P4380Echocardiographically determined myocardial work An emerging bioassay for clinical studies Results from the STAAB cohort study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Morbach ◽  
F Sahiti ◽  
T Tiffe ◽  
V Cejka ◽  
M Breunig ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Cohort Study ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Work Efficiency ◽  
Negative Work ◽  
Constructive Work ◽  
Global Work ◽  
Isovolumic Relaxation

Abstract Introduction A novel echocardiographic method to non-invasively determine myocardial work based on speckle-tracking derived longitudinal strain and blood pressure has recently been validated and offers new opportunities to study the mechanistic associations. Heart failure patients with prolonged electrical conduction (ie, left bundle branch block) exhibit reduced myocardial global work efficiency (GWE) due to an increase in global wasted work (GWW), which could be improved by biventricular pacing. We here investigated the association of ETI and myocardial work in a non-diseased population. Methods The Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study carefully characterized a representative sample of the population of a medium-sized town in Germany, aged 30–79 years and free from heart failure. Off-line analysis of the standardized, quality-controlled transthoracic echocardiograms regarding myocardial work yields the following parameters: global constructive work (GCW): work performed during shortening in systole and adding negative work during lengthening in isovolumic relaxation; global wasted work (GWW): negative work performed during lengthening in systole adding work performed during shortening in isovolumic relaxation; and global work efficiency (GWE): GCW/(GCW+GWW). Results We performed myocardial work analysis in 935 individuals from the sample of the first planned STAAB interim analysis who were in sinus rhythm, had preserved left ventricular ejection fraction and were free from significant valvular disease (51% female, 53±12 years). In linear regression including age, sex, heart rate, and ETI, we found increasing heart rate (64±10 bpm), QRS width (95±12 ms), QT interval (414±28 ms), and PQ interval (164±28 ms) associated with lower GWE (−0.11, −0.02, −0.03, and −0.001, respectively; all p<0.05) and higher GWW (+2.64, +0.29, +0.79, +0.16 mmHg%, respectively; all p<0.05). Conclusion In subjects free of overt cardiac disease, GWE strongly associated with ETI. Prolonged atrio-ventricular and intra-ventricular coupling and repolarization was associated with an increase in wasted work, while constructive work was not affected. These findings not only suggest a positive effect on myocardial energetics by reducing the heart rate, but also advocate the concept of myocardial work as a bioassay that is responsive to subtle changes. Myocardial work holds promise to be further studied in diseased patient groups. Acknowledgement/Funding German Ministry of Research and Education within the Comprehensive Heart Failure Centre Würzburg (BMBF 01EO1004 and 01EO1504)

scholarly journals 411 Recompensation induces distinct changes in myocardial work in patients with acutely decompensated heart failure and reduced vs preserved left ventricular ejection fraction

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
C Morbach ◽  
F Sahiti ◽  
C Henneges ◽  
M Breunig ◽  
M Kaspar ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Decompensated Heart Failure ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Work Efficiency ◽  
Ventricular Ejection Fraction ◽  
Acutely Decompensated Heart Failure ◽  
Constructive Work ◽  
Global Work

