Sex-Based Differences in the Epidemiology, Clinical Characteristics, and Outcomes Associated with Worsening Heart Failure Events in a Learning Health System.

BACKGROUND: Differences in demographics, risk factors, and clinical characteristics may contribute to variations in men and women in terms of the prevalence, clinical setting, and outcomes associated with worsening heart failure (WHF) events. We sought to describe sex-based differences in the epidemiology, clinical characteristics, and outcomes associated with WHF events across clinical settings. METHODS AND RESULTS: We examined adults diagnosed with HF from 2010 to 2019 within a large, integrated health care delivery system. Electronic health record data were accessed for hospitalizations, emergency department (ED) visits and observation stays, and outpatient encounters. WHF was identified using validated natural language processing algorithms and defined as ≥1 symptom, ≥2 objective findings (including ≥1 sign), and ≥1 change in HF-related therapy. Incidence rates and associated outcomes for WHF were compared across care setting by sex. We identified 1,122,368 unique clinical encounters with a diagnosis code for HF, with 124,479 meeting WHF criteria. These WHF encounters existed among 102,116 patients, of whom 48,543 (47.5%) were women and 53,573 (52.5%) were men. Women experiencing WHF were older and more likely to have HF with preserved ejection fraction compared with men. The clinical settings of WHF were similar among women and men: hospitalizations (36.8% vs 37.7%), ED visits or observation stays (11.8% vs 13.4%), and outpatient encounters (4.4% vs 4.9%). Women had lower odds of 30-day mortality after an index hospitalization (adjusted odds ratio 0.88, 95% confidence interval 0.83-0.93) or ED visit or observation stay (adjusted odds ratio 0.86, 95% confidence interval 0.75-0.98) for WHF. CONCLUSIONS: Women and men contribute similarly to WHF events across diverse clinical settings despite marked differences in age and left ventricular ejection fraction.

Developing Clinical Risk Prediction Models for Worsening Heart Failure Events and Death by Left Ventricular Ejection Fraction.

Background There is a need to develop electronic health record-based predictive models for worsening heart failure (WHF) events across clinical settings and across the spectrum of left ventricular ejection fraction (LVEF). Methods and Results We studied adults with heart failure (HF) from 2011 to 2019 within an integrated health care delivery system. WHF encounters were ascertained using natural language processing and structured data. We conducted boosted decision tree ensemble models to predict 1-year hospitalizations, emergency department visits/observation stays, and outpatient encounters for WHF and all-cause death within each LVEF category: HF with reduced ejection fraction (EF) (LVEF <40%), HF with mildly reduced EF (LVEF 40%-49%), and HF with preserved EF (LVEF ≥50%). Model discrimination was evaluated using area under the curve and calibration using mean squared error. We identified 338 426 adults with HF: 61 045 (18.0%) had HF with reduced EF, 49 618 (14.7%) had HF with mildly reduced EF, and 227 763 (67.3%) had HF with preserved EF. The 1-year risks of any WHF event and death were, respectively, 22.3% and 13.0% for HF with reduced EF, 17.0% and 10.1% for HF with mildly reduced EF, and 16.3% and 10.3% for HF with preserved EF. The WHF model displayed an area under the curve of 0.76 and mean squared error of 0.13, whereas the model for death displayed an area under the curve of 0.83 and mean squared error of 0.076. Performance and predictors were similar across WHF encounter types and LVEF categories. Conclusions We developed risk prediction models for 1-year WHF events and death across the LVEF spectrum using structured and unstructured electronic health record data and observed no substantial differences in model performance or predictors except for death, despite differences in underlying HF cause.

Association Between Participation in a Heart Failure Telemonitoring Program and Health Care Utilization and Death Within an Integrated Health Care Delivery System.

