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Background: ATTR cardiomyopathy is classically described in patients with heart failure with preserved ejection fraction (HFpEF). We sought to understand the prevalence, characteristics, and survival of patients at the time of diagnosis, had heart failure with HFpEF (≥50%), HfmrEF: (41-49%), HFrEF ( ≤40%). Methods: A retrospective institutional amyloid registry study of 585 patients diagnosed with wild-type (WT) or variant ATTR-CM from 2011-2020. Cox proportional hazards models were used to assess probability of transplant-free survival. Results: In our cohort, (median age 77 [71,83], 84% male, 25% African-American (AA), median eGFR 58 [46,73], 28% had HFrEF (n= 165), 17% HFmrEF (n=97), and 55% with HFpEF (n=323). After adjusting for Age, sex, race, NT-proBNP, and eGFR, HFrEF patients had worse survival than those with HFpEF (HR, 0.47[95% CI, 0.33-0.68, p(Fig 1a) AA patients had higher rates of HTN, DM, and variant TTR (72% vs. 9%, p(Fig 1b). AA variant (43/108,41%) were more likely to present as HFrEF than Caucasian variants (4/41, 9.8%), p=0.001. Conclusions: Forty-five percent of patients diagnosed with ATTR-CM presented with LVEF ≤50% at the time of diagnosis, confirming that clinical suspicion for diagnosis of ATTR-CM should extend beyond HFpEF presentation. Reduced LVEF is an independent prognostic factor in patients with ATTR-CM. Racial disparities in the LVEF at presentation are present in both variant and WT ATTR. Further investigation into co-morbid, genetic, and racial factors associated with the presenting phenotype of ATTR amyloid is needed.

Background: Challenges remain in our understanding of implications of right ventricle (RV) dysfunction in heart failure. Cardiac magnetic resonance imaging (CMR) is the reference standard for RV quantification, but has seldomly been studied for this purpose in cardiomyopathy patients. We evaluated the predictors and outcomes of reduced CMR-derived right ventricle function in non-ischemic cardiomyopathy (NICM). Methods: Adult NICM patients undergoing CMR quantifying the RV during 2002-2017 were retrospectively studied. Multivariable linear and Cox proportional hazards regression were used to identify factors associated with reduced RV ejection fraction (RVEF) and adverse outcomes. The primary endpoint was all-cause mortality, heart transplant and/or left ventricular assist device implantation. Results: Amongst 624 NICM patients, mean age was 52.7±15.9 years, 253 (40.5%) were female, and RVEF was 43±13%. Factors independently associated with RVEF (beta-coefficients, P-values) were male (-3.26, P Conclusion: Reduced RVEF was prevalent in NICM patients, and was independently associated with worse prognosis in NICM. Important clinical and CMR factors associated with lower RVEF were identified, as well as the optimal prognostic RVEF thresholds.

Background: The impact of cardiomyopathy on left atrial function is currently unclear. The aim of this study was to assess the predictors of left atrial function in patients with non-ischemic dilated cardiomyopathy (NICM) utilizing cardiovascular magnetic resonance (CMR) assessment. Methods: We evaluated 251 NICM patients who underwent CMR in our study, between 12/2008 - 1/2014. LA volumes were measured by the modified biplane method from 2- and 4-chamber long axis views at end-systole and end-diastole. Left atrial ejection fraction (LAEF) was calculated. Multivariable linear regression was performed to determine significant covariate associations with LA EF. Results: We studied 251consecutive patients (61 % male), mean age of 52.5 ± 15.5 years . The results of the multivariable linear regression are provided in Figure 1. Younger age, female sex, and less myocardial fibrosis were significantly associated with higher LAEF (p=0.008, p= 0.004, and p= 0.031, respectively). Additionally, increasing left ventricular end diastolic volume index (LVEDVi) and left ventricular ejection fraction (LVEF) was significantly associated with increasing LAEF (both with a significance of p Conclusions: In patients with NICM, age, sex, LVEDVi, LVEF, myocardial fibrosis, and LAVi were independently associated with LAEF. Keywords: Nonischemic cardiomyopathy, left atrial ejection fraction, left atrial function, cardiovascular magnetic resonance

Introduction: The WATCH-DM score can predict risk of heart failure (HF) in patients with diabetes. Hypothesis: Addition of natriuretic peptide (NP) levels will improve WATCH-DM performance in individuals with dysglycemia. Methods: Adults with diabetes/pre-diabetes free of HF at baseline from 4 cohort studies (ARIC, CHS, FHS, and MESA) were included. The integer- [WATCH-DM(i)] and machine learning-based [WATCH-DM(ml)] scores were used to estimate the 5-year risk of incident HF. Discrimination was assessed by Harrell's concordance index (C-index) and calibration by the Greenwood-Nam-D'Agostino (GND) statistic. Improvement in model performance with the addition of NP-levels was assessed by C-index, Brier score, and continuous net reclassification improvement (NRI). Results: Of the 8,938 participants included, 3,554 (39.8%) had diabetes and 432 (4.8%) developed HF within 5-years. Among 5,384 (60.2%) participants with pre-diabetes, 647 (12.0%) developed incident HF. The WATCH-DM(ml) and (i) scores demonstrated high discrimination for predicting HF risk in diabetes (C-indices=0.76 and 0.69), pre-diabetes (0.83 and 0.72), and overall cohort (0.80 and 0.71), respectively, with no evidence of miscalibration (GND=P >0.10). A greater improvement in C-index was observed with the addition of NP-levels at lower WATCH-DM(i) scores with degradation of risk discrimination at higher scores (Fig. A). Calibration was also improved with addition of NP-levels at lower compared to higher WATCH-DM(i) scores (Fig. B). A greater improvement in reclassification was observed by combing WATCH-DM(i) score with selected NP-levels assessment in low (score Conclusions: The WATCH-DM risk score can accurately predict incident HF risk in community-based individuals with dysglycemia. The addition of NP-levels improves risk prediction among adults with low/intermediate but not high HF risk.