Abstract Funding Acknowledgements German Research Foundation (BMBF 01EO1004 and 01EO1504) OnBehalf Acute Heart Failure Registry Background & Aim A new, less load-dependent echocardiographic tool to determine left ventricular (LV) myocardial work (MyW) based on longitudinal strain and blood pressure has recently been introduced and validated against invasive measurements. We investigated the impact of change in N-terminal pro-B-natriuretic peptide (NT-proBNP; i.e. surrogate of recompensation) during the hospital phase on changes in MyW (global work efficiency [GWE]; global constructive work [GCW]; and global wasted work [GWW]), in patients admitted for acutely decompensated heart failure (AHF). Methods The AHF registry is a monocentric prospective follow-up study that comprehensively phenotypes consecutive patients hospitalized for AHF. Echocardiography was performed and NT-proBNP measured on the day of admission and within 72 hours prior to discharge. MyW assessment was performed off-line using EchoPAC (GE, version 202). In order to quantify changes in MyW and NT-proBNP, we used the respective discharge-to-admission ratio (DAR). Local polynomial regression was applied to model these associations in patients with LV ejection fraction (LVEF) &lt;40% vs ≥40%. Results We analyzed 111 patients: mean age 73 ± 11 yrs; 32% female; 46 patients (41.4%) with LVEF &lt; 40%. The median [Q1, Q3] NT-proBNP level at admission was 5883 pg/ml (2589, 10188). Median length of stay in hospital was 12.0 days (9.0, 16.5). The DAR for NT-proBNP was 0.55 (0.34; 0.80) indicating that the majority of patients experienced a marked lowering of NT-proBNP. The figure demonstrates that the association between DAR of MyW parameters and DAR of NT-proBNP showed distinct profiles depending on admission LVEF. E.g., in panel A, the arrows indicate that a NT-proBNP reduction by 50% was associated with a 45% increment in GCW if admission LVEF was &lt;40%, but with an 8% increment only if LVEF was ≥40%. Conclusions Our preliminary analysis indicates that a decrease in NT-proBNP may be associated with an improvement in GCW and GWE in patients with reduced LVEF, while these parameters were non-responsive in the other patient group. Although these results require confirmation in a larger cohort, they encourage further research in to MyW as a less load-dependent measure of LV function, shedding new light on echocardiographically manifest alterations of myocardial texture and the timing of healing processes after an acute cardiac event. Figure Discharge-to-admission ratio (DAR) of A) global work efficiency (GWE, &gt;1= improvement), B) global constructive work (GCW, &gt;1= improvement), and C) global wasted work (GWW, &lt;1 = improvement) as a function of discharge to admission NT-proBNP in acute heart failure patients with left ventricular ejection fraction ≥ and &lt;40%. Abstract 411 Figure

scholarly journals Global wasted myocardial is unrelated to conventional markers of systolic and diastolic function in patients with acute heart failure

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
F Sahiti ◽  
C Morbach ◽  
C Henneges ◽  
M Breunig ◽  
V Cejka ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitral Valve ◽  
Acute Heart Failure ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Negative Work ◽  
High Urgency ◽  
Constructive Work ◽  
Global Work

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The AHF Register is supported by an unrestricted grant of Behringer Ingelheim, and grants of the German Ministry of Research and Education within the Comprehensive Heart Failure Center, Würzburg (BMBF 01E01004 and 01E01504) onbehalf AHF Registry Background & Aim Myocardial Work (MyW) analysis quantifies myocardial performance using non-invasively derived pressure-strain loops. It is considered less load-dependent than left ventricular ejection fraction (LVEF) and longitudinal strain, since it integrates blood pressure into the assessment. We assessed associations between MyW indices, natriuretic peptide (NT-proBNP), and conventional markers of systolic and diastolic cardiac function mirroring the hemodynamic changes occurring during hospitalization, in patients hospitalized for acute heart failure (AHF). Methods Consecutive patients (≥18 years) hospitalized for AHF with serial high-quality pairs of echocardiograms (i.e., early after hospitalization and prior to discharge) were eligible. Exclusion criteria were high output AHF, cardiogenic shock, and being listed for high urgency transplantation. The following MyW measures [definition in brackets] were analyzed from the stored recordings: Global constructive work (GCW) [sum of positive work performed during systolic shortening plus negative work during lengthening in isovolumetric relaxation (IVR)], global wasted work (GWW) [sum of negative work performed during systolic lengthening plus work performed during shortening in IVR], global work efficiency (GWE) [constructive work/(constructive work + wasted work)]; global work index (GWI) [total work performed from mitral valve closure to mitral valve opening]. Associations were determined using scatter plots and Pearson Product-Moment correlation coefficients. Results N = 126 patients (73 ± 12 years, 37% female) were eligible. GWI and GCW proved significantly correlated with surrogates measured both on admission and at discharge, NT-proBNP, LVEF, and e’ (Table). By contrast, GWW did not correlate with any of these variables. GWE was also correlated with NT-proBNP (and e’ at discharge), but at both time points respective correlations were more pronounced. Conclusion In patients hospitalized for AHF, GWI, GCW and GWE were associated with conventional parameters of myocardial stress and LV dysfunction. In contrast, GWW was unrelated with any of these established markers. Future studies in larger cohorts and with longer-term follow-up need to clarify to what extent might GWW carry complementary clinical and prognostic significance. Abstract Figure.

