Cardiopulmonary exercise testing (CPET) may potentially differentiate heart failure (HF) with preserved ejection fraction (HFpEF) from noncardiac causes of dyspnea (NCD). While contemporary ...guidelines for HF recommend using CPET for identifying causes of unexplained dyspnea, data supporting this practice are limited. This study aimed to determine the diagnostic value of expired gas analysis to distinguish HFpEF from NCD. Exercise stress echocardiography with simultaneous expired gas analysis was performed in patients with HFpEF (n = 116) and those with NCD (n = 112). Participants without dyspnea symptoms were also enrolled as controls (n = 26). Exercise capacity was impaired in patients with HFpEF than in controls and those with NCD, evidenced by lower oxygen consumption (VO
), but there was a substantial overlap between HFpEF and NCD. Receiver operating characteristic curve analyses showed modest diagnostic abilities of expired gas analysis data in differentiating individuals with HFpEF from the controls; however, none of these variables clearly differentiated between HFpEF and NCD (all areas under the curve < 0.61). Expired gas analysis provided objective assessments of exercise capacity; however, its diagnostic value in identifying HFpEF among patients with symptoms of exertional dyspnea was modest.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
The aim of this study was to determine the prevalence of collecting system invasion (CSI) on multiphasic CT, validate the pathological findings, and investigate the relationship between CSI ...and clinical outcomes in patients with renal cell carcinomas (RCC).
Methods
Patients pathologically diagnosed with RCC between January 2008 and December 2017 were retrospectively enrolled in this study. They were divided into two groups according to the presence of CSI on multiphasic CT images. Patients’ clinical characteristics, radiological findings, and overall survival (OS) and recurrence-free survival (RFS) rates were analyzed and compared between the groups. In addition, the correlation of radiological findings with pathological findings was investigated.
Results
Among the included 347 kidneys of 340 patients, CSI was observed in 11 kidneys (3%; 95% confidence interval, 1.3–5.0%). In all the 11 kidneys, the tumors were pathologically diagnosed as clear cell RCC, and in one kidney, the tumor also had sarcomatoid features. When pathological CSI served as the standard of reference, the sensitivity, specificity, and accuracy of CSI on CT were 50%, 99.7%, and 97.1%, respectively. The OS and RFS rates were not significantly different between patients with CSI on CT and those without CSI.
Conclusion
This study found that the prevalence of RCC-related CSI was 3%. Because of the low prevalence, we cannot exclude the possibility that CSI on CT would be associated with the OS and RFS. Further studies are needed to determine whether CSI on CT can be an independent prognostic factor for survival in patients with RCC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Background Exercise‐induced high heart rate may impair exercise tolerance by reducing diastolic filling time and ventricular filling in heart failure with preserved ejection fraction (HFpEF). Given ...the importance of chronotropic response, we hypothesized that reduction in diastolic filling time because of exercise‐induced increased heart rate would not impair cardiac output reserve and exercise capacity. We sought to determine the association between heart rate, diastolic filling time, hemodynamics, and exercise capacity in HFpEF. Methods and Results Patients with HFpEF (n=66) and controls without HF (n=107) underwent bicycle exercise echocardiography with simultaneous expired gas analysis to measure oxygen consumption. Diastolic filling time was assessed by the overlap time between mitral E‐ and A‐waves (longer overlap time indicates shorter diastolic filling duration). Overlap time increased (ie, diastolic filling time shortened) in HFpEF and controls as heart rate increased with exercise, and the relationship was similar between the groups. Greater heart rate response correlated with higher cardiac output ( r =0.51, P <0.0001) and oxygen consumption ( r =0.50, P <0.0001) during peak exercise. Shorter diastolic filling time, as assessed by longer overlap time, was correlated with higher cardiac output ( r =0.47, P <0.0001) and peak oxygen consumption ( r =0.38, P =0.007), not with E/e′ or right ventricular‐pulmonary artery uncoupling. Longer overlap time was associated with mitral A velocity ( r =0.53, P <0.0001) and left atrial booster pump strain ( r =0.42, P <0.0001). Conclusions Shortening of diastolic filling interval in tandem with increased heart rate during exercise does not limit cardiac output reserve or exercise capacity in HFpEF.
