Improvement In Global Left Ventricular Function Research Articles

Imaging of Myocardial αvβ3 Integrin Expression for Evaluation of Myocardial Injury After Acute Myocardial Infarction.

[68Ga]Ga-NODAGA-Arg-Gly-Asp (RGD) is a PET tracer targeting αvβ3 integrin, which is upregulated during angiogenesis soon after acute myocardial infarction (AMI). We prospectively evaluated determinants of myocardial uptake of [68Ga]Ga-NODAGA-RGD and its associations with left ventricular (LV) function in patients after AMI. Methods: Myocardial blood flow and [68Ga]Ga-NODAGA-RGD uptake (60 min after injection) were evaluated by PET in 31 patients 7.7 ± 3.8 d after primary percutaneous coronary intervention for ST-elevation AMI. Transthoracic echocardiography of LV function was performed on the day of PET and at the 6-mo follow-up. Results: PET images showed increased uptake of [68Ga]Ga-NODAGA-RGD in the ischemic area at risk (AAR), predominantly in injured myocardial segments. The SUV in the segment with the highest uptake (SUVmax) in the ischemic AAR was higher than the SUVmean of the remote myocardium (0.73 ± 0.16 vs. 0.51 ± 0.11, P < 0.001). Multivariable predictors of [68Ga]Ga-NODAGA-RGD uptake in the AAR included high peak N-terminal pro-B-type natriuretic peptide (P < 0.001), low LV ejection fraction, low global longitudinal strain (P = 0.01), and low longitudinal strain in the AAR (P = 0.01). [68Ga]Ga-NODAGA-RGD uptake corrected for myocardial blood flow and perfusable tissue fraction in the AAR predicted improvement in global longitudinal strain at follow-up (P = 0.002), independent of peak troponin, N-terminal pro-B-type natriuretic peptide, and LV ejection fraction. Conclusion: [68Ga]Ga-NODAGA-RGD uptake shows increased αvβ3 integrin expression in the ischemic AAR early after AMI that is associated with regional and global systolic dysfunction, as well as increased LV filling pressure. Increased [68Ga]Ga-NODAGA-RGD uptake predicts improvement of global LV function 6 mo after AMI.

Impact of procedure‐related conduction disturbances after transcatheter aortic valve implantation on myocardial performance and survival evaluated by conventional and speckle tracking echocardiography

Although procedure-related new cardiac conduction disturbances (CCDs) remain an important issue in transcatheter aortic valve implantation (TAVI), their effect on myocardial function and overall patient outcome remains unclear. The goal of this study was to analyze the influence of procedure-related CCDs on systolic and diastolic LV performance and on patient survival after TAVI. Ninety-five patients who underwent TAVI for severe symptomatic aortic stenosis (AS) and had a complete follow-up were evaluated with respect to procedure-related CCDs. Left ventricular (LV) performance was measured using standard echocardiographic parameters and speckle tracking analysis. Survival was assessed during longer-term follow-up (mean: 29.1±16.9months). After TAVI, the improvement of global LV function expressed as ejection fraction (LVEF; from 45.5±10.0 to 47.8±13.9%, P=.13) was not significant. New CCDs were found in 35.7% of TAVI recipients. A comparison between patients with and without new CCDs showed that LV systolic function improved in those without CCDs, while it tended to deteriorate in patients with CCDs (change in LVEF: 5.5±12.3% vs -4.9%±11.5%, P=.001; change in global longitudinal strain (GLS): -1.1±4.6% vs 1.2±4.5%, P=.01). Changes in diastolic function did not differ significantly between the groups (changes in transmitral E/A-ratio: -0.3±0.6 vs -0.5±0.5, P=.1). Kaplan-Meier survival analysis revealed no significant differences between the two cohorts (P=.795). Procedure-related conduction abnormalities after TAVI lead to an LBBB-related dyssynchrony with impairment of LV performance but not of overall survival.

