Mean Baseline Ejection Fraction Research Articles

Reducing the Incidence of Post – Myocardial Infarction Heart Failure in an Era of Improved Primary Percutaneous Coronary Intervention through Novel Therapeutics (Protein Kinase C Beta II Inhibitor)

Heart failure (HF) complicating myocardial infarction (MI) remains a major source of morbidity, mortality and a huge health-care burden in the world. The incidence of symptomatic HF after primary percutaneous coronary intervention (PPCI) has been widely reported. PPCI has improved early survival of MI, but its impact on downstream HF is deliberated. Infarct size is the major determinant of the development of HF and prognosis. Efforts to reduce the size will therefore have a significant impact on the incidence of HF after PPCI. Resuscitation of the ischemic myocardium, heavily rests on timely reperfusion. However, cardiomyocyte death still occurs due to ischemic/reperfusion (I/R) injury mediated by oxidative stress. This phenomenon is known to largely contribute to the size of infarct. Activation by protein kinase C-βII (PKCβII) is attributed to the generation of reactive oxygen species (ROS) during this process and inhibition of this drive could salvage the myocardial tissue and subsequently preserve cardiac function. We hypothesized that myristic acid (Myr) and trans-activator of transcription (Tat) conjugated PKCβII inhibitor (Myr-Tat-PKCβII-) will exhibit robust cardioprotective effects in an in vivo porcine model, reflective of our ex vivo rat hearts model. Male Yorkshire pigs underwent regional I/R by occluding the second branch of the left anterior descending artery (LAD). This was achieved in the catheterization laboratory guided by fluoroscopy. A bolus of Myr-Tat-PKCβII- or scrambled control was infused into the LAD during reperfusion. Cardiac function was evaluated by an echocardiogram during the entire procedure, and assessed as the relative change at the end of 3hr reperfusion compared to baseline. Post-reperfused hearts were stained with Evans Blue dye to identify the area a risk and 1% triphenyltetrazolium chloride to delineate the area of necrosis. Infarct size and ejection fraction (EF) were analyzed via Student’s t- test. From mean baseline EF (61.4±0.5%), Myr-Tat-PKCβII- preserved EF with a relative change of 1.2±2.8% compared to 8.9±2.2% in control hearts (p<0.05) at the end of reperfusion. Myr-Tat-PKCβII- reduced infarct size to 13.5±3.9% (n=4) compared to scrambled control hearts (27.5 ±7.9%, n=6). These results suggest Myr-Tat-PKCβII- significantly preserve EF after PPCI and reduce infarct size when given at reperfusion onset. This study gives a solid premise for future examination of Myr-Tat-PKCβII- in an 8 week in-vivo, porcine MI survival study.

P176 GLOBAL LONGITUDINAL STRAIN AS A PREDICTOR OF RESPONSE TO CARDIAC CONTRACTILITY MODULATION IN PATIENTS WITH HEART FAILURE: A CASE SERIES

Abstract Background Cardiac contractility modulation (CCM) in heart failure (HF) patients with reduced ejection fraction (HFrEF) is an innovative therapy which may contribute to increased exercise capacity and quality of life and reduced hospitalizations. With speckle–tracking echocardiography and global longitudinal strain (GLS), changes in myocardial function can be detected with greater sensitivity than conventional approaches for measuring diastolic and systolic function, including left ventricular ejection fraction. We aim to analyze the usefulness of GLS in detecting improvement in systolic function and response to CCM treatment. Methods We studied 5 patients with CCM referred to our outpatient cardiology clinic. All patients underwent complete echocardiography with evaluation of GLS and ejection fraction. Follow–ups were performed at 1, 3, and 6 months. Results All patients were men (mean age 65.3±15.7 yrs). Mean baseline ejection fraction was 37.1±9.3%, mean GLS was 7.7±3.1%, and patients had mild–to–moderate left ventricular enlargement (mean indexed telediastolic volumes 101.4±8.7 ml/m2). Follow–up performed at the first month showed values similar to baseline values. Between the third and sixth months, a non–significant improvement in ejection fraction and GLS was recorded (EF 40.75±9.6% p=0.51; GLS 8.9±4.2 p=0.62). Indexed telediastolic volumes were reduced (101.4±9.3 ml/m2 vs 89.5±7.4 ml/m2 p=0.05). Conclusions CCM therapy seems to be useful in achieving volumetric remodeling in patients with HFrEF. GLS assessment may be useful in detecting improvement in systolic function. Further studies with larger samples and longer follow–up are needed to confirm these results.

Abstract 14364: Protein Kinase C Beta II Inhibitor Provides Cardiovascular Protection When Combined With Conjugated Myristic Acid and Trans-Activator of Transcription in Porcine Ischemia-Reperfusion Injury