BACKGROUND: The clinical usefulness of remote telemonitoring to reduce postdischarge health care use and death in adults with heart failure (HF) remains controversial. METHODS AND RESULTS: Within a large integrated health care delivery system, we matched patients enrolled in a postdischarge telemonitoring intervention from 2015 to 2019 to patients not receiving telemonitoring at up to a 1:4 ratio on age, sex, and calipers of a propensity score. Primary outcomes were readmissions for worsening HF and all-cause death within 30, 90, and 365 days of the index discharge; secondary outcomes were all-cause readmissions and any outpatient diuretic dose adjustments. We matched 726 patients receiving telemonitoring to 1985 controls not receiving telemonitoring, with a mean age of 75 ± 11 years and 45% female. Patients receiving telemonitoring did not have a significant reduction in worsening HF hospitalizations (adjusted rate ratio [aRR] 0.95, 95% confidence interval [CI] 0.68-1.33), all-cause death (adjusted hazard ratio 0.60, 95% CI 0.33-1.08), or all-cause hospitalization (aRR 0.82, 95% CI 0.65-1.05) at 30 days, but did have an increase in outpatient diuretic dose adjustments (aRR 1.84, 95% CI 1.44-2.36). All associations were similar at 90 and 365 days postdischarge. CONCLUSIONS: A postdischarge HF telemonitoring intervention was associated with more diuretic dose adjustments but was not significantly associated with HF-related morbidity and mortality.

Increased Rate of Pump Thrombosis and Cardioembolic Events Following Ventricular Tachycardia Ablation in Patients Supported With Left Ventricular Assist Devices.

Ventricular arrhythmias are common following left ventricular assist device implantation (LVAD), and the effects of ventricular tachycardia (VT) ablation on thrombosis and embolic events are unknown. We aimed to assess LVAD thrombosis, stroke, and embolic event rates after VT ablation. Left ventricular assist device implantation patients from two academic centers who underwent endocardial VT ablation between 2009 and 2016 were compared to a control group with VT who were not ablated and followed for one year. The primary composite outcome was confirmed or suspected LVAD thrombosis, stroke, or other embolic event. Survival analysis was conducted with Kaplan-Meier curves, log-rank tests, and Cox regression. Forty-three LVAD patients underwent VT ablation, and 73 LVAD patients had VT but were not ablated. Patients who were ablated were more likely have VT prior to LVAD (p = 0.04), monomorphic VT (p < 0.01), and to be on antiarrhythmics (p < 0.01). Fifty-eight percent of the patients in the ablation group experienced the primary composite outcome (11% had confirmed device thrombosis [DT], 41% suspected DT, 39% had a stroke or embolic event) compared to 30% in the control group (12% with confirmed DT, 11% with suspected DT, 14% with stroke or embolic event) (p = 0.002). In multivariable regression, ablation was an independent predictor of the primary composite outcome (hazard ratios, 2.24; 95% confidence interval, 1.09-4.61; p = 0.03). Patients with LVADs referred for endocardial VT ablation had elevated rates of DT and embolic events.

The Effects of Hemodynamic Unloading in African Americans Implanted with Left Ventricular Assist Devices.

We aim to evaluate the echocardiographic/hemodynamic effects of left ventricular assist devices in African American (AA) versus non-AA patients undergoing ramp speed optimization and its subsequent effect on readmissions. In 65 patients (26 AA), no differences in baseline echocardiographic/hemodynamic parameters were noted. During ramp testing, there was a significantly greater increase in cardiac output (slope: 0.29 ± 0.24 vs. 0.15 ± 0.12, p < 0.01) with more rapid decrease in left ventricular end-diastolic diameter (slope: -0.21 ± 0.14 vs. -0.13 ± 0.07 L/min, p < 0.01) in the AA group. AAs had higher all-cause, but similar heart failure readmission rate as compared with the non-AA group.

Outflow Cannula Systolic Slope in Patients With Left Ventricular Assist Devices: A Novel Marker of Myocardial Contractility.

