scholarly journals CARNITINE INSUFFICIENCY IS ASSOCIATED WITH ADVERSE OUTCOMES IN PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION

Author(s):  
Y. Kinugasa ◽  
S. Sugihara ◽  
K. Yamada ◽  
M. Miyagi ◽  
K. Matsubara ◽  
...  

Background: L-carnitine is an essential nutrient that plays a vital role in fatty acid energy metabolism of the heart and skeletal muscles. Primary or secondary carnitine insufficiency contributes to progressive left ventricular systolic dysfunction and physical frailty. However, the clinical features of patients with heart failure with preserved ejection fraction (HFpEF) and carnitine insufficiency remain unclear. Objectives: The present study aimed to evaluate the clinical characteristics and outcomes of these patients. Design: A prospective cohort study. Setting: Tottori University hospital. Participants: 117 patients who were hospitalized with HFpEF (ejection fraction ≥45%). Measurement: All measurements were obtained at hospital discharge. Carnitine insufficiency was defined as the lowest quantile of free carnitine level (<56.3 μmol/L) or the highest quantile of acylcarnitine to free carnitine ratio (≥0.35). Nutritional status and physical activity were assessed by the Geriatric Nutritional Risk Index (GNRI) and Barthel index (BI). Left ventricular diastolic function was assessed by echocardiography. The composite endpoints were hospitalization for heart failure and death from cardiac causes. Results: Patients with carnitine insufficiency (44.4%) had lower values of GNRI and BI, higher B-type natriuretic peptide levels, and lower early diastolic mitral annular velocity in the subgroups with sinus rhythm compared with those with preserved carnitine (all p<0.05). During a mean follow-up of 472±249 days, composite endpoints occurred in 26.5% of patients. Multivariate Cox hazard analysis showed that carnitine insufficiency was an independent predictor of cardiac events (p<0.05). Conclusions: Carnitine insufficiency is associated with adverse outcomes in patients with HFpEF.

Author(s):  
Fang-Fei Wei ◽  
Yuzhong Wu ◽  
Ruicong Xue ◽  
Xiao Liu ◽  
Xin He ◽  
...  

It remains debated whether pulse pressure is associated with left ventricular traits and adverse outcomes over and beyond mean arterial pressure (MAP) in patients with heart failure (HF) with preserved ejection fraction. We investigated these associations in 3428 patients with HF with preserved ejection fraction (51.5% women; mean age, 68.6 years) enrolled in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist). We computed association sizes and hazards ratios with 1-SD increase in MAP and pulse pressure. In multivariable-adjusted analyses, association sizes ( P ≤0.039) for MAP were 0.016 cm and 0.014 cm for septal and posterior wall thickness, −0.15 for E/A ratio, −0.66 for E/e′, and −0.64% for ejection fraction, independent of pulse pressure. With adjustment additionally applied for MAP, E/A ratio and longitudinal strain increased with higher pulse pressure with association sizes amounting to 0.067 ( P =0.026) and 0.40% ( P =0.023). In multivariable-adjusted analyses of both placebo and spironolactone groups, lower MAP and higher pulse pressure predicted the primary composite end point ( P ≤0.028) and hospitalized HF ( P ≤0.002), whereas MAP was also significantly associated with total mortality ( P ≤0.007). Sensitivity analyses stratified by sex, median age, and region generated confirmatory results with exception for the association of adverse outcomes with pulse pressure in patients with age ≥69 years. In conclusion, the clinical application of MAP and pulse pressure may refine risk estimates in patients with HF with preserved ejection fraction. This finding may help further investigation for the development of HF with preserved ejection fraction preventive strategies targeting pulsatility and blood pressure control.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Sunaga ◽  
S Hikoso ◽  
T Yamada ◽  
Y Yasumura ◽  
M Uematsu ◽  
...  