Prompt reperfusion is vital to resuscitating ischemic myocardium. However, cardiomyocyte death still occurs due to ischemia-reperfusion (I/R) injury, which is mediated in part by oxidative stress. Major sources of reactive oxygen species (ROS) during I/R are NADPH oxidase (NOX-2) and mitochondria, which are principally activated by protein kinase C βII (PKCβII). Previously, myristic acid (Myr) and trans-activator of transcription (Tat) conjugated PKCβII inhibitor (Myr-Tat-PKCβII-; N-Myr-Tat-CC-SLNPEWNET) exhibited cardioprotective effects in ex vivo rat hearts. In this study, we hypothesize that Myr-Tat-PKCβII- will mitigate cardiac injury in an in vivo porcine myocardial I/R model compared to scrambled peptide controls. Male Yorkshire pigs (38-50kg) underwent regional I(1hr)/R(3hrs) through balloon-assisted occlusion of the second diagonal branch of the left anterior descending coronary artery (LAD) supplying ~40% of the anterior portion of the myocardium. During reperfusion (balloon deflation), a bolus of Myr-Tat-PKCβII- or scrambled control was infused into the LAD. Cardiac function was evaluated as the relative change in ejection fraction (EF) at the end of 3hr reperfusion compared to baseline. Serial measurements of serum creatine phosphokinase (CPK), troponin I, and myoglobin were evaluated to assess cardiac injury. Post-reperfused hearts were stained with Evans Blue dye to identify the area at risk (AR) and 1% triphenyltetrazolium chloride to demarcate the area of necrosis (AN). Infarct size (AN/AR), EF, and cardiac injury markers were analyzed via Student’s t-test. Myr-Tat-PKCβII- preserved EF with a relative change of 1.2±2.8% compared to 8.9±2.2% in control hearts (p<0.05) from mean baseline EF (61.4±0.5%). Myr-Tat-PKCβII- significantly decreased myoglobin levels at 1hr reperfusion (135±132ng/mL, n=4) compared to scrambled control (1022±346ng/mL, n=3 p<0.05). Myr-Tat-PKCβII- reduced infarct size to 13.5±3.9% (n=4) compared to scrambled control hearts (27.5±7.9%, n=6). CPK and troponin I levels were comparable in both groups. These results suggest Myr-Tat-PKCβII- mitigates cardiac injury when given at reperfusion onset. Future studies will examine Myr-Tat-PKCβII- in an 8 week in-vivo, porcine MI survival study.

Outcomes In Patients On Chronic Inotropic Support Who Are Not Candidates For Advanced Heart Failure Therapies

Introduction Significant therapeutic advancements including guideline-directed-therapy (GDMT) and device implantation have improved outcomes in heart failure patients. Their impact on patients with advanced heart failure requiring chronic inotropic support who are not candidates for left ventricular assist device (LVAD) or heart transplant (HT) is not well studied. We aimed to study outcomes in these patients discharged on inotropes while comparing the dobutamine and milrinone cohorts. Methods We conducted a retrospective multi-center study from Jan 2015 to May 2019. A total of 249 patients who were hospitalized with refractory stage-D heart failure and discharged on continuous long-term milrinone or dobutamine therapy were included. Patients who were candidates for HT or LVAD and those discharged on comfort measures were excluded. Multivariable logistic regression was utilized to assess odds of mortality in these patients. Results Overall mean age was 64.8 ±13.4 years. Majority of the patients were males, Caucasian and had a pre-implanted cardiac device. Common comorbidities included CAD, diabetes, hypertension and CKD. Age and baseline comorbidities were similar in both groups except for CKD which was more prevalent in dobutamine group (59.4 vs 52.0; p-value=0.02). Overall, mean baseline Ejection Fraction was 20.2%, similar in both groups (p=0.71). Patients on dobutamine had higher baseline cardiac indices than milrinone group (Fick 2.0 vs 1.8; p-value=0.048, Thermodilution 2.0 vs 1.6; p-value=0.002). Overall, 1-year mortality was 70.7 %. Patients on milrinone had lower 1-year-mortality compared to dobutamine group (58.1% vs 85.0%; P-value<0.01). Unadjusted odds ratio (OR) for milrinone group was 0.24 (CI 0.13-0.46, p-value=p<0.001). When adjusted for age, sex, race and BMI, OR was 0.29 (CI 0.15-0.58, p-value=0.001). Milrinone cohort had more patients discharged on beta blocker (42.9 vs 8.6; p-value <0.001). Other GDMT was also more common on discharge in milrinone group, though statistical significance was not reached. Six patients became candidates for advanced therapies (LVAD/HT). (See Table) Conclusion Mortality remains high in patients started on chronic inotropes who are not candidates for LVAD/HT. Milrinone may have better patient outcomes as compared to dobutamine but larger comparative controlled studies are needed to confirm this. Significant therapeutic advancements including guideline-directed-therapy (GDMT) and device implantation have improved outcomes in heart failure patients. Their impact on patients with advanced heart failure requiring chronic inotropic support who are not candidates for left ventricular assist device (LVAD) or heart transplant (HT) is not well studied. We aimed to study outcomes in these patients discharged on inotropes while comparing the dobutamine and milrinone cohorts. We conducted a retrospective multi-center study from Jan 2015 to May 2019. A total of 249 patients who were hospitalized with refractory stage-D heart failure and discharged on continuous long-term milrinone or dobutamine therapy were included. Patients who were candidates for HT or LVAD and those discharged on comfort measures were excluded. Multivariable logistic regression was utilized to assess odds of mortality in these patients. Overall mean age was 64.8 ±13.4 years. Majority of the patients were males, Caucasian and had a pre-implanted cardiac device. Common comorbidities included CAD, diabetes, hypertension and CKD. Age and baseline comorbidities were similar in both groups except for CKD which was more prevalent in dobutamine group (59.4 vs 52.0; p-value=0.02). Overall, mean baseline Ejection Fraction was 20.2%, similar in both groups (p=0.71). Patients on dobutamine had higher baseline cardiac indices than milrinone group (Fick 2.0 vs 1.8; p-value=0.048, Thermodilution 2.0 vs 1.6; p-value=0.002). Overall, 1-year mortality was 70.7 %. Patients on milrinone had lower 1-year-mortality compared to dobutamine group (58.1% vs 85.0%; P-value<0.01). Unadjusted odds ratio (OR) for milrinone group was 0.24 (CI 0.13-0.46, p-value=p<0.001). When adjusted for age, sex, race and BMI, OR was 0.29 (CI 0.15-0.58, p-value=0.001). Milrinone cohort had more patients discharged on beta blocker (42.9 vs 8.6; p-value <0.001). Other GDMT was also more common on discharge in milrinone group, though statistical significance was not reached. Six patients became candidates for advanced therapies (LVAD/HT). (See Table) Mortality remains high in patients started on chronic inotropes who are not candidates for LVAD/HT. Milrinone may have better patient outcomes as compared to dobutamine but larger comparative controlled studies are needed to confirm this.