Left ventricular (LV) unloading with a LV assist device (LVAD) reverse remodels the heart and may lead to favorable changes in cellular architecture and LV geometry promoting myocardial recovery. Currently, there are no standardized methods for evaluating myocardial recovery. This study assesses the systolic slope of the LVAD outflow cannula as a marker for myocardial contractility. Doppler echocardiography (transthoracic echocardiogram [TTE]) of the LVAD outflow cannula and TTE of the LV cavity were prospectively collected in 57 patients with LVADs. Systolic acceleration of the LVAD outflow cannula was measured in each patient as the peak change of velocity over time (dv/dt) during systole from continuous-wave Doppler signal acquired from the LVAD outflow cannula. Ventricular volumes were concurrently measured by TTE. In a subset of 10 patients, the systolic slope was measured during each stage of a ramp study to study the properties of this parameter across a variety of loading conditions. The systolic slope of the LVAD outflow cannula was successfully measured in 53 of 57 patients (93%). Systolic slope strongly correlated with ejection fraction (EF) (R = 0.92). Analysis of systolic slope stratified by EF (EF >30%, EF 20-30%, EF 10-20%, and EF <10%) revealed systolic slopes that were significantly different between the groups (1,371 cm/s ± 324; 983 cm/s ± 122; 578 cm/s ± 139; and 495 cm/s ± 107, respectively; p < 0.001). Systolic slope did not change significantly across variable preload and afterload conditions during a ramp study. Systolic slope of the LVAD outflow cannula strongly correlates with EF and can be used to assess underlying myocardial contractility across a variety of LVAD loading conditions.

Impact of Cardiac Resynchronization Therapy on Left Ventricular Unloading in Patients with Implanted Left Ventricular Assist Devices.

Cardiac resynchronization therapy (CRT) and left ventricular assist devices (LVADs) are common heart failure therapies; however, little is known regarding the concomitant use of these devices. We aim to evaluate unloading differences in LVAD patients with and without active biventricular pacing. Left ventricular assist device patients with and without CRT prospectively underwent ramp hemodynamic/echocardiographic testing. Patients with >95% biventricular pacing comprised the active CRT pacing group; all others (no device, implantable cardioverter defibrillator only, CRT without biventricular pacing) were categorized into the non-CRT pacing group. Invasive hemodynamics and echocardiographic characteristics (left ventricular end-diastolic/systolic diameter and valvular regurgitation) were measured at baseline and at incremental speed changes. Unloading slopes were calculated using linear regression modeling for individual hemodynamics and echocardiographic characteristics across speeds. Among 62 LVAD patients (age 59.6 ± 11.4 years, 60% male), 25 had active CRT pacing. There was no significant difference in echocardiographic or hemodynamic characteristics at baseline or final set speeds between CRT groups. Similarly, no significant differences were noted in the unloading characteristics. In LVAD patients, active biventricular pacing is unlikely to improve echocardiographic or hemodynamic characteristics.

Home Inotropes in Patients Supported with Left Ventricular Assist Devices.

There is little data outlining the use of outpatient inotropic medications in patients with existing left ventricular assist devices (LVADs). This case series explores this patient population and seeks to define the indications, complications, and safety of dual support. A retrospective chart review was conducted for all patients on LVAD and then subsequently started on home inotropes post device implant. Eight patients met inclusion criteria. The indications for inotropes were right ventricular failure, aortic insufficiency with biventricular failure, LVAD thrombosis with contraindication to device exchange, and cannula malposition with elevated pulmonary vascular resistance. Mean duration of combined support was 273 ± 170 days. Cardiac index improved from 1.96 ± 0.24 to 2.31 ± 0.35 L/min/m(2) after inotropes (p = 0.02). There was no change in hospital admissions. The most common reason for readmission was heart failure symptoms, followed by bleeding. Five patients died during the study period, one underwent heart transplant, and two remain on inotropic support. Home inotropes may be indicated in selected continuous flow left ventricular assist device (CF-LVAD) patients with refractory right ventricular failure or impaired LVAD function. Inotropes can improve hemodynamics and provide palliation of symptoms. However, long-term inotrope use does not reduce hospital readmissions and is associated with multiple complications related to the need for an indwelling intravenous line.

Association of Inflow Cannula Position with Left Ventricular Unloading and Clinical Outcomes in Patients with HeartMate II Left Ventricular Assist Device.

