Improvement In EF Research Articles

Abstract 21041: Cardiac Resynchronization Therapy for Pacemaker Induced Cardiomyopathy Results in Super Response

Background: Sustained right ventricular (RV) pacing can cause cardiomyopathy due to electrical dyssynchrony. Cardiac resynchronization therapy (CRT) can lead to reverse left ventricular (LV) remodeling by minimizing conduction delay. We hypothesized that CRT in pacemaker induced cardiomyopathy (PICM) would result in a greater improvement in EF compared to other causes of cardiomyopathy. Objective: To determine the change in ejection fraction after CRT upgrade in patients with PICM. Methods: A retrospective EMR review was conducted for individuals who underwent CRT upgrade between January 1, 2010 and January 31, 2016. Inclusion criteria were normal EF prior to pacemaker placement, RV pacing ≥ 80% and EF ≤ 45% prior to CRT upgrade. Frequency of improvement in EF of greater than or equal to 5% and 10% were calculated. Results: The study population included 22 patients with average age 69.7 ± 13.1 and average EF of 36.8 ± 6.9% at the time of CRT upgrade. Eight patients had aortic stenosis prior to CRT upgrade. Sixteen patients (73%) experienced at least 5% improvement in EF one year after upgrade to CRT and 12 patients (55%) improved by at least 10%. Average change in EF was 9.2 ± 12.3% compared to 4.6% improvement in all-comers with heart failure in the MIRACLE study. Ninety-two percent of participants without aortic stenosis had improvement in EF of at least 10% or to greater than 50% compared to only 8.3% of participants with aortic stenosis experiencing this degree of improvement (p=0.002). Conclusion: In patients with PICM, EF improvement after CRT upgrade is higher than in all-comers. Furthermore, the presence of concomitant aortic stenosis was associated with an attenuated improvement in EF.

Abstract 21053: Single Centre Experience of Portico TM Transcatheter Aortic Valve Implantation

Background: The Portico TM nitinol based self-expanding transcatheter aortic valve implantation (TAVI) system has the capability of being fully repositioned and retrieved in situ. This study investigates the feasibility and performance of Portico TM valve in subjects with severe symptomatic aortic stenosis up to 6 months post procedure. Hypothesis: The Portico TM system is safe and feasible in the treatment of patients with severe aortic stenosis. Methods: TAVI with the Portico TM system was performed in 83 subjects with severe AS using transfemoral (n=78), subclavian (n=4) and transaortic (n=1) access. Valve sizes included 23mm (n=5), 25mm (n=12), 27mm (n=31) and 29mm (n=35). Transthoracic echocardiography (TTE) was conducted pre and post-procedure and at 1mth and 6months in outpatient clinical follow-ups to evaluate aortic valve (AV) gradients and paravalvular regurgitation. Major stroke, vascular complications and mortality were also assessed in this cohort. Results: The mean age was 82±9yrs, with mean STS score of 5.0% and mean Euroscore II of 5.7%. The mean AV gradient improved significantly from baseline 47±17mmHg to 11±6 mmHg at 1mth and this decrease was sustained at 6 months post procedure; p<0.0001. There were no cases of severe paravalvular regurgitation by TTE at 6 months. The 30-day mortality was 1.2% (n=1) and 6 months mortality was 6.0% (n=5). Two patients (2.4%) had post procedure stroke and both were treated with intravenous thrombolysis with improvement in their symptoms, one patient (1.2%) had major vascular complications requiring vascular intervention and 10 patients (12%) required permanent pacemaker implantation. With regards to patients with impaired LV function, 12 patients (14.4%) had an EF < 55% prior to the TAVI procedure. In this group, there was a 15% improvement in EF at 6 months. Furthermore, 89% of all subjects improved at least one NYHA class at 30 days post procedure and 84% of the subjects improved at least one NYHA class at 6 months follow up. Conclusion: From our single center experience, the repositionable transcatheter Portico TM valve is feasible, safe and promising in the management of severe symptomatic aortic stenosis.

UTILITY OF NON-INVASIVE CORONARY FLOW PATTERN VERSUS FRACTIONAL FLOW PRESSURE DROP FOR LEFT ANTERIOR CORONARY ARTERY STENTING

