Linearity of the left ventricular end-systolic pressure-volume relation in patients with severe heart failure

To test the hypothesis that alterations in left ventricular (LV) mechanoenergetics and the LV inotropic response to afterload manifest early in the evolution of heart failure, we examined six anesthetized dogs instrumented with LV micromanometers, piezoelectric crystals, and coronary sinus catheters before and after 24 h of rapid ventricular pacing (RVP). After autonomic blockade, the end-systolic pressure-volume relation (ESPVR), myocardial O2 consumption (MV˙o 2), and LV pressure-volume area (PVA) were defined at several different afterloads produced by graded infusions of phenylephrine. Short-term RVP resulted in reduced preload with proportionate reductions in stroke work and the maximum first derivative of LV pressure but with no significant reduction in baseline LV contractile state. In response to increased afterload, the baseline ESPVR shifted to the left with maintained end-systolic elastance ( E es). In contrast, after short-term RVP, in response to comparable increases in afterload, the ESPVR displayed reduced E es ( P < 0.05) and significantly less leftward shift compared with control ( P< 0.05). Compared with the control MV˙o 2-PVA relation, short-term RVP significantly increased the MV˙o 2 intercept ( P< 0.05) with no change in slope. These results indicate that short-term RVP produces attenuation of afterload-induced enhancement of LV performance and increases energy consumption for nonmechanical processes with maintenance of contractile efficiency, suggesting that early in the development of tachycardia heart failure, there is blunting of length-dependent activation and increased O2requirements for excitation-contraction coupling, basal metabolism, or both. Rather than being adaptive mechanisms, these abnormalities may be primary defects involved in the progression of the heart failure phenotype.

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Left ventricular spherical dilation and regional contractile dysfunction in dogs with heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.273.3.h1058 ◽

1997 ◽

Vol 273 (3) ◽

pp. H1058-H1067 ◽

Cited By ~ 7

Author(s):

M. Suzuki ◽

C. P. Cheng ◽

N. Ohte ◽

W. C. Little

Keyword(s):

Heart Failure ◽

Structural Changes ◽

Contractile Function ◽

Systolic Pressure ◽

Left Ventricular ◽

Stroke Work ◽

End Diastolic Volume ◽

Work Area ◽

Rv Pacing ◽

Volume Relation

Left ventricular (LV) short- and long-axis contractile function and LV structural changes were serially measured in eight instrumented dogs during the development of congestive heart failure (CHF) induced by rapid right ventricular (RV) pacing. After 10 days of pacing, LV end-diastolic volume (VED) had not increased; however, the slope of LV end-systolic pressure-volume relation had decreased from 7.4 +/- 2.6 to 4.9 +/- 1.1 mmHg/ml (P < 0.05), and the slope of LV stroke work-VED relation had fallen from 78.4 +/- 9.1 to 64.2 +/- 7.2 mmHg (P < 0.05). The slopes of end-systolic pressure-dimension relation and the stroke work area-end-diastolic dimension relation in the short axes (i.e., anteroposterior and septal-lateral) had decreased by 30% (P < 0.05), whereas the slopes of the long-axis (i.e., apical-basal) relations were unchanged (not significant). After 20 days of pacing, VED had significantly increased by 14% due to selective dilation of the short axes by 7%, and LV global contractility had further declined with a 40% contractile depression in the short axes and a 25% contractile depression in the long axis. After 30 days, the long-axis dimension at end diastole was also significantly increased with a further increase in the short-axis dimensions. In contrast to the spherical dilation occurring during CHF, acute volume loading of normal animals produced symmetrical LV dilation. These observations suggest that heterogeneous contractile depression initiates the spherical end-diastolic chamber dilation in pacing-induced CHF.

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Three-Dimensional Right Ventriculo-Arterial Coupling as an Independent Correlate of Severe Heart Failure Symptoms in Patients with Dilated Cardiomyopathy

10.22541/au.163254704.43778322/v1 ◽

2021 ◽

Author(s):

Aura Vijiiac ◽

Sebastian Onciul ◽

Silvia Deaconu ◽

Radu Vatasescu ◽

Claudia Guzu ◽

...

