratios and 95% confidence intervals for all-cause and cardiovascular hospitalizations were respectively 1.18 (0.99–1.42; p =0.068) and 1.14 (0.94–1.39; p =0.182). Conclusions: In a propensity-matched population of ambulatory chronic heart failure patients who were balanced in all measured baseline covariates, serum magnesium level 2 mEq/L or less was associated with increased cardiovascular mortality, but had no association with cardiovascular hospitalization. [Copyright &y& Elsevier]

Abstract: The majority of heart failure (HF) patients are older adults and most HF-related adverse events occur in these patients. However, the independent association of age and outcomes in HF is not clearly determined. We categorized 7788 ambulatory HF patients who participated in the Digitalis Investigation Group (DIG) trial as younger (<65 years) and older (≥65 years). Propensity scores for older age were calculated for each patient and used to match 2381 pairs of younger and older patients. The associations of older age with mortality and hospitalization during a median 40 months of follow-up were assessed using matched Cox regression models. All-cause mortality occurred in 877 older patients versus 688 younger patients (hazard ratio when older age was compared with younger age (HR)=1.26; 95% confidence interval (CI)=1.12–1.41; p <0.0001). Older patients, when compared with propensity-matched younger patients, also had significantly higher mortality rates due to cardiovascular causes (HR=1.14; 95% CI=1.00–1.30; p =0.044) and worsening heart failure causes (HR=1.32; 95% CI=1.07–1.62; p =0.009). No significant association was found between age and hospitalization due to all causes (HR=1.08; 95% CI=0.99–1.18; p =0.084) and cardiovascular causes (HR=1.03; 95% CI=0.93–1.13; p =0.622). However, hospitalization due to HF was significantly increased in older patients (HR=1.14; 95% CI=1.01–1.28; p =0.041). In ambulatory HF patients, older age although associated with increased mortality, was not associated with increased hospitalizations except for those due to worsening HF. [Copyright &y& Elsevier]

Hypertension is a risk factor for heart failure and stroke. However, the effect of hypertension on stroke in patients with heart failure has not been well studied. In the Digitalis Investigation Group trial, 3,674 (47%) of the 7,788 patients had a history of hypertension. Probability or propensity scores for a history of hypertension were calculated for each patient through use of a multivariable logistic regression model and were then used to match 2,386 pairs of patients with and without a history of hypertension. Kaplan-Meier and matched Cox regression analyses were used to estimate associations of a history of hypertension hospitalization for stroke during 37 months of median follow-up. After matching, patients without and with a history of hypertension had a mean systolic blood pressure of 127 mm Hg. Hospitalization for stroke occurred in 90 patients (rate, 129/10,000 person-years of follow-up) without a history of hypertension and 121 patients (rate, 178/10,000 person-years of follow-up) with a history of hypertension (hazard ratio when hypertension was compared with no hypertension = 1.52; 95% confidence interval = 1.11 to 2.08; p = 0.010). This association was also observed among patients with baseline systolic blood pressure <140 mm Hg (hazard ratio = 1.35; 95% confidence interval =1.01 to 1.81; p = 0.044). In conclusion, a history of hypertension was associated with increased risk of hospitalization for stroke among patients with heart failure who were balanced in all measured baseline covariates, including blood pressure. [Copyright &y& Elsevier]

The independence of association between elevated jugular venous pressure (JVP) and outcomes in heart failure (HF) has not been well studied. The objective of propensity-matched study was to determine if an elevated JVP had intrinsic associations with outcomes in chronic systolic and diastolic HF. Of the 7,788 participants in the Digitalis Investigation Group trial, 1,020 (13%) had elevated JVP at baseline. Propensity scores for elevated JVP were estimated for all patients based on 32 baseline characteristics and were used to match 827 pairs of patients with normal and elevated JVP. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated to compare outcomes associated with elevated versus normal JVP during 34 months of median follow-up. Before matching, all-cause mortality occurred in 31% and 47% (unadjusted HR 1.70, 95% CI 1.54 to 1.88, p <0.0001), and all-cause hospitalization occurred in 60% and 71% (unadjusted HR 1.35, 95% CI 1.25 to 1.47, p <0.0001) of patients with normal and elevated JVP, respectively. After matching, all-cause mortality occurred in 48% and 45% (matched HR 0.95, 95% CI 0.80 to 1.12, p = 0.521), and all-cause hospitalization occurred in 70% and 70% (matched HR 0.97, 95% CI 0.87 to 1.09, p = 0.613) of patients with normal and elevated JVP, respectively. Elevated JVP had no intrinsic associations with cardiovascular mortality (matched HR 0.93, 95% CI 0.77 to 1.12, p = 0.440) or hospitalization for HF (matched HR 0.94, 95% CI 0.78 to 1.14, p = 0.532). In conclusion, an elevated JVP is a marker of higher burden of sickness and poor outcomes. However, elevated JVP had no intrinsic association with mortality or hospitalization in chronic HF. [Copyright &y& Elsevier]