Background and Aim: To assess the usefulness of coronary flow reserve as a guide in patient with left anterior descending coronary artery lesion during percutaneous coronary intervention in comparison with fractional flow reserve. Methods: The study included 80 patients with left anterior descending artery stenotic lesions, proved by coronary angiography, in the cardiac catheterization laboratory of the Faculty of Military Hospital, during the period from November 2012 to June 2014. All patients were subjected to all of the following: Complete history taking, full general and local examination, ECG analysis. All our patient were assessed by Doppler wire to measure pressure drop at LAD lesion and also by non-invasive coronary flow pattern utilizing transthoracic echo-Doppler study. Then we compare the results of both values on the basis of the improvement in left ventricular ejection fraction( by biplane Simpson rule) to find the cut point at which we can document that this LAD lesion deserve stenting . Results: FFR was negatively correlated with significant correlation with EF improvement with R value of -0.575 and P-value of 0.008,figure. Also there is strong inversed relation with lesion percent with R-value of-0.468 and P-value of 0.01. The correlation between FFR and improvement in wall motion score was significantly inversed with R-value of -0.519 and P-value of 0.03. Also there was strong correlation between FFR and CFR ,P-value was 0.00 and R-value was+0.436. CFR has strong reciprocal correlation with FFR (P-value was 0.00 and R-value was. inve+0.436. There is significant correlation of CFR with EF improvement with R value of -0.583and P-value of 0.002. Also there is significant correlation of CFR with lesion percent with R-value of -0.585and P-value of 0.001, figure. The correlation between CFR and wall motion score was significant with R-value of-0.393 and P-value of 0.03. The optimal cutoff values for coronary flow reserve of <1.75 was the best value for indication of stenting of an intermediate coronary lesion. A sensitivity of 92% and a specificity of 87%. On the other hand the best cut-of value of fractional flow reserve was <0.75 for indication of stenting for an intermediate coronary artery lesion with a sensitivity of 94% and specificity of 86%. Conclusions: The current study showed Coronary flow reserve measurements by TTE in the distal to mid LAD were feasible in most patients with an optimal cut-off value < 1.75 showed high accuracy to detect angiographically significant stenoses in the LAD. This is comparable to <0.75 as an optimal cut-off value of FFR to detect angiographically significant stenoses. CFR measurement utilizing TTE might be considered as a simple non-invasive tool for functional status of an intermediate coronary artery lesion for stenting. Key Words: LAD (left anterior descending artery ), coronary flow reserve, fractional flow reserve.

O16-2 - Long-term Outcomes of Isolated CABG with Reduced Left Ventricular Function

Background: We assessed the long-term outcomes of CABG comparing patients with preserved and reduced left ventricular (LV) function. Methods: Consecutive 965 patients who underwent isolated CABG between 2002 and 2016, were enrolled. Of these, 164 patients (17%) were with reduced left ventricular function (EF <40%) (Group lwEF) and the other 801 patients were with preserved LV function (Group pvEF). All CABG were performed via median sternotomy (98.2%) or small left thoracotomy either on- (21.2%) or off-pump (78.8%). Results: Mean follow-up period was 3.7 years. Mean age was 69 vs 68 years (Group pvEF vs Group lwEF) and male patients were significantly less prevalent in Group pvEF (77% vs 87%). Mean number of graft anastomoses was 3.1 vs 3.3 (P = .049). The overall survival and freedom from MACCE were significantly better in Group pvEF than Group lwEF (91% vs 78% and 70% vs 58% at 5 years, respectively). In Group lwEF, small preoperative LV end-systolic volume was independent predictor of significant EF improvement. Although the use of bilateral internal thoracic arteries (BITA) as well as off-pump CABG (OPCAB) positively affected long-term survival in Group pvEF, no significant difference was observed in Group lwEF. Conclusion: The surgical outcomes of CABG in the patients with reduced LV function was poor and BITA use or OPCAB did not provide favorable impact in those patients.

Outflow tract ventricular premature beats ablation in the presence or absence of structural heart disease: Technical considerations and clinical outcomes.

BackgroundPremature ventricular beats (PVBs) are early depolarization of the myocardium originating in the ventricle. In case of very frequent PVBs, patients are severely symptomatic with impaired quality of life and are at risk of pre-syncope, syncope, heart failure, and sudden cardiac death particularly in the presence of structural heart disease. Ventricular outflow tracts are the most common sites of origin of idiopathic PVBs especially in patients without structural heart disease. We examined the role of radiofrequency catheter ablation in suppression of monomorphic PVBs of outflow tract origin in the presence or absence of structural heart disease, and its impact on improvement of left ventricular (LV) systolic function.MethodsThirty-seven highly symptomatic patients with PVBs burden exceeding 10% were enrolled, provided that PVBs are monomorphic, originating in ventricular outflow tracts and regardless the presence or absence of structural heart disease. Patients were divided into 2 groups according to PVB site origin (RVOT vs. LVOT). 3D electro-anatomical mapping modalities were used in all patients employing activation mapping technique in the majority of cases. Acute success was considered when PVBs completely disappeared or when residual sporadic PVBs ≤ 1 beats/min or ≤10 beats/30 min after RF ablation. Patients were followed up for a mean period of 5.4 ± 1.2 months with long-term success defined as complete disappearance or marked reduction by more than 75% in the PVBs absolute number on 24 h holter monitoring.ResultsMean age of the study group was 39.9 ± 12.97 years, including 22 (59.4%) males. PVBs originated in RVOT in 17 cases and in LVOT in the remaining 20 cases. Prevalence of structural heart disease and consequently shortness of breath was higher in LVOT group. Initial ECG localization matched EP localization in the majority (94%) of cases. R wave duration index was the only significant independent predictor for RVOT origin with cut off value of <0.3 (P = 0.0057) upon multivariate analysis. Acute success was encountered in 32 (86%) patients with all cases of failure in the LVOT group. Recurrence occurred in 5 (15%) cases without significant difference between both groups. All cases of recurrence had residual PVBs at the end of the procedure. 18 cases out of the study group showed significant improvement of their EF (>5%) at the end of the follow-up period with no significant differences between both groups (p = 0.09). A linear correlation was observed between PVBs burden at follow up and magnitude of improvement of LV EF, particularly in patients with resting LV dysfunction and increased LV internal dimensions.ConclusionsRF ablation is an effective and safe method for elimination of outflow tract PVBs irrespective of their origin and the presence or absence of structural heart disease. PVBs burden after ablation appears to be the main determinant for reversal of PVB induced myopathy particularly in those with increased LV internal dimensions.