Introduction: Cardiopulmonary exercise stress test (CPET) is an essential prognostic tool in patients with heart failure with reduced ejection fraction (HFrEF) for advanced therapy evaluation. We studied the predictive utility of the metabolic gain index (MGI), which reflects the relative gain of the CPET-estimated stroke volume by the relative change in the product of VO 2 and heart rate (HR) from resting to peak exercise. This novel MGI aims to reflect cardiac reserve function, and, overall prognosis in HFrEF patients. Hypothesis: The MGI is an independent predictor of adverse outcomes in patients with HFrEF. Methods: We reviewed electronic medical records of 843 HFrEF patients (LVEF ≤40%) undergoing CPET from 12/2012 to 9/2020. The MGI was calculated using the formula, [(Peak VO 2 x Peak HR)-(Resting VO 2 x Resting HR)]/(Resting VO 2 x Resting HR). Patients with hypotensive or bradycardia response during exercise were excluded. Primary outcome was the composite of all-cause mortality, LVAD implantation, and heart transplantation. Multivariable Cox proportional hazard models and log rank test were used. For subgroup analysis, patients were stratified by the RER, age, sex, BMI, and beta-blocker use. Results: In our study cohort (mean age 56.2±12.2 years, 73% men, 85% with beta-blockers, mean LVEF 24.8±8.0 %, 16% with BMI ≥35 kg/m 2 , and 75% with RER >1.05), there were 279 (33.1%) patients developed adverse events during median follow up time of 897 days. Lower MGI was independently associated with increased risk of the adverse outcomes with adjustment for age, sex, comorbidities, LVEF, and peak VO 2 (quartile 1 vs 4, hazard ratio 1.83, 95% CI 1.03-3.25, p =0.040, Figure 1A ), especially in patients with RER > 1.05, BMI < 35 kg/m 2 , and without beta-blocker use ( Figure 1B ). Conclusions: Lower MGI is associated with poor prognosis independently of peak VO 2 . The prognostic value of MGI needs to be further corroborated in other multicenter HFrEF cohorts.

Introduction: Theobromine is a naturally occurring substance found in cocoa products. Theobromine may have beneficial cardiovascular effects through various mechanisms. We used the NHANES database to analyze associations between theobromine consumption and cardiovascular health outcomes. Methods: The NHANES database represents a nationally representative population which was used to construct the study population from 1996-2016. We assessed multiple demographic factors and compared differences amongst those who consumed various amounts of theobromine to those who did not. The primary outcome measures were hypertension and lipid profiles. Results: Among 42,038 NHANES survey participants, 37569 and 4469 of the participants reported never consuming theobromine and consuming theobromine, respectively. Table 1 demonstrates baseline characteristics of those reporting no theobromine consumption in comparison to the theobromine consuming participants (100-400md/g and 400-850mg/d). Moderate to high amounts of theobromine consumption was observed in participants who were older with higher BMI and more education and were more likely to be tobacco users in comparison to those with no theobromine consumption (all p-values Conclusions: We observed that individuals who consumed moderate to high amounts of theobromine had associated improvements in lipid profile parameters as well as reduced blood pressure. Theobromine may represent a complementary non-pharmacologic supplementation to typical lifestyle modifications to improve cardiovascular outcomes. Further prospective studies are needed to better clarify this potential association.

Background Impaired health status as measured by standardized tools such as Kansas City Cardiomyopathy Questionnaire (KCCQ), Duke Activity Status Index (DASI) and six-minute walk test (6MWT) has been shown to predict hospitalization and mortality in patients with chronic heart failure. However, prognostic implications of these measurements in response to guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF) remained to be elucidated. Purpose We hypothesized that impaired health status were predictive of persistently elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) after 6 and 12 months of therapeutic optimization in HFrEF. Methods Data on the GUIDE-IT trial that included protocolized HFrEF drug titration were analyzed. Patients who did not have NT-proBNP at 12 months were excluded. KCCQ overall and clinical summary scores, and DASI scores at baseline and 6 months were calculated. Six-minute walk test (6MWT) distance at baseline were also available. Response to medical therapy was defined as having NT-proBNP at 12 months of less than 1,000 pg/mL. Median value of each measurement was used as a cutoff. Multivariate logistic regression analysis was used to determine independent associations between different QOL scores and NT-proBNP response after adjustment for age, comorbidities, baseline EF, NYHA functional class, and NT-proBNP. Results There were 193 (43%) responders. Compared with those who responded to the medical therapy, non-responders were older, and more likely to have comorbidities including coronary artery disease, stroke, PAD, AF, hypertension, COPD, DM, CKD, and dyslipidemia, as well as lower EF, NHYA functional class and higher baseline NT-proBNP. After adjustment for baseline characteristics, lower KCCQ (either overall or summary) scores at baseline and 6 months, and lower DASI scores at 6 months (but not baseline) were independently associated with lower likelihood of response to GDMT (Table). In contrast, baseline 6MWT distance did not predict non-response to GDMT after adjustments. Conclusions Only impaired baseline KCCQ scores were predictive of persistently elevated NT-proBNP, while lower KCCQ and DASI scores at 6 month were predictive of persistently elevated NT-proBNP. Funding Acknowledgement Type of funding sources: None. Health Status Score below Median and ORs