4305The interrelation of left ventricular geometry with myocardial work

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F Sahiti ◽  
C Morbach ◽  
T Tiffe ◽  
V Cejka ◽  
M Breunig ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cohort Study ◽  
Left Ventricular ◽  
Work Efficiency ◽  
Negative Work ◽  
Lv Mass ◽  
Lv Volumes ◽  
Relationship Of ◽  
The Relationship ◽  
Isovolumic Relaxation

Abstract Introduction A novel echocardiographic method to non-invasively determine myocardial work based on speckle-tracking derived longitudinal strain and blood pressure has recently been validated and offers new opportunities to study mechanistic associations. Left ventricular (LV) dilation and LV hypertrophy are acknowledged precursors of myocardial dysfunction and ultimately heart failure, but the mechanisms are still not well understood. We aimed to assess the association of LV geometry and myocardial work in a non-diseased population. Methods The Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study carefully characterized a representative sample of the population of a medium-sized town in Germany, aged 30–79 years. By off-line analysis of the standardized, quality-controlled transthoracic echocardiograms the following parameters describing myocardial work can be derived. Global constructive work (GCW): work performed during shortening in systole and adding negative work during lengthening in isovolumic relaxation; global wasted work (GWW): negative work performed during lengthening in systole adding work performed during shortening in isovolumic relaxation; global work efficiency (GWE): GCW/(GCW+GWW). Further, LV volumes and mass were measured and indexed to body surface area. Results Myocardial work analysis was performed in 1568 individuals, who were in sinus rhythm, had preserved LV ejection fraction (EF), and were free from significant valvular disease (50.3% female, aged 53±12 years). In linear regression, we included age, sex, LVEF, low-density lipoprotein (LDL), glycosylated hemoglobin (HbA1c), heart rate, body mass index, hypertension as well as LV mass index (LVMi) and LV end-diastolic volume index (LVEDVi) as parameters of LV geometry. We found increasing LVEDVi (52±10 mL/m2), associated with higher GWW (+0.35, p<0.001) and lower GWE (–0.01, p<0.05), while increasing LVMi (73±17 g/m2) was associated with both, higher GWW (+0.23, p<0.01) and GCW (+1.6, p<0.05) resulting in a lower GWE (–0.09, p<0.01). Conclusion The new echocardiography-based method to non-invasively assess myocardial work offers new insights into the relationship of LV geometry and myocardial work in a non-diseased population. While larger LV volumes were associated with more wasted work, higher LV mass was associated with an increase in both constructive and wasted work. Both alterations of LV geometry adversely affected myocardial work efficiency. This new echocardiographic method is change-sensitive and thus holds promise to further explore the relationship of LV geometry with myocardial work in different disease entities. Acknowledgement/Funding Funding of the STAAB cohort study in the frame of the Comprehensive Heart Failure Center, BMBF 01EO1004 and 01EO1504

scholarly journals 164 Effect of cardiac contractility modulation therapy on myocardial work in patients with heart failure with reduced ejection fraction

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Daniele Masarone ◽  
Stefano De Vivo ◽  
Vittoria Errigo ◽  
Antonio D’ Onofrio ◽  
Giuliano D’Alterio ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Contractility ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Contractility Modulation ◽  
Reduced Ejection Fraction ◽  
Constructive Work ◽  
Global Work ◽  
The Impact