‘Optimized’ LV only pacing using a dual chamber pacemaker as a cost effective alternative to CRT

BackgroundCardiac Resynchronization therapy (CRT) remains largely under-used in developing countries owing to the high cost of therapy. In this pilot study, we explore ‘optimized’ Left Ventricle Only Pacing (LVOP) as a cost effective alternative to cardiac resynchronization therapy in selected patients with heart failure. HypothesisIn economically poorer patients with heart failure, left bundle branch block (LBBB) and intact AV node conduction, synchronization can be obtained using a dual chamber pacemaker (leads in right atrium and Left ventricle) with the help of 2D strain imaging. Methods and results4 patients underwent LVOP for symptomatic heart failure. Post procedure ‘optimization’ was done using 12 lead electrocardiography and 2D- Strain imaging. Difference between Time to Peak longitudinal strain and Aortic valve Closure (Diff TPL-AC) was calculated for each segment at different AV delays and the AV delay with the smallest Diff TPL-AC was programmed. The mean AV delay that resulted in electrical and mechanical synchrony was 150 ms. After a mean follow up of 6 months, all patients had improved by at least 1 NYHA class. The mean reduction in QRS duration post procedure was −54.5 ± 22.82 ms and the mean improvement in EF was 7 ± 2.75%. ConclusionOptimized LVOP using 2D strain and ECG can be a cost-effective alternative to CRT in patients with LBBB, heart failure and normal AV node conduction.

Abstract P240: Clinical Outcomes in Patients With Takotsubo’s Cardiomyopathy Who Have Undergone Cardiac Catherterization at Presentation vs. Those Who Have Not: A Two Community Based Hospitals Experience

Background: Diagnosis of Takotsubo’s Cardiomyopathy (TC) remains a challenge due to similar presentation to acute coronary syndrome. Coronary catheterization (CC) proven clean coronaries is important to diagnose TC. However, it is not uncommon that CC is occasionally delayed due to unstable medical condition and/or high risk for CC. We hypothesized that patients with TC had similar outcomes whether they underwent CC at presentation or were diagnosed using non-invasive imaging techniques. Methods: Retrospective chart review of data from Memorial Hospital of Rhode Island and Kent Hospital, two community based hospitals, from June 2008 to March 2016 was done. Thirty nine adult patients &gt; 18 years of age admitted to the intensive care unit or medical floor with chest pain, shortness of breath, elevated troponin, EKG changes, and new non-regional wall motion abnormalities or reduce ejection fraction, with suspected TC were enrolled. Patients were divided into 2 groups based on diagnostic approach of TC: Baseline echo findings suggestive of TC with EF improvement at follow up (non-CC) vs. clean coronaries by CC. Outcomes of the two groups were compared using Chi-square analysis, analysis of variance (ANOVA) and Mann-Whitney Test appropriately. Results: Out of 39 patients, 20 underwent CC while 19 did not. Mean age was not different between the 2 groups (69.1±11.8 vs. 62.4±14.0, p= NS) but CC group had more females (95 %, 19 of 20 vs 68.4%, 13 of 19; p=0.031). Most common chief complaint at the time of admission in both groups was shortness of breath (60.0%, 12 of 20 vs 68.4%, 13 of 19; p=0.548). Admission heart rate was significantly higher in non-CC vs. CC patients (102.3± 19.3 vs 85.4±85.4; p=0.007). Third troponin was higher in non-CC group (1.926 ± 2.667 vs 0.775± 1.378, p=0.017). All other admission and in-hospital findings and drug management in both groups were similar. Both CC and non-CC groups had comparable outcomes: intubation (15%, 3 of 20 vs 21.1%, 4 of 19) , heart failure (21.2 %, 4 of 20 vs 15.8%, 3 of 19), shock (0 %, 0 of 20 vs 5.3% 1 of 19 ), stroke (5 %, 1 of 20 vs 0%, 0 of 19), death (5.3 % 1 of 20 vs 5.3% 1 of 19 ), recovery (65%,13 of 20 vs 52.9 % 10 of 19) p=NS for all. ICU admission (42.1%, 8 of 20 vs 52.6%, 10 of 19; p=NS) and length of stay (8.21±7.82 days vs 5.75±5.67 days; p=NS) was not significantly different between the 2 groups. Both groups showed analogous improvement in ejection fraction (21.92 ± 13.96 vs 20.63 ± 13.21; p= 0.835) on a follow up Echo done within 2 weeks to 6 months. Conclusion: This study shows no difference in outcomes between TC patients diagnosed with CC or TTE on admission. However, CC should still be done on admission for diagnosis of TC until large non-invasive diagnostic imaging modalities (such as myocardial perfusion echocardiogram) trials show high specificity for diagnosis of TC.