Apical Sparing Strain Imaging In Patients With Hypertensive Emergency: A Study Of Patients Characteristics And Prognostic Value

<h3>Objective</h3> What are the clinical characteristics and prognostic values of patients with apical sparing strains compared to those with a normal strain pattern in hypertensive emergency? <h3>Background</h3> Differences in strain values among segments on the standard bull's eye model can give clues to different disease patterns. A pattern of apical sparing (AS) has been associated with cardiac amyloidosis, hypertrophic cardiomyopathy, hypertension, and aortic stenosis. Changes in longitudinal strain predict subsequent development of heart failure or reduction in left ventricular ejection fraction in patients undergoing cardiotoxic chemotherapy. <h3>Methods</h3> We conducted a historical cohort study of all patients with an admission diagnosis of hypertensive emergency who had an echocardiogram done with evaluation of the strain pattern. Patients with AS were compared to those without AS on the following characteristics: demographics (age, race, sex), comorbidities as measured by the Charlson Weighted Index of Comorbidity (CWIC), ejection fraction and laboratory values including creatinine and hemoglobin levels on admission, pro-BNP (if available), discharge disposition and readmission within 30 days. Patients were followed in time (via medical records) from the initial admission to collect any other ejection fraction data on echocardiogram that were in the medical records. <h3>Results</h3> There were 946 unique patients admitted with a diagnosis of hypertensive urgency or emergency. A total of 120 patients had an evaluation of the strain pattern on the echocardiogram. Approximately one-third [n=35] of patients admitted to the hospital with hypertensive emergency had apical sparing strain versus two-third [n=85] has non-apical sparing (figure 1). Forty percent and sixty percent of AS patients were males and females respectively, whereas, 55% and 45% of non-AS patients were males and females respectively. The mean age at admission was 58.2 ± 14.7 in AS and 60.6 ± 14.3 in non-apical sparing patients. A 97.1% of AS and 85.9% of non-AS patients were black p = 0.071. The mean baseline ejection fraction (EF) was 48.89% ± 12.55 and follow-up EF was 50.83% ± 12.63 in the apical sparing group p=0.58. On the other hand, the mean baseline EF was 53.47% ± 13.92, and follow-up EF% was 54.72% ± 14.83 in the non-apical sparing group p=0.39. The readmission rate within 30 days from discharge was 17.1% in AS versus 21.2% non-AS group. <h3>Conclusion</h3> The data showed a higher prevalence of AS strains in black patients and female patients. Patients with AS were younger than those without AS. The baseline and follow-up ejection fraction were similar in both study groups. Almost one-third of patients admitted to the hospital with hypertensive emergency/urgency have an apical sparing pattern. To summarize, the apical sparing pattern is not exclusive to cardiac amyloidosis and it is more commonly seen in hypertensive heart disease.

B-PO01-049 LOW LEFT ATRIAL VOLTAGE PREDICTS IMPROVEMENT IN SYSTOLIC FUNCTION POST ATRIAL FIBRILLATION ABLATION IN PATIENTS WITH SYSTOLIC HEART FAILURE

Catheter Ablation of Atrial Fibrillation (AF) in patients with heart failure with reduced ejection fraction (HFrEF) is associated with decrease in all-cause mortality, and improvement in left ventricular ejection fraction (EF). Predictors of EF improvement post-AF ablation is not known. To explore predictors of EF improvement post AF ablation in patients with HFrEF. A retrospective chart review of patients who underwent catheter ablation for AF within last 6 years was performed. Patients undergoing catheter ablation for paroxysmal or persistent AF with EF <45% were included. Baseline clinical information, echo and left atrial (LA) voltage data from EP study at the time of ablation was collected on REDCAP. One-way analysis of variance was used to compare between two groups. Out of 263 patients who underwent catheter ablation, 82 (32%) had HFrEF. The mean age was 59.1±11.4; 27% were female. Median follow-up echo post-ablation was at 175 days (IQR 66, 451). Baseline clinical characteristics and results are shown in the table. Mean baseline EF was 30.1±11.4. Mean improvement in EF after ablation was 17±11.8. As compared to baseline, EF improved by at least 5% in 80% of the patients who underwent ablation. Patients with improved EF had significantly higher average total voltage in the LA compared to patients who had no improvement in EF (1.70±1.16 vs 1.00±0.82, p=0.02*). In the multivariable model, after adjusting for other risk factors, LA average total voltage was significantly higher in the group with improved EF (p=0.04*). In patients with HFrEF undergoing catheter ablation for AF low average left atrial voltage predicted lack of improvement in EF.Tabled 1Baseline characteristics comparison between patients with and without improvement in EFEF Improved (n=51)EF not improved (n=13)P-ValueAge58.7+12.557.3+11.70.71Female13 (25%)3 (23%)0.85Hypertension47 (92%)13 (100%)0.17Diabetes Mellitus15 (29%)3 (23%)0.64Cerebrovascular Accident7 (14%)3 (23%)0.42Coronary Artery disease18 (35%)3 (23%)0.39Baseline EF29.1+11.233.4+12.90.29Average total voltage1.70+1.161.00+0.820.02* Open table in a new tab

Chronology of cardiac dysfunction after permanent pacemaker implantation: an observational 2\xa0year prospective study in North India

