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The renal-cardiac connection in subjects with preserved ejection fraction: a population based study.

ABSTRACT: Chronic kidney disease (CKD) is prevalent and is associated with increased cardiovascular morbidity and mortality. The interaction between diastolic dysfunction (DD) and CKD in subjects with preserved systolic function is not well defined. This study sought to determine the association between renal function and DD in subjects with preserved ejection fraction.Through the Rochester Epidemiology Project, subjects who underwent echocardiography over 2 years with EF ≥50% were identified and the clinical data were obtained. Glomerular filtration rate (GFR) was estimated using the modification of diet in renal disease equation. Linear regression was used to test for association of GFR and DD. DD was defined as follows: Grade 2 or pseudonormal pattern (0.75 < E/A ≤ 1.5, E/e' ≥ 10, DT > 140 ms, ΔE/A ≥ 0.5, and PV S < D) or Grade 3+ or restrictive pattern (E/A > 1.5, E/e' ≥ 10, DT < 140 ms, and PV S < D). Cox regression was used to assess correlation of GFR and DD with time-to-event outcomes. A total of 2056 patients were identified. There was significant correlation between worsening GFR and degree of DD assessed by echo Doppler E/e' ratio (P = 0.005), left ventricular mass index (P = 0.004), and right ventricular systolic pressure (P = 0.01). Worsening GFR was associated with increased mortality, development of heart failure, and hospitalization (P < 0.001). Within each GFR group, abnormal DD was associated with a higher risk of the clinical outcomes. No interaction between GFR and DD was noted, suggesting an increased risk of events associated with abnormal DD across ranges of GFR.Worsening GFR was associated with a greater degree of diastolic dysfunction and adverse clinical outcomes. Within each GFR group, the presence of DD was associated with increased morbidity and mortality. Further studies are warranted to determine if improving DD in patients with CKD will benefit clinical outcomes.

SUBMITTER: Jain A

PROVIDER: S-EPMC5542734 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Project description:BackgroundThe prevalence and clinical significance of right ventricular (RV) systolic dysfunction (RVD) in patients with heart failure and preserved ejection fraction (HFpEF) are not well characterized.Methods and resultsConsecutive, prospectively identified HFpEF (Framingham HF criteria, ejection fraction ≥50%) patients (n=562) from Olmsted County, Minnesota, underwent echocardiography at HF diagnosis and follow-up for cause-specific mortality and HF hospitalization. RV function was categorized by tertiles of tricuspid annular plane systolic excursion and by semiquantitative (normal, mild RVD, or moderate to severe RVD) 2-dimensional assessment. Whether RVD was defined by semiquantitative assessment or tricuspid annular plane systolic excursion ≤15 mm, HFpEF patients with RVD were more likely to have atrial fibrillation, pacemakers, and chronic diuretic therapy. At echocardiography, patients with RVD had slightly lower left ventricular ejection fraction, worse diastolic dysfunction, lower blood pressure and cardiac output, higher pulmonary artery systolic pressure, and more severe RV enlargement and tricuspid valve regurgitation. After adjustment for age, sex, pulmonary artery systolic pressure, and comorbidities, the presence of any RVD by semiquantitative assessment was associated with higher all-cause (hazard ratio=1.35; 95% confidence interval, 1.03-1.77; P=0.03) and cardiovascular (hazard ratio=1.85; 95% confidence interval, 1.20-2.80; P=0.006) mortality and higher first (hazard ratio=1.99; 95% confidence interval, 1.35-2.90; P=0.0006) and multiple (hazard ratio=1.81; 95% confidence interval, 1.18-2.78; P=0.007) HF hospitalization rates. RVD defined by tricuspid annular plane systolic excursion values showed similar but weaker associations with mortality and HF hospitalizations.ConclusionsIn the community, RVD is common in HFpEF patients, is associated with clinical and echocardiographic evidence of more advanced HF, and is predictive of poorer outcomes.

Project description:BACKGROUND:Why some but not all patients with severe aortic stenosis (SevAS) develop otherwise unexplained reduced systolic function is unclear. We investigate the hypothesis that reduced creatine kinase (CK) capacity and flux is associated with this transition. METHODS:We recruited 102 participants to 5 groups: moderate aortic stenosis (ModAS) (n=13), SevAS, left ventricular (LV) ejection fraction ?55% (SevAS-preserved ejection fraction, n=37), SevAS, LV ejection fraction <55% (SevAS-reduced ejection fraction, n=15), healthy volunteers with nonhypertrophied hearts with normal systolic function (normal healthy volunteer, n=30), and patients with nonhypertrophied, non-pressure-loaded hearts with normal systolic function undergoing cardiac surgery and donating LV biopsy (non-pressure-loaded heart biopsy, n=7). All underwent cardiac magnetic resonance imaging and 31P magnetic resonance spectroscopy for myocardial energetics. LV biopsies (AS and non-pressure-loaded heart biopsy) were analyzed for CK total activity, CK isoforms, citrate synthase activity, and total creatine. Mitochondria-sarcomere diffusion distances were calculated by using serial block-face scanning electron microscopy. RESULTS:In the absence of failure, CK flux was lower in the presence of AS (by 32%, P=0.04), driven primarily by reduction in phosphocreatine/ATP (by 17%, P<0.001), with CK kf unchanged (P=0.46). Although lowest in the SevAS-reduced ejection fraction group, CK flux was not different from the SevAS-preserved ejection fraction group (P>0.99). Accompanying the fall in CK flux, total CK and citrate synthase activities and the absolute activities of mitochondrial-type CK and CK-MM isoforms were also lower (P<0.02, all analyses). Median mitochondria-sarcomere diffusion distances correlated well with CK total activity (r=0.86, P=0.003). CONCLUSIONS:Total CK capacity is reduced in SevAS, with median values lowest in those with systolic failure, consistent with reduced energy supply reserve. Despite this, in vivo magnetic resonance spectroscopy measures of resting CK flux suggest that ATP delivery is reduced earlier, at the moderate AS stage, where LV function remains preserved. These findings show that significant energetic impairment is already established in moderate AS and suggest that a fall in CK flux is not by itself a necessary cause of transition to systolic failure. However, because ATP demands increase with AS severity, this could increase susceptibility to systolic failure. As such, targeting CK capacity and flux may be a therapeutic strategy to prevent and treat systolic failure in AS.

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The renal-cardiac connection in subjects with preserved ejection fraction: a population based study.

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