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      Increased Left Ventricular Stiffness Impairs Exercise Capacity in Patients with Heart Failure Symptoms Despite Normal Left Ventricular Ejection Fraction

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          Abstract

          Aims. Several mechanisms can be involved in the development of exercise intolerance in patients with heart failure despite normal left ventricular ejection fraction (HFNEF) and may include impairment of left ventricular (LV) stiffness. We therefore investigated the influence of LV stiffness, determined by pressure-volume loop analysis obtained by conductance catheterization, on exercise capacity in HFNEF. Methods and Results. 27 HFNEF patients who showed LV diastolic dysfunction in pressure-volume (PV) loop analysis performed symptom-limited cardiopulmonary exercise testing (CPET) and were compared with 12 patients who did not show diastolic dysfunction in PV loop analysis. HFNEF patients revealed a lower peak performance ( P = .046), breathing reserve ( P = .006), and ventilation equivalent for carbon dioxide production at rest ( P = .002). LV stiffness correlated with peak oxygen uptake ( r = −0.636, P < .001), peak oxygen uptake at ventilatory threshold ( r = −0.500, P = .009), and ventilation equivalent for carbon dioxide production at ventilatory threshold ( r = 0.529, P = .005). Conclusions. CPET parameters such as peak oxygen uptake, peak oxygen uptake at ventilatory threshold, and ventilation equivalent for carbon dioxide production at ventilatory threshold correlate with LV stiffness. Increased LV stiffness impairs exercise capacity in HFNEF.

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          Myocardial structure and function differ in systolic and diastolic heart failure.

          Loek van Heerebeek, Ger Stienen, Wolfgang A Linke … (2006)
          To support the clinical distinction between systolic heart failure (SHF) and diastolic heart failure (DHF), left ventricular (LV) myocardial structure and function were compared in LV endomyocardial biopsy samples of patients with systolic and diastolic heart failure. Patients hospitalized for worsening heart failure were classified as having SHF (n=22; LV ejection fraction (EF) 34+/-2%) or DHF (n=22; LVEF 62+/-2%). No patient had coronary artery disease or biopsy evidence of infiltrative or inflammatory myocardial disease. More DHF patients had a history of arterial hypertension and were obese. Biopsy samples were analyzed with histomorphometry and electron microscopy. Single cardiomyocytes were isolated from the samples, stretched to a sarcomere length of 2.2 microm to measure passive force (Fpassive), and activated with calcium-containing solutions to measure total force. Cardiomyocyte diameter was higher in DHF (20.3+/-0.6 versus 15.1+/-0.4 microm, P<0.001), but collagen volume fraction was equally elevated. Myofibrillar density was lower in SHF (36+/-2% versus 46+/-2%, P<0.001). Cardiomyocytes of DHF patients had higher Fpassive (7.1+/-0.6 versus 5.3+/-0.3 kN/m2; P<0.01), but their total force was comparable. After administration of protein kinase A to the cardiomyocytes, the drop in Fpassive was larger (P<0.01) in DHF than in SHF. LV myocardial structure and function differ in SHF and DHF because of distinct cardiomyocyte abnormalities. These findings support the clinical separation of heart failure patients into SHF and DHF phenotypes.
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            Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure.