Keyword(s):

Heart Failure ◽

Pulmonary Artery ◽

Right Ventricular ◽

Dilated Cardiomyopathy ◽

Three Dimensional ◽

Severe Heart Failure ◽

Systolic Pressure ◽

Left Ventricular ◽

Pulmonary Artery Systolic Pressure ◽

Characteristic Analysis

Background: Right ventricular-pulmonary artery coupling (RVPAC) is a predictor of outcome in pulmonary hypertension. However, the role of this parameter in dilated cardiomyopathy (DCM) remains to be established. The aim of this study was to assess the contribution of RVPAC to the occurrence of severe heart failure (HF) symptoms in patients with DCM using three-dimensional (3D) echocardiography. Methods: We prospectively screened 139 outpatients with DCM, 105 of whom were enrolled and underwent 3D echocardiographic assessment. RVPAC was estimated non-invasively as the 3D right ventricular stroke volume (SV) to end-systolic volume (ESV) ratio. Severe HF symptoms were defined by New York Heart Association (NYHA) class III or IV. We evaluated differences in RVPAC across NYHA classes and the ability of RVPAC to predict severe symptoms. Results: Mean left ventricular (LV) ejection fraction was 28±7%. Mean RVPAC was 0.77±0.30 and it was significantly more impaired with increasing symptom severity (p=0.001). RVPAC was the only independent correlate of severe HF symptoms, after adjusting for age, diuretic use, LV systolic function, LV diastolic function and pulmonary artery systolic pressure (OR 0.035 [95% CI, 0.004 – 0.312], p=0.003). By receiver-operating characteristic analysis, the RVPAC cut-off value for predicting severely symptomatic status was 0.54 (area under the curve=0.712, p<0.001). Conclusion: 3D echocardiographic SV/ESV ratio is an independent correlate of severe HF symptoms in patients with DCM. 3D RVPAC might prove to be a useful risk stratification tool for these patients, should it be further validated in larger studies.

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Inotropic effect of enoximone in patients with severe heart failure: Demonstration by left ventricular end-systolic pressure-volume analysis

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(87)80316-9 ◽

1987 ◽

Vol 9 (5) ◽

pp. 1117-1123 ◽

Cited By ~ 48

Author(s):

Howard C. Herrmann ◽

Terrence D. Ruddy ◽

G. William Dec ◽

H. William Strauss ◽

Charles A. Boucher ◽

...

Keyword(s):

Heart Failure ◽

Severe Heart Failure ◽

Systolic Pressure ◽

Left Ventricular ◽

Inotropic Effect ◽

Volume Analysis

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Cardiac mitofusin-1 is declined in non-responding patients with idiopathic dilated cardiomyopathy

European Heart Journal ◽

10.1093/ehjci/ehaa946.3601 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

Y Hsiao ◽

I Shimizu ◽

T Wakasugi ◽

S Jiao ◽

T Watanabe ◽

...

Keyword(s):

Electron Microscopy ◽

Heart Failure ◽

Ventricular Myocytes ◽

Severe Heart Failure ◽

Left Ventricular ◽

Neonatal Rat ◽

Heart Failure Patients ◽

Underlying Mechanisms ◽

Neonatal Rat Ventricular Myocytes ◽

Mitofusin 1

Abstract Background/Introduction Mitochondria are dynamic regulators of cellular metabolism and homeostasis. The dysfunction of mitochondria has long been considered a major contributor to aging and age-related diseases. The prognosis of severe heart failure is still unacceptably poor and it is urgent to establish new therapies for this critical condition. Some patients with heart failure do not respond to established multidisciplinary treatment and they are classified as “non-responders”. The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Purpose Studies indicate mitochondrial dysfunction has causal roles for metabolic remodeling in the failing heart, but underlying mechanisms remain to be explored. This study tried to elucidate the role of Mitofusin-1 in a failing heart. Methods We examined twenty-two heart failure patients who underwent endomyocardial biopsy of intraventricular septum. Patients were classified as non-responders when their left-ventricular (LV) ejection fraction did not show more than 10% improvement at remote phase after biopsy. Fourteen patients were classified as responders, and eight as non-responders. Electron microscopy, quantitative PCR, and immunofluorescence studies were performed to explore the biological processes or molecules involved in failure to respond. In addition to studies with cardiac tissue specific knockout mice, we also conducted functional in-vitro studies with neonatal rat ventricular myocytes. Results Twenty-two patients with IDCM who underwent endomyocardial biopsy were enrolled in this study, including 14 responders and 8 non-responders. Transmission electron microscopy (EM) showed a significant reduction in mitochondrial size in cardiomyocytes of non-responders compared to responders. Quantitative PCR revealed that transcript of mitochondrial fusion protein, Mitofusin-1, was significantly reduced in non-responders. Studies with neonatal rat ventricular myocytes (NRVMs) indicated that the beta-1 adrenergic receptor-mediated signaling pathway negatively regulates Mitofusin-1 expression. Suppression of Mitofusin-1 resulted in a significant reduction in mitochondrial respiration of NRVMs. We generated left ventricular pressure overload model with thoracic aortic constriction (TAC) in cardiac specific Mitofusin-1 knockout model (c-Mfn1 KO). Systolic function was reduced in c-Mfn1 KO mice, and EM study showed an increase in dysfunctional mitochondria in the KO group subjected to TAC. Conclusions Mitofusin-1 becomes a biomarker for non-responders with heart failure. In addition, our results suggest that therapies targeting mitochondrial dynamics and homeostasis would become next generation therapy for severe heart failure patients. Funding Acknowledgement Type of funding source: None