Abstract Background Malnutrition is associated with adverse prognosis in heart failure patients. However, in patients with heart failure with preserved ejection fraction (HFpEF), the effects of change in nutritional status during hospitalization on prognosis is unknown. Geriatric nutritional risk index (GNRI) is a widely used objective index for evaluating nutritional status. Low GNRI (<92) has moderate or severe nutritional risk and high GNRI (≥92) has no or low nutritional risk. Purpose The purpose of this study was to clarify the effect of change in GNRI during hospitalization on one-year mortality and the association between the value of GNRI and one-year mortality in patients with HFpEF. Methods We prospectively registered patients with HFpEF in PURSUIT-HFpEF registry when they were hospitalized for heart failure in 29 hospitals. Preserved ejection fraction was defined as more than 50% of left ventricular ejection fraction. Of the 486 patients who registered PURSUIT-HFpEF, 228 cases with one-year follow-up data were examined. GNRI was calculated as follows: 14.89 × serum albumin (g/dl) + 41.7 × body mass index/22. Results Mean age was 81±10 years and 100 patients (44%) were male. During a median [interquartile range] follow-up period of 374 [342, 400] days, 28 patients (12%) died. Mortality was significantly higher in patients with low GNRI at admission (n=65) than those with high GNRI at admission (n=163) (26% vs. 9%, log-rank P=0.011) and higher in patients with low GNRI at discharge (n=109) than those with high GNRI at discharge (n=119) (22% vs. 6%, log-rank P=0.002). Multivariate analysis with Cox proportional hazard model with patient characteristics at admission revealed that low GNRI at admission was independently associated with mortality (hazard ratio: 0.96, 95% CI: 0.93–0.99, P=0.035) and that with patient characteristics at discharge revealed that low GNRI at discharge was independently associated with mortality (hazard ratio: 0.94, 95% CI: 0.91–0.97, P<0.001). We also compared mortality by dividing patients into 4 group according to whether GNRI was high or low at the time of admission and discharge. Patients with low GNRI at admission and at discharge (n=59) exhibited the highest mortality, on the other hand, patients with high GNRI at admission and low GNRI at discharge (n=50) exhibited higher mortality than those with high GNRI both at admission and at discharge (n=113) (Low and low: 28% vs. High and low: 14% vs. High and high: 6% vs. Low and high: 0%, log-rank P=0.010). All cause mortality Conclusion GNRI at admission or at discharge was independently associated with one-year mortality in patients with HFpEF. Moreover, worsening GNRI during hospitalization is associated with the worse prognosis. It is important to prevent lowering GNRI during treatment of acute decompensated HFpEF. Acknowledgement/Funding Roche Diagnostics, FUJIFILM Toyama Chemical


2020 ◽  
Vol 9 (17) ◽  
Author(s):  
Daniel N. Silverman ◽  
Mehdi Rambod ◽  
Daniel L. Lustgarten ◽  
Robert Lobel ◽  
Martin M. LeWinter ◽  
...  

Background Increases in heart rate are thought to result in incomplete left ventricular (LV) relaxation and elevated filling pressures in patients with heart failure with preserved ejection fraction (HFpEF). Experimental studies in isolated human myocardium have suggested that incomplete relaxation is a result of cellular Ca 2+ overload caused by increased myocardial Na + levels. We tested these heart rate paradigms in patients with HFpEF and referent controls without hypertension. Methods and Results In 22 fully sedated and instrumented patients (12 controls and 10 patients with HFpEF) in sinus rhythm with a preserved ejection fraction (≥50%) we assessed left‐sided filling pressures and volumes in sinus rhythm and with atrial pacing (95 beats per minute and 125 beats per minute) before atrial fibrillation ablation. Coronary sinus blood samples and flow measurements were also obtained. Seven women and 15 men were studied (aged 59±10 years, ejection fraction 61%±4%). Patients with HFpEF had a history of hypertension, dyspnea on exertion, concentric LV remodeling and a dilated left atrium, whereas controls did not. Pacing at 125 beats per minute lowered the mean LV end‐diastolic pressure in both groups (controls −4.3±4.1 mm Hg versus patients with HFpEF −8.5±6.0 mm Hg, P =0.08). Pacing also reduced LV end‐diastolic volumes. The volume loss was about twice as much in the HFpEF group (controls −15%±14% versus patients with HFpEF −32%±11%, P =0.009). Coronary venous [Ca 2+ ] increased after pacing at 125 beats per minute in patients with HFpEF but not in controls. [Na + ] did not change. Conclusions Higher resting heart rates are associated with lower filling pressures in patients with and without HFpEF. Incomplete relaxation and LV filling at high heart rates lead to a reduction in LV volumes that is more pronounced in patients with HFpEF and may be associated with myocardial Ca 2+ retention.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Natasha Cuk ◽  
Jae H Cho ◽  
Donghee Han ◽  
Joseph E Ebinger ◽  
Eugenio Cingolani

