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.

SR Ca(2+)-ATPase activity and expression in ventricular myocardium of dogs with heart failure

1997 ◽  
Vol 273 (1) ◽  
pp. H12-H18 ◽  
Author(s):  
R. C. Gupta ◽  
H. Shimoyama ◽  
M. Tanimura ◽  
R. Nair ◽  
M. Lesch ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atpase Activity ◽  
Sodium Dodecyl ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Maximal Velocity ◽  
Protein Levels ◽  
Lv Dysfunction ◽  
Lv Ejection Fraction ◽  
Tissue Specimens

The purpose of this study was to examine the activity and expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase in left ventricular (LV) myocardium of dogs with chronic heart failure (HF). LV and right ventricular (RV) tissue specimens were obtained from six normal (NL) control dogs and six dogs with chronic HF (LV ejection fraction, 23 +/- 2%) produced by multiple sequential intracoronary microembolizations. Thapsigargin-sensitive Ca(2+)-ATPase activity was measured in isolated SR membrane fractions prepared from LV and RV myocardium. Ca(2+)-ATPase expression, using a specific dog myocardium monoclonal antibody, was measured in sodium dodecyl sulfate (SDS) extract prepared from LV and RV myocardium. Ca(2+)-ATPase activity in both ventricles of NL or HF dogs increased with increasing Ca2+ concentration and reached a plateau at 3 microM Ca2+. The maximal velocity (Vmax, mumol Pi released.min-1.mg-1) of Ca(2+)-ATPase activity was significantly lower in LV of HF dogs compared with NL (0.15 +/- 0.01 vs. 0.23 +/- 0.01, P < 0.05), whereas the affinity of the Ca2+ pump for Ca2+ was unchanged. LV tissue levels of Ca(2+)-ATPase (densitometric units/5 micrograms noncollagen protein) were also significantly lower in LV myocardium of HF dogs compared with NL (3.52 +/- 0.43 vs. 5.53 +/- 0.47, P < 0.05). No significant differences in Ca(2+)-ATPase activity or expression were observed in RV myocardium of HF dogs compared with NL. We conclude that SR Ca(2+)-ATPase activity and protein levels are reduced in LV myocardium of dogs with chronic HF. This abnormality of the SR Ca2+ pump of the failed LV can result in impaired Ca2+ uptake and ultimately to Ca2+ overload and global 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.

P5655Efficacy of new-generation atrial antitachycardia pacing for atrial tachyarrhythmias in patients with left ventricular dysfunction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Kamakura ◽  
K Nakajima ◽  
N Kataoka ◽  
M Wada ◽  
K Yamagata ◽  
...  
Keyword(s):  
Success Rate ◽  
Left Atrium ◽  
Persistent Atrial Fibrillation ◽  
Left Ventricular ◽  
Control Group ◽  
Lv Function ◽  
Antitachycardia Pacing ◽  
Atrial Tachyarrhythmias ◽  
Lv Dysfunction ◽  
New Generation

Abstract Background The progression to persistent atrial fibrillation (AF) is associated with a worse clinical outcome in patients with previous atrial tachyarrhythmias. New-generation atrial antitachycardia pacing (ATP) (Reactive ATP) reduced the progression to persistent AF in patients with pacemaker and preserved left ventricular (LV) function. However, little is known about the efficacy of Reactive ATP in patients with cardiac implantable electronic devices (CIED) and LV dysfunction. Purpose We aimed to investigate the efficacy of Reactive ATP for atrial tachyarrhythmias in patients with LV dysfunction (LV ejection fraction [LVEF] <40%). Methods This study included 423 patients with CIED and previous atrial tachyarrthythmias. Reactive ATP was programmed in 284 patients (ATP group) and 139 were implanted with a dual-chamber device without ATP function (control group). The differences in the success rate of ATP and incidence of progression to persistent AF (≥7 days) between the ATP and control groups were evaluated in 108 patients with LVEF <40% (reduced LVEF) and 315 with LVEF ≥40% (preserved LVEF). Patients with persistent AF were excluded from this study. Results During 710±337 days of follow-up period, 16 patients (15%) with reduced LVEF and 51 (16%) with preserved LVEF progressed to persistent AF (p=0.88). The mean ATP success rate was lower in patients with reduced LVEF than in those with preserved LVEF, although not statistically significant (reduced LVEF: 27.2±19.4% and preserved LVEF: 35.1±29.2%, p=0.12). The incidence of progression to persistent AF was significantly lower in the ATP group than in the control group both in patients with reduced and preserved LVEF (log-rank, reduced LVEF: p=0.0070 and preserved LVEF: p<0.0001) (Figure). Multivariate analysis showed that use of Reactive ATP and smaller left atrium were associated with lower incidences of persistent AF, while LVEF was not predictive of progression to persistent AF (Reactive ATP: hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.17–0.46, p<0.0001, left atrium diameter: HR 1.03, 95% CI 1.00–1.07, p=0.030). Figure 1 Conclusions Reactive ATP was effective in preventing AF progression in patients with LV dysfunction.