Abstract Aims Cardiac contractility modulation therapy (CCMT) has been shown to reduce hospitalizations and to improve quality of life in heart failure patients with reduced ejection fraction (HFrEF) who remain symptomatic despite disease-modifying therapies. Strain imaging derived myocardial work (MW) is an emerging tool for evaluating left ventricular mechanics by incorporating systolic deformation and afterload burden in the analysis. To evaluate prospectively the impact of CCMT in HFrEF patients on MW derived parameters in relation to standard echocardiographic indices. Methods and results We recruited 12 HFrEF patients with indications to CCMT according to current clinical practice. A comprehensive echo-Doppler evaluation, including speckle tracking derived assessment of global longitudinal strain (GLS), was performed before and after three months from the CCM device implantation. Parameters of MW such as global work index (GWI), global constructive work (GCW) global wasted work (GWW), and global work efficiency (GWE) were calculated according to standardized procedures. Median values (interquartile range) were compared for all those parameters from baseline and 3-month follow-up with Wilcoxon Rank Sum test for continuous variables. At three months from CCM implant an improvement of LVEF [from 32% (27–34) to 36% (29–39), P &lt; 0.05], GLS [from 7.4% (6.2–11.2) to 9.9% (7.5–9.4), P &lt; 0.05], GWI [from 461 mmHg (372–613) to 589 mmHg (413–696), P &lt; 0.05], GCW [from 800 mmHg (620–930) to 970 mmHg (644–1009), P = 0.236], and GWE [from 73% (65–78) to 85% (78–87), P &lt; 0.05] was observed, with a consistent reduction of GWW [from 161 mmHg (148–227) to 125 mmHg (101–188), P &lt; 0.05]. We also found a positive correlation between the magnitude of LVEF improvement and the baseline values of GCW (r = 0.727, P = 0.011). Conclusions At 3 months, CCMT significantly improves standard and advanced left ventricular systolic function indices. This improvement is due to the increase of constructive work and a reduction of wasted work. In addition, the increase of left ventricular ejection fraction can be predicted by the global constructive work levels at baseline.

Abstract P137: Nonspecific ST-T Change In Electrocardiogram Was Associated With A Reduced Constructive Myocardial Work In Hypertensive Patients With Preserved Ejection Fraction

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Joji Ishikawa ◽  
Saori Nakamura ◽  
Ayumi Toba ◽  
Masashi Miyawaki ◽  
Ruri Shimizu ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Volume Index ◽  
Left Ventricular Ejection ◽  
Work Efficiency ◽  
Ventricular Ejection Fraction ◽  
Hypertensive Patients ◽  
Constructive Work ◽  
Global Work

Background: Nonspecific ST-T change in electrocardiogram can be observed in hypertensive heart disease with preserved left ventricular ejection fraction (LVEF); however, the relationship between nonspecific ST-T change and global myocardial work in echocardiography was unclear. Methods: We evaluated global longitudinal strain (GLS), GWI (global work index), GCW (global constructive work), GWW (global wasted work), GWE (global work efficiency), using offline analyzing system (View Pal, GE) in 196 hypertensive patients with preserved LVEF (>50%). Nonspecific ST-T change and major ST-T change (depression of ST in V5 lead >1mV) was also evaluated in electrocardiogram. Results: Mean age was 79.3±8.2 years (men 37.8%). Compared with patients with no ST-T change, those with nonspecific and major ST-change had a smaller absolute value of GLS (-20±3, -18±4, -14±5%, P<0.001) and had smaller constructive work load [GWI (2140±488, 1915±472, 1523±776 mmHg%, P<0.001), GCW (2410±514, 2165±471, 1694±784 mmHg%, P<0.01)]. Additionally, those with nonspecific and major ST-T change had an increased wasted myocardial work [GWW (87±61, 109±58, 138±71 mmHg%, P<0.001)], and this resulted in reduction of myocardial work efficiency [GWE (95±4,93±3,87±12%,P<0.001)]. Even after adjustment for age, sex, diabetes, dyslipidemia, EF, LV mass index, relative wall thickness, parameters of diastolic function (E/A, E/e’, left atrial volume index, tricuspid valve regurgitant flow velocity), and electrocardiogram LVH of Cornell product and Sokolow-Lyon voltage, the patients with nonspecific ST-T change had a significantly smaller LV global constructive work. [GWI (2243±41 vs. 1998±96 mmHg%, P=0.025), GCW (2501±45 vs. 2210±105 mmHg%, P=0.015)]. Conclusion: In hypertensive patients with preserved LVEF, nonspecific ST-T change in electrocardiogram was associated with a reduced constructive work in LV.

