P1472Predicting significant ventricular arrhythmias in STEMI patients in middle-range and preserved EF

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Krljanac ◽  
D Trifunovic ◽  
M Asanin ◽  
L Savic Spasic ◽  
S Aleksandric ◽  
...  
Keyword(s):  
Systolic Function ◽  
Deformation Analysis ◽  
First Year ◽  
End Point ◽  
Mechanical Dispersion ◽  
Middle Range ◽  
Roc Area ◽  
Myocardial Deformation Imaging ◽  
Lv Systolic Function ◽  
Contraction And Relaxation

Abstract Background Predicting malignant ventricular and sudden cardiac death (SCD) in STEMI patients with middle-range and preserved EF is challenge. Aim To identify the best parameters to predict composite end-point defined as secondary VF, sustained/non-sustained VT and sudden death, 48h after and during the first year of follow up after STEMI in patients with middle-range and preserved EF. Methods In the 192 consecutive STEMI patients (pts) 57.8±10.4yr, 69.9% males, in PREDICT-VT study (NCT03263949) treated with pPCI, with EF ≥40%, early echo (5±2 days) was done including conventional parameters and comprehensive speckle tracking left ventricle (LV) deformation analysis with longitudinal (L), circumferential (C) strain (S; %) strain rate (SR, 1/sec), index mechanical dispersion (IMD) and rotational LV mechanics. Results Thirteen patients (8.3%) reached the end-point. Classical parameters of LV systolic function, including LVEF, wall motion score index and parameters of diastolic dysfunction were not significant predictors of the malignant arrhythmias. IMD of late rotation rate (63.7 vs. 40.7ms, p=0.055) and late diastolic untwisting rate (−48.85 vs. −63.18°/s, p=0.059) had trend to become the significant predictors. CS in papillary muscle level in endo and mid layers predicted the primary end-point (endo: −20.5±11.8 vs. −24.9±4.6, mid: −14.6±3.9 vs. −17.0±2.1, epi: −10.1±3.3 vs. −11.8±1.8) (table). Parameter of circumferencial mechanics ROC area 95% CI p Cutt-off Sens Spec PM endo (%) 0.302 0.146–0.458 0.038 −22.75 70 67 PM mid (%) 0268 0.153–0.383 0.015 −15.65 80 62 Conclusion Myocardial deformation imaging offers deeper insight into complex mechanical abnormalities during LV contraction and relaxation in STEMI patients with middle-range and preserved EF that predicts serious arrhythmic events.

scholarly journals P1381 The utility of left ventricle deformation in patients with myocarditis with midle-range and preserved ejection fraction

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
G Krljanac ◽  
I Veljic ◽  
A Ristic ◽  
R Maksimovic ◽  
I Milinkovic ◽  
...  
Keyword(s):  
Heart Failure ◽  
Speckle Tracking ◽  
Systolic Function ◽  
Acute Myocarditis ◽  
Deformation Analysis ◽  
Mechanical Dispersion ◽  
Middle Range ◽  
Myocardial Deformation Imaging ◽  
Lv Systolic Function ◽  
Insight Into