Abstract 432: Elamipretide (BendaviaTM) Restores Aldehyde Dehydrogenase-2 Protein Levels and 4-Hydroxy-2-Nonenal Protein Adducts in Left Ventricular Myocardium of Dogs with Heart Failure

Background: Reactive aldehydes such as 4-hydroxy-2-nonenal (4-HNE) are generated in the failing heart and contribute to cardiomyocyte injury and death and progressive left ventricular (LV) dysfunction. Aldehyde dehydrogenase-2 (ALDH2) plays a pivotal role in detoxifying mitochondrial (MITO) reactive aldehydes. We previously showed that long-term therapy with Elamipretide (ELA, Bendavia TM ), a novel MITO targeting peptide, improves LV systolic function and normalizes MITO function and rate of ATP synthesis in dogs with heart failure (HF). In this study, we examined the effects of long-term treatment with ELA on protein levels of 4-HNE adducts and ALDH2 in LV myocardium of dogs with coronary microembolization-induced HF (LV ejection fraction ~30%). Methods: LV tissue from 14 HF dogs randomized to 3 months monotherapy with subcutaneous injections of ELA (0.5 mg/kg once daily, n=7) or saline (control, CTR, n=7) and tissue from 6 normal (NL) dogs was used in the study. Using LV tissue extracts, 4-HNE protein adducts levels were quantified using a commercially available Elisa kit and expressed as ng/mg. In isolated MITO fractions prepared from LV tissue, protein levels of ALDH2 and porin, the latter used as an internal loading control, were determined by Western blotting coupled with Chemiluminescence. Band intensity was expressed in densitometric units (DU). Results: No changes in protein level of porin was observed among the 3 study groups (NL: 0.26±0.02; CTR: 0.24±0.01; BEN: 0.26±0.01 DU). 4-HNE protein adducts levels were increased in CTR dogs compared to NL dogs and treatment with ELA partially restored 4-HNE to near normal levels (NL: 185±21; CTR: 399±35*; ELA: 252 ± 18† ng/mg, *=p&lt;0.05 vs. NL; †=p&lt;0.05 vs. CTR). Compared to NL, dogs, ALDH2 protein levels were significantly reduced in HF CTR dogs (0.49±0.02 vs. 1.16±0.10; p&lt;0.05). Treatment with ELA significantly increased ALDH2 protein compared to untreated CTR (0.74±0.02 DU, p&lt;0.05). Conclusions: Long-term therapy with ELA normalizes ALDH2 and 4-HNE levels in LV myocardium of dogs with HF. Improved protein levels of ALDH2 in HF after therapy with ELA can account, in part, for the observed improvement of global LV function elicited by long-term therapy with ELA.

Effect of balloon mitral valvotomy on left ventricular function in rheumatic mitral stenosis

AimMitral stenosis (MS) is found to produce left ventricular (LV) dysfunction in some studies. We sought to study the left ventricular function in patients with rheumatic MS undergoing balloon mitral valvotomy (BMV). Ours is the first study to analyze effect of BMV on mitral annular plane systolic excursion (MAPSE), and to quantify prevalence of longitudinal left ventricular dysfunction in rheumatic MS. MethodsIn this prospective cohort study, we included 43 patients with severe rheumatic mitral stenosis undergoing BMV. They were compared to twenty controls whose distribution of age and gender were similar to that of patients. The parameters compared were LV ejection fraction (EF) by modified Simpson's method, mitral annular systolic velocity (MASV), MAPSE, mitral annular early diastolic velocity (E′), and myocardial performance index (MPI). These parameters were reassessed immediately following BMV and after 3 months of procedure. ResultsMASV, MAPSE, E′, and EF were significantly lower and MPI was higher in mitral stenosis group compared to controls. Impaired longitudinal LV function was present in 77% of study group. MAPSE and EF did not show significant change after BMV while MPI, MASV, and E′ improved significantly. MASV and E′ showed improvement immediately after BMV, while MPI decreased only at 3 months follow-up. ConclusionsThere were significantly lower mitral annular motion parameters including MAPSE in patients with rheumatic mitral stenosis. Those with atrial fibrillation had higher MPI. Immediately after BMV, there was improvement in LV long axis function with a gradual improvement in global LV function. There was no significant change of MAPSE after BMV.