Aims
Lung congestion in patients with heart failure (HF) has traditionally been treated using interventions that reduce pulmonary capillary hydrostatic pressure. The transient receptor potential ...vanilloid 4 (TRPV4) channel regulates fluid transit across the pulmonary capillary‐interface, and represents a novel target to reduce lung water, independent of pulmonary capillary hypertension. This pilot study examined the safety and potential efficacy of TRPV4 blockade as a novel treatment for
HF.
Methods and results
In this randomized, double‐blind, placebo‐controlled crossover pilot trial, 11 subjects with chronic, compensated HF were treated with a novel TRPV4 antagonist (GSK2798745) or placebo. The primary endpoint was lung diffusing capacity for carbon monoxide (DLCO) after 7 days of treatment with GSK2798745 as compared to placebo. Secondary endpoints included additional diffusion parameters, spirometry and safety assessments. Compared to placebo, treatment with GSK2798745 resulted in a trend to improvement in DLCO (placebo: −0.336 mL/mmHg/min; GSK2798745: +0.458 mL/mmHg/min; treatment difference: +0.793 mL/mmHg/min; 95% confidence interval: −0.925 to 2.512) that was not statistically significant. GSK2798745 was well‐tolerated with no serious adverse events.
Conclusion
In this pilot trial, GSK2798745 was found to be safe and well‐tolerated, with a trend toward improved gas transfer. Further investigation is warranted in larger studies to determine whether treatment with TRPV4 antagonists or alternative treatments targeting capillary permeability might be effective to improve lung congestion, pulmonary gas transfer and clinical status in patients with acute or chronic
HF.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Transforming growth factor beta (TGF-β) has been shown to play a critical role in pathogenesis of pulmonary arterial hypertension (PAH) although the precise role of TGF-β signaling remains uncertain. ...A recent report has shown that periostin (Pn) is one of the most upregulated proteins in human PAH lung compared with healthy lungs. We established type I TGF-β receptor knockout mice specifically with Pn expressing cell (Pn-Cre/Tgfb1fl/fl mice). Increases in PA pressure and pulmonary artery muscularization were induced by hypoxia of 10% oxygen for 4 weeks. Lung Pn expression was markedly induced by 4 week-hypoxia. Pn-Cre/Tgfb1fl/fl mice showed lower right ventricular pressure elevation, inhibition of PA medial thickening. Fluorescent co-immunostaining showed that Smad3 activation in Pn expressing cell is attenuated. These results suggest that TGF-β signaling in Pn expressing cell may have an important role in the pathogenesis of PAH by controlling medial thickening.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives The purposes of this study were to examine left atrial (LA) functional reserve in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and to determine whether LA ...strain has an incremental diagnostic value over clinical and conventional echocardiographic parameters. Background Patients with HFpEF have multiple cardiovascular reserve abnormalities. Although the LA is dysfunctional in HFpEF, the diagnostic value of LA strain remains unknown. Methods The LA at rest and during passive leg lifts was echocardiographically assessed in 40 patients with HFpEF and in 46 patients with hypertension without HF (HT controls). Global peak atrial longitudinal strain during ventricular systole (global LAS ) and booster strain during atrial contraction (global LAB ) were assessed using speckle tracking. Results Patients with HFpEF had an enlarged LA and reduced LA emptying fraction compared with HT controls at rest, while LA stroke volume (SV) was similar between the groups. During leg lifts, increases in LA reservoir and contractile function (i.e., global LAS and LAB ) were blunted in HFpEF patients compared with HT controls, resulting in impaired LASV responses. Global LAS and LAB during leg lifts accurately differentiated HFpEF from HT controls (areas under the curve: 0.95 and 0.92, respectively). Resting global LAS had a significant incremental diagnostic value over clinical (age and sex) and conventional echocardiographic parameters (E/E′ ratio, left ventricular mass index, and maximum LA volume index) (global chi-square: 49.6 vs. 30.8; p < 0.0001). The diagnostic value was further improved by adding global LAS during leg lifts (global chi-square: 72.2 vs. 49.6; p < 0.0001). Conclusions An enlarged LA compensates for LA dysfunction and maintains LASV at rest in patients with HFpEF. However, depressed LA reserve affects LA performance during leg lifts. Evaluation of LA function, including LA strain using leg lifts, might provide incremental diagnostic value for HFpEF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
More than half of patients with heart failure have a preserved ejection fraction (HFpEF). The prevalence of HFpEF has been increasing worldwide and is expected to increase further, making it an ...important health-care problem. The diagnosis of HFpEF is straightforward in the presence of obvious objective signs of congestion; however, it is challenging in patients presenting with a low degree of congestion because abnormal elevation in intracardiac pressures may occur only during physiological stress conditions, such as during exercise. On the basis of this hemodynamic background, current consensus guidelines have emphasized the importance of exercise stress testing to reveal abnormalities during exercise, and exercise stress echocardiography (i.e., diastolic stress echocardiography) may be used as an initial diagnostic approach to HFpEF owing to its noninvasive nature and wide availability. However, evidence supporting the use of this method remains limited and many knowledge gaps exist with respect to diastolic stress echocardiography. This review summarizes the current understanding of the use of diastolic stress echocardiography in the diagnostic evaluation of HFpEF and discusses its strengths and limitations to encourage future studies on this subject.