Abstract Background Predicting malignant ventricular arrhythmias and heart failure in patients (pts) with acute myocarditis and middle-range and preserved EF is challenge Aim: to define whether quantification of myocardial mechanics in early, acute phase of myocarditis offers more information to predict six months outcome of patients.Methods: In the 36 consecutive pts with myocarditis, middle age 32.86 ± 12.04yr, 75% males, echocardiography exam was done 1-3 day of diseases, including conventional parameters and comprehensive speckle tracking LV deformation analysis with longitudinal (L), circumferential (C) strain (S;%), strain rate (SR, 1/sec) and rotational LV mechanics. Results: The most patients were present as infarct-like myocarditis (80.56%), the others patients were present as heart failure-like (11.11%) and arrhythmia-like myocarditis (8.33%). At admission 27 (90%) pts had chest pain, 20 (66.7%) pts had ECG changes, 15 (50%) pts had symptoms of heart failure, 5 (16.7%) pts had arrhythmias. Amount of edema and fibrosis assessed by cardiovascular magnetic resonance (CMR) and echo correlate significantly. Classical and conventional parameters of LV systolic function, and deformation were not significantly different between groups. However, mechanical dispersion index (IMD) of global LS and systolic S were significantly different between groups (p < 0.05). Conclusion: Myocardial deformation imaging, like speckle tracking echocardiography, offers deeper insight into complex mechanical abnormalities during not only LV contraction but LV relaxation in longitudinal directions in patients with acute myocarditis. Infarct-like Arrhythmia-like Heart failure-like p EF (%) 57.5 ± 5.42 54.7 ± 12.9 58.3 ± 6.8 NS GLS endo (%) -20.8 ± 2.59 -19.78 ± 2.27 -17.36 ± 5.65 NS GLS (mid (%) -18.31 ± 2.4 -17.31 ± 1.52 -15.3 ± 5.10 NS GLS epi (%) -16.15 ± 2.28 -15.20 ± 0.92 -13.55 ± 4.68 NS IMD LS (ms) 37.04 ± 7.71 33.04 ± 6.58 60.75 ± 38.56 0.008 CS endo (%) -26.39 ± 6.93 -21.59 ± 3.88 -25.17 ± 6.48 NS CS mid (%) -17.32 ± 6.77 -13.03 ± 2.07 -15.95 ± 4.41 NS CS epi (%) -10.99 ± 6.89 -7.13 ± 0.72 -9.53 ± 2.73 NS IMD CS (ms) 47.69 ± 8.86 41.43 ± 23.92 41.01 ± 20.51 NS IMD SL peak S* 12.27 (21) 13.96 (4) 20.28 (84) 0.042 *Median and range values are presented.

P5977Predicting significant ventricular arrhythmias in STEMI patients: never-ending challenge, still more place for myocardial deformation imaging?

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Krljanac ◽  
D Trifunovic ◽  
M Asanin ◽  
L Savic Spasic ◽  
S Aleksandric ◽  
...  
Keyword(s):  
Rotation Rate ◽  
Ventricular Arrhythmias ◽  
Speckle Tracking ◽  
Myocardial Deformation ◽  
Deformation Analysis ◽  
First Year ◽  
Deformation Imaging ◽  
End Point ◽  
Myocardial Deformation Imaging ◽  
Malignant Arrhythmias

Abstract Background Malignant ventricular arrhythmias in STEMI patients carry ominous prognosis including sudden cardiac death (SCD). According to the current guidelines only EF<35%, 40 days after STEMI, is indication for ICD implantation. Recently, index of myocardial dispersion (IMD) estimated by myocardial deformation imaging (speckle tracking echocardiography) was documented to provide better risk stratification. Aim To define whether quantification of myocardial mechanics early after pPCI using modern echocardiography offers information more to predict malignant arrhythmias during the first year after STEMI. Methods In the 226 consecutive STEMI patients (pts) 57.8±10.4yr, 71.7% males, in PREDICT-VT study (NCT03263949) treated with pPCI early echo (5±2 days) was done including conventional parameters and comprehensive speckle tracking LV deformation analysis with longitudinal (L), circumferential (C) strain (S;%) and strain rate (SR, 1/sec) and rotational LV mechanics. ROC analysis was performed to identify the best parameters to predict composite end-point defined as secondary VF, sustained/non-sustained VT and SCD, 48h after pPCI and during the first year of follow up. Results Twenty two patients (9.7%) reached the end-point. Classical parameters of LV systolic function, including LVEF, wall motion score index; global, systolic LS, CS and parameters of diastolic dysfunction were not significant predictors of the malignant arrhythmias. Early L SR, systolic C SR, IMD of global rotation and late rotation rate predicted the primary end-point (table). Parameter ROC area 95% CI p Cutt-off Sens Spec Longirudinal mechanics   SR E (1/sec) 0.687 0.577–0.796 0.019 0.69 64 65   IMD S (ms) 0.752 0.666–0.838 0.002 66.1 71 72 Circumferencial mechanics   SR S (1/sec) 0.732 0.613–0.852 0.002 −1.22 71 67 Rotational mechanics   Global IMD (ms) 0.329 0.177–0.481 0.036 82.9 63 62   Late rotation rate IMD (ms) 0.318 0.196–0.442 0.026 41.1 65 64 Conclusion Myocardial deformation imaging offers deeper insight into complex mechanical abnormalities during LV contraction and relaxation in longitudinal, circumferential and rotational directions (impaired and asynchronous deformations) in STEMI patients and predicts serious arrhythmic events.