scholarly journals 48 Correlation of left ventricular myocardial work indices and invasive measurement of stroke work

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Federico Landra ◽  
Giulia Elena Mandoli ◽  
Benedetta Chiantini ◽  
Maria Barilli ◽  
Giacomo Merello ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Transplantation ◽  
Left Ventricular ◽  
Advanced Heart Failure ◽  
Left Ventricular Ejection ◽  
Stroke Work ◽  
Work Index ◽  
Stroke Work Index ◽  
Constructive Work ◽  
Global Work

Abstract Aims A novel echocardiographic method allows to non-invasively assess myocardial work using pressure–strain loops. Even though left ventricular myocardial work has already emerged as a promising prognostic tool for various pathological conditions, its relationship with invasively-derived corresponding indices has not been assessed in humans yet. This study aimed to explore the correlation between left ventricular myocardial work (LVMW) indices and invasively derived left ventricular stroke work index (LVSWI) in a cohort of patients with advanced heart failure (HF) considered for heart transplantation. Methods and results All consecutive patients with advanced heart failure considered for heart transplantation from 2016 to 2021 that had already performed right heart catheterization (RHC) as part of the workup and with an available echocardiographic exam were included (n = 91). Myocardial work analysis was performed in 44 patients, according to exclusion criteria. Conventional LV functional parameters and LVMW indices, including LV global work index (LVGWI), LV global constructive work (LVGCW), LV global wasted work (LVGWW), LV global work efficiency (LVGWE), and other were calculated and compared with invasively measured LV stroke work index (LVSWI). Median age was 60 years [interquartile range (IQR): 54–63]. Median time between RHC and echocardiography was 0 months (IQR: 0–1). For the most part, etiology of HF was non-ischaemic (61.4%) and all patients were either on class NYHA II (61.4%) or III (27.3%). Median left ventricular ejection fraction was 25% (IQR: 22.3–32.3), median NT-proBNP 1377 pg/ml (IQR: 646–2570). Among conventional parameters of LV function, LVEF did not significantly correlate with LVSWI (r = 0.308; P = 0.050) whereas LV global longitudinal strain (LVGLS) did (r = −0.337; P = 0.031). With regard to LVMW indices, some of them demonstrated correlation with LVSWI, particularly LVGWI (r = 0.425; P = 0.006), LVGCW (r = 0.506; P = 0.001), LV global positive work (LVGPW; r = 0.464; P = 0.003), and LV global systolic constructive work (LVGSCW; r = 0.471; P = 0.002). Conclusions Among left ventricular myocardial work indices, LVGCW correlated better with invasively derived stroke work, thus representing a powerful and reliable tool for a more comprehensive evaluation of myocardial function.

scholarly journals Myocardial work: a new way to predict fibrosis in patients with hypertrophic cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Valentim Goncalves ◽  
S Aguiar Rosa ◽  
L Moura Branco ◽  
A Galrinho ◽  
A Fiarresga ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Global Longitudinal Strain ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Prognostic Information ◽  
Ventricular Ejection Fraction ◽  
Significant Fibrosis ◽  
Constructive Work ◽  
Global Work