BackgroundThe purpose of this study is to evaluate cardiac functions using transthoracic echocardiography, change in lead parameters and electrocardiogram (ECG) morphology in patients undergoing permanent pacemaker implantation over a follow-up period of 6 months.MethodsThis is a prospective study in patients undergoing permanent pacemaker implantation in a tertiary care hospital. Patients undergoing permanent pacemaker implantation were enrolled for up to one year and Echocardiographic parameters (by 2 blind operators) and ECG parameters were recorded at admission (within 24 h), before discharge (within 7 days of pacemaker implantation), after 1 month (± 7 days) and after 6 months (± 7 days) of follow-up.ResultsA total of 96 patients (60.4% males and 39.6% female, mean age 66.65 years) were implanted with permanent pacemaker. The mean QRS duration was 133.18 ms and increased significantly to 146.03 ms by 6 months despite septal lead placement in majority (92%) of patients. The mean baseline ejection fraction of 51.47 decreased significantly to 47.83 by 6 months. Diastolic parameters like left atrial volume index, early to late diastolic transmitral flow velocity (E/A) and early diastolic mitral annular tissue velocity (E/e′) showed a significant increase (> 5%) from baseline by the end of first week. By the end of first month, systolic dysfunction of RV sets in with significant (> 5%) change from baseline in parameters like Right ventricle myocardial performance index, transannular plane systolic excursion and right ventricle systolic excursion velocity (RVS′).ConclusionWe have observed that pacemaker recipients with baseline reduced left ventricle (LV) systolic functions perform significantly worse compared to those with baseline normal cardiac functions and had a higher rate of deterioration of LV function. RV dysfunction is the first abnormality that occurs, by 1 week followed by LV dysfunction which starts by 1 month and the diastolic dysfunctions precede the systolic dysfunction. QRS duration also showed a gradual increase despite septal lead placement in majority (92%) and lead parameters showed no significant change over 6 months.

Vasoplegia induces high energy demand and depletes cardiac energetics: a new insight into physiological concepts of cardiac work and a model for acute heart failure?

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): British Heart Foundation Background / Introduction Hearts subjected to constant high workload will, over time, fail. We hypothesized vasoplegia would create a high cardiac energy demand and deplete cardiac energy reserves, a mechanism causing failure. With 31Phosphorus Magnetic Resonance Spectroscopy, we can measure energy: ATP usage (via creatine kinase flux) and reserves of phosphocreatine (PCr/ATP ratio). Methods: Ten healthy volunteers were recruited mean age 37, mean BMI 22.4, 5 male, 5 female. A nitrate vasodilator (Glyceryl trinitrate, GTN) was used to induce vasoplegia, with MRI and MRS measurements taken before and during. Results There was reduced preload (falls in end diastolic volume and right atrial area) and afterload (mean blood pressure fall 14mmHg, p &amp;lt;0.0001). Subjects mounted reflex tachycardia (mean heart rate rise 9bpm, p &amp;lt; 0.0001) and inotropy (mean baseline ejection fraction increase 5%, p = 0.0002) hence cardiac output and rate pressure product were maintained (baseline CO 6.24 ± 1.45 L/min vs GTN 6.49 ± 1.43 L/min, p = 0.37; baseline RPP = 6929 ± 976 mmHg.bpm vs GTN 7214 ± 1051 mmHg.bpm, p = 0.06). There was a 58% increase in Creatine Kinase activity (kf) (baseline 0.158 s-1 vs GTN 0.249 s-1, p = 0.006) and CK flux (baseline 1.79 ± 0.78 umol/g/s vs GTN 2.59 ± 1.07 umol/g/s, p = 0.03), demonstrating increased ATP transfer. PCr/ATP fell (from 2.17 ± 0.2 to 1.99 ± 0.22, p = 0.027). Baseline PCr/ATP positively correlated with the change in stroke volume (R2 = 0.66, p = 0.005) during administration of GTN. In addition, whilst at rest, CK kf correlated with rate pressure product (R2 = 0.56, p = 0.03), there was no correlation seen during GTN. Conclusions We have shown vasoplegia increases energy demand upon the heart, despite unchanged cardiac output and rate pressure product. Further, we have shown a fall in Phosphocreatine/ATP ratio, suggesting this ATP transfer outstripped oxidative phosphorylation and the phosphocreatine pool was depleted in order to maintain ATP delivery. We speculate that progressive depletion of energetics in the context of high energy demand drives hearts under constant stress into failure. In addition, we demonstrate that the magnitude of the resting phosphocreatine pool relates to ability to augment stroke volume during stress and suggest that this may be protective against a decline into failure. Further work is needed, but PCr/ATP may be an important biomarker for treatments that target myocardial energetics to protect against failure. Abstract Figure 1

P3792The impact of elective cardioversion for atrial fibrillation in heart failure patients

Abstract Introduction Severe left ventricular systolic dysfunction (LVSD) is associated with worse outcomes in heart failure (HF) patients. Persistent atrial fibrillation (AF) is common in this patient group. As part of a nurse-led cardioversion service at a district general hospital we assessed the impact of elective cardioversion (DCCV) for AF in patients with LVSD on their ejection fraction (EF), and compared outcomes in patients selectively pre-treated with amiodarone for their DCCV. Methods A retrospective analysis was undertaken of DCCV for AF over 5 years, recording demographic, medication, serial echocardiogram (TTE), and outcome data. Significant LVSD was classified as moderate (ejection fraction [EF] 35–45%) or severe (EF&lt;35%). All patients treated with amiodarone had baseline and serial thyroid, liver, renal function monitored, were counselled on side effects and followed up. Results 103 patients with significant LVSD and follow-up TTE underwent DCCV, with a median age of 66 (IQR 58–73) and mean CHA2DS2-VASc 2.5. Overall mean baseline EF was 30% (SD ±11), overall follow-up EF (regardless of repeat TTE rhythm) was 42% (SD ±12), and the mean delta EF +12% improvement (SD ±11). At follow-up TTE, 66% (68/103) of patients were in sinus rhythm (SR) and 34% (35/103) in AF. 62/68 (91%) patients in SR at follow-up TTE were also treated with HF medications, vs 33/35 (94%) of those in AF. 61/68 (90%) of patients in SR at follow-up TTE had any improvement in EF vs 21/35 (60%) patients in AF (p=0.0007). For patients in SR the mean baseline EF was 31% (SD ±10) and mean follow-up EF 47% (SD ±9), vs the AF at repeat TTE patients' mean baseline EF 27% (SD ±12) and mean follow-up EF 35% (SD ±13). The mean delta EF of patients still in SR at follow-up scan was 15% (SD ±10) vs 8% (SD ±11) for patients who had reverted to AF (p=0.0004). Prior analysis of our data-set including patients awaiting repeat TTE demonstrated a significant improvement in 6 month AF recurrence rate. Table 1. Comparing outcomes with amiodarone pre-treatment for patient with follow-up EF data Acute DCCV Success Mean Baseline EF Mean Repeat EF Mean Delta EF AF Recurrence to 6 months Amiodarone 17/17 (100%) 29% (SD 11) 45% (SD 11) 15% (SD 13) 6/17 (35%) No Amiodarone 80/86 (93%) 30% (SD 11) 42% (SD 12) 12% (SD 10) 50/86 (58%) P value 0.59 0.22 0.11 Conclusion Restoration of SR in a cohort of patients with AF, severe LVSD, on good medical therapy significantly improves left ventricular EF. This reinforces the importance of maintaining SR for HF patients. There was also a trend towards improved medium term outcomes in patients pre-treated with amiodarone. Further study into long-term rhythm control and ablation outcomes is needed.