Abstract 14432: Myocardial Work in Stage I and II Hypertensive Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Akshar Jaglan ◽  
Sarah Roemer ◽  
Ana C Perez Moreno ◽  
Bijoy K Khandheria
Keyword(s):  
Systolic Function ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Deformation Analysis ◽  
Hypertensive Patients ◽  
Reduced Ejection Fraction ◽  
Work Index ◽  
Significant Difference ◽  
Global Work ◽  
Lv Systolic Function

Introduction: Myocardial work is a novel parameter that can be used in a clinic setting to assess left ventricular (LV) pressures and deformation. This study sought to distinguish patterns of global myocardial work index in hypertensive vs. non-hypertensive patients. Methods: Fifty (25 male, mean age 60±14 years) hypertensive patients and 15 (7 male, mean age 38±12 years) control patients underwent transthoracic echocardiography at rest. Hypertensive patients were divided into stage 1 (26 patients) and stage 2 (24 patients) based on the 2017 American College of Cardiology guidelines. We excluded patients with suboptimal image quality for myocardial deformation analysis, reduced ejection fraction (EF), valvular heart disease, and arrhythmia. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were estimated from LV pressure strain loops utilizing proprietary software from speckle-tracking echocardiography. LV systolic and diastolic pressures were estimated using a noninvasive brachial artery cuff. Results: Global longitudinal strain (GLS) and EF were preserved between the two groups with no statistically significant difference whereas there was a statistically significant difference in the GWI (p<0.01), GCW (p=0.03), GWW (p<0.01), and GWE (p=0.03) (Figure and Table). Conclusions: Myocardial work gives us a closer look at the relationship between LV pressure and contractility in settings of increased load dependency whereas LVEF and GLS cannot. We show how myocardial work is an advanced assessment of LV systolic function in hypertensive patients.

scholarly journals Mechanical dispersion is associated with clinical and subclinical coronary artery disease in patients on chronic renal replacement therapy with normal left ventricular ejection fraction

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
M Stefanovic ◽  
I Stankovic ◽  
T Jemcov ◽  
A Janicijevic ◽  
N Zec ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Systolic Function ◽  
Calcium Score ◽  
Coronary Calcium ◽  
Coronary Calcium Score ◽  
Dialysis Patients ◽  
Mechanical Dispersion ◽  
Artery Disease ◽  
Lv Systolic Function