Autologous Mesenchymal Stem Cells Produce Concordant Improvements in Regional Function, Tissue Perfusion, and Fibrotic Burden When Administered to Patients Undergoing Coronary Artery Bypass Grafting

Although accumulating data support the efficacy of intramyocardial cell-based therapy to improve left ventricular (LV) function in patients with chronic ischemic cardiomyopathy undergoing CABG, the underlying mechanism and impact of cell injection site remain controversial. Mesenchymal stem cells (MSCs) improve LV structure and function through several effects including reducing fibrosis, neoangiogenesis, and neomyogenesis. To test the hypothesis that the impact on cardiac structure and function after intramyocardial injections of autologous MSCs results from a concordance of prorecovery phenotypic effects. Six patients were injected with autologous MSCs into akinetic/hypokinetic myocardial territories not receiving bypass graft for clinical reasons. MRI was used to measure scar, perfusion, wall thickness, and contractility at baseline, at 3, 6, and 18 months and to compare structural and functional recovery in regions that received MSC injections alone, revascularization alone, or neither. A composite score of MRI variables was used to assess concordance of antifibrotic effects, perfusion, and contraction at different regions. After 18 months, subjects receiving MSCs exhibited increased LV ejection fraction (+9.4 ± 1.7%, P=0.0002) and decreased scar mass (-47.5 ± 8.1%; P<0.0001) compared with baseline. MSC-injected segments had concordant reduction in scar size, perfusion, and contractile improvement (concordant score: 2.93 ± 0.07), whereas revascularized (0.5 ± 0.21) and nontreated segments (-0.07 ± 0.34) demonstrated nonconcordant changes (P<0.0001 versus injected segments). Intramyocardial injection of autologous MSCs into akinetic yet nonrevascularized segments produces comprehensive regional functional restitution, which in turn drives improvement in global LV function. These findings, although inconclusive because of lack of placebo group, have important therapeutic and mechanistic hypothesis-generating implications. http://clinicaltrials.gov/show/NCT00587990. Unique identifier: NCT00587990.

Value of Three-Dimensional Speckle-Tracking Longitudinal Strain for Predicting Improvement of Left Ventricular Function After Acute Myocardial Infarction

Identification of patients with reversible left ventricular (LV) dysfunction has important prognostic implications after acute myocardial infarction (AMI). This study aimed to determine the value of LV segmental and global longitudinal strains assessed with 3-dimensional (3D) speckle-tracking analysis in predicting improvement of LV function after AMI. One hundred fifty-three patients (80% men, 59 ± 11 years old) with AMI and treated with primary percutaneous coronary intervention underwent 3D echocardiography. LV segmental and global 3D longitudinal strains were assessed with speckle-tracking analysis using a novel dedicated software. At 6-month follow-up, improvement in segmental LV function was defined as a decrease of ≥1 grade in segmental wall motion score. Improvement in global LV function was defined as an absolute improvement ≥5% in LV ejection fraction. Segments with functional improvement at follow-up showed a significantly higher baseline 3D longitudinal strain compared to segments without improvement (-16.4 ± 4.0% vs -7.6 ± 3.5%, p <0.001). A cut-off value of -11.1% for segmental 3D longitudinal strain had 92% sensitivity and 91% specificity in predicting functional improvement. In addition, 67 patients (44%) showed an improvement in global LV function at 6-month follow-up. These patients showed significantly higher baseline global 3D longitudinal strain compared to patients without improvement (-16.7 ± 2.1% vs -13.3 ± 2.6%, p <0.001). Global 3D longitudinal strain provided incremental value over clinical and conventional echocardiographic variables in predicting global LV function improvement (c-statistic improved from 0.64 to 0.71 to 0.84). In conclusion, longitudinal strain assessed by 3D speckle-tracking analysis is an important predictor for segmental and global LV function improvement after AMI.

Prediction of functional recovery after revascularization in patients with chronic ischaemic left ventricular dysfunction: head-to-head comparison between 99mTc-sestamibi/18F-FDG DISA SPECT and 13N-ammonia/18F-FDG PET

(18)F-FDG PET is an important modality for myocardial viability assessment in patients with left ventricular (LV) dysfunction. Dual-isotope simultaneous acquisition (DISA) SPECT may be an alternative to PET. The aim of this study was to compare the diagnostic performance of PET and DISA SPECT for the prediction of improvement in regional and global LV function as well as LV reverse remodelling after revascularization. Patients (n=47) with chronic coronary artery disease and LV dysfunction underwent DISA SPECT (with (99m)Tc-sestamibi and (18)F-FDG) and PET (with (13)N-ammonia and (18)F-FDG) on the same day to assess viability. All patients underwent revascularization and recovery of function was derived from serial magnetic resonance imaging studies. Of 264 revascularized, dysfunctional segments, 143 (54%) improved in function. For prediction of improvement in regional LV function, PET and DISA SPECT had similar sensitivity (90% versus 89%, NS) and specificity (86% versus 86%, NS). For prediction of improvement in global LV function, sensitivity was 83% for DISA SPECT and 86% for PET (p=NS), whereas both modalities had a specificity of 100%. Finally, sensitivity and specificity for the prediction of LV reverse remodelling were also similar for DISA SPECT and PET. In patients undergoing revascularization, DISA SPECT and PET predict the improvement in regional and global LV function and LV remodelling equally well post revascularization.