Abstract Aims Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) adds prognostic information in patients with hypertrophic cardiomyopathy (HCM). Whether Myocardial work (MW), a new parameter on transthoracic echocardiographic (TTE), can predict significant fibrosis in HCM patients is unknown. Methods Single-centre evaluation of consecutively recruited HCM patients in which TTE and CMR were performed. MW and related indices were calculated from global longitudinal strain (GLS) and from estimated left ventricular pressure curves. The extent of LGE was quantitatively assessed. LGE ≥15% was chosen to define significant fibrosis. Logistic regression analysis was used to find the variables associated with LGE ≥15% and cut-off values were determined. Results Among the thirty-two patients analysed mean age was 57±16 years, 18 (56%) were male patients and the mean left ventricular ejection fraction by TTE was 67±8%. Global constructive work (GCW), global work index and GLS were significant predictors of LGE ≥15%. A cut-off ≤1550 mmHg% of GCW was able to predict significant fibrosis with a sensitivity of 92% and a specificity of 79%, while the best cut-off for GLS (&gt;−15%) had a sensitivity of 86% and a specificity of 72%. Conclusion GCW was the best parameter to predict significant left ventricular myocardial fibrosis in CMR, suggesting its utility in patients who may not be able to have a CMR study. Myocardial Work and LGE in CMR in HCM Funding Acknowledgement Type of funding source: None

scholarly journals Respiratory-related heart rate variability in progressive experimental heart failure

2005 ◽  
Vol 289 (4) ◽  
pp. H1729-H1735 ◽  
Author(s):  
Sophie Motte ◽  
Myrielle Mathieu ◽  
Serge Brimioulle ◽  
Anne Pensis ◽  
Lynn Ray ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Spectral Analysis ◽  
Left Ventricular ◽  
Right Atrial ◽  
Left Ventricular Ejection ◽  
Total Power ◽  
Progressive Heart Failure ◽  
Atrial Natriuretic

Heart failure is associated with autonomic imbalance, and this can be evaluated by a spectral analysis of heart rate variability. However, the time course of low-frequency (LF) and high-frequency (HF) heart rate variability changes, and their functional correlates during progression of the disease are not exactly known. Progressive heart failure was induced in 16 beagle dogs over a 7-wk period by rapid ventricular pacing. Spectral analysis of heart rate variability and respiration, echocardiography, hemodynamic measurements, plasma atrial natriuretic factor, and norepinephrine was obtained at baseline and every week, 30 min after pacing interruption. Progressive heart failure increased heart rate (from 91 ± 4 to 136 ± 5 beats/min; P < 0.001) and decreased absolute and normalized (percentage of total power) HF variability from week 1 and 2, respectively ( P < 0.01). Absolute LF variability did not change during the study until it disappeared in two dogs at week 7 ( P < 0.05). Normalized LF variability increased in moderate heart failure ( P < 0.01), leading to an increased LF-to-HF ratio ( P < 0.05), but decreased in severe heart failure ( P < 0.044; week 7 vs. week 5). Stepwise regression analysis revealed that among heart rate variables, absolute HF variability was closely associated with wedge pressure, right atrial and pulmonary arterial pressure, left ventricular ejection fraction and volume, ratio of maximal velocity of early (E) and atrial (A) mitral flow waves, left atrial diameter, plasma norepinephrine, and atrial natriuretic peptide (0.45 < r < 0.65, all P < 0.001). In tachycardia-induced heart failure, absolute HF heart rate variability is a more reliable indicator of cardiac dysfunction and neurohumoral activation than LF heart rate variability.

First clinical trial with etomoxir in patients with chronic congestive heart failure

2000 ◽  
Vol 99 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Stephan SCHMIDT-SCHWEDA ◽  
Christian HOLUBARSCH
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Sarcoplasmic Reticulum ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Stroke Volume ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