Nurse Practitioner Led Cardiac Gym Clinic for Heart Failure Patients; A New Initiative

Objective: The onsite hospital cardiac gym provides patients of the Advanced Heart Failure Service with a safe environment to exercise. Benefits of exercise in heart failure (HF) have been well documented [[1]NHF&CSANZ Guidelines for the prevention, detection and management of chronic heart failure in Australia. 2011; Google Scholar]. The HF nurse practitioner (NP) initiated a NP gym clinic aiming to provide clinical support and prompt solutions to presenting problems combined with medication management. NPs have been proven to improve outcomes for HF patients [[2]Kaan A. Dunne J. Development of a Nurse Practitioner Role in Heart Failure Management: An Australian Experience.Prog Cardiovasc Nurs. 2001; 16: 33-34Crossref PubMed Scopus (3) Google Scholar]. Management of HF includes optimisation of angiotension receptor antagonists and betablockers [[1]NHF&CSANZ Guidelines for the prevention, detection and management of chronic heart failure in Australia. 2011; Google Scholar] Design: The NP is onsite at the cardiac gym 1 day per week. This retrospective study reviews data collected over 12 months. Method: NP reviewed 74 patients, 63 male for 322 episodes. Average age 52 years (SD 12.8) with varying aetiology of heart failure, ejection fraction 27.4% (SD 12.9). Results: NP initiated 62% of cases, 59% for routine follow up and 41% due to a symptom change. Of symptoms reported, 51% were shortness of breath + - fluid overload. Treatment included medication optimisation and blood work. Most cases were independently managed by the NP without consultation with medical staff. Improvement in EF on echocardiogram increased to 38.4% (SD 13.6). Patient satisfaction was positive on survey. Conclusion: The presence of an NP in the cardiac gym proved to be a valuable adjunct to exercise. Patients were uptitrated to maximal doses of HF medications where tolerated. Improvement in EF on echo was statistically significant.

A combined cellular and surgical ventricular reconstruction therapeutic approach produces attenuation of remodeling in infarcted rats

BackgroundLeft ventricular reconstruction (LVR) has been shown to provide transient benefits to the LV structure and function of infarcted hearts; however, long-term results have been disappointing as LVR-induced benefits are typically not sustained. We hypothesized that administration of cardiosphere-derived cells (CDCs), which promote myocardial repair and regeneration, may result in long-term preservation of the beneficial effects of LVR in ischemic cardiomyopathy. MethodsWistar Kyoto rats underwent myocardial infarction (MI) and two weeks later were randomized into 3 groups: in Group 1 (n=9), LVR was performed by plication of the infarcted apex and CDCs were injected in the infarct border zone (IBZ); group 2 animals (n=9) underwent LVR and received vehicle solution in the IBZ; and Group 3 animals (n=10) were injected with vehicle solution in the IBZ without undergoing LVR. Echocardiograms were performed at baseline, 4 days post-apex plication, and at 3 months post-MI. ResultsAt baseline, all animal groups had a comparable LVEF, LV end–diastolic volume (EDV) and LV end-systolic volume (ESV). Four days post-LV apex plication, Group 1 and Group 2 animals exhibited comparable significant improvement in EF and comparable significant reduction in LVEDV and LVESV. Three months post-MI, Group 1 animals had a decreased LVEDV, decreased LVESV, less impaired CS, increased peak systolic torsion and increased EF compared to animals in Groups 2 and 3. ConclusionIn infarcted rat hearts, intramyocardial delivery of CDCs in conjunction with LVR resulted in significant and sustained amelioration of LV remodeling and improvement in LV function compared to LVR alone.

Abstract 13490: Cardiac Progenitor Cell Therapy in Right Heart Failure With Preserved Ejection Fraction

Background: Hear failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterized by normal EF with abnormal relaxation. Although the significance of HFpEF in right ventricle (RV) remains elusive as well as cell therapy responses in HFpEF patients with single ventricular heart diseases (SHD) have not yet clarified. Purpose: We investigated the underlying mechanisms and potential benefits of cardiosphere-derived cell (CDC) therapy in HFpEF includes rat models and human SHD. Methods: Pulmonary artery banding (PAB) was created in rats for 4 weeks as RV failure models. In human study, 40 patients, aged 2.2±1.4 years, 91% diagnosed as RV type SHD, were analyzed. Both rat and human studies were defined as follows (HFpEF; EF≧40%, HFrEF; EF&lt;40%), and intracoronary CDC infusion responses were assessed. Results: Rats received PAB showed RV dysfunction with significant cardiac fibrosis those were addressed by increased expression of heart failure or fibrosis related genes in both HFpEF and HFrEF rats rather than controls. CDC infusion led to marked increase in EF in rats with HFrEF but not HFpEF. Although CDC infusion did not augment EF in HFpEF, this treatment significantly decreased interstitial fibrosis and improved myocardial elastance in both HFpEF and HFrEF compared with baseline. Furthermore, CDC treatment markedly reduced Col1, Col3, NPPA and MMP2 expressions in both groups, whereas inflammatory cytokine such as Ccl2 and IL6 decreased only in HFrEF. Notably, CDC infusion did not affect the expression of MMP9, TIMP1 and TIMP2 in both groups. In human study, there was no difference in the incidence of late gadolinium enhancement detected by cMRI in two groups (20% in HFrEF and 15% in HFpEF); however, HFrEF but not HFpEF patients demonstrated a marked improvement in EF and reduced ventricular volumes and mass one year after CDC infusion. In contrast, the beneficial effects of CDC therapy could be observed by improved myocardial strain, elastance, and diastolic function in both groups. Conclusions: Our translational and clinical research of HFpEF in RV suggests that CDC infusion may have significant impact on diastolic relaxation and myocardial stiffening improvements to reverse ventricular fibrosis and remodeling leading to RV failure.