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Since coronary artery disease (CAD) is the leading cause of mortality in patients with end-stage renal failure, early detection of CAD in these patients presenting with still normal left ventricular (LV) systolic function is of clinical importance. Aim To investigate the correlation between electrical and mechanical dispersion and CAD in dialysis patients with normal LV systolic function. Material and methods: This prospective study included 78 dialysis patients who underwent a 12-channel electrocardiogram and echocardiographic examination to determine electrical and mechanical myocardial dispersion. A coronary calcium score using cardiac computed tomography was also assessed in a group of 20 patients without known CAD. Electrical dispersion was defined as the difference between the longest and shortest corrected QT interval (QTc). Mechanical dispersion (MD) was defined as either standard deviation of mechanical contraction duration of all LV segments (MD_SD) or the difference between the longest and shortest duration of mechanical contraction (MD_delta). The duration of mechanical contraction was determined by myocardial strain analysis. Results Previously known CAD was present in 11 (14%) patients, while pathologic Q wave was absent in all patients. No significant correlation was observed between QTc dispersion and both MD parameters (p &gt; 0.05 for both). Both MD parameters (p = 0.007 for MD_SD; p = 0.026 for MD_delta), but not electrical dispersion (p = 0.584), showed a discriminative power for detecting previously known CAD (Figure). In patients without known CAD, neither QTc dispersion nor MD_SD showed a correlation with coronary calcium score (p &gt; 0.05 for both). MD_delta showed a strong correlation with both total and coronary calcium score in the territory of the left anterior descending coronary artery (r = 0.62; p = 0.004) in patients without previously known CAD. Conclusion Mechanical dispersion is associated with known CAD in dialysis patients with normal LV systolic function. The range of mechanical myocardial contraction duration (MD_delta) correlates with subclinical coronary atherosclerosis. Figure. Discriminative power of mechanical and electrical dispersion for the detection of coronary artery disease Abstract Figure.

scholarly journals Impact of renin angiotensin system inhibitor on 3-year clinical outcomes in acute myocardial infarction patients with preserved left ventricular systolic function: a prospective cohort study from Korea Acute Myocardial Infarction Registry (KAMIR)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kyung-Hee Kim ◽  
◽  
Byoung Geol Choi ◽  
Seung-Woon Rha ◽  
Cheol Ung Choi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Clinical Outcomes ◽  
Systolic Function ◽  
Renin Angiotensin System ◽  
Coronary Intervention ◽  
Left Ventricular ◽  
First Year ◽  
Percutaneous Coronary ◽  
Lv Systolic Function

Abstract Background Patients with acute myocardial infarction (AMI) are usually treated with angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) if ACEIs are not tolerated. However, there is no data regarding the impact of switching from ACEIs to ARBs on long-term clinical outcomes in AMI patients with preserved left ventricular (LV) systolic function especially beyond 1 year. To investigate the effectiveness of treatment with ACEIs or ARBs on clinical outcomes over 3 years in AMI patients with preserved LV systolic function following percutaneous coronary intervention. Method It is a prospective cohort study using data from a nationwide large scale registry with 53 hospitals involved in treatment of acute myocardial infarction (AMI) in Korea. Between March 2011 and September 2015, we enrolled 6236 patients with AMI who underwent primary percutaneous coronary intervention and had a left ventricular ejection fraction ≥ 50%. Main outcome measures composite of total death or recurrent AMI over 3 years after AMI. Patients were divided into an ACEI group (n = 2945), ARB group (n = 2197), or no renin-angiotensin system inhibitor (RASI) treatment (n = 1094). We analyzed patients who changed treatment. Inverse probability of treatment weighting (IPTW) analysis was also performed. Results After the adjustment with inverse probability weighting, the primary endpoints at 1 year, AMI patients receiving ACEIs showed overall better outcomes than ARBs [ARBs hazard ratio (HR) compared with ACEIs 1.384, 95% confidence interval (CI) 1.15–1.71; P = 0.003]. However, 33% of patients receiving ACEIs switched to ARBs during the first year, while only about 1.5% switched from ARBs to ACEIs. When landmark analysis was performed from 1 year to the end of the study, RASI group showed a 31% adjusted reduction in primary endpoint compared to patients with no RASI group (HR, 0.74; 95% CI 0.56–0.97; P = 0.012). Conclusions This result suggests that certain patients got benefit from treatment with ACEIs in the first year if tolerated, but switching to ARBs beyond the first year produced similar outcomes. RASI beyond the first year reduced death or recurrent AMI in AMI patients with preserved LV systolic function. CRIS Registration number: KCT0004990.