Background A novel hemodynamic parameter obtained from the cardiopulmonary exercise testing (CPET), the hemodynamic gain index (HGI), was developed and shown to be a strong independent predictor of all-cause mortality in a large male cohort. The HGI also strongly correlates with exercise parameters such as peak oxygen consumption and metabolic equivalents (METs). However, prognostic implications of the HGI have not been externally validated with subgroup analyses based on sex, heart failure (HF), coronary artery disease (CAD) and the use of beta-blockers. Purpose We aimed to validate the prognostic value of the HGI in men, women, and patients with and without HF, CAD, and beta-blocker use. Methods We identified 126,356 consecutive patients undergoing treadmill exercise testing for symptom evaluation between 1/1/1991–02/27/2015. HGI was calculated using the formula, [(SBPpeak x HRpeak) − (SBPrest x HRrest)] / (SBPrest x HRrest). Univariable and multivariable cox regression models were used to determine the associations between the HGI stratified by quartiles and all-cause mortality at 10 years with adjustment for cardiovascular risk factors (age, sex, diabetes, hypertension, dyslipidemia, chronic kidney disease, smoking status and body mass index) and exercise testing parameters (chronotropic reserve index, METs, abnormal heart rate recovery, and total exercise time). Results In our study cohort, mean age was 53.5±12.6 years. There were 74,724 (59.1%) male, 5,940 (4.7%) HF, 21,123 (16.7%) CAD, and 30,568 (24.2%) beta-blocker-using patients. During the mean follow up of 8.7 years, 9,929 (7.9%) died. Mean HGI was 2.0±1.2 bpm/mmHg. Lower HGI was associated with all-cause mortality in the entire cohort (Figure 1A, log rank p Conclusions HGI is an independent predictor of long-term mortality after adjusted for traditional cardiovascular risk factors, and exercise performance across patient subgroups. Funding Acknowledgement Type of funding sources: None. Figure 1. Kaplan-Meier curve and Cox regression

Introduction: Microalbuminuria can be a presentation of microvascular complication in diabetes mellitus (DM). Hypothesis: Microalbuminuria is associated with impaired exercise performance in chronic HF with DM patients. Methods: We retrospectively analyzed a cardiopulmonary exercise testing (CPET) database in 255 chronic HF patients with DM that had urine microalbumin test between December 2012 and September 2019. Demographic data and CPET parameters were compared between the patients who had and had not microalbuminuria which was defined by microalbumin/creatinine ratio ≥ 30 mg/g. Peak oxygen consumption (peak VO 2 ) ≤ 14 ml/kg/min and ≤ 12 ml/kg/min if had history of beta-blocker uses were classified as low peak VO 2 and used in multivariable analysis. Results: There were a total 92 patients (36.1%) that had microalbuminuria. Mean age was not significant different between the patients with and without microalbuminuria (57.7 vs 59.4 years, p = 0.26). The patients with microalbuminuria had lower body mass index (BMI; 30.8 vs. 32.7 kg/m 2 , p = 0.014) and had more history of beta-blocker (BB) uses (81.5% vs. 69.3%, p = 0.038), no significant different in other medication uses. Left ventricular ejection fraction (LVEF) was significant lower in patients with microalbuminuria (35.8% vs. 41.5%, p = 0.028). The patients with microalbuminuria had significant higher prevalence of low peak VO 2 (45.7% vs. 30.1%, p = 0.015) and lower peak stroke work (VO 2 /HR; 11.5 vs. 12.8 ml/ beat, p = 0.008). No significant different in ventricular efficiency slope (VE/VCO 2 ; 37.1 vs. 35.4, p = 0.094), Multivariable analysis showed that proteinuria was independently associated with low peak VO 2 after adjusted for age, sex, BMI LVEF, history of BB uses, VE/VCO 2 and HR at peak VO 2 , (odds ratio = 3.83, p < 0.001). Conclusions: Microalbuminuria was independently associated with low peak oxygen consumption in chronic HF with DM patients.

Introduction: Amyloid cardiomyopathy (ACM) is recognized increasingly as a cause of advanced heart failure. There are limited data describing clinical outcomes for ACM patients who receive durable mechanical circulatory support (MCS). Methods: This analysis included adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) with a primary diagnosis of dilated cardiomyopathy (DCM, N=19,921), non-amyloid restrictive cardiomyopathy (RCM, N=248), or ACM (N=48) who received durable MCS of any type or strategy from 2005-2017. We compared baseline characteristics and adverse events for the 3 groups. The primary endpoint was death with heart transplantation as a competing risk with follow-up censored at device explantation. Results: Patients with ACM (N=48) were older (61 y [IQR 55-69] versus 58 y [IQR 49-66] for DCM and 55 y [IQR 46-62] for non-amyloid RCM, P Conclusion: Compared to DCM or non-amyloid RCM patients, those with durable MCS for ACM have the highest risk of early adverse events and lowest survival. These data highlight concerns with durable MCS for ACM.