Abstract 13819: Delayed Enhancement Cardiac Magnetic Resonance Imaging Predicts Response to Cardiac Resynchronization Therapy

Introduction: Primary predictors of cardiac resynchronization therapy (CRT) are based on conduction system characteristics, such as QRS duration and morphology. The ability of MRI to predict CRT response is less understood. Methods: We studied 83 patients who received cardiac MRI with gadolinium delayed enhancement (DE) prior to CRT. Patients had preCRT EF ≤ 40%, preCRT QRS ≥ 120ms, and paired ~1 year postCRT echocardiograms. MRIs were read without knowledge of patient characteristics or CRT outcomes and echocardiograms were read in a core-lab blinded to MRI results. Results: Patients were classified as having no DE (n=27), only septal midwall DE (n=20), or scar / DE (transmural, subendocardial, or subepicardial) (n=36). Prior to CRT, those with septal midwall DE (25 ± 7) had lower EFs than those with scar / DE (31 ± 6, p=0&lt;0.01), but not statistically different from those without DE (29 ± 6). Those without DE had better (p&lt;0.001) EF (14.2 ± 10 units) and LVESV improvements (-42 ± 21%) following CRT than those with midwall DE (EF: 2.1 ± 9 units; LVESV: -3 ± 35%) or those with scar / DE (EF: 1.4 ± 8 units; LVESV: -5 ± 25%). There was no difference in CRT response between non-ischemics with septal midwall DE and patients with scar / DE. In univariate regression models LBBB tended (p=0.12) to predict a beneficial EF response to CRT while presence of midwall DE was highly significant (p&lt;0.001) for predicting a lack of response in the 47 patients without scar. In a multivariate model including many baseline characteristics, septal midwall DE provided predictive value (p&lt;0.001) for EF response whereas the common predictors of gender (p=0.693) and LBBB (p=0.913) did not. Conclusions: DE cardiac MRI is a good predictor of response to CRT. The absence of any DE predicts a significant improvement in EF and LV volumes. In the idiopathic non-ischemic population the presence of septal midwall DE was a better negative predictor of response than more traditional characteristics of LBBB and gender. In addition, the presence of transmural, subendocardial, or subepicardial scar also predicted lack of improvement in LV function and volumes with CRT. The information obtained from DE MRI could help determine which patients would be best helped by CRT.

Abstract 13142: Implantable Cardioverter Defibrillators Continue to Offer Mortality Benefit After Improvement in Ejection Fraction to Above 35%: Results From the Sudden Cardiac Death in Heart Failure Trial

Introduction: Patients (pts) discovered to have low ejection fraction (EF ≤ 35%) frequently show increase in EF to &gt; 35% over time. The efficacy of implantable cardioverter defibrillators (ICD) to improve survival is unknown in these pts. Hypothesis: Mortality benefit with ICD therapy is less in pts whose EF improves to &gt; 35% than those whose EF remains ≤ 35%. Methods: A total of 1875 (74%) participants of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) had a repeat assessment of EF 13.5 ± 6 months after randomization. We stratified them by EF ≤ 35% and &gt; 35% based on the 1 st repeat EF after randomization and compared all-cause mortality of 649 pts randomized to placebo vs. 624 pts randomized to ICD (602 pts randomized to amiodarone were not analyzed). Follow-up started at the time of 1 st repeat EF assessment. Results: Repeat EF was &gt; 35% in 186 (30%) pts in the ICD group and 185 (29%) pts in the placebo group (mean EF increased from 26±7% to 46±8%). The all-cause mortality rate was lower in the ICD group vs. placebo group, both in pts whose EF remained ≤ 35% and in those whose EF improved to &gt; 35% (Table). Compared to placebo, the unadjusted hazard ratio for ICD effect on mortality was 0.72 (95% CI 0.55-0.95) in pts with repeat EF ≤ 35% and 0.58 (95% CI 0.29-1.17) in those with repeat EF &gt; 35%. After adjustment for potential confounders, the estimated effect of ICD was 0.64 (95% CI 0.48-0.85) and 0.62 (95% CI 0.29-1.30) in patients with repeat EF ≤ 35% or &gt; 35%, respectively (Table). We found no evidence of an interaction between treatment assignment and repeat EF for prediction of mortality (p=0.93), suggesting that the ICD effect was similar in patients with EF ≤ 35% or &gt; 35%. Conclusions: Pts with an improvement in EF to &gt; 35% accrued a similar relative reduction in mortality with ICD therapy as those whose EF remained ≤ 35%. However, the absolute benefit of ICD therapy was less in pts with repeat EF &gt; 35% due to the lower mortality risk in this group.