Acute coronary syndromes in chronic kidney disease patients: the good, the bad or the ugly?

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Saleiro ◽  
D De Campos ◽  
J Lopes ◽  
R Teixeira ◽  
J.P Sousa ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Systolic Function ◽  
Lv Function ◽  
Angiotensin Ii Antagonist ◽  
All Cause Mortality ◽  
Group A ◽  
Lv Ejection Fraction ◽  
Group B ◽  
Lv Systolic Function

Abstract Background Patients with chronic kidney disease (CKD) are at increased risk of composite cardiovascular (CV) events and all-cause mortality. However, current aggressiveness of therapeutic strategies may minimize the course of the disease. Aim To assess the prognostic impact of optimized medical treatment in a CKD population with acute coronary syndrome (ACS). Methods 355 ACS patients admitted to a single coronary care with CKD who were discharged from hospital were included. Those with end-stage renal disease were excluded. Three groups were created based on the KDIGO classification: Group A (Stage 3A, eGFR [estimated glomerular filtration rate] 45–59mL/min/1.73 m2) N=190; Group B (Stage 3B, eGFR 30–44mL/min/1.73 m2) N=113; and Group C (Stage 3B, eGFR 15–29mL/min/1.73 m2) N=52. The primary endpoint was long-term all-cause mortality. Kaplan-Meyer survival curves and Cox regression were done. The median of follow-up was 32 (IQ 15–70) months. Results Groups were similar regarding demographics, CV risk factors, ACS type, heart failure diagnosis, left ventricular (LV) systolic function, peak troponin, multivessel disease, treatment option (PCI, CABG or OMT) and medical therapy at discharge. More advance renal failure patients had a higher prevalence of diabetes mellitus (DM), a lower haemoglobin, a higher NT-proBNP and were less likely to receive ACE inhibitors/angiotensin II antagonist at discharge. 170 patients met the primary outcome. Kaplan-Meyer curves showed decreased survival with worse renal function (Group A 68% vs Group B 57% vs Group C 37%, Log Rank P=0.006 – Figure 1). After adjustment for age, DM, haemoglobin, NT-proBNP, LV systolic function and ACE inhibitors/angiotensin II antagonist at discharge, eGFR was not associated with increased death (HR 1.00, 95% CI 0.98–1.01). In this model, only age (HR 1.04, 95% CI 1.01–1.07), haemoglobin (HR 0.86, 95% CI 0.979–0.94), Nt-proBNP (HR 1.00, 95% CI 1.00–1.00) and impaired LV function (LV ejection fraction 40–49%: HR 2.95, 95% CI 1.89–4.81; LV ejection fraction &lt;40%: HR 2.15, 95% CI 1.44–3.21) remained associated with the outcome. Conclusion The worse outcome attributed to CKD after an ACS seems to be related not the eGFR itself but to associated comorbidities such as age, anaemia, fluid overload and impaired LV function. The fact that some of these comorbidities may be altered by intensive therapy indicates that CKD patients should also be candidates to optimized medical treatment. Funding Acknowledgement Type of funding source: None

scholarly journals Acute recoordination rather than functional hemodynamic improvement determines reverse remodelling by cardiac resynchronisation therapy

2021 ◽  
Author(s):  
Philippe C. Wouters ◽  
Geert E. Leenders ◽  
Maarten J. Cramer ◽  
Mathias Meine ◽  
Frits W. Prinzen ◽  
...  
Keyword(s):  
Systolic Function ◽  
Cardiac Resynchronisation Therapy ◽  
Left Ventricular ◽  
Lv Function ◽  
Peak Strain ◽  
Cardiac Resynchronisation ◽  
Reverse Remodelling ◽  
Resynchronisation Therapy ◽  
Lv Systolic Function