THE PARASAIL STUDY- CANADIAN REAL WORLD EXPERIENCE USE OF SACUBITRIL/VALSARTAN IN PATIENTS WITH HEART FAILURE AND REDUCED EJECTION FRACTION

PARASAIL was a Canadian prospective, multicenter, open-label study with the objective of characterizing over a 12 months period the real-life effectiveness, tolerability and safety of sacubitril/valsartan (Sac/Val) in patients with heart failure with reduced ejection fraction (HFrEF). Participants were HFrEF outpatients with an ejection fraction of ≤ 40%, NYHA class II or III and on stable doses of ACEI or ARB and treated as per CCS guidelines and clinical judgment. The suggested starting dose of Sac/Val was 24/26 mg bid replacing ACEI or ARB, with an up-titration to 49/51 mg bid then to 97/103 mg bid every 2-4 weeks, however, the decision to up-titrate was left to the investigator’s discretion. Key exclusion criteria included symptomatic hypotension and/or SBP below 100 mmHg, estimated GFR below 30mL/min/1.73m2, angioedema or necessity to use ACEI or ARB concomitantly. Tolerability was assessed by; 1) assessing the number of patients remaining on the Sac/Val target dose of 97/103 mg bid at Month 6 (primary objective) and at Month 12; 2) measuring time to up-titration to the Sac/Val 49/51 mg dose and Sac/Val 97/103 mg dose; 3) measuring the number of dose reduction from Sac/Val 97/103 mg. Patients (n=302) had a mean age of 64 years, 80% male, 90% Caucasian, mostly NYHA Class II (83%), and 45% had prior heart failure-related hospitalization. The mean baseline ejection fraction was 29 ± 7.5% and blood pressure was 122/73 mmHg. Sac/Val starting dose of 24/26 mg was used for most patients (90%). At Month 6, 195 patients (64.6%) remained on the Sac/Val 97/103 mg dose, 46 patients (15.2%) remained on the 49/51 mg dose and 29 patients (9.6%) remained on the 24/26 mg dose. The majority of patients (65%) achieved the maximum dose of Sac/Val 97/103 mg at 12 weeks. At Month 12, 62% of the patients remained on the maximum dose of Sac/Val. Only a small proportion of patients (12%) have been down-titrated after achieving the maximal target dose of Sac/Val. Overall, the treatment was well tolerated with a discontinuation rate of 13% at Month 12. PARASAIL trial describes real-life tolerability and safety of Sac/Val in a Canadian HFrEF patient population. The results presented here showthat the target dose of Sac/Val 97/103 mg is generally achievable.

Impact of a Comprehensive Heart Failure Self Care Review

Introduction Heart failure (HF) is one of the common reasons for hospital admissions in patients 65 years and older. Despite recent advances, patients are still frequently hospitalized with efforts to reduce readmissions. The 2013 ACCF/AHA guidelines list HF education, including self-care, as a class I recommendation. The purpose of this study is to assess self-care education in a HF clinic. Methods Since July 2015, 57 patients new to Advanced Integrated Medical and Surgical (AIMS) HF program were enrolled. After informed consent and baseline data collection including the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Morisky Medication Adherence Score (MMAS-4), New York Heart Association (NYHA) functional classification, and medication knowledge score, patients underwent self-care education using a standardized self-care education tool developed by the PI. The education was customized based on health literacy as assessed by the Rapid Assessment of Adult Literacy in Medicine (REALM) score. Patients were contacted at 6 and 12-months for re-assessment of outcomes. Changes in numerical values were compared pre- and post-intervention using paired student's t tests and changes in categorical variables were compared using Wilcoxon Signed Ranks test. Results Twelve-month analysis was completed in 50 patients. Of these, 100% were Caucasian and 74% (37) were male, with a mean age of 66.7 ± 10.6 years. Mean baseline ejection fraction (EF) was 29.2% ± 13.3% and ranged from 15-60%. Most patients (74%, n = 37) were NYHA class III at baseline. NYHA functional class significantly improved from baseline: I-2 (4%), II-10 (20%), III-37 (74%), IV-1 (2%) to 12 months post-intervention: I-11 (23%), II-10 (21%), III-25 (53%), IV-1 (2%), p = 0.003. The following KCCQ parameters also significantly improved: symptom burden score pre-72.8 ± 25.1 vs post-82.4 ± 22.9, p = 0.02, total symptom score pre-73.0 ± 23.2 vs post-81.1 ± 21.4, p = 0.03, self-efficacy pre-80.9 ± 20.1 vs post-92.9 ± 10.9, p Conclusion A customized self-care HF review using a standardized tool was associated with significant improvements in NYHA class and improvements in patients’ perceptions of symptom burden, self-efficacy, QOL, social limitation, and overall KCCQ summary scores at 12-months post intervention. Medication adherence and knowledge also improved. Larger, longitudinal studies are further warranted to assess the durability of results and to determine if these improvements translate into other improved clinical outcomes.