Background: Functional mitral regurgitation (MR) grading by echocardiography is often challenging, and cardiac magnetic resonance (CMR) may provide more accurate and reproducible assessment, however optimal CMR thresholds have not been established. We aimed to determine clinically significant thresholds of MR-volume and MR-fraction by CMR in patients with non-ischemic cardiomyopathy (NICM). Methods: All patients having CMR with confirmed NICM between 2001/4/1-2019/3/31 were retrospectively studied. Time to death, heart transplant and/or left ventricular assist device is the primary endpoint, and receiver-operative (ROC) characteristics analyses were used to identify significant cut-points for MR-volume and MR-fraction. Results: Mean MR-volume was 11±12% and MR-fraction 14±13% in 840 NICM patients. C-statistics for the primary endpoint (141 events) were MR-volume 0.629 (95%CI: 0.577-0.691) and MR-fraction 0.594 (95%CI 0.542-0.647). Thresholds of MR-volume≥10mL and MR-fraction≥15% had the highest products of sensitivities and specificities (57.4%, 56.8%; and 54.6%, 63.4% respectively) reflecting elevated risk. MR-volume≥35mL and MR-fraction≥40% were associated the best combination of positive and negative predictive values (40.1%, 84.2%; and 38.4%, 84.6% respectively) representing severe risk. The figure illustrates Kaplan-Meier curves of the primary endpoint, categorized into three subgroups based on aforementioned MR-volume and MR-fraction thresholds. Conclusion: Adverse prognosis are observed when MR-volume≥10mL or MR-fraction≥15%, with increasing risk of adverse outcomes as functional MR severity increased in NICM. The proposed MR thresholds from this study for elevated and severe risk are lower than current valvular regurgitation guidelines, suggesting the need for separate classification schema for functional MR.

Introduction: NT-proBNP has been widely used as a diagnostic and prognostic marker for both acute and chronic HF. Previous studies suggested that impaired renal function was the major contributor of an extreme elevation of NT-proBNP levels in patients with chronic HF rather than elevated cardiac filling pressure. Therefore, extremely elevated NT-proBNP levels may provide prognostic value in patients with cardiorenal syndrome. Hypothesis: Extremely elevated NT-proBNP levels are predictive of incident dialysis and dialysis dependence in chronic HF patients developing AKI Methods: Electronic medical records of 478 adult chronic HF patients admitted to the Cleveland Clinic between 2011 and 2016, who developed AKI during the hospital stay and had baseline NT-proBNP before renal consultation were reviewed. We analyzed the association between baseline NT-proBNP and incident dialysis, and dialysis dependence. Dialysis dependence was defined as patients undergoing dialysis within 72 hours of discharge. Results: Mean age was 67.6±13.3 years, 55.9% were male, and 37.7% had CKD. There were no significant differences in baseline characteristics and serum creatinine between patients with and without incident dialysis. Median NT-proBNP was 7,994 pg/mL (IQR; 3,109-19,357 pg/mL). There were 207 (43.3%) patients required dialysis, and 138 patients (66.7%) became dialysis dependent. Higher NT-proBNP was associated with increased risk of incident dialysis (Q 4 vs 1, OR 1.85, 95% C.I. 1.10-3.09, P =0.020), and dialysis dependence (Q4 vs 1, OR 2.96, 95% C.I. 1.25-7.00, P =0.014). However, in multivariate analysis adjusting for age, gender, hypertension, and baseline creatinine, only the association between NT-proBNP and incident dialysis remained statistically significant (Q4 vs 1, OR 1.77, 95% C.I. 1.03-3.02, P =0.038, Figure). Conclusions: Extremely elevated NT-proBNP was independently associated with incident dialysis in chronic HF patients developing AKI.

Introduction: Circulating blood troponin complexes and free fractions remain poorly characterised in different conditions where troponin is detectable in blood Hypothesis: The aim of the study was to compare the differences in troponin-I(TnI) complexes/free-forms in end stage renal disease (ESRD) compared to acute myocardial infarction(AMI) Methods: Blood was collected from patients with AMI(n=7) or ESRD(n=4) at two time points (a)As early as possible after AMI or at initial contact with ESRD patients and (b)24-48 hours later. Western blotting was carried out with HyTest cTnI-560cc antibody on plasma extracted from whole blood. Densitometry analysis was performed and evaluated using the independent samples T-test and paired T-test as appropriate Results: Prominent bands were noted at ~45,~37 and ~25 kDa respectively representing low molecular weight(LMW) TnI-TnT-TnC complex, binary TnI-TnC complex and free-TnI. At time-point (a), there was no difference in these bands between STEMI and CKD patients. Interestingly, at time-point (b), AMI patients had significantly lower intensity of the 45kDa and 37kDa bands compared to CKD patients(for 45 kDa band mean difference was 54.3±19.4 AU, p=0.02; for 37 kDa band mean difference was 27.7±10.5 AU, p=0.03) as well as compared to the initial STEMI samples taken at time-point (a)(for 45 kDa band mean difference was 41.4±8.1 AU, p=0.002; for 37 kDa band mean difference was 16.7±6.3 AU, p=0.002) ,however there was no difference in the 25kDa band Conclusions: AMI patients had progressively lesser quantities of circulating LMW-ITC and binary IC complexes following AMI compared to ESRD patients, but similar quantities of circulating free TnI. This indicates a constant release of LMW-ITC and binary-IC complexes from the myocardium or reduced glomerular filtration of these complexes in ESRD while in the AMI patients, the LMW-ITC and binary I-C complexes appear to be progressively eliminated from plasma after the initial release