AbstractPurpose: Cardiac resynchronisation therapy (CRT) improves left ventricular (LV) function acutely, with further improvements and reverse remodelling during chronic CRT. The current study investigated the relation between acute improvement of LV systolic function, acute mechanical recoordination, and long-term reverse remodelling after CRT. Methods: In 35 patients, LV speckle tracking longitudinal strain, LV volumes & ejection fraction (LVEF) were assessed by echocardiography before, acutely within three days, and 6 months after CRT. A subgroup of 25 patients underwent invasive assessment of the maximal rate of LV pressure rise (dP/dtmax,) during CRT-implantation. The acute change in dP/dtmax, LVEF, systolic discoordination (internal stretch fraction [ISF] and LV systolic rebound stretch [SRSlv]) and systolic dyssynchrony (standard deviation of peak strain times [2DS-SD18]) was studied, and their association with long-term reverse remodelling were determined. Results: CRT induced acute and ongoing recoordination (ISF from 45 ± 18 to 27 ± 11 and 23 ± 12%, p < 0.001; SRS from 2.27 ± 1.33 to 0.74 ± 0.50 and 0.71 ± 0.43%, p < 0.001) and improved LV function (dP/dtmax 668 ± 185 vs. 817 ± 198 mmHg/s, p < 0.001; stroke volume 46 ± 15 vs. 54 ± 20 and 52 ± 16 ml; LVEF 19 ± 7 vs. 23 ± 8 and 27 ± 10%, p < 0.001). Acute recoordination related to reverse remodelling (r = 0.601 and r = 0.765 for ISF & SRSlv, respectively, p < 0.001). Acute functional improvements of LV systolic function however, neither related to reverse remodelling nor to the extent of acute recoordination. Conclusion: Long-term reverse remodelling after CRT is likely determined by (acute) recoordination rather than by acute hemodynamic improvements. Discoordination may therefore be a more important CRT-substrate that can be assessed and, acutely restored.

scholarly journals Intracoronary Injection of Autologous CD34+ Cells Improves One-Year Left Ventricular Systolic Function in Patients with Diffuse Coronary Artery Disease and Preserved Cardiac Performance—A Randomized, Open-Label, Controlled Phase II Clinical Trial

2020 ◽  
Vol 9 (4) ◽  
pp. 1043 ◽  
Author(s):  
Pei-Hsun Sung ◽  
Yi-Chen Li ◽  
Mel S. Lee ◽  
Hao-Yi Hsiao ◽  
Ming-Chun Ma ◽  
...  
Keyword(s):  
Systolic Function ◽  
Coronary Intervention ◽  
Left Ventricular ◽  
Diffuse Coronary Artery Disease ◽  
Cd34 Cells ◽  
Group 2 ◽  
Artery Disease ◽  
One Year ◽  
Lv Systolic Function ◽  
Group 1

This phase II randomized controlled trial tested whether intracoronary autologous CD34+ cell therapy could further improve left ventricular (LV) systolic function in patients with diffuse coronary artery disease (CAD) with relatively preserved LV ejection fraction (defined as LVEF >40%) unsuitable for coronary intervention. Between December 2013 and November 2017, 60 consecutive patients were randomly allocated into group 1 (CD34+ cells, 3.0 × 107/vessel/n = 30) and group 2 (optimal medical therapy; n = 30). All patients were followed for one year, and preclinical and clinical parameters were compared between two groups. Three-dimensional echocardiography demonstrated no significant difference in LVEF between groups 1 and 2 (54.9% vs. 51.0%, respectively, p = 0.295) at 12 months. However, compared with baseline, 12-month LVEF was significantly increased in group 1 (p < 0.001) but not in group 2 (p = 0.297). From baseline, there were gradual increases in LVEF in group 1 compared to those in group 2 at 1-month, 3-months, 6-months and 12 months (+1.6%, +2.2%, +2.9% and +4.6% in the group 1 vs. −1.6%, −1.5%, −1.4% and −0.9% in the group 2; all p < 0.05). Additionally, one-year angiogenesis (2.8 ± 0.9 vs. 1.3 ± 1.1), angina (0.4 ± 0.8 vs. 1.8 ± 0.9) and HF (0.7 ± 0.8 vs. 1.8 ± 0.6) scores were significantly improved in group 1 compared to those in group 2 (all p < 0.001). In conclusion, autologous CD34+ cell therapy gradually and effectively improved LV systolic function in patients with diffuse CAD and preserved LVEF who were non-candidates for coronary intervention (Trial registration: ISRCTN26002902 on the website of ISRCTN registry).