The PARASAIL study- Patient Reported Outcomes from the Canadian Real World Experience use of Sacubitril/Valsartan in Patients with Heart Failure and Reduced Ejection Fraction

Background PARASAIL is the first Canadian prospective, multicenter, open-label study which aims at characterizing the real-life effectiveness and safety of sacubitril/valsartan (Sac/Val) in patients with heart failure with reduced ejection fraction (HFrEF) treated for a 12 months period. Here we present the final analysis results of the PARASAIL Study for the tolerability and effect of sacubitril/valsartan (Sac/Val) on quality of life (QoL). Methods Participants were HFrEF outpatients with an ejection fraction of ≤ 40%, NYHA class II or III and on stable doses of ACEI or ARB with additional HF treatment as per CCS guidelines. The suggested starting dose of Sac/Val was 24 mg/26 mg bid replacing ACEI or ARB, with an up-titration to 49 mg/51 mg bid then to 97 mg/103 mg bid every 2-4 weeks or as per clinical judgement. Symptomatic hypotension and/or SBP below 100 mmHg, estimated GFR below 30mL/min/1.73m2, angioedema or necessity to use ACEI or ARB concomitantly, were amongst the exclusion criteria. Changes in quality of life was measured with the patients Minnesota living with HF questionnaire (MLHFQ), EQ-5D questionnaire and patient global assessment (PGA) at baseline and at 4, 12 and 24 weeks after conversion to Sac/Val. Results Patients (n=302) had a mean age of 64 years, 80% male, 90% Caucasian, mostly NYHA Class II (83%), with a mean baseline ejection fraction of 29 ± 7.5% and blood pressure of 122/73 mmHg. Sac/Val starting dose of 24/26 mg was used for most patients (90%) and up-titration to maximum dose of Sac/Val was achieved for the majority (65%) at 12 weeks. Quality of life significantly improved: 52% of patients reported a significant improvement of their overall scores at week 4, 59% at week 12 and 64% at week 24 as measured with PGA. Using MLHFQ, patients experienced a 19%, 21% and 23% decrease in the score compared to baseline at weeks 4 and 24 with respectively (all p Conclusion The PARASAIL trial was designed to evaluate the real-life therapeutic effectiveness, tolerability and safety of Sac/Val in HFrEF patients. Although the lack of a comparator group limits the interpretation, the results shown by the validated questionnaires indicate a potential early and sustained improvement in Quality of Life at week 4, week 12 and week 24 of treatment with Sac/Val compared to baseline, in line with results from PARADIGM.

292 - Impact of a Comprehensive Heart Failure Self-Care Review 12-Month Assessment

Purpose: Heart failure (HF) is one of the most common reasons for hospital admissions in patients ≥65 years. Despite recent advances, patients are still frequently hospitalized with efforts to reduce readmissions. The 2013 ACCF/AHA guidelines list HF education, including self-care, as a class I recommendation. The purpose of this study is to assess a self-care education program in a HF clinic. Methods: Since July 2015, 49 patients new to the Advanced Integrated Medical and Surgical (AIMS) program for HF were enrolled in the study. After informed consent and baseline data collection including the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Morisky Medication Adherence Score (MMAS-4), and medication knowledge score, patients underwent self-care education with the Principal Investigator (PI) using a standardized self-care education tool developed by the PI. The education was customized based on health literacy as assessed by the Rapid Assessment of Adult Literacy in Medicine (REALM) score. Patients were contacted at 6 and 12-months for re-assessment of clinical outcomes. Changes in numerical values were compared pre- and post-intervention using paired student's t tests and changes in categorical variables were compared using Wilcoxon Signed Ranks test. Results: Twelve-month interim analysis was completed in 25 patients. Of these, 100% were Caucasian and 64% (16) were male, with a mean age of 70.6 ± 8.1 years. Mean baseline ejection fraction (EF) was 34.5%±12.5% and ranged from 15–60%. Most patients (80%, n = 20) were New York Heart Association (NYHA) class III at baseline. The following KCCQ parameters significantly improved at 12-months: symptom burden score pre-65.0 ± 25.7 vs post-77.1 ± 26.1, P = .03, total symptom score pre-66.2 ± 24.8 vs post-76.5 ± 22.6, P = .046, self-efficacy pre-78.1 ± 19.2 vs post-90.4 ± 12.3, P = .002; quality of life (QOL) pre-56.4 ± 24.5 vs post-70.3 ± 19.9, P = .003; social limitation pre-59.2 ± 34.1 vs post-80.8 ± 20.2, P < .001; overall summary score pre-62.5 ± 24.1 vs post-76.1 ± 20.0, P < .001; and clinical summary score pre-67.3 ± 23.6 vs post-76.8 ± 22.6, P = .03. Patients also experienced improvements in their MMAS-4 score; pre-0.48 ± 0.6 vs post 0.05 ± 0.2, P = .002. Percentage score on knowledge assessment also increased from 75 + 2 to 95 + 8, P < .001. Conclusion: A customized self-care HF review using a standardized tool was effective in improving patients' perceptions of symptom burden, self-efficacy, QOL, social limitation, overall and clinical KCCQ summary scores at 12-months post intervention. Medication adherence and knowledge also improved. Larger, longitudinal studies are further warranted to determine if these improvements translate into improved clinical outcomes.