Impact of early initiation of corticosteroid therapy on cardiac function and rhythm in patients with cardiac sarcoidosis

BackgroundThere is limited data on the effect of corticosteroid therapy in patients with cardiac sarcoidosis (CS). We sought to examine the impact of early initiation of corticosteroid therapy, within a month of CS diagnosis, on left ventricular ejection fraction (LVEF), ventricular arrhythmias (VAs), and atrioventricular (AV) block. MethodsWe retrospectively identified 30 CS patients from a large university sarcoidosis clinic. The effect of early initiation of corticosteroid therapy on LVEF was assessed by serial echocardiography, and on VAs and AV block was assessed by Holter monitoring and/or device interrogations. ResultsThe median time from diagnosis of extra-cardiac sarcoidosis to CS was 40months. 90% (27/30) of the CS patients received corticosteroid therapy and 85% percent (23/27) had early initiation of corticosteroid therapy. Fourteen patients (47%) had reduced EF<50%. 9/14 patients who had early initiation of corticosteroid therapy had improvement in mean EF (25% to 46%, P<0.001); 5/14 patients who had a delay in initiation or who did not receive corticosteroids had no improvement in mean EF (41% to 37%, P=0.47). Fourteen patients (47%) had VAs and 5 patients (17%) had advanced AV block. Early initiation of corticosteroid therapy resulted in no VA recurrences in 8/11 patients (72%), and complete recovery of AV conduction in 2/3 patients (67%). Patients with VAs (n=3) or advanced AV block (n=2) who failed to receive early corticosteroid therapy did not show improvement. ConclusionsThere is often a delay in manifestation of cardiac sarcoidosis for several years from the diagnosis of extra-cardiac sarcoidosis. Prompt initiation of corticosteroid therapy in CS patients may improve outcomes whereas delayed initiation of corticosteroids or failure to use corticosteroids may be associated with worse outcomes.

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

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&lt;0.05) LV EDP (45%), Tau (29%), E/e’ (23%) and increased (P&lt;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&lt;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&lt;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.

Heart Failure With Improved Ejection Fraction: Clinical Characteristics, Correlates of Recovery, and Survival: Results From the Valsartan Heart Failure Trial.

Heart failure with recovered or improved ejection fraction (HFiEF) has been proposed as a new category of HF. Whether HFiEF is clinically distinct from HF with persistently reduced ejection fraction remains to be validated. Of the 5010 subjects enrolled in the Valsartan Heart Failure Trial (Val-HeFT), 3519 had a baseline left ventricular EF of <35% and a follow-up echocardiographic assessment of EF at 12 months. Of these, 321 (9.1%) patients who had a 12-month EF of >40% constituted the subgroup with HFiEF. EF improved from 28.7±5.6% to 46.5±5.6% in the subgroup with HFiEF and remained reduced (25.2±6.2% and 27.5±7.1%) in the subgroup with HF with reduced ejection fraction. The group with HFiEF had a less severe hemodynamic, biomarker, and neurohormonal profile, and it was treated with a more intense HF medication regimen. Subjects who had higher blood pressure and those treated with a β-blocker or randomized to valsartan had greater odds of being in the HFiEF group, whereas those with an ischemic pathogenesis, a more dilated left ventricle, and a detectable hs-troponin had lower odds of an improvement in EF. Recovery of the EF to >40% was associated with a better survival compared with persistently reduced EF. Our data support HFiEF as a stratum of HF with reduced ejection fraction with a more favorable outcome, which occurs in a minority of patients with HF with reduced ejection fraction who have a lower prevalence of ischemic heart disease, a less severe hemodynamic, biomarker, and neurohormonal profile, and who are treated with a more intense HF medication regimen. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336.