Does fusion contribute to the improvement of LV systolic function of heart failure patients when pacing the LV with varying AV delays?

1999 ◽  
Vol 5 (3) ◽  
pp. 39
Author(s):  
Angelo Auricchio ◽  
Jiang Ding ◽  
Yinghong Yu ◽  
Andrew Kramer ◽  
Rod Salo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systolic Function ◽  
Heart Failure Patients ◽  
Lv Systolic Function

Abstract 90: Bendavia (MTP-131), a Novel Mitochondria-Targeting Peptide, Improves ADP-Stimulated Mitochondrial Respiration in Cardiomyocytes Isolated From Dogs with Chronic Heart failure

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Hani Sabbah ◽  
Ramesh C Gupta ◽  
Sharad Rastogi ◽  
Paula Mohyi ◽  
Kristina Szekely
Keyword(s):  
Heart Failure ◽  
Mitochondrial Respiration ◽  
Systolic Function ◽  
Atp Synthesis ◽  
Vehicle Control ◽  
Electrode System ◽  
Lv Function ◽  
Targeting Peptide ◽  
Lv Systolic Function ◽  
Mitochondria Targeting

Background: Mitochondria (MITO) of failed human hearts and hearts of dogs with experimental heart failure (HF) manifest structural and functional abnormalities characterized by hyperplasia and reduced organelle size and reduced respiration. These abnormalities lead to reduced ATP synthesis that adversely impacts LV function. We previously showed that chronic therapy (3 months) with Bendavia (MTP-131), a novel mitochondria-targeting peptide, improves LV systolic function in dogs with heart failure (HF), reverses MITO abnormalities and normalizes mitochondria ATP synthesis in myocardium from Bendavia-treated HF dogs. In the present study we examined the direct effects of Bendavia on mitochondria ADP-stimulated state 3 respiration in freshly isolated cardiomyocytes from dogs with advanced chronic HF. Methods: Cardiomyocytes were isolated from LV free wall of 3 untreated dogs with HF produced by intracoronary microembolizations (LV ejection fraction <30%). A standard collagenase-based enzymatic process was used for isolation that yielded ~70% viable rod-shaped cardiomyocytes that excluded trypan blue. Equal aliquotes of cardiomyocytes were incubated in 0, 0.01, 0.10, 1.0 and 10 μM concentration of Bendavia for one hour at 37°C. At the end of incubation, ADP-stimulated state-3 respiration was measured using a Clark electrode system and quatified in nAtom Oxygen/min/mg protein. Results: State-3 respiration in the absence of Bendavia (Vehicle-Control) was 248±9 nAtom Oxygen/min/mg protein. Compared to vehicle-control, incubation of failing cardiomyocytes with Bendavia significantly increased state-3 respiration to 303±33 at 0.01 μM, p<0.05; 405±39 at 0.10 μM, p<0.05; 371±28 at 1.0 μM, p<0.05; and 346±29 at 10.0 μM, p<0.05. Conclusions: Results of this study indicate that the effects of Bendavia on mitochondrial respiration in cardiomyocytes is direct and not a consequence of improved global LV structure or function. Furthermore, the results indicate that the improvement in mitochondrial respiration after treatment with Bendavia can occur early after initiation of therapy (within one hour) and is dose-dependent up to concentrations of 0.10 μM.

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