Atrial fibrillation (AF) and heart failure (HF), common in older adults, are associated with poor outcomes. However, little is known about their impact, independent of each other. We studied 5,673 community-dwelling adults aged ⩾65 years in the Cardiovascular Health Study. Baseline prevalent AF and HF were centrally adjudicated, and 116 patients had AF only, 219 had HF only, 39 had both, and 5,263 had neither. The Cox proportional hazards model was used to estimate age-gender-race-adjusted hazard ratio (aHR) and 95% confidence intervals (CIs) for all-cause, cardiovascular (CV), and non-CV mortalities. Participants had a mean age of 73 years (±6 years), 58% were women, and 15% African-American. During 13 years of follow-up, all-cause mortality occurred in 43%, 66%, 74%, and 85% of those with neither, AF only, HF only, and both, respectively. Compared with neither, aHR (95% CIs) for all-cause mortality associated with AF only, HF only, and both was 1.36 (1.08 to 1.72), 2.31 (1.97 to 2.71), and 3.04 (2.15 to 4.29), respectively. Similar associations were observed with CV mortality, but HF only also had greater non-CV mortality (aHR 1.72, 95% CI 1.35 to 2.18). Compared with AF alone, aHR (95% CIs) associated with HF alone for all-cause, CV, and non-CV mortalities was 1.69 (1.29 to 2.23), 1.73 (1.20 to 2.51), and 1.64 (1.09 to 2.46), respectively. Compared with HF alone, those with both conditions had greater CV but not all-cause mortality. In conclusion, community-dwelling older adults with AF have greater mortality than those without but lesser than those with HF, and both conditions were associated with greater CV and all-cause mortalities, whereas only those with HF had greater non-CV mortality. [ABSTRACT FROM AUTHOR]

Abstract: Background: Reduced right ventricular ejection fraction (RVEF) is associated with poor outcomes in patients with chronic systolic heart failure (HF). Although most HF patients are older adults, little is known about the relationship between low RVEF and outcomes in older adults with systolic HF. Methods: Of the 2008 Beta-Blocker Evaluation of Survival Trial (BEST) participants with systolic HF (left ventricular ejection fraction ≤35%) 822 were ≥65years and had data on baseline RVEF estimated by gated-equilibrium radionuclide ventriculography. Using RVEF ≥40% (n=308) as reference, we examined association of RVEF 30–39% (n=214), 20–29% (n=206) and <20% (n=94) with outcomes using Cox regression models. Results: All-cause mortality occurred in 36%, 40%, 39% and 56% of patients with RVEF ≥40%, 30–39%, 20–29% and <20% respectively. Compared with RVEF ≥40%, unadjusted hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality associated with RVEF 30–39%, 20–29% and <20% were 1.19 (0.90–1.57; P=0.220), 1.13 (0.84–1.51; P=0.423) and 1.97 (1.43–2.73; P<0.001) respectively. Respective multivariable-adjusted HR''s (95% CI''s) for all-cause mortality were 1.19 (0.88–1.60; P=0.261), 1.00 (0.73–1.39; P=0.982) and 1.70 (1.14–2.53; P=0.009). Adjusted HR''s (95% CI''s) associated with RVEF <20% (versus ≥40%) for cardiovascular mortality and HF mortality were 1.79 (1.17–2.76; P=0.008) and 1.97 (1.02–3.83; P=0.045) respectively. RVEF had no independent association with sudden cardiac death, all-cause or HF hospitalization. Conclusions: Abnormally low RVEF is a significant independent predictor of mortality, but not of HF hospitalization, in older adults with systolic HF. [Copyright &y& Elsevier]