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Right ventricular function and its coupling with the pulmonary circulation in acute heart failure

European Heart Journal ◽

10.1093/ehjci/ehaa946.1218 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Barki ◽

M Losito ◽

M.M Caracciolo ◽

F Bandera ◽

M Rovida ◽

...

Keyword(s):

Heart Failure ◽

Acute Heart Failure ◽

Acute Phase ◽

Pulmonary Circulation ◽

Heart Function ◽

Systolic Pressure ◽

Left Ventricular ◽

Response To Treatment ◽

The Right ◽

B Lines

Abstract Background The right ventricle (RV) is extremely sensitive to hemodynamic changes and increased impedance. In acute heart failure (AHF), the development of pulmonary venous congestion and the increase of left ventricular (LV) filling pressures favors pulmonary vascular adverse remodeling and ultimately RV dysfunction, leading to the onset of symptoms and to a further decay of cardiac dynamics. Purpose The aim of the study was to evaluate RV morphology and functional dynamics at admission and discharge in patients hospitalized for AHF, analyzing the role and the response to treatment of the RV and its coupling with pulmonary circulation (PC). Methods Eighty-one AHF patients (mean age 75.75±10.6 years, 59% males) were prospectively enrolled within 24–48 hours from admission to the emergency department (ED). In either the acute phase and at pre-discharge all patients underwent M-Mode, 2-Dimensional and Doppler transthoracic echocardiography (TTE), as well as lung ultrasonography (LUS), to detect an increase of extravascular lung water (EVLW) and development of pleural effusion. Laboratory tests were performed in the acute phase and at pre-discharge including the evaluation of NT-proBNP. Results At baseline we observed a high prevalence of RV dysfunction as documented by a reduced RV systolic longitudinal function [mean tricuspid annular plane systolic excursion (TAPSE) at admission of 16.47±3.86 mm with 50% of the patients exhibiting a TAPSE<16mm], a decreased DTI-derived tricuspid lateral annular systolic velocity (50% of the subjects showed a tricuspid s' wave<10 cm/s) and a reduced RV fractional area change (mean FAC at admission of 36.4±14.6%). Furthermore, an increased pulmonary arterial systolic pressure (PASP) and a severe impairment in terms of RV coupling to PC was detected at initial evaluation (mean PASP at admission: 38.8±10.8 mmHg; average TAPSE/PASP at admission: 0.45±0.17 mm/mmHg). At pre-discharge a significant increment of TAPSE (16.47±3.86 mm vs. 17.45±3.88; p=0.05) and a reduction of PASP (38.8±10.8 mmHg vs. 30.5±9.6mmHg, p<0.001) was observed. Furthermore, in the whole population we assisted to a significant improvement in terms of RV function and its coupling with PC as demonstrated by the significant increase of TAPSE/PASP ratio (TAPSE/PASP: 0.45±0.17 mm/mmHg vs 0.62±0.20 mm/mmHg; p<0.001). Patients significantly reduced from admission to discharge the number of B-lines and NT-proBNP (B-lines: 22.2±17.1 vs. 6.5±5 p<0.001; NT-proBNP: 8738±948 ng/l vs 4227±659 ng/l p<0.001) (Figure 1). Nonetheless, no significant changes of left atrial and left ventricular dimensions and function were noted. Conclusions In AHF, development of congestion and EVLW significantly impact on the right heart function. Decongestion therapy is effective for restoring acute reversal of RV dysfunction, but the question remains on how to impact on the biological properties of the RV. Funding Acknowledgement Type of funding source: None

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The crosstalk of HDAC3, microRNA-18a and ADRB3 in the progression of heart failure

Cell & Bioscience ◽

10.1186/s13578-020-00523-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jingtao Na ◽

Haifeng Jin ◽

Xin Wang ◽

Kan Huang ◽

Shuang Sun ◽

...