Role of myocardial perfusion single photon emission CT (Sepct) in predicting improvement of myocardial function following revascularisation in patients with poor left ventricular function

We used a combined rest-stress Tc-sestamibi redistribution imaging using SPECT scan to identify viable myocardium and predict improved left ventricular (LV) function after revascularisation in patients with severe LV dysfunction. 57 patients were studied retrospectively with severe LV dysfunction Ejection Fraction (EF)<30%. Regional and global LV functions were evaluated preop and 12 weeks post-coronry artery bypass grafting (CABG) with radionucleide ventriculography. Preoperatively, patients were classified into those with eight or more viable segments (out of 15 segments) and those with seven or less viable segments. 31 out of 43 (72%) patients with more than eight viable segments had shown significant improvement in LVEF (from 0.29 ± 0.01 to 0.36 ± 0.06) postoperatively. Out of the remaining 12 patients, 3 had persistent akinesia with deterioration of symptoms whereas others had shown sympomatic improvement. In the other group, 11 out of 14 patients (78%) with seven or less segments viable had not shown any improvement in their LVEF. The imaging also identified the segments that improved function after CABG. Out of a total 285 segments in 57 patients, 238 segments were studied. Among these, 178 segments were hypokinetic, 48 segments akinetic and 12 dyskinetic. Preoperatively, 160 out of 178 (90%) with hypokinesia had shown viability whereas 26/48 (54%) in akinetic group and 9/12 dyskinetic segments had shown viability with rest showing no viability. Postoperative imaging had shown improvement in these groups as follows: hypokinetic 88% (141/160); akinetic 62% (16/26); dyskinetic 48% (4/9). In patients with coronary artery disease (CAD)-and severely depressed LV function. preoperative imaging using SPECT identifies viability in many akinetic or dyskinetic myocardial segments, and these segments frequently improve function after CABG. The presence of numerous akinetic but viable myocardial segments before surgery correlated significantly with improvement in global LV function after bypass surgery.

Global Left Ventricular Remodeling with the Acorn Cardiac Support Device: Hemodynamic and Angiographic Findings in Dogs with Heart Failure

Preventing progressive left ventricular (LV) remodeling is paramount in the treatment of heart failure. In recent years, several surgical approaches have been implemented with the objective of improving LV function through amelioration of progressive LV remodeling. These included surgical reduction of LV size, the so-called Batista procedure, dynamic cardiomyoplasty and mitral valve repair to limit or eliminate functional mitral regurgitation. While the Batista procedure and dynamic cardiomyoplasty have for all practical purposes been abandoned, the lessons learned from these procedures gave rise to a new generation of devices aimed at preventing progressive LV dilation and restoring LV shape by passive mechanical containment of the failing LV. One such device is the Acorn Cardiac Support Device (CSD) or the CorCap. Studies in dogs with intracoronary microembolization-induced moderate and advanced heart failure have shown that long-term monotherapy with the CSD not only prevents progressive LV dilation but, in effect, partially reverses this phenotype. These studies have also shown that the CSD restores, albeit in part, progressive LV chamber sphericity and attenuates functional mitral regurgitation. These benefits were accompanied by improvement in global LV function along with improvements of remodeling at the cellular level. The findings were largely responsible for initiating safety and feasibility clinical trials with the CSD and ultimately, the initiation of the Acorn efficacy trial that was completed in 2004. This review will focus on studies conducted in dogs with heart failure and, specifically on hemodynamic, angiographic and echocardiographic results from these studies that provided support for the CSD as a successful technology targeting "reverse LV remodeling" for the treatment of heart failure.