Women have a greater risk of heart failure with preserved ejection fraction (HFPEF) than men do, yet the basis for this disparity remains unclear. Greater arterial stiffness and afterload causes left ...ventricular (LV) diastolic dysfunction, a central mechanism of HFPEF. Because of smaller body habitus, previous reports have used body surface area as a surrogate of the size of the aorta. We performed a comprehensive hemodynamic evaluation of elderly patients with preserved EF and evaluated sex differences in the associations between LV function and afterload, before and after adjusting for the aortic sizes.
Four hundred and forty-three patients (mean age: 73 years, 169 women) who underwent clinically indicated echocardiography and computed tomography (CT) were identified. Linear regression analyses were performed to assess the independent contributions of sex to and its interaction with LV function before and after adjusting for CT-derived aortic length and volume. Although blood pressures were similar between the sexes, women had greater arterial elastance, lower arterial compliance, and greater LV ejection fraction (all p<0.001). Sex differences were detected in the associations between LV afterload and relaxation (mitral e') as well as in the left atrial (LA) emptying fraction, but not in LA size. These differences remained significant after adjusting for the aortic length and volume. Sensitivity analyses in an age-matched subgroup (n = 324; 162 of each sex) confirmed the robustness of these sex disparities in LV diastolic function and afterload.
Women had worse LV relaxation than men did against the same degree of afterload, before and even after adjusting for the aortic sizes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A gas exchange analysis with the cardiopulmonary exercise test is effective in discriminating non-cardiogenic components of limited exercise tolerance and is important for use in combination with the ...diastolic stress test. An 80-year-old woman with progressive exertional dyspnoea, hypertension, and untreated bronchial asthma was diagnosed with heart failure with a preserved ejection fraction by invasive testing. Diuretics were initiated, which resulted in partial symptom improvement. A subsequent non-invasive test revealed a reduced breathing reserve, suggesting exertional dyspnoea complications linked to lung disease. Bronchodilators were administered, which further improved the symptoms.
Abstract Background End-stage renal disease is a major clinical and public health problem, and cardiovascular disease accounts for half of the mortality in hemodialysis patients. An existing ...mortality risk score (AROii score) or N-terminal pro-brain natriuretic peptide (NT-proBNP) level have modest predictive power, but there is room for improvement. There are emerging cardiac biomarkers (soluble isoforms of ST2 sST2, galectin-3 Gal-3), and uremic toxicity (indoxyl sulfate IS). We sought to determine whether these biomarkers predict cardiovascular outcomes in hemodialysis patients, and have incremental prognostic value over the clinical score and NT-proBNP level. Methods A total of 423 hemodialysis patients were prospectively followed for primary (all-cause death) and secondary endpoints (a composite of all-cause death or cerebro-cardiovascular events). Results During a mean follow-up of 2.1 ± 0.4 years, there were 48 all-cause deaths and 78 composite outcomes. sST2, Gal-3, and NT-proBNP were associated with all-cause deaths but IS was not in both log-rank test and receiver operating characteristic analysis. Both sST2 and Gal-3 had independent and incremental prognostic value for both outcomes over the AROii score and NT-proBNP. Although adding sST2 did not reclassify over the model based AROii score and NT-proBNP for all-cause death, further addition of Gal-3 did. Subgroup analyses of patients with left ventricular ejection fraction measurement (n=301) corroborated these results, where the two biomarkers remained independent and incremental for both all-cause death and composite outcome after adjusting for the risk score and the ejection fraction. Conclusions Both sST2 and Gal-3 had independent and incremental prognostic values over NT-proBNP and an established risk score in patients with hemodialysis. Assessment of sST2 and Gal-3 further enhances risk stratification.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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