Is the Pleotropic Effect of Ranolazine is Due to its Antioxidant Action

AbstractBACKGROUND: Ranolazine is indicated as antianginal drug. We observed that it has other pleotropic effects also. So, we want to study the effect of Ranolazine in improvement of left ventricular (LV) function in obstructive coronary artery (CAD) diseased patients along with ACC/AHA guidelines of treatment. And to see the mode of improvement in LV function is due to its antioxidant effect.MATERIALS AND METHODS: We recruited CAD patient between the age group 18-80 yrs with LV dysfunction in whom ischemic component was treated. Cases received ranolazine 500 mg two times a day and controls without the drug. Both groups received standard drug therapy according to ACC/AHA guidelines of treatment CAD. For all these patients at basal and at 6 months of follow up, all baseline and demographic parameters, clinical features and symptomatology with blood chemistry parameters were collected. In addition Two Dimensional echocardiography (EF, MAV), Treadmill test (METs) and plasma oxidative stress levels (MDA) will be performed at 0 day (day of recruitment) and at 6 months. MDA concentration was tested by using the method described by Draper and Hadley based on TBA reactivity. Normal Range of MDA is 3.60 ± 0.90 Nano mole/ml.RESULTS: 100 cases and 40 controls were recruited for this study. Male: Female ratio was 3.4:1 in cases and in controls. The mean age of cases was 56.8 ± 9.6 yrs in cases and 55.1 ± 12 yrs in controls. There was no difference in demographic features and risk factor profile in between the cases and controls expect smoking ( high in cases). Even in echo EF was comparable but MAV is more in cases than controls (9.5 ±2.1 vs 8.8±1.8) which are also not statistically significant.There is statistically significant improvement of EF either by dimension (48.3 ± 9.6 vs 43.8±8.4 %, p= 0.008) or volume (p=0.018) method of estimation and peak mitral annular velocity in cases (9.8±1,8 vs 8.7± 1.8 cm/sec, p= 0.001) who received additional ranolazine therapy than controls.MDA at 6 months in cases was decreases to 3.4±0.8 nano mole/dl where as in controls increased to 3.9±0.7 nano mole/dl. Out of 100 cases we could able to get Treadmill test done only for 89 patients with modified Bruce protocol and there was a statistically significant improvement in the number of metabolic equivalents at 6 months in cases comparison to basal exercise capacity (6.8± 2.4 vs 8.2 ± 8.1 METS, p= 0.05).ConclusionsRanolazine can act as not only an anti anginal drug but also it was shown to have positive effects on improving LV function (improvement in EF and mitral annular velocities) and improving the exercise capacity (increased METs by TMT). These effects may be due to reduction in the oxidative stress (decreased MDA levels).

The Impact of Known Heart Disease on Long-Term Outcomes of Catheter Ablation in Patients with Atrial Fibrillation and Left Ventricular Systolic Dysfunction: A Multicenter International Study.

Catheter ablation for AF is an effective treatment for patients with AF and systolic LV dysfunction; however, the clinical outcome is variable. We evaluated the impact of cardiomyopathy etiology on long-term outcomes post-catheter ablation. Patients undergoing AF ablation across 3 centers (2 Australian, 1 UK) from 2002 to 2014, with LVEF<45% were evaluated. Patients were stratified into those with known heart disease as a cause of cardiomyopathy (KHD), and those with idiopathic dilated cardiomyopathy (IDCM). One hundred and one patients (IDCM = 77, KHD = 24) with AF and LVEF <45% underwent AF ablation. The KHD group (ischemic HD in 67%) were older (61 ± 7 vs. 55 ± 11 years, P = 0.005), with a higher CHADS2 score (2.0 ± 0.8 vs. 1.6 ± 0.7, P = 0.016), but otherwise well matched. After mean follow-up of 36 ± 23 months, AF control was greater in the IDCM group (82% vs. 50% in KHD, P < 0.001). On multivariate analysis IDCM was associated with long-term AF control (P = 0.033). The IDCM group had less functional impairment at follow-up (NYHA class 1.5 ± 0.7 vs. 2.0 ± 0.8, P = 0.005) and improved LVEF (50 ± 11% vs. 38 ± 10%, P < 0.001). Super responders (EF improvement >15%) were overwhelmingly in the IDCM group (94% vs. 6%, P < 0.001) with greater AF control (89% vs. 61%, P < 0.001). All-cause mortality was significantly higher in the KHD group (17% vs. 1.3%, P = 0.002). IDCM was associated with greater AF control, and improvement in symptoms and LVEF compared to patients with KHD post-AF ablation. AF is an important reversible cause of HF in patients with an unexplained CM and catheter ablation an effective treatment option.

Prediction of Post-revascularization Ejection Fraction in Patients with Coronory Artery Disease Using Cavity-to-Myocardial Ratio of Thallium Reinjection Image (Multicenter Trial)

Background: We reported the high correlation between cavity-to-myocardial (C/M) count ratio at stress and rest thallium SPECT, and stress-rest EF calculated by MUGA test, this was confirmed by others. This correlation was explained partially by the functional mass. On the other hand, two important prognostic parameters should be considered before any revascularization technique: (1) Identification of viable myocardium and its amount, (2) Prediction of EF improvement post revascularization. Aim of the study: Correlating EF (C/M) on RD and RI image (EFRD & EFRI) image to actual EF (prevascularization EF1) and 1 year post revascularization EF2. Patients and methods: 78 patients with CAD (68 males and 10 females with mean age of 54.2+9 years) had been subjected to: (1) St-RD-RI thallium SPECT with assessment of reversible or fixed perfusion defects and calculation of C/M and consequently the EFC/M at the three settings. (2) Assessment of EF by MUGA at rest pre and 1 year post revascularization EF1 & EF2 respectively. These patients had been subjected to revascularization either by PTCA and stent (23/78 i.e., 29.5%) or by CABG (55/78, i.e., 70.5%). Results: Out of the 1560 myocardial segments (20 segments × 78 patients), 780 (50%) segments had abnormal resting wall motion. 441/780 (56.5%) of these segments were either of normal thallium uptake or with reversible perfusion defects while the rest (43.5%) showed fixed defects. 233/441 (52.8%) of those normal uptake or reversible segments showed recovery of wall motion post revascularization (PRV) while only 29/339 (15.1%) showed similar improvements. EFRI was found higher than EFRD in 44/78 of patients, no change in 23/78 patients and worsened in 11/78 patients with total agreements of 63/78 (80.8%) with EF2. On the other hand, EFRD was matched with EF1 in 64/78 of patients. 30/64 (46.9%) showed higher EF2, 23/64 (35.9%) showed similar EF2 while 11/64 (17.2%) showed lower EF2. The rest of cases 14/78 showed mismatch between EFRD and EF1 with higher values of EFRD. These patients still had higher values of EFRI and EF2 than EFRD. Conclusion: (1) Mismatch between EFRD and EF1 is an indication of presence of stunning myocardium and of good prognosis. (2) EFRI can be used to predict EF2 and so helps on selecting patients who can benefit from revascularization.