Abstract 115: Beta-blocker Therapy in Cocaine Users With Heart Failure: Insights From an Urban Academic Center

Background: Beta-blockers are first line agents for reduction of symptoms, hospitalization and mortality in heart failure patients with reduced ejection fraction (HFrEF). The safety and efficacy of continuous beta-blocker therapy (BBT) in patients who use cocaine remain controversial and available literature is limited. We aimed to evaluate clinical outcomes of BBT among HFrEF patients who use cocaine. Methods: We conducted a retrospective chart review of 90 patients with a diagnosis of heart failure based on ICD9-CM codes and baseline ejection fraction (EF) &lt;40% who tested positive for cocaine on urine toxicology test at the time of index admission. We included patients age 18 or older with at least 3 months of follow up. Baseline EF was obtained from the earliest available echocardiogram report in 2011 and repeat EF was obtained from follow up echocardiogram reports while on BBT. We described baseline patient characteristics, comorbidities and outcomes (change in EF during study period, re-hospitalizations and mortality). Results: In our study population (mean age = 56.1 ± 7.8 years), the mean baseline EF was 24.1% (std=9.0). The mean overall change in EF among patients on continuous BBT was 1.9% (std=14.6; p-value=0.2) over a mean follow-up time of 15.5 months (std=8.6). Thirty-nine percent (n=35, mean follow up=15.7 months) of our study population had a decrease in EF (mean change= -10.6%; std=6.8), 22% (n=20, mean follow up=17.4 months) had no change in EF and 39% (n=35, mean follow up=14.3 months) had an increase in EF (mean change= +14.3%; std=7.5). There was an average of 3.2(std=3.3) re-hospitalizations. Ninety-two percent (n=83) were alive at the end of the study period. Conclusion: Continuous beta-blocker therapy in HFrEF patients who abuse cocaine has variable effects on left ventricular EF. Large observational studies are needed to further elucidate the efficacy and safety of long-term beta-blocker therapy in this population.

Risk of ventricular tachyarrhythmias following improvement of left ventricular ejection fraction in patients with implantable cardiac defibrillators implanted for primary prevention of sudden cardiac death.

In patients who undergo implantable cardiac defibrillator (ICD) implantation for primary prevention of sudden cardiac death (SCD), data is unclear whether their ICD generator needs to be replaced at end of life if their left ventricular ejection fraction (EF) improves. Despite improvement in EF, the underlying scar may represent a potential substrate for ventricular arrhythmias. Data on 280 patients who underwent ICD implantation for primary prevention of SCD was obtained from two centers. Patients were followed for any improvement in EF to ≥35%. All arrhythmic events during follow-up, including appropriate and inappropriate shocks/ATP, were recorded. Thirty percent (n = 86/280) of patients improved their EF to >35% of which 41% (n = 37) underwent a generator change by the study ending period with the rest not yet at ERI. Mean baseline EF in patients with and without target EF improvement was 26 ± 7 and 23 ± 7% (p = 0.2). After excluding patients whose arrhythmic events data were unavailable, the final sample consisted of 62 patients in the EF improvement group and 156 patients in the group without EF improvement. In the group with EF improvement, appropriate events (shock + ATP) were noted in 19% of patients (n = 12/62) and inappropriate shocks and ATP in 6% of (n = 4/62) patients after their EF improved to >35%. Four patients received appropriate therapies when their EF was low prior to improvement. In contrast, in patients who had no improvement in EF, 27% (n = 43/156) received an appropriate therapy (p = 0.6) while 11% (n = 18/156) (p = 0.2) received inappropriate shocks and ATP. All-cause mortality was higher in patients without subsequent improvement in EF versus those with EF improvement (31 vs. 15% (p = .005). There was no significant difference in the number of appropriate therapies received by each group. Patients continue to be at high risk for sudden cardiac death despite improvement in EF.

Reduction in 18F-fluorodeoxyglucose uptake on serial cardiac positron emission tomography is associated with improved left ventricular ejection fraction in patients with cardiac sarcoidosis

BackgroundCardiac positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) has been used to diagnose and monitor cardiac sarcoidosis (CS). It is not known whether a reduction in myocardial inflammation, as measured by FDG uptake, is associated with improvement in LV ejection fraction (EF). MethodsFor 23 patients with CS followed by a total of 90 serial PET exams (median 4 per patient), two physicians blinded to EF quantified the maximum of standardized uptake value (SUV) and volume of inflamed tissue above two distinct thresholds to assess the intensity and extent of FDG uptake on each study. Using gated 82Rubidium rest myocardial perfusion images, EF was measured blinded to all clinical and FDG data. To account for clustering and differences in scan frequency, a longitudinal mixed effects model was used to evaluate the relationship between FDG uptake and changes in EF on interval scans. ResultsAmong 23 patients with serial PET exams (mean age 49, 74% male, mean baseline EF 43% ± 13%), the median time between the first and last scan was 2.0 years. Overall, 91% were treated with corticosteroids, 78% with ACE/ARB, 83% with beta-blockers, and 83% had ICDs. Longitudinal regression demonstrated a significant inverse linear relationship between maximum SUV and EF with an expected increase in EF of 7.9% per SUV reduction of 10 g·mL−1 (P = .008). Likewise, in an analysis based on volume, there was an increase in EF of 2.1% per 100 cm3 decrease in volume of inflamed tissue using a threshold of 2.7 g·mL−1 (P = .028) and an increase in EF of 3.8% per 100 cm3 decrease (P = .022) using a SUV threshold of 4.1 g·mL−1. ConclusionsIn a longitudinal cohort of CS patients, a reduction in the intensity and extent of myocardial inflammation on FDG PET is associated with improvement in EF. These data suggest serial PET scanning may help guide titration of immunosuppressive therapy to improve or prevent heart failure in CS.

Heart failure with preserved and reduced ejection fraction: Different phenotypes in old-elderly patients?