Background: Functional mitral regurgitation (MR) is associated with poor outcomes and the prognostic role of cardiac magnetic resonance imaging (CMR) quantification of secondary MR has rarely been studied. We evaluated the associations between CMR-derived MR-fraction and adverse outcomes in non-ischemic cardiomyopathy (NICM) patients. Methods: We retrospectively studied 840 consecutive NICM patients undergoing CMR during 2001/4/1-2019/3/31. Multivariable Cox proportional hazards regression was performed for MR-fraction and two composite endpoints: primary (time to death, heart transplant and/or left ventricular assist device) and secondary (primary endpoint plus heart failure hospitalizations). Results: The cohort had mean age of 53.0±15.9 years, 319 (38.0) were female, and mean MR-fraction of 14±13% by CMR. There were 141 (16.8%) primary and 223 (26.5%) secondary endpoints over a mean follow-up of 3.6±3.0 years. Multivariable analyses results are shown in the Table. MR-fraction was independently associated with the primary and secondary endpoints with hazards ratios of 1.13 (95%CI 1.07-1.20) and 1.13 (95%CI 1.07-1.19) respectively per 5% increase in MR-fraction. MR-fraction provided stronger prognostic power compared to late gadolinium enhancement (LGE) in both models. Older age and diabetes were independently associated with both composite endpoints, while lower LVEF was independently associated with the secondary endpoint only. Conclusion: CMR quantification of functional MR is a powerful predictor of adverse outcomes and demonstrated stronger associations with poor prognosis compared to LGE and left ventricular remodeling in a large cohort of patients with NICM.

Background Since cardiorenal syndrome has been increasingly recognised as the intense interaction between the heart and the kidneys, we hypothesised that in patients with acute kidney injury (AKI), a biomarker of cardiovascular stress and heart failure (HF), N-terminal pro-brain natriuretic peptide (NT-proBNP), can predict adverse renal outcomes. Purpose The purpose of this study was to investigate the ability of NT-proBNP to predict need for dialysis and dialysis dependence in patients with AKI. Methods We analysed the association between baseline NT-proBNP measured before renal consultation, and need for dialysis and dialysis dependence, using a cohort of 1,052 AKI patients admitted to the Cleveland Clinic between 2011 and 2016. AKI was defined as acute increase in serum creatinine (Cr) of at least 0.3 mg/dL or 50% from baseline. Dialysis dependence was defined as patients still need dialysis within 72 hours of discharge. Results Mean age was 65.8±13.6 years, 57% were male, 45.4% had chronic HF and 28.2% had chronic kidney disease (CKD). There was no significant difference in chronic HF, CKD, or baseline Cr between AKI patients with and without dialysis. Median NT-proBNP was 6,484.50 pg/mL (interquartile range 2,200.75–15,717.50 pg/mL). We observed that 43.1% had dialysis (among them 67.8% became dialysis dependence). After adjustment for age, gender, hypertension, and baseline Cr, higher NT-proBNP levels were associated with greater likelihood of needing dialysis [quartile (Q) 4 vs. 1, Odd ratio (OR) 1.98, 95% confidence interval (CI) 1.38–2.85, P Conclusion Elevated NT-proBNP was independently associated with need for dialysis and dialysis dependence in patients with AKI. Figure 1 Funding Acknowledgement Type of funding source: None

Purpose Hemodynamic monitoring plays a critical role in the perioperative management of patients supported by continuous-flow left ventricular assist devices (CF-LVAD). Data published on left atrial pressure monitoring (LAPm) in patients with CF-LVAD support is limited. Our primary aim was to examine the safety and impact of direct LAPm in patients undergoing CF-LVAD implantation. Methods Retrospective data on demographics, LAPm, hemodynamics, and endpoints were extracted on patients at our institution with CF-LVAD implants from January 2017-June 2019. The decision to use a LAPm is based on institutional standards related to right ventricular failure risk and/or presence of severe pulmonary hypertension. The primary safety endpoint of LAPm was a composite of mediastinal bleeding requiring transfusion, cardiac tamponade, and LA thrombus. Secondary endpoints were LAPm device malfunction leading to premature LAPm removal and lack of hemodynamic trends, air embolism, surrogates of left ventricular (LV) unloading, inhaled epoprostenol use, and post-implant ICU and hospital length of stay (LOS). Statistical analyses were by two-tailed Student's t-test or chi-square tests (SAS, version 9.4). Results Of the 242 patients (mean age 58.1 ± 11.0 years), 88.4% had durable centrifugal pumps for destination therapy (58.3%). Most had Intermacs status 2-4 (95.5%) at implant. One hundred fifty-three patients (63.2%) had LAPm for a median of 20h. Prior to LAPm explant, 90.2% had an LAP Conclusion Use of LAPm to guide management is both safe and feasible in patients requiring CF-LVADs. In the vast majority of this cohort, we were able to achieve optimal LV unloading. Future analyses are warranted to better understand the clinical outcomes’ associations of LAPm on CF-LVAD parameters.

This paper originally published with problems in the metadata, the original article has been corrected.

The New York Heart Association (NYHA) is used to classify severity of heart failure and estimate prognosis. Its dependence on the physician’s opinion regarding what constitutes “ordinary physical activity” or “slight” and “marked” limitation makes it subjective with low concordance between physicians.1, 2 Objective measures like cardiopulmonary testing are expensive, inconvenient, and time-consuming. Wearable devices like fitness trackers can provide objective 24/7 data and can potentially overcome these limitations.3 How such data will be perceived by clinicians is an unanswered and increasingly important and relevant question as many companies are participating in a U.S. Food and Drug Administration pilot program for clearing such devices.4 We report the results of a small study to determine the perception of such data by heart failure specialists and its potential impact on the management of such cases.