Keyword(s):

Heart Failure ◽

Expression Patterns ◽

Systolic Pressure ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Ventricular Pressure ◽

Luciferase Reporter ◽

Left Ventricular Ejection ◽

Tunel Staining ◽

Ventricular Ejection Fraction

Abstract Background Heart failure (HF) is a clinical syndrome characterized by left ventricular dysfunction or elevated intracardiac pressures. Research supports that microRNAs (miRs) participate in HF by regulating targeted genes. Hence, the current study set out to study the role of HDAC3-medaited miR-18a in HF by targeting ADRB3. Methods Firstly, HF mouse models were established by ligation of the left coronary artery at the lower edge of the left atrial appendage, and HF cell models were generated in the cardiomyocytes, followed by ectopic expression and silencing experiments. Numerous parameters including left ventricular posterior wall dimension (LVPWD), interventricular septal dimension (IVSD), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LEVDP), heart rate (HR), left ventricular pressure rise rate (+ dp/dt) and left ventricular pressure drop rate (-dp/dt) were measured in the mice. In addition, apoptosis in the mice was detected by means of TUNEL staining, while RT-qPCR and Western blot analysis were performed to detect miR-18a, HDAC3, ADRB3, cMyb, MMP-9, Collagen 1 and TGF-β1 expression patterns. Dual luciferase reporter assay validated the targeting relationship between ADRB3 and miR-18a. Cardiomyocyte apoptosis was determined by means of flow cytometry. Results HDAC3 and ADRB3 were up-regulated and miR-18a was down-regulated in HF mice and cardiomyocytes. In addition, HDAC3 could reduce the miR-18a expression, and ADRB3 was negatively-targeted by miR-18a. After down-regulation of HDAC3 or ADRB3 or over-expression of miR-18a, IVSD, LVEDD, LVESD and LEVDP were found to be decreased but LVPWD, LVEF, LVFS, LVSP, + dp/dt, and −dp/dt were all increased in the HF mice, whereas fibrosis, hypertrophy and apoptosis of HF cardiomyocytes were declined. Conclusion Collectively, our findings indicate that HDAC3 silencing confers protection against HF by inhibiting miR-18a-targeted ADRB3.

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Anaemia and heart failure

Open Medicine ◽

10.2478/s11536-010-0060-3 ◽

2011 ◽

Vol 6 (1) ◽

pp. 11-25

Author(s):

Enrico Vizzardi ◽

Tania Bordonali ◽

Elena Tanghetti ◽

Marco Metra ◽

Livio Cas

Keyword(s):

Heart Failure ◽

Ventricular Dysfunction ◽

Severe Heart Failure ◽

Left Ventricular ◽

Favourable Effect ◽

Heart Failure Trial ◽

Patients With Heart Failure ◽

Darbepoetin Alpha ◽

Main Determinants ◽

Independent Determinant

AbstractAnaemia is one of the most frequent co-morbidities in patients with heart failure. Its prevalence increases from 4% to7% in subjects with asymptomatic left ventricular dysfunction to >30% in patients with severe heart failure. Renal insufficiency, activation of inflammatory mediators and treatment with renin-angiotensin antagonists seem to be its main determinants. The results of many studies agree in providing evidence that anaemia is a powerful independent determinant of survival in patients with heart failure. However, the mechanisms of this relation are still not fully understood. Moreover a favourable effect of the correction of anaemia on prognosis has not yet been shown. Also In addition to this, controlled studies assessing its effects on exercise tolerance have yielded controversial results. Further research is needed to assess the effect of correcting anaemia in chronic heart failure (CHF) patients; ongoing reduction of events with RED-HF (Darbepoetin alpha in heart failure) trial will help define the role.

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Abstract 65: Anemia-related Heart Failure in Sub-saharan African Sickle Cell Disease Patients

Circulation Research ◽

10.1161/res.121.suppl_1.65 ◽

2017 ◽

Vol 121 (suppl_1) ◽

Author(s):

Adebayo C Atanda ◽

Yahya Aliyu ◽

Oluwafunmilayo Atanda ◽

Aliyu Babadoko ◽

Aisha Suleiman ◽

...