BackgroundPatients with heart failure with preserved ejection fraction (HFPEF) represent an important group of patients presenting in clinical practice. However, whether it is an earlier stage of heart failure with reduced ejection fraction (HFREF) remains uncertain. We evaluated the potential progression of HFPEF to HFREF. Methods and resultsWe evaluated retrospectively 178 patients (mean age 80.5±5.8years; 75.3% females) with heart failure with preserved ejection fraction from a specialized Internal Medicine unit, offering an integrated usual care. Diagnosis of heart failure with preserved ejection fraction was made according to European guidelines. The main objective was to evaluate the progression to systolic dysfunction, defined by left ventricular ejection fraction less than 45%. Mean baseline left ventricular ejection fraction was 64.6±7.2. After a mean follow-up of 24-months, mean baseline ejection fraction was 67.1±9.3%. Only five patients (2.8%) progressed to HFREF. Brain natriuretic peptide values were significantly higher in those patients who progressed. ConclusionsThese results strongly suggest that heart failure with preserved and reduced ejection fraction could be distinct pathophysiological entities, at least in elderly patients.

High Cumulative Doses of Pegylated Liposomal Doxorubicin Are Not Associated with Cardiac Toxicity in Patients with Gynecologic Malignancies

Purpose: The purpose of this study was to determine the cardiac safety of pegylated liposomal doxorubicin (PLD) in patients receiving high cumulative doses of PLD. Materials and Methods: A retrospective chart review of women with gynecologic malignancies treated at Roswell Park Cancer Institute from 2002 through 2007 who received cumulative doses of PLD ≧400 mg/m² was performed. Results: Forty-two of 116 patients met the inclusion criteria. The mean age at initiation of PLD therapy was 63 years. The mean cumulative dose of PLD was 663.9 mg/m² (range 400–1,524 mg/m²). The mean cumulative number of cycles of PLD given was 9.8 (range 5–25). Multigated acquisition (MUGA) scans were obtained in 93% (39/42) of patients prior to or immediately following their first dose of PLD. The mean baseline ejection fraction was 63% (range 49–76%). Follow-up MUGA scans were performed on 7 patients (17%). Two of these patients had a decrease in their ejection fraction, but of only 3 and 1%. The remaining 5 patients who had follow-up MUGA scans had an average increase in their left ventricular ejection fraction of 4% (range 1–9%). No patients developed clinical evidence of congestive heart failure while being treated with PLD. There were no treatment interruptions or discontinuations due to cardiac toxicity. Conclusion: Cumulative doses of PLD ≧400 mg/m² are not associated with clinically evident cardiac toxicity in gynecologic oncology patients.

Left ventricular dysfunction in patients receiving cardiotoxic cancer therapies: Are clinicians responding appropriately?

9527 Background: Cancer survivors treated with anthracyclines and/or trastuzumab are at risk for cardiotoxicity. Left ventricular (LV) systolic dysfunction (symptomatic or asymptomatic) represents a Class I indication for therapy with beta-blockers and angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) according to American College of Cardiology/American Heart Association heart failure guidelines. We designed this study to examine treatment practices for patients with cancer therapy-associated LV dysfunction, and the real-world adoption of treatment guidelines. Methods: After IRB approval, we identified all patients who received anthracycline and/or trastuzumab cancer therapy at Stanford University from October 1, 2005 to October 31, 2007 using an institutional pharmacy database. Out of 6,530 total cycles of chemotherapy administered, we identified all unique patients who had at least one echocardiogram performed before and after the start of chemotherapy using an institutional echocardiography database. Details of the chemotherapy regimen, cardiac risk factors, cardiac imaging results, concomitant medications, and referrals/consultations were examined for these patients. Results: A total of 88 patients met inclusion criteria. Ninety-two percent were treated with anthracyclines, 25% with trastuzumab in combination with anthracyclines, and 8% with trastuzumab alone. Mean baseline ejection fraction (EF) was 60%, with 13% of patients having a baseline EF below normal. A total of 41% had LV dysfunction (EF less than 55%) during or after cancer therapy. Of these patients, 56% received beta-blocker therapy, 47% received ACE-I or ARB therapy, and 50% were referred for cardiology consultation. Of the patients with asymptomatic LV dysfunction (75% of the LV dysfunction cohort), 41% received beta-blocker therapy, 33% received ACE-I or ARB therapy, and 37% received cardiology consultation. Conclusions: In real-world clinical practice, many cancer survivors with cardiotoxicity are not adequately evaluated and treated from a cardiovascular standpoint. Multidisciplinary collaboration between oncologists and cardiologists is needed to improve the quality of care for these patients. No significant financial relationships to disclose.

T'ai Chi exercise in patients with chronic heart failure.

To review the physiological and psychosocial effects of a 12-week T'ai Chi program (TC) in patients with heart failure (HF) as previously reported in a clinical trial. We randomized 30 patients with chronic HF (left ventricular ejection fraction < or =40%) to receive TC plus usual care (n = 15), or usual care alone (wait-list control, n = 15). Outcome measures included quality of life, exercise capacity, B-type natriuretic peptide, catecholamine levels, heart rate variability, and sleep stability. The mean age (+/-SD) of patients was 64 +/- 13 years, mean baseline ejection fraction (+/-SD) was 23 +/- 7%, and median New York Heart Association Class was 2 (range 1-4). At 12 weeks, patients who participated in TC showed improved quality of life (mean change -17 +/- 11 vs. 8 +/- 15, Minnesota Living with HF Questionnaire, p = 0.001), increased exercise capacity (mean change 85 +/- 46 vs. -51 +/-58 m, 6-min walk, p = 0.001), and decreased B-type natriuretic peptide (mean change -48 +/- 104 vs. 90 +/- 333 pg/ml, p = 0.03) compared to the control group. Those who participated in TC also showed improvement in sleep stability (increase in high-frequency coupling +0.05 +/- 0.10 vs. -0.06 +/- 0.09 proportion of estimated total sleep time, p = 0.04; reduction in low-frequency coupling -0.09 +/- 0.09 vs. +0.13 +/- 0.13 proportion of estimated total sleep time, p < 0.01), compared to the control group. TC may enhance quality of life, exercise capacity, and sleep stability in patients with chronic HF.