Purpose Limited data exists on the use continuous-flow left ventricular assist device (CF-LVAD) in patients with cardiac amyloidosis (CA). The largest single center analysis on CF-LVAD support in patients with CA reports a 50% mortality at 6-months. Our primary aim was to examine the survival and morbidity of our patients with diagnosed CA and supported by CF-LVAD. Methods Data on demographics, type of cardiac amyloidosis, pre-implant echocardiographic features, and post-implant survival and morbidity outcomes was retrospectively extracted on patients with CA and supported by CF-LVAD at our institution from January 2009-October 2019. Descriptive statistics are reported. Results Six patients with diagnosed CA (mean age 64 ± 9 years) were supported by CF-LVAD (3 centrifugal, 3 axial) for a median 32.3 months (range 8.4, 48.3). Table 1 depicts pertinent patient demographics, survival and morbidity. Four patients had ATTR amyloid, and 2 had AL amyloidosis. LV ejection fraction (10-45%) and end-diastolic dimension (4.4-6.0 cm) varied pre-implant. All 6 patients were alive at 6-months on CF-LVAD support. Overall, 2 patients died, 2 were bridged to heart transplant, and 2 remain on destination therapy. One patient required a right ventricular assist device and dialysis immediately post-implant, and two patients had hospital re-admission for right heart failure. Various etiologies contributed to re-hospitalizations post-implant (data not shown). With CF-LVAD support, the patients with AL amyloid survived for a median 47.8 months. Conclusion Our limited experience in patients with cardiac amyloidosis highlights the feasibility of supporting these patients with CF-LVAD as bridge to transplant or destination therapy. Future analyses are warranted to refine careful patient selection to improve outcomes, with particular consideration to the interplay between right ventricular hemodynamics and renal function.

Purpose Optimal hemodynamics is associated with improved outcomes in patients with continuous-flow left ventricular assist device (CF-LVAD). Our primary aim was to define the hemodynamic profiles of patients on CF-LVADs, and explore the impact of partial LV unloading on the prevalence of elevated right atrial pressure (RAP) in these patients. Methods Retrospective data on demographics and invasive hemodynamics (early post-implant during index hospitalization and late post-discharge at median 4.7 months) were extracted on patients at our institution with CF-LVAD implants from January 2017-July 2019. Hemodynamic profiles are categorized as optimal or non-optimal (Table 1), and partial LV unloading is defined as pulmonary capillary wedge pressure (PCWP) >15 mm Hg. Statistical analyses used the Fisher's exact test (SAS, version 9.4). Results Two hundred fifty-nine patients had CF-LVAD implants. Seventy-eight patients (mean age 57.1 ± 10.2 years) had invasive hemodynamics at both time-points early post-implant and late post-discharge (Table 1). Early post-implant, 15 patients (32.1%) had optimal hemodynamics and 71 patients (68%; 18 LHF, 28 BiV HF, and 7 RHF) had non-optimal hemodynamics. The majority of patients with RAP >12 mm Hg had a coexisting elevated PCWP [early post-implant (28 of 35 patients, 80%) or late post-discharge (22 of 28 patients, 78.6%)]. The absence (hazard ratio 2.99, p=0.01) versus presence (hazard ratio 0.72 p=0.34) of early partial LV unloading in the setting of an elevated RAP is associated with an increased risk of death and hospitalizations at 6-months post-implant. Conclusion Partial LV unloading with concomitant elevated RAP early post-implant is associated with better event-free survival in comparison to patients with isolated elevated RAP. Future analysis of a validation cohort on these observations and their association with long-term outcomes is warranted.

Purpose PIONEER-HF established the safety of the angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril-valsartan (S/V), in patients hospitalized with acute decompensated heart failure after achieving hemodynamic stability. We have previously shown that transitioning patients in cardiogenic shock directly from intravenous (IV) vasoactive (i.e. vasodilators or inotropes) drugs to S/V can be done safely with tolerance to one-month follow-up. Here we further characterize the hemodynamic impact of S/V after patients have been optimized on vasoactive therapy. Methods A single-center, retrospective analysis of all patients with HFrEF (EF Results Twenty-two patients with HFreF and cardiac index below 2.2 L/min/m2 were admitted to the CICU and newly initiated on S/V. Table 1a contains baseline characteristics and vasoactive therapy given. All patients were weaned off vasoactive medications prior to transfer out of CICU. Patients maintained their significant hemodynamic improvement on transition from IV to oral vasoactive therapy. There was an increase in Pulmonary Artery Pulsatility index (PAPi) with S/V therapy (Table 1b). Patients who did not tolerate ARNI initiation had lower filling pressures and systolic blood pressure compared to patients who tolerated ARNI initiation. Seventeen patients were discharged home on S/V, and 94% remained on S/V one-month in follow-up. Conclusion ICU patients can be successfully bridged from vasoactive IV therapy to oral S/V with sustained hemodynamic improvement garnered from vasoactive agents. We also observed improvement in PAPi with S/V compared to both admission and vasoactive therapy. These encouraging findings merit further prospective study.

