scholarly journals Ranolazine combined with enalapril or metoprolol prevents progressive LV dysfunction and remodeling in dogs with moderate heart failure

2008 ◽  
Vol 295 (5) ◽  
pp. H2149-H2155 ◽  
Author(s):  
Sharad Rastogi ◽  
Victor G. Sharov ◽  
Sudhish Mishra ◽  
Ramesh C. Gupta ◽  
Brent Blackburn ◽  
...  
Keyword(s):  
Heart Failure ◽  
Oral Treatment ◽  
Capillary Density ◽  
Cellular Level ◽  
Left Ventricular ◽  
Lv Function ◽  
Systolic Volume ◽  
Moderate Heart Failure ◽  
Beneficial Effects ◽  
Lv Dysfunction

Acute intravenous infusion of ranolazine (Ran), an anti-ischemic/antiangina drug, was previously shown to improve left ventricular (LV) ejection fraction (EF) without a concomitant increase in myocardial oxygen consumption in dogs with chronic heart failure (HF). This study examined the effects of treatment with Ran alone and in combination with metoprolol (Met) or enalapril (Ena) on LV function and remodeling in dogs with HF. Dogs ( n = 28) with microembolization-induced HF were randomized to 3 mo oral treatment with Ran alone [375 mg twice daily (bid); n = 7], Ran (375 mg bid) in combination with Met tartrate (25 mg bid; n = 7), Ran (375 mg bid) in combination with Ena (10 mg bid; n = 7), or placebo (PL; Ran vehicle bid; n = 7). Ventriculographic measurements of LV end-diastolic volume (EDV) and end-systolic volume (ESV) and LV EF were obtained before treatment and after 3 mo of treatment. In PL-treated dogs, EDV and ESV increased significantly. Ran alone prevented the increase in EDV and ESV seen in the PL group and significantly increased EF, albeit modestly, from 35 ± 1% to 37 ± 2%. When combined with either Ena or Met, Ran prevented the increase in EDV, significantly decreased ESV, and markedly increased EF compared with those of PL. EF increased from 35 ± 1% to 40 ± 1% with Ran + Ena and from 34 ± 1% to 41 ± 1% with Ran + Met. Ran alone or in combination with Ena or Met was also associated with beneficial effects at the cellular level on histomorphometric parameters such as hypertrophy, fibrosis, and capillary density as well as the expression for pathological hypertrophy and Ca2+ cycling genes. In conclusion, Ran prevented progressive LV dysfunction and global and cellular myocardial remodeling, and Ran in combination with Ena or Met improved LV function beyond that observed with Ran alone.

scholarly journals Darbepoetin-α prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure

2008 ◽  
Vol 295 (6) ◽  
pp. H2475-H2482 ◽  
Author(s):  
Sharad Rastogi ◽  
Makoto Imai ◽  
Victor G. Sharov ◽  
Sudhish Mishra ◽  
Hani N. Sabbah
Keyword(s):  
Heart Failure ◽  
Caspase 3 ◽  
Hypoxia Inducible Factor ◽  
Left Ventricular ◽  
Stem Cell Marker ◽  
Lv Function ◽  
Systolic Volume ◽  
Beneficial Effects ◽  
End Diastolic Volume ◽  
End Systolic Volume

In anemic patients with heart failure (HF), erythropoietin-type drugs can elicit clinical improvement. This study examined the effects of chronic monotherapy with darbepoetin-α (DARB) on left ventricular (LV) function and remodeling in nonanemic dogs with advanced HF. HF [LV ejection fraction (EF) ∼25%] was produced in 14 dogs by intracoronary microembolizations. Dogs were randomized to once a week subcutaneous injection of DARB (1.0 μg/kg, n = 7) or to no therapy (HF, n = 7). All procedures were performed during cardiac catheterization under general anesthesia and under sterile conditions. LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF were measured before the initiation of therapy and at the end of 3 mo of therapy. mRNA and protein expression of caspase-3, hypoxia inducible factor-1α, and the bone marrow-derived stem cell marker c-Kit were determined in LV tissue. In HF dogs, EDV and ESV increased and EF decreased after 3 mo of followup. Treatment with DARB prevented the increase in EDV, decreased ESV, and increased EF. DARB therapy also normalized the expression of HIF-1α and active caspase-3 and enhanced the expression of c-Kit. We conclude that chronic monotherapy with DARB prevents progressive LV dysfunction and dilation in nonanemic dogs with advanced HF. These results suggest that DARB elicits beneficial effects in HF that are independent of the presence of anemia.