Damaging Cardiac and Cancer Genetic Variants in the LVAD Population

Abstract&#x0D; Background: Next generation sequencing technology, coupled with population genetic databases, have made broad genetic evaluation relatively inexpensive and widely available. Our objective was to assess the prevalence of potentially damaging cancer and cardiac gene variants in advanced non-ischemic cardiomyopathy patients.&#x0D; Methods: Explanted human heart tissue procured at LVAD placement was obtained from the University of Nebraska Medical Center Heart Tissue Bank. Genomic DNA was isolated from tissues and amplified by PCR using targeted ampliseq primer pools from an inherited disease panel. Individual libraries were amplified by emulsion PCR on Ion Sphere particles and sequencing was performed on a PGM sequencer (Ion torrent) using the Ion 316 chip. The Ion Torrent browser suite was used to map the reads and call the variants. The identified single nucleotide polymorphisms, insertions, and deletions were then annotated and characterized with ANNOVAR. Non-synonymous mutations with a population frequency of less than or equal to 1% were identified and analyzed utilizing an open source integrative genomics viewer. Amino acid substitution effects on protein function were determined by a bioinformatics algorithm. Myocardial recovery was defined as an improvement in EF to greater than 45% at three months post implant.&#x0D; Results: Our sample population included 12 males and 2 females with an average age of 49 and an average EF at presentation of 17%. Damaging cardiac gene variants were present in 11/14 patients. Only 1 of the 11 patients with damaging cardiac gene variants improved their ejection fraction to greater than 45% post LVAD. Two of the 2 patients without mutations improved their ejection fraction to greater than 45%, p-value=.04. Nine of the 14 patients in this population had damaging oncogene mutations.&#x0D; Conclusions: Damaging variants in cancer and cardiac genes are common in end-stage non-ischemic cardiomyopathy patients undergoing LVAD placement. Genetic variation likely contributes to disease progression and cancer risk.

Abstract 13881: Cardiac Progenitor Cell Infusion in Patients With Univentricular Heart Diseases in Heart Failure With Preserved Ejection Fraction

Backgrounds: The clinical outcomes of heart failure with reduced and preserved ejection fraction (HFrEF and HFpEF) after staged palliations in patients with univentricular heart disease remain unknown as is the question whether cardiosphere-derived cell (CDC) transfer may have impact on either type of cardiac dysfunction. Purpose: We sought to characterize the heart failure patients, include HFrEF and HFpEF, with single ventricular physiology and investigate the clinical responsiveness after CDC therapy. Methods: Forty-three patients, aged 2.2±1.4 years, undergoing staged shunt procedures were divided into two groups by cardiac function based on cMRI (HFrEF: EF&lt;40%, n=30; HFpEF: EF&gt;40%, n=13). Results: Compared with HFpEF patients, HFrEF patients showed increased cardiac volume (P=0.02) and mass index (P=0.04), those were associated with reduced global circumferential strain in HFrEF compared with HFpEF (P=0.0004). There was no difference in the incidence of late gadolinium enhancement detected by cMRI in both groups (20% in HFrEF and 15% in HFpEF). When patients underwent staged shunt procedures, HFpEF group had significant reduction in EF (P=0.03) and atrial strain (P=0.047), resulting in increase in Tei index 1 month after palliation (P=0.02). To investigate whether CDC infusion may affect the cardiac function in these two types of HF, patients were subjected to receive CDC injection 1 month post palliation. In contrast to HFpEF group, HFrEF patients demonstrated a marked improvement in EF (P=0.0006), right ventricular elastance (P=0.0005) 3 months after CDC infusion. Similarly, diastolic function improvements were found in CDC-treated HFrEF group but HFpEF patients as shown by increased atrial fractional area change (P=0.01) and reduced E-wave/e’sr (P=0.049). However, patients with HFpEF showed no improvement in diastolic function but significantly reduced dP/dt at 3 months (P=0.04). These beneficial effects by CDCs could not be seen in remaining 20 patients who were assigned to treat as palliation alone without CDC injection. Conclusions: HFpEF is common in univentricular heart diseases and that may have early perioperative right ventricular dysfunction and could be CDC therapy-resistant leading to latent heart failure.