Purpose Heart failure-related hospitalization (HFH) after continuous-flow left ventricular assist device (CF-LVAD) implant remains prevalent. Our primary aim was to better elucidate the extent of HFH in patients supported by HM3 resulting from predominant right (RHFS) versus left (LHFS) HF syndrome. We also re-classified INTERMACS-defined RHF by the underlying HFS phenotype. Methods Retrospective data were extracted on patients with HFH post-HM3 implant at our institution (January 2017-May 2019) for demographics, hemodynamics by echocardiogram and/or right heart catheterization, and detailed physical exam findings. Data from each HFH were used to categorize the underlying HFS phenotypes (Table 1). HFH is defined as re-hospitalization post-index implant with a fluid overload syndrome and use of parenteral diuretics. INTERMACS RHF is defined by elevated right atrial pressure requiring the use of varying degrees of right ventricular support, including the sole use of parenteral diuretics. Statistical analyses used the Fisher exact t-test (SAS, version 9.4). Results One hundred forty-three patients defined the HM3 study cohort. Twenty-three patients (mean age 57.7 ± 11.2 years) had HFH (16.1% prevalence), with a median time to first HFH of 65.6 days post-implant. HFH was due to LHFS in 11 patients (47.8%; 2 LHFS and 9 BiV HFS) and predominant RHFS in 12 patients (52.2%). Twenty-one patients met criteria for INTERMACS-defined RHF (14.7% prevalence). By categorical phenotyping, an elevated pulmonary capillary wedge pressure (PCWP) >15 mm Hg was noted in 42.9% of these cases. Conclusion BiV HFS and predominant RHFS account for most HFH post-HM3 implant. LHFS account for nearly half of the post-discharge INTERMACS-defined RHF re-hospitalizations. Further examination of the predictors and underlying causes of partial LV unloading, and the implications on long-term outcomes including survival and functional capacity is warranted.

Purpose PAPi (pulmonary artery pulsatility index) is a predictor of early right ventricular failure (RVF) post left ventricular assist device (LVAD) implantation and has been studied using hemodynamics from single, isolated time points. Since multiple clinical factors and therapies are known to impact RV function in pre-LVAD patients, we hypothesized that serial PAPi measurements would provide incremental risk stratification for early post-LVAD RVF. Methods A total of 394 consecutive patients undergoing primary durable LVAD implantation at our center from 2004 to 2017 were retrospectively enrolled. Serial invasive hemodynamics obtained during inpatient swan guided therapy (77%) or consecutive outpatient right heart catheterizations were recorded. The lowest, highest (“Best”), change (“Delta”) and most proximal PAPi to LVAD implant were calculated. RVF was defined as need for RVAD or prolonged inotrope use > 14 days post-operatively. Multivariate logistic regression determining independent associates of early RVF was performed. Results RVF occurred in 82 of the 394 patients (21%). Those who developed early RVF had significantly lower mean Delta PAPi (2.0 vs 5.3, p Conclusion The best PAPi achieved during medical optimization prior to LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying RV reserve.

Purpose Right ventricular dysfunction (RVD) and mitral regurgitation (MR) are associated with poor outcomes after left ventricular assist device (LVAD) implantation, and residual MR post-implantation may be associated with poor RV outcomes. We sought to assess predictors of change in MR in patients implanted with continuous flow (CF) LVADs. Methods 286 patients implanted with CF-LVADs between Jan 2011 - Dec 2015 were analyzed. Demographic, laboratory, clinical and hemodynamic data were obtained from electronic records. Echocardiograms within 3-months prior to and within 3-months after surgery were reviewed. A total of 35 potential predictors of change in MR severity pre and post LVAD underwent initial univariable analysis. Variables with p Results Mean age was 57 (± 12) years, 84% were male, bean LVEF was 17 (± 6.4) %, and indexed left ventricular end diastolic volume (LVEDVi) was 130 (± 61) ml/m2. For changes in MR post-op, age, LVEDVi, indexed left atrial volume, degree of pre-op MR, diabetes mellitus, CKD, INTERMACS level, cardiac output, cardiac index, RV stroke work index, sphericity index, average mitral annular diameter, tenting area and coaptation length were identified. On multivariable analysis, LVEDVi and degree of pre-op MR were significant predictors (p = 0.010 and Conclusion For changes in degree of MR, higher pre-operative LVEDVi was associated with worse MR post-surgery, and more severe pre-op MR was associated with improvement in degree of MR post-operatively. These findings suggest pre-implant echocardiographtic assessment of LV size and MR severity can identify patients at increased risk of post-LVAD significant MR. Further analysis is needed to verify the findings of this exploratory study and to determine the effect on clinical outcomes.

Background: Endothelial glycocalyx degradation has been associated with multiple pathophysiological processes in cardiovascular disease. Aims: To explore the role of glycocalyx shedding markers in pathophysiology of HFrEF. Methods: In 123 HFrEF patients, the concentration, prognostic value, and association of glycocalyx shedding markers with other disease processes were investigated. Results: Median HA levels and syndecan-1 levels in HFrEF patients were, respectively, 29.4 (10.7;61.6) ng/mL and 48.5 (33.6;80.8) ng/mL. Overall, HA-levels were significantly higher in HFrEF patients compared to healthy subjects, but only 31% of HFrEF patients had HA-levels above the cutoff of normal. There was no significant difference among HFrEF patients and healthy subjects regarding syndecan-1 levels. HFrEF patients with elevated HA-levels had a significantly worse outcome (log rank = 0.01) which remained significant after correction for established risk factors (HR 2.53 (1.13-5.69); P = .024). There was no significant relation between levels of shedding markers and neurohumoral activation (PRA, serum aldosterone, NT-proBNP), myocardial injury (HS-trop), inflammation (CRP), or other baseline characteristics. Conclusions: The glycocalyx shedding marker HA is significantly elevated in a subgroup of HFrEF patients and an independent predictor for worse clinical outcome. Glycocalyx shedding might be an additional factor in the pathophysiology of HF which warrants further investigation. P.N., F.V., P.M. and W.M. are researchers for the Limburg Clinical Research Program (LCRP) UHasselt - ZOL - Jessa, supported by the foundation Limburg Sterk Merk (LSM), Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. P.M. is supported by a doctoral fellowship by the Research Foundation-Flanders (FWO grant-number: 1127917N)