Differential atrial and ventricular expression of myocardial BNP during evolution of heart failure

1998 ◽  
Vol 274 (5) ◽  
pp. H1684-H1689 ◽  
Author(s):  
Andreas Luchner ◽  
Tracy L. Stevens ◽  
Daniel D. Borgeson ◽  
Margaret Redfield ◽  
Chi-Ming Wei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Arterial Pressure ◽  
Left Atrium ◽  
Limit Of Detection ◽  
Tissue Concentration ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Lv Function ◽  
Lv Dysfunction

Although brain natriuretic peptide (BNP) of myocardial origin is important in cardiovascular and renal function and as a marker of cardiac dysfunction, the expression of BNP in atrial and ventricular myocardium remains controversial both under normal conditions and in heart failure. We therefore determined left atrial and left ventricular (LV) gene expression and tissue concentration as well as circulating BNP during the evolution of rapid ventricular pacing-induced congestive heart failure (CHF) in the dog. Early LV dysfunction after 10 days of pacing was characterized by impaired LV function but maintained arterial pressure, and overt CHF after 38 days of pacing was characterized by further impaired LV function and decreased systemic arterial pressure. Under normal conditions, cardiac BNP mRNA and cardiac tissue BNP were of atrial origin. In early LV dysfunction, BNP mRNA and tissue BNP were markedly increased in the left atrium in association with an increase in circulating BNP but remained below or at the limit of detection in the LV. In overt CHF, BNP mRNA was further increased in the left atrium and first increased in the LV, together with an increase in LV tissue BNP and a further increase in circulating BNP. In the progression of CHF, early LV dysfunction is characterized by a selective increase in atrial BNP expression in association with increased circulating BNP. Overt CHF is characterized by an additional recruitment of ventricular BNP expression and a further increase in circulating BNP. These studies provide important new insight into the local and temporal regulation of cardiac BNP gene expression during the progression of heart failure and underscore the predominant endocrine role of atrial myocardium under normal conditions and in early LV dysfunction.

scholarly journals Cloud Connected Non-Invasive Medical Device for Instant Left Ventricular Dysfunction Assessment via Any Smartphone (Preprint)

2018 ◽  
Author(s):  
Mark Skowronski ◽  
Kaustubh Kale ◽  
Steven Borzak ◽  
Robert Chait
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Medical Device ◽  
Gold Standard ◽  
Left Ventricular ◽  
Assessment System ◽  
Lv Function ◽  
Time Intervals ◽  
Cardiac Time Intervals ◽  
Lv Dysfunction