Keyword(s):

Heart Failure ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Systolic Pressure ◽

Left Ventricular ◽

Hemoglobin Level ◽

Sub Saharan Africa ◽

Cell Disease ◽

Jet Velocity ◽

Sub Saharan

Introduction: Anemia has been implicated in heart failure. Existing literatures, involving predominantly African-Americans, suggests that Sickle Cell Disease (SCD) maybe linked to various cardiovascular complications including pulmonary hypertension and left venticular dysfunction. Peculiarly, our study involves exclusively Sub-Saharan population. Method: We conducted a cross sectional observational study of 208 hydroxyurea-naive consecutive SCD patients aged 10-52 years at steady state and 94 healthy non-matched controls who were studied in an out patient clinic in Sub-Saharan Africa. SCD patients were required to have electrophoretic or liquid chromatography documentation of major sickling phenotypes. Control group was required to have non-sickling phenotypes. Cardiac measurements were performed with TransThoracic Echo according to American Society of Echocardiography guidelines. Hemoglobin level was also obtained. Results: Hemoglobin level in SCD group (8.5+/- 1.5) was significant (P<0.001) compared to control (13.8+/- 1.7). Although SCD group had significantly higher values of left ventricular (LV) size, there was no qualitative evidence of LV dysfunction. SCD group had higher values of Ejection Fraction but not statistically significant. There was no evidence of LV wall stiffening to impair proper filling in SCD group, with the ratio of early to late ventricular filling velocities, E/A ratio elevated (1.7+/-0.4 compared to 1.6+/- 0.4; P=0.010). Right ventricular systolic pressure was determined using the formula of 4x Tricuspid Reugurgitant jet (TRV) square as an indirect measurement of Pulmonary arterial systolic pressure. SCD patients had significantly higher mean±SD values for tricuspid regurgitant jet velocity than did the controls (2.1±0.6 vs. 1.8±0.5; p= 0.001). Within the SCD group, there was no clear pattern of worsening diastolic function with increased TRV. Furthermore, E/A had a significant positive relationship with jet velocity in bivariate analysis (R=0.20; P=0.013). Conclusions: We were unable to demonstrate existence of anemia-associated left ventricular dysfunction in Sub-Saharan African with SCD. Further studies is required to highlight the reason behind this finding.

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Abstract 16574: Heart Failure Biomarkers (NT-proBNP, Gal-3, sST2) Correlate With Right Ventricular Systolic Pressure and Provide Insight to Poor CRT Response: A BIOCRT Substudy

Circulation ◽

10.1161/circ.132.suppl_3.16574 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Roderick C Deaño ◽

Jackie Szymonifka ◽

Qing Zhou ◽

Jigar H Contractor ◽

Zachary Lavender ◽

...

Keyword(s):

Heart Failure ◽

Right Ventricular ◽

Systolic Pressure ◽

Fold Increase ◽

Left Ventricular ◽

Cardiac Resynchronization ◽

Cardiac Transplant ◽

Right Ventricular Systolic Pressure ◽

Ventricular Systolic Pressure ◽

Crt Response

Objective: Patients with heart failure (HF) and pulmonary hypertension (PH) have worse outcomes after cardiac resynchronization therapy (CRT). The relationship of circulating HF biomarkers and right ventricular systolic pressure (RVSP) may provide insight to the mechanism between PH and poor CRT response. Methods: In 90 patients (age 65 ± 13, 78% male, EF 26 ± 8%, RVSP 44 ± 12 mmHg) undergoing CRT, we measured baseline RVSP by echocardiography and obtained peripheral blood samples drawn at the time of device implantation. We measured levels of established and emerging HF biomarkers (Table 1). CRT non-response was defined as no improvement of adjudicated HF Clinical Composite Score at 6 months. Major adverse cardiac event (MACE) was defined as composite endpoint of death, cardiac transplant, left ventricular assist device, and HF hospitalization within 2 years. Results: There were 34% CRT non-responders and 27% had MACE. Per 1 unit increase in log-transformed RVSP, there was an 11-fold increase risk of having CRT non-response (odd ratio [OR] 11.0, p=0.01) and over 5-fold increase of developing 2-year MACE (hazard ratio [HR] 5.8, p=0.02). When comparing patients with severe PH (RVSP>60 mmHg) to those without PH (RVSP < 35 mmHg), there was an 8-fold increase in CRT nonresponse (OR 8.4, p=0.03) but no difference in MACE (p=NS). RVSP was correlated with increased biomarker levels of myocardial stretch and fibrosis, but not myocardial necrosis (Table 1). Conclusions: Higher RVSP is associated with greater rates of CRT non-response and adverse clinical outcomes. The mechanistic association between severe PH and CRT nonresponse may be explained by the biomarker profile reflective of myocardial wall stretch and fibrosis.

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