Abstract 360: Implantation of an Induced Pluripotent Stem Cell Derived Cardiomyocyte Tissue Engineered Patch Improves Left Ventricular Function and Electro-mechanical Coupling in Rats With Heart Failure

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Jordan J Lancaster ◽  
Giuliana Repetti ◽  
Amitabh Pandey ◽  
Kyle Weigand ◽  
Joseph J Bahl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Diastolic Function ◽  
Hospital Readmissions ◽  
Left Ventricular ◽  
Dermal Fibroblasts ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Mechanical Coupling ◽  
Induced Pluripotent

Background: Chronic Heart Failure (CHF) is the leading cause of hospital readmissions and mortality in the US. Here we report the effects of surgically delivering a human bioengineered patch of human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) and fibroblasts on left ventricular (LV) function in rats with CHF. We evaluate improvements in LV systolic and diastolic function, electromechanical coupling and gene expression after patch implantation. Methods: Adult male Sprague-Dawley rats underwent left coronary artery ligation and were randomized to Sham (N=8), CHF (N=8-21), and CHF+hiPSC-CM patch (N=20-24). Heterogeneous hiPSC-CMs were seeded and co-cultured onto a vicryl matrix embedded with human dermal fibroblasts. Echocardiography was performed at 3 and 6 weeks post-randomization. Hemodynamic pressure measurements were performed at 6 weeks post-ligation with Millar solid state micromanometer pressure catheters. Open chest Electrophysiologic (EP) mapping was performed at 6 weeks post ligation. Gene expression was evaluated through qRT-PCR. Results: 48 hours into culture hiPSC-CMs patches displayed synchronized and spontaneous contractions which developed in robustness over time. At maximal robustness, contractions were visualized across the full thickness of the construct. Contractions were recorded at 36 + 5 beats BPM. Three weeks after patch implantation (6 weeks post ligation) the hiPSC-CM patch decreased (P<0.05) LV EDP (45%), Tau (29%), E/e’ (23%) and increased (P<0.05), e’/a’ (36%) with trending improvements in EF (14%) and e’ (20%). EP studies show electro-mechanical coupling between the patch and the native myocardium with normal activation through the patch and increases (P<0.05) voltage amplitude in CHF versus hiPSC-CM patch treated rats (1±0.5 mV vs 6±1.5mV). Rats treated with the hiPSC-CM patch showed significant (P<0.05) fold expression of Cx43 (3.3), ANG-1 (13.63), VEGF (3.8), βMYH7 (6.4) and IGF-1 (22.9) versus control. Conclusion: Cardiac patch implantation with hiPSC derived cardiomyocytes is an effective and feasible method of treating CHF with improvements in systolic function, diastolic function, and electro-mechanical coupling in rats with CHF.

Cardiac sympathetic activation in patients with pulmonary arterial hypertension

2012 ◽  
Vol 302 (10) ◽  
pp. R1153-R1157 ◽  
Author(s):  
Susanna Mak ◽  
Klaus K. Witte ◽  
Abdul Al-Hesayen ◽  
John J. Granton ◽  
John D. Parker
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Sympathetic Activity ◽  
Ventricular Myocardium ◽  
Connective Tissue Disorder ◽  
Left Ventricular ◽  
Lv Function ◽  
Sympathetic Activation ◽  
Lv Dysfunction ◽  
Pulmonary Arterial

Patients with congestive heart failure (CHF) due to left ventricular (LV) dysfunction have sympathetic activation specifically directed to the myocardium. Although pulmonary arterial hypertension (PAH) is associated with increased systemic sympathetic activity, its impact on sympathetic drive to ventricular myocardium is unknown. Fifteen patients with PAH (9 women; 54 ± 12 years) were studied: 10 with idiopathic PAH and 5 with a connective tissue disorder. We measured hemodynamics, as well as radiolabeled and endogenous concentrations of arterial and coronary sinus norepinephrine (NE). These measures were repeated after inhaled nitric oxide (NO). Measurement of transcardiac NE concentrations and the cardiac extraction of radiolabeled NE allowed calculation of the corrected transcardiac gradient of NE (CTCG of NE). Comparative data were collected from 15 patients (9 women: 55 ± 12 yr) with normal LV function and 15 patients with CHF (10 women; 53 ± 12 yr). PAH patients had elevated arterial NE concentrations compared with those with normal LV function but were similar to those with CHF. The CTCG of NE was higher in those with PAH than in the normal LV group (3.6 ± 2.2 vs. 1.5 ± 0.9 pmol/ml; P < 0.01) but similar to that seen in those with CHF (3.3 ± 1.4; P = NS). Inhaled NO, which reduced pulmonary artery pressure and increased cardiac output, had no effect on cardiac sympathetic activity. Therefore, cardiac sympathetic activation occurs in PAH. The mechanism of this activation remains uncertain but does not involve elevations in left heart filling pressure.

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 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.

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