BACKGROUND Left Ventricular (LV) dysfunction is the inability of the heart to effectively pump blood through the circulatory system, leading to compensation and eventually heart failure (HF). Ninety-one million American adults with predisposing conditions are at risk for HF and need better screening and diagnosis to prevent disease progression, and 24 million Americans with diagnosed HF need better monitoring to reduce the high hospital readmission rates (25% within 30 days; 50% within 6 months). This epidemic of HF is causing a significant burden on our health care system, with $20 billion in direct medical cost related to HF and $1 billion in in-patient hospital costs annually. Clinical interventions based on standard measurements (blood pressure, weight, electrocardiograms) have not demonstrated a significant reduction in readmissions or all-cause mortality within 180 days after enrollment. Successful treatment may be determined from 2D transthoracic echocardiography (echo) or right heart catherization, but these gold standard methods have limitations of cost, accessibility, and availability of sonographers and cardiologists. An alternative is the HEMOTAG CardioPulmonary Assessment System (CPAS), a new cloud-connected medical device that delivers cardiac time intervals comparable to the gold standard measurements of an echo from an easy-to-use, noninvasive device accessible via any smartphone. OBJECTIVE Given the clinical and economic impact of LV dysfunction and in view of the cost and accessibility of existing devices, there is a need for accurate, absolute, and actionable measurements, available instantly through a noninvasive and easy-to-use system. With the ability of provide rapid assessment of LV dysfunction in adults, keeping patients healthy and safe. The objective of the current study was to compare HEMOTAG to an echo for accuracy in assessment of LV dysfunction, using heart sounds and an ECG signal transduced via 3 thoracic electrodes. METHODS One hundred twenty-three consecutive patients undergoing 2D transthoracic echocardiograms were recruited at an outpatient cardiology clinic from March 2016 through February 2017. Conventional echo variables and cardiac time intervals were assessed, and all patients were analyzed using HEMOTAG which recorded multi-channel acoustic and ECG data. LV dysfunction was assessed using the 2016 American Society of Echocardiography (ASE) standard and compared to cardiac time intervals from HEMOTAG. Patients were separated by age for comparisons. HEMOTAG indices were then assessed to identify normal/abnormal LV function. RESULTS ASE diagnoses: 46 normal, 21 heart failure with preserved ejection fraction (HFpEF), 15 heart failure with reduced ejection fraction (HFrEF), and 41 indeterminate patients. HFrEF was defined as EF <53%, and systolic time ratio (STR=pre-ejection period/ejection time). 0.3 was a sensitive measure for detecting reduced EF as in HFrEF. Detecting EF <53% in patients older than 60: HEMOTAG STR sensitivity=65%, specificity=80%, AUC=.765; Echo STR sensitivity=85%, specificity=80%, AUC=0.895. CONCLUSIONS HEMOTAG represents a potentially widely applicable technology for the assessment of LV dysfunction via a noninvasive approach, providing absolute assessment (without requiring certified technicians to operate or interpretation of an echo) and enabling rapid, real-time, anywhere, anytime assessment of LV dysfunction.

scholarly journals In silico identification of potential calcium dynamics and sarcomere targets for recovering left ventricular function in rat heart failure with preserved ejection fraction

2021 ◽  
Vol 17 (12) ◽  
pp. e1009646
Author(s):  
Stefano Longobardi ◽  
Anna Sher ◽  
Steven A. Niederer
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Rat Heart ◽  
Cardiac Mechanics ◽  
Thick Filament ◽  
Cellular Level ◽  
Left Ventricular ◽  
Lv Function ◽  
Calcium Dynamics ◽  
Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is a complex disease associated with multiple co-morbidities, where impaired cardiac mechanics are often the end effect. At the cellular level, cardiac mechanics can be pharmacologically manipulated by altering calcium signalling and the sarcomere. However, the link between cellular level modulations and whole organ pump function is incompletely understood. Our goal is to develop and use a multi-scale computational cardiac mechanics model of the obese ZSF1 HFpEF rat to identify important biomechanical mechanisms that underpin impaired cardiac function and to predict how whole-heart mechanical function can be recovered through altering cellular calcium dynamics and/or cellular contraction. The rat heart was modelled using a 3D biventricular biomechanics model. Biomechanics were described by 16 parameters, corresponding to intracellular calcium transient, sarcomere dynamics, cardiac tissue and hemodynamics properties. The model simulated left ventricular (LV) pressure-volume loops that were described by 14 scalar features. We trained a Gaussian process emulator to map the 16 input parameters to each of the 14 outputs. A global sensitivity analysis was performed, and identified calcium dynamics and thin and thick filament kinetics as key determinants of the organ scale pump function. We employed Bayesian history matching to build a model of the ZSF1 rat heart. Next, we recovered the LV function, described by ejection fraction, peak pressure, maximum rate of pressure rise and isovolumetric relaxation time constant. We found that by manipulating calcium, thin and thick filament properties we can recover 34%, 28% and 24% of the LV function in the ZSF1 rat heart, respectively, and 39% if we manipulate all of them together. We demonstrated how a combination of biophysically based models and their derived emulators can be used to identify potential pharmacological targets. We predicted that cardiac function can be best recovered in ZSF1 rats by desensitising the myofilament and reducing the affinity to intracellular calcium concentration and overall prolonging the sarcomere staying in the active force generating state.

scholarly journals Apoptosis in severe, compensated pressure overload predominates in nonmyocytes and is related to the hypertrophy but not function

2011 ◽  
Vol 300 (3) ◽  
pp. H1062-H1068 ◽  
Author(s):  
Ricardo J. Gelpi ◽  
Misun Park ◽  
Shumin Gao ◽  
Sunil Dhar ◽  
Dorothy E. Vatner ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systolic Pressure ◽  
Pressure Overload ◽  
Wall Stress ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Lv Dysfunction ◽  
The Face ◽  
Canine Models