Introduction: Sudden death due to ventricular arrhythmias (VA) is one of the main causes of mortality in patients with heart failure and preserved ejection fraction (HFpEF). Ventricular fibrosis in HFpEF has been suspected as a substrate of VA, but the degree of fibrosis has not been well characterized. Hypothesis: HFpEF patients with increased degree of fibrosis will manifest more VA. Methods: Cedars-Sinai medical records were probed using Deep 6 artificial intelligence data extraction software to identify patients with HFpEF who underwent cardiac magnetic resonance imaging (MRI). MRI of identified patients were reviewed to measure extra-cellular volume (ECV) and degree of fibrosis. Ambulatory ECG monitoring (Ziopatch) of those patients were also reviewed to study the prevalence of arrhythmias. Results: A total of 12 HFpEF patients who underwent cardiac MRI were identified. Patients were elderly (mean age 70.3 ± 7.1), predominantly female (83%), and overweight (mean BMI 32 ± 9). Comorbidities included hypertension (83%), dyslipidemia (75%), and coronary artery disease (67%). Mean left ventricular ejection fraction by echocardiogram was 63 ± 8.7%. QTc as measured on ECG was not significantly prolonged (432 ± 15 ms). ECV was normal in those patients for whom it was available (24.2 ± 3.1, n = 9) with 3/12 patients (25%) demonstrating ventricular fibrosis by MRI (average burden of 9.6 ± 5.9%). Ziopatch was obtained in 8/12 patients (including all 3 patients with fibrosis) and non-sustained ventricular tachycardia (NSVT) was identified in 5/8 (62.5%). One patient with NSVT and without fibrosis on MRI also had a sustained VA recorded. In those patients who had Ziopatch monitoring, there was no association between presence of fibrosis and NSVT (X2 = 0.035, p = 0.85). Conclusions: Ventricular fibrosis was present in 25% of HFpEF patients in this study and NSVT was observed in 62.5% of those patients with HFpEF who had Ziopatch monitoring. The presence of fibrosis by Cardiac MRI was not associated with NSVT in this study; however, the size of the cohort precludes broadly generalizable conclusions about this association. Further investigation is required to better understand the relationship between ventricular fibrosis by MRI and VA in patients with HFpEF.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Inder S Anand ◽  
Scott D Solomon ◽  
Brian Claggett ◽  
Sanjiv J Shah ◽  
Eileen O’Meara ◽  
...  

Background: Plasma natriuretic peptides (NP) are helpful in the diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) and predict adverse outcomes. Levels of NP beyond a certain cut-off level are often used as inclusion criteria in clinical trials to ensure that the patients have HF, and to select patients at higher risk. Whether treatments have a differential effect on outcomes across the spectrum of NP levels is unclear. In the I-Preserve trial a benefit of irbesartan on all outcomes was only seen in HFpEF patients with low but not high NP levels. We hypothesized that in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, spironolactone might have a greater benefit in patients with lower NP levels. Methods and Results: BNP (n=468) or NT-proBNP (n=400) levels were available at baseline in 868 patients with HFpEF enrolled in the natriuretic peptide stratum (BNP ≥100 pg/mL or an NT- proBNP ≥360 pg/mL) of the TOPCAT trial. In a multi-variable Cox regression model, that included age, gender, region (Americas vs. Russia/Georgia), atrial fibrillation, diabetes, eGFR, BMI and heart rate, higher BNP or NT-proBNP as a continuous, standardized log-transformed variable or grouped by terciles (see Figure for BNP & NT-proBNP tercile values) was independently associated with an increased risk of the primary endpoint of cardiovascular mortality, aborted cardiac arrest, or hospitalization for heart failure (Figure-1). There was a significant interaction between the effect of spironolactone and baseline BNP or NT-proBNP terciles for the primary outcome (P=0.02, Figure-2), with greater benefit of the drug in the lower compared to higher NP terciles. Conclusions: The benefit of spironolactone in lower risk HFpEF patients may indicate effects of the drug on early, but not late higher-risk stage of the disease. These findings question the strategy of using elevated NP as a patient selection criterion in HFpEF trials.


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