A pooled analysis of coronary arterial patency and left ventricular function after intravenous thrombolysis for acute myocardial infarction

Individual studies of patency rates and left ventricular (LV) function after thrombolysis have generally been limited by small numbers of observations, wide confidence intervals, and limited numbers of time points. To obtain a more reliable estimate of patterns of patency and LV ejection fraction, a systematic overview of angiographic studies was performed after intravenous thrombolytic therapy. A total of 14,124 angiographic observations from 58 studies evaluating patency after no thrombolytic agent, streptokinase, standard dose tissue-type plasminogen activator (t-PA), accelerated dose t-PA, or anistreplase (anisoylated plasminogen streptokinase activator complex [APSAC]) were included. At 60 and 90 minutes, streptokinase had the lowest patency rates of 48% and 51%, respectively, standard dose t-PA and APSAC had similar intermediate rates of approximately 60% and 70%, and accelerated t-PA had the highest patency rates of 74% and 84%. By 2 to 3 hours and longer, the patency rates were similar for the various regimens. Reocclusion rates in studies including 1,172 patients randomized to t-PA versus a nonfibrin-specific agent were higher after t-PA (13.4% vs 8.0%, p = 0.002). Ten studies enrolling 4,088 patients treated with thrombolytic therapy versus control demonstrated a modest improvement in mean LV ejection fraction in the thrombolytic group at each of the times after thrombolytic therapy: hour 4, day 1, day 4, day 7 to 10, and day 10 to 28 after thrombolysis. By 4 days, mean ejection fraction was 53% versus 47% (thrombolytic vs control therapy, p < 0.01); by 10 to 28 days it was 54.1% and 51.5%, respectively. In conclusion, this pooled analysis shows that accelerated t-PA resulted in higher 90-minute coronary arterial patency rates than other standard regimens, but that by 2 to 3 hours the rates were similar, and that reocclusion rates were higher after t-PA than nonfibrinspecific agents. Thrombolytic therapy resulted in only a small improvement in global LV function compared with results in the control group, which was fully apparent by 4 days after treatment.

Quantitative planar rest-redistribution 201Tl imaging in detection of myocardial viability and prediction of improvement in left ventricular function after coronary bypass surgery in patients with severely depressed left ventricular function.

Although many patients with multivessel coronary artery disease (CAD) and severely depressed left ventricular (LV) function will benefit from coronary artery bypass graft surgery (CABG), surgeons may be reluctant to perform CABG on these patients without evidence of myocardial viability in regions of severe asynergy. We hypothesized that quantitative planar rest-redistribution 201Tl imaging would identify viable myocardium and predict improved regional and global function after revascularization in patients with depressed LV function and CAD. Twenty-one patients (mean LV ejection fraction, 0.27 +/- 0.05) were studied. Regional and global LV functions were evaluated before and 8 weeks after CABG with radionuclide ventriculography. Segments were prospectively classified as showing normal, mildly reduced, or severely reduced viability on the basis of quantitative analysis of defect severity and redistribution on planar resting 201Tl imaging. By 201Tl criteria, 90% of hypokinetic segments were classified with normal or mildly reduced viability. Among akinetic or dyskinetic segments, 20% had normal 201Tl uptake, 53% had mildly reduced viability, and only 27% had severely reduced viability. 201Tl viability criteria identified segments that improved function after CABG. Sixty-two percent of severely asynergic segments with normal viability and 54% with mildly reduced viability improved function after surgery, but only 23% with severely reduced viability improved function (p = 0.002). When only adequately revascularized segments were considered, the predictive value of a positive preoperative viability scan for functional improvement was 73%. The greatest improvement in global LV function after CABG occurred in patients with the greatest number of asynergic segments classified as viable before surgery (p < 0.01). In 10 patients with more than seven viable, asynergic segments, mean LV ejection fraction increased significantly after CABG (0.29 +/- 0.07 to 0.41 +/- 0.11, p = 0.002). In 11 patients with seven or fewer viable, asynergic segments, mean LV ejection fraction remained unchanged after revascularization (0.27 +/- 0.05 to 0.30 +/- 0.08, p = NS). In patients with CAD and severely depressed LV function, preoperative quantitative planar rest-redistribution. 201Tl imaging identifies viability in many asynergic myocardial segments, and these segments frequently improve function after CABG. The presence of numerous asynergic but viable myocardial segments before surgery correlated significantly with improvement in global LV function after bypass surgery.