It is widely held that myocyte apoptosis in left ventricular hypertrophy (LVH) contributes to left ventricle (LV) dysfunction and heart failure. The main goal of this investigation was to determine if there is a statistical relationship among LV hypertrophy, apoptosis and LV function, and importantly whether the apoptosis occurs in myocytes or nonmyocytes in the heart. We used both rat and canine models of severe LVH induced by chronic thoracic aortic banding with resultant LV-aortic pressure gradients 145–155 mmHg and increases in LV/body weight of 58 and 70%. These models also provided the ability to examine transmural apoptosis in LVH. In both models, the overwhelming majority (88%) of apoptotic cells were nonmyocytes. The regressions for apoptosis vs. LVH were stronger for nonmyocytes than myocytes and also stronger in the subendocardium than the subepicardium. Importantly, LV systolic and diastolic wall stresses were normal, indicating that the apoptosis could not be attributed to LV stretch or heart failure. In addition, there was no relationship between the extent of apoptosis and LV ejection fraction, which actually increased ( P < 0.05), in the face of elevated LV systolic pressure, indicating that greater apoptosis did not result in a decrease in LV function. Thus, in response to chronic, severe pressure overload, LVH in the absence of LV dilation, and elevated LV wall stress, apoptosis occurred predominantly in nonmyocytes in the myocardial interstitium, more in the subendocardium than the subepicardium. The extent of apoptosis was linearly related to the amount of LV hypertrophy, but not to LV function.

scholarly journals Heart failure in survivors of out-of-hospital cardiac arrest – factors associated with reduced systolic ventricular function at follow-up

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H.S.Z Bahrami ◽  
J Kjaergaard ◽  
J.H Thomsen ◽  
F Lippert ◽  
L Koeber ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Arrest ◽  
Hospital Discharge ◽  
Left Ventricular ◽  
Lv Function ◽  
Funding Source ◽  
Factors Associated ◽  
Lv Dysfunction ◽  
Hospital Cardiac Arrest

Abstract Background Survival after out-of-hospital cardiac arrest (OHCA) has increased in recent years but is still only 10%. Little is known about the association between post-resuscitation comorbidity and heart failure after discharge from the initial OHCA-admission. Purpose In OHCA-survivors we aimed to describe predictors of left ventricular (LV) dysfunction, defined as LV ejection fraction (LVEF) &lt;40%, at follow-up. Methods A consecutive cohort of OHCA-patients with cardiac cause from 2007 to 2011 without a pre-OHCA congestive heart failure diagnosis (according to the Danish National Patient Registry, which holds data on all Danish citizens) were retrospectively examined. Logistic regression analyses were used to assess factors associated with LV dysfunction (LVEF &lt;40%) at follow-up after a median of 6 months. Follow-up was not performed systematically in the OHCA-survivors and data from follow-up was assessed by reading of patient charts. Results A total of 365 OHCA-survivors with a mean age of 61 years were discharged alive from hospital. LVEF &lt;40% at hospital discharge was seen in 54% (n=184, 7% missing), and at follow-up after a median of 6 months 19% (n=69) of the total OHCA-cohort of survivors still had LV dysfunction. Factors associated with LV dysfunction at follow-up were chronic ischemic heart disease (IHD) prior to OHCA (odds ratio (OR) = 2.9 (95% CI: 1.2 – 7.1)) and ST-elevation myocardial infarction (STEMI) as cause of OHCA (OR = 2.9 (1.4–6.0)), whereas age, gender, high comorbidity burden prior to OHCA or pre-hospital circumstances (including shockable cardiac arrest rhythm) were not. Conclusion More than half of OHCA-survivors with LVEF &lt;40% at hospital discharge improved LV function and LV dysfunction at follow-up after a median of 6 months after discharge was present in 1 in 5 (19%) of the cohort. Chronic IHD and STEMI were the only factors significantly associated with LV dysfunction at follow-up. A systematic follow-up including echocardiography in the outpatient clinic for OHCA-survivors is recommended especially in patients with reduced LV function at discharge and in STEMI-patients in order to assess the appropriateness of heart failure medication and an implantable cardiac defibrillator. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Danish Foundation Trygfonden