In the failing human myocardium, both impaired calcium homoeostasis and alterations in the levels of contractile proteins have been observed, which may be responsible for reduced contractility as well as diastolic dysfunction. In addition, levels of a key protein in calcium cycling, i.e. the sarcoplasmic reticulum Ca2+-ATPase, and of the α-myosin heavy chain have been shown to be enhanced by treatment with etomoxir, a carnitine palmitoyltransferase inhibitor, in normal and pressure-overloaded rat myocardium. We therefore studied, for the first time, the influence of long-term oral application of etomoxir on cardiac function in patients with chronic heart failure. A dose of 80 mg of etomoxir was given once daily to 10 patients suffering from heart failure (NYHA functional class II–III; mean age 55±4 years; one patient with ischaemic heart disease and nine patients with dilated idiopathic cardiomyopathy; all male), in addition to standard therapy. The left ventricular ejection fraction was measured echocardiographically before and after a 3-month period of treatment. Central haemodynamics at rest and exercise (supine position bicycle) were defined by means of a pulmonary artery catheter and thermodilution. All 10 patients improved clinically; no patient had to stop taking the study medication because of side effects; and no patient died during the 3-month period. Maximum cardiac output during exercise increased from 9.72±1.25 l/min before to 13.44±1.50 l/min after treatment (P < 0.01); this increase was mainly due to an increased stroke volume [84±7 ml before and 109±9 ml after treatment (P < 0.01)]. Resting heart rate was slightly reduced (not statistically significant). During exercise, for any given heart rate, stroke volume was significantly enhanced (P < 0.05). The left ventricular ejection fraction increased significantly from 21.5±2.6% to 27.0±2.3% (P < 0.01). In acute studies, etomoxir showed neither a positive inotropic effect nor vasodilatory properties. Thus, although the results of this small pilot study are not placebo-controlled, all patients seem to have benefitted from etomoxir treatment. Etomoxir, which has no acute inotropic or vasodilatory properties and is thought to increase gene expression of the sarcoplasmic reticulum Ca2+-ATPase and the α-myosin heavy chain, improved clinical status, central haemodynamics at rest and during exercise, and left ventricular ejection fraction.

scholarly journals β-Blocker Doses and Heart Rate in Patients with Heart Failure: Results from the National Norwegian Heart Failure Registry

2020 ◽  
Vol 5 (1) ◽  
pp. 1-10
Author(s):  
Torfinn Eriksen-Volnes ◽  
Arne Westheim ◽  
Lars Gullestad ◽  
Eva Kjøl Slind ◽  
Morten Grundtvig
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Sinus Rhythm ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Categorical Variables ◽  
Target Dose ◽  
Β Blocker ◽  
Β Blockers

Background: Use of β-blockers and titration to the highest tolerated dose are highly recommended by the European Society of Cardiology (ESC) guidelines for treatment of chronic heart failure (HF) with a reduced ejection fraction (HFrEF), but little attention has been paid to the achieved heart rate (HR) during this treatment. Objectives: The aim of the present study was to examine the achieved HR in relation to the use of β-blockers in these patients. Methods: All of the patients (n = 2,689) in the National Norwegian Heart Failure Registry as part of the Norwegian Cardiovascular Disease Registry with a sinus rhythm and left ventricular ejection fraction (LVEF) <40% at stable follow-up visiting specialised hospital outpatient HF clinics in Norway were included. The β-blocker doses were calculated as a percent of the target dose according to ESC HF guidelines. Differences between baseline variables according to the achieved HR were analysed by the Student’s t test for continuous variables and Pearson’s χ2 test for categorical variables. Linear regression was used to determine the predictors of HR ≥70 beats/min (bpm) in the multivariate analysis. Results: One third of the patients had a resting HR ≥70 bpm. Of the patients with an HR ≥70 bpm, 72.3% used less than the target dose of β-blocker; they were younger and had a higher NYHA class, more diabetes mellitus and chronic obstructive pulmonary disease (COPD), and higher N-terminal pro-B type natriuretic peptide (NT-proBNP) levels and estimated glomerular filtration rates compared to the patients with an HR <70 bpm. The 1-year mortality was 3.1, 3.7, 5.8, and 9.1% among the patients with an HR <70, 70–79, 80–89, and >89 bpm, respectively. Only 2 patients used ivabradine. Conclusions: In patients with HFrEF and sinus rhythm, an HR ≥70 bpm was associated with worse clinical variables and outcomes. A high proportion of the patients who had an HR ≥70 bpm was not treated with or/did not tolerate the target dose of a β-blocker, although the β-blocker dose was higher than in patients with an HR <70 bpm. This may suggest that increased efforts should be made to further increase the β-blocker dose, and treatment with ivabradine could be considered among patients with an HR ≥70 bpm.

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