ObjectivesTo determine whether venous congestion, rather than impairment of cardiac output, is primarily associated with the development of worsening renal function (WRF) in patients with advanced decompensated heart failure (ADHF).BackgroundReduced cardiac output is traditionally believed to be the main determinant of WRF in patients with ADHF.MethodsA total of 145 consecutive patients admitted with ADHF treated with intensive medical therapy guided by pulmonary artery catheter were studied. We defined WRF as an increase of serum creatinine ≥0.3 mg/dl during hospitalization.ResultsIn the study cohort (age 57 ± 14 years, cardiac index 1.9 ± 0.6 l/min/m2, left ventricular ejection fraction 20 ± 8%, serum creatinine 1.7 ± 0.9 mg/dl), 58 patients (40%) developed WRF. Patients who developed WRF had a greater central venous pressure (CVP) on admission (18 ± 7 mm Hg vs. 12 ± 6 mm Hg, p < 0.001) and after intensive medical therapy (11 ± 8 mm Hg vs. 8 ± 5 mm Hg, p = 0.04). The development of WRF occurred less frequently in patients who achieved a CVP

Background Our group recently reported that elevated intra-abdominal pressure (IAP, defined as ≥ 8 mm Hg) can be associated with renal dysfunction in patients with advanced decompensated heart failure (ADHF). We hypothesize that in the setting of persistently elevated IAP and progressive renal insufficiency refractory to intensive medical therapy, mechanical fluid removal can be associated with improvements in IAP and renal function. Methods and Results The renal and hemodynamic profiles of 9 consecutive, volume-overloaded subjects with ADHF and elevated IAP, refractory to intensive medical therapy, were prospectively collected. All subjects experienced progressive elevation of serum creatinine and IAP in response to intravenous loop diuretics. Within 12 hours after mechanical fluid removal via paracentesis (n = 5, mean volume removed 3187 ± 1772 mL) or ultrafiltration (n = 4, mean volume removed 1800 ± 690 mL), there was a significant reduction in IAP (from 13 ± 4 mm Hg to 7 ± 2 mm Hg, P = .001), with corresponding improvement in renal function (serum creatinine from 3.4 ± 1.4 mg/dL to 2.4 ± 1.1 mg/dL, P = .01) without significantly altering any hemodynamic measurement. Conclusion In volume-overloaded patients admitted with ADHF refractory to intensive medical therapy, we observed a reduction of otherwise persistently elevated IAP with corresponding improvement in renal function after mechanical fluid removal.

Elevated red cell distribution width (RDW) has been associated with poor long-term outcomes in patients with systolic dysfunction. The relationship between baseline RDW and reverse ventricular remodeling in advanced heart failure patients undergoing cardiac resynchronization therapy (CRT) has not been established. The authors reviewed the pre-implant and follow-up echocardiograms of 233 patients undergoing the new implantation of a CRT device at the Cleveland Clinic between December 2001 and November 2006. Patients were included in the final cohort if they had an RDW level within 7 days of CRT implantation, a left ventricular ejection fraction (LVEF) ≤40%, and New York Heart Association class II to IV symptoms. Patients with a reduction in left ventricular end-systolic volume ≥15% following CRT were considered “responders.” Multivariate models were created to assess the relationship between baseline RDW elevation with progressive remodeling and all-cause mortality. Of 233 patients, 217 patients met inclusion criteria. Patients in the highest RDW quartile (>16.1) derived significantly less improvement in LVEF (3.5%±9.3% vs 10.1%±10.9%, P=.001) than patients in the lowest quartile (

s S39 on immune system function in relationship to INTERMACS class prior to MCSD-implantation is virtually non-existent. We hypothesized that preMCSD peripheral blood mononuclear cell (PBMC) gene expression profiling (GEP) by next-generation sequencing (NGS) identifies a subgroup of patients with higher risk of post MCSD MODS. Methods: PBMC samples from 8 AdHF patients (53±25 years old) undergoing MCSD implantation included in the prospective MultiOrgan Dysfunction Expression (MOD-E) profiling study between August 2012 2013. Obtained 1 day before surgery, and at days 1, 3, 5 and 8 postoperatively were collected for 3 INTERMACS level 3 patients (n= 3) and 5 patients (n= 5) INTERMACS level 1-2. Purified mRNA was subjected to whole-genome NGS analysis. Differentially expressed genes where identified by Two-way ANOVA and Benjamini-Hochberg correction. Only those with fold change of at least 1.5 were included in the analysis. Hierarchically clustering was used for visualization. Biological significance was assessed by gene ontology and pathway analysis. Results: Compared to INTERMACS level 3, patients in the higher risk categories had dramatic differences in their gene expression profiles before and across all 5 time points (Figure 1). Over 3100 different genes were identified and mechanistically linked to the systemic inflammatory response by their biological significance. Gene ontology and pathway analysis revealed significant enrichment of immune related categories and pathways. Conclusion: In AdhF patient facing MCSD-implantation, NGS-based PBMC GEP correlates with clinical severity as assessed by INTERMACS class prior to as well as early after MCSD-implantation and may be further develop to assist in improved patient selection.