Abstract 567: Ivabradine Improved Cardiac Function, Fibrosis And Hyperexcitability In Rat Post-myocardial Infarction Severe Heart Failure.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paul Milliez ◽  
Johnny Nehme ◽  
Estelle Robidel ◽  
Camille Rodriguez ◽  
JaneLise Samuel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Sinus Node ◽  
Severe Heart Failure ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Adult Rats ◽  
Beneficial Effects ◽  
Lv Dysfunction

The selective sinus node I f current inhibitor Ivabradine (Iva) reduces heart rate (HR) without any other hemodynamic effects. We investigated in a rat model of post-MI severe heart failure, the effects of a chronic Iva administration on LV function, structure and electrical remodelling. Methods . MI was induced by coronary artery ligation in adult rats: echocardiography and Holter ECG were performed 2 months (m) after MI i.e. before randomization (n=12/group) into MI and MI+Iva (10 mg/kg/d) groups, and 3 m later. In ventricles, collagen was quantified after Sirius red staining of section and ACE and AT1-receptor mRNA expression (normalized to GAPDH) was assayed by RT-PCR. Results : 2m-post MI, all rats displayed severe decreased LVEF, and increased LVEDP compared to sham-operated (28%±3 vs 66%±5 and 32±2 vs 10±1 mmHg, respectively; p<0.05). In 5m-post-MI, LVEF and LVEDP were stabilized with Iva (31±1% and 24±2 mmHg), while they were worsened in MI groups (21±3% and 38±2mmHg). Blood pressure, body and heart weights were similar in MI and MI+Iva. Iva reduced HR (RR: 201±5 vs 179±3 ms in MI; p<0.05) and ventricular premature beats (514±152 vs 4717±1363/day for MI; p<0.05), and improved HR variability (SDRR: 5±1.5 vs 3.9± 0.6 for MI; p<0.05). There were no effects of Iva on duration (ms) of PR (45±3 vs 44±3), QRS (51±3 vs 46±3) and QT (106±7 vs 99±6, for MI and MI+Iva, respectively). The increased ventricular collagen in MI (4.0±0.1 vs 0.8±0.2 % in sham; p<0.05) was markedly reduced in MI+Iva (1.8±0.1%, p<0.0001 vs MI). The increases in ventricular gene expression of ACE and AT-1 receptor in MI rats (2.5 and 6 folds versus sham operated, respectively, p<0.05) were completely blunted by Iva treatment. Conclusion: Iva treatment of the post-MI heart failure: 1- markedly reduced HR and ventricular excitability and without harmful effects on conduction; 2- prevented worsening of LV dysfunction and remodelling, and 3- induced a downregulation of cardiac RAAS transcripts. Thus, through its negative chronotropic effects, Iva allowed the maintenance of cardiac function below the threshold for a tissular RAAS stimulation even in severe post-MI cardiac failure. Such beneficial effects of Iva on cardiac remodelling open new perspectives for the treatment of severe heart failure

scholarly journals Left ventricular function monitoring in heart failure

2019 ◽  
Vol 21 (Supplement_M) ◽  
pp. M17-M19 ◽  
Author(s):  
Jelena Čelutkienė ◽  
Ilaria Spoletini ◽  
Andrew J S Coats ◽  
Ovidiu Chioncel
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Consensus Meeting ◽  
Left Ventricular Ejection ◽  
Lv Function ◽  
Prognostic Information ◽  
Ventricular Ejection Fraction ◽  
Lv Dysfunction ◽  
Key Points

Abstract Imaging modalities are used for screening, risk stratification and monitoring of heart failure (HF). In particular, echocardiography represents the cornerstone in the assessment of left ventricular (LV) dysfunction. Despite the well-known limitations of LV ejection fraction, this parameter, repeated assessment of LV function is recommended for the diagnosis and care of patients with HF and provides prognostic information. Left ventricular ejection fraction (LVEF) has an essential role in phenotyping and appropriate guiding of the therapy of patients with chronic HF. This document reflects the key points concerning monitoring LV function discussed at a consensus meeting on physiological monitoring in the complex multi-morbid HF patient under the auspices of the Heart Failure Association of the ESC.

Sign in / Sign up

Export Citation Format

Share Document