            W. Gregory Hundley, Sabrina Stewart, Peter Brubaker … (2002)
            Many older patients with symptoms of congestive heart failure have a preserved left ventricular ejection fraction (LVEF). However, the pathophysiology of this disorder, presumptively termed diastolic heart failure (DHF), is not well characterized and it is unknown whether it represents true heart failure. To assess the 4 key pathophysiological domains that characterize classic heart failure by systematically performing measurements in older patients with presumed DHF and comparing these results with those from age-matched healthy volunteers and patients with classic systolic heart failure (SHF). Observational clinical investigation conducted in 1998 in a general community and teaching hospital in Winston-Salem, NC. A total of 147 subjects aged at least 60 years. Fifty-nine had isolated DHF defined as clinically presumed heart failure, LVEF of at least 50%, and no evidence of significant coronary, valvular, or pulmonary disease. Sixty had typical SHF (LVEF < or =35%). Twenty-eight were age-matched healthy volunteer controls. Left ventricular structure and function, exercise capacity, neuroendocrine function, and quality of life. By echocardiography, mean (SE) LVEF was 60% (2%) in patients with DHF vs 31% (2%) in those with SHF and 54% (2%) in controls. Mean (SE) LV mass-volume ratio was markedly increased in patients with DHF (2.12 [0.14] g/mL) vs those with SHF (1.22 [0.14] g/mL) (P<.001) and vs controls (1.49 [0.17] g/mL) (P =.002). Peak oxygen consumption by expired gas analysis during cycle ergometry was similar in the DHF and SHF groups (14.2 [0.5] and 13.1 [0.5] mL/kg per minute, respectively; P =.40) and in both was markedly reduced compared with healthy controls (19.9 [0.7] mL/kg per minute) (P =.001 for both). Ventilatory anaerobic threshold was similar in the DHF and SHF groups (9.1 [0.3] and 8.7 [0.3] mL/kg per minute, respectively; P<.001) and in both was reduced compared with healthy controls (11.5 [0.4] mL/kg per minute) (P<.001). Norepinephrine levels were similar in the DHF (306 [64] pg/mL) and SHF (287 [62] pg/mL) groups (P =.56) and in both were markedly increased vs healthy controls (169 [80] pg/mL) (P =.007 and.03, respectively). Brain natriuretic peptide was substantially increased in both the DHF (56 [30] pg/mL) and the SHF (154 [28] pg/mL) groups compared with healthy controls (3 [38] pg/mL) (P =.02 and.001, respectively). Quality-of-life decrement score as assessed by the Minnesota Living with Heart Failure Questionnaire was substantially increased from the benchmark score of 10 in both groups (SHF: 43.8 [3.9]; DHF: 24.8 [4.4]). Patients with isolated DHF have similar though not as severe pathophysiologic characteristics compared with patients with typical SHF, including severely reduced exercise capacity, neuroendocrine activation, and impaired quality of life.
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              Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction: a comparative Doppler-conductance catheterization study.

              Mario Kasner, Dirk Westermann, Paul Steendijk … (2007)
              Various conventional and tissue Doppler echocardiographic indexes were compared with pressure-volume loop analysis to assess their accuracy in detecting left ventricular (LV) diastolic dysfunction in patients with heart failure with normal ejection fraction (HFNEF). Diastolic dysfunction was confirmed by pressure-volume loop analysis obtained by conductance catheter in 43 patients (19 men) with HFNEF. Their Doppler indexes were compared with those of 12 control patients without heart failure symptoms and with normal ejection fraction. Invasively measured indexes for diastolic relaxation (tau, dP/dt(min)), LV end-diastolic pressure, and LV end-diastolic pressure-volume relationship (stiffness, b [dP/dV], and stiffness constant, beta) were correlated with several conventional mitral flow and tissue Doppler imaging indexes. Conventional Doppler indexes correlated moderately with the degree of LV relaxation index, tau (E/A: r=-0.36, P=0.013; isovolumic relaxation time: r=0.31, P=0.040) and b (deceleration time: r=0.39, P=0.012) but not with beta, in contrast to the tissue Doppler imaging indexes E'/A'(lateral) (r=-0.37, P=0.008) and E/E'(lateral) (r=0.53, P<0.001). Diastolic dysfunction was detected in 70% of the HFNEF patients by mitral flow Doppler but in 81% and 86% by E'/A'(lateral), and E/E'(lateral), respectively. Of all echocardiographic parameters investigated, the LV filling index E/E'(lateral) was identified as the best index to detect diastolic dysfunction in HFNEF in which the diagnosis of diastolic dysfunction was confirmed by conductance catheter analysis. We recommend its use as an essential tool for noninvasive diagnostics of diastolic function in patients with HFNEF.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cardiol Res Pract
                Journal ID (publisher-id): CRP
                Title: Cardiology Research and Practice
                Publisher: SAGE-Hindawi Access to Research
                ISSN (Electronic): 2090-0597
                Publication date Collection: 2011
                Publication date (Electronic): 2 March 2011
                Volume: 2011
                Electronic Location Identifier: 692862
                Affiliations
                Department of Cardiology and Pulmonology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany
                Author notes

                Academic Editor: H. O. Ventura

                Article
                DOI: 10.4061/2011/692862
                PMC ID: 3051202
                PubMed ID: 21403885
                SO-VID: 9dd45ed5-ee9d-43f6-8116-73b507028fb1
                Copyright © Copyright © 2011 David Sinning et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 14 December 2010
                Date accepted : 8 January 2011
                Categories
                Subject: Clinical Study

                ScienceOpen disciplines: Cardiovascular Medicine
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine

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