The relationship between the HeartMate II left ventricular assist device (LVAD) position and pump thrombosis has been reported. However, further clinical implications of device position are unknown. This study aimed to investigate optimal device position for better left ventricular (LV) unloading and patient prognosis. Patients undergoing a ramp test with right heart catheterization after HeartMate II LVAD implantation were enrolled to this study. Device position was quantified from the chest X-ray obtained at the time of the ramp test: (1) inflow cannula angle relative to horizontal line, (2) pump angle relative to spine, (3) pump depth, (4) angle between inflow cannula and pump, and (5) angle between pump and outflow graft. LV unloading was assessed by pulmonary capillary wedge pressure at set LVAD speed. Fifty-four patients (60 years old and 34 male [63%]) were enrolled. Nobody experienced device malfunction during the study period. Increased LV unloading (i.e., lower pulmonary capillary wedge pressure) was associated with a narrower inflow cannula angle relative to horizontal line. Inflow cannula angle <75° was associated with higher 1 year heart failure readmission-free survival rate (p < 0.05, hazards ratio 7.56 [95% confidence interval 2.32-24.7]). In conclusion, HeartMate II LVAD inflow cannula position was associated with LV unloading and patient prognosis. Prospective studies to ensure optimal device positioning and target better clinical outcomes are warranted.

Residual native left ventricular function optimization using quantitative 3D echocardiographic assessment of rotational mechanics in patients with left ventricular assist devices.

Preservation of native left ventricular (LV) function in patients supported with LV assist device (LVAD) may be beneficial to attain optimal hemodynamics and enhance potential recovery. Currently, LVAD speed optimization is based on hemodynamic parameters, without considering residual native LV function. We hypothesized that alternatively, LV rotational mechanics can be quantified by 3D echocardiography (3DE), and may help preserve native LV function while optimizing LVAD speed. The goal of this study was to test the feasibility of quantifying the effects of LVAD implantation on LV rotational mechanics and to determine whether conventional speed optimization maximally preserves native LV function. We studied 55 patients with LVADs, who underwent 3DE imaging and quantitative analysis of LV twist. Thirty patients were studied before and after LVAD implantation. The remaining 25 patients were studied during hemodynamic ramp studies. The pump speed at which LV twist was maximal was compared with the hemodynamics-based optimal speed. LV twist decreased following LVAD implantation from 4.2 ± 2.7 to 2.3 ± 1.9° (P < 0.01), reflecting the constricting effects on native function. With lower pump speeds, no significant changes were noted in LV twist, which peaked at a higher speed. In 11/25 (44%) patients, the conventional hemodynamic/2DE methodology and 3DE assessment of maximal residual function did not indicate the same optimal conditions, suggesting that a higher pump speed would have better preserved native function. In conclusion, quantitative 3DE analysis of LV rotational mechanics provides information, which together with hemodynamics may help select optimal pump speed, while maximally preserving native LV function.

Echocardiographic Predictors of Hemodynamics in Patients Supported With Left Ventricular Assist Devices.

BACKGROUND: The assessment of hemodynamics in patients supported with left ventricular assist devices (LVADs) is often challenging. Physical examination maneuvers correlate poorly with true hemodynamics. We assessed the value of novel transthoracic echocardiography (TTE)-derived variables to reliably predict hemodynamics in patients supported with LVAD. METHODS AND RESULTS: A total of 102 Doppler-TTE images of the LVAD outflow cannula were obtained during simultaneous invasive right heart catheterization (RHC) in 30 patients supported with continuous-flow LVADs (22 HMII, 8 HVAD) either during routine RHC or during invasive ramp testing. Properties of the Doppler signal though the outflow cannula were measured at each ramp stage (RS), including the systolic slope (SS), diastolic slope (DS), and velocity time integral (VTI). Hemodynamic variables were concurrently recorded, including Doppler opening pressure (MAP), heart rate (HR), right atrial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP), Fick cardiac output (CO) and systemic vascular resistance (SVR). Univariate and multivariate regression analyses were used to explore the dependence of PCWP, CO, and SVR on DS, SS, VTI, MAP, HR, and RS. Multivariate linear regression analysis revealed significant contributions of DS on PCWP (PCWPpred = 0.164DS + 4.959; R = 0.68). Receiver operating characteristic (ROC) curve analysis revealed that PCWPpred could predict an elevated PCWP ≥18 mm Hg with a sensitivity (Sn) of 94% and specificity (Sp) of 85% (area under the ROC curve 0.88). CO could be predicted by RS, VTI, and HR (COpred = 0.017VTI + 0.016HR + 0.12RS + 2.042; R = 0.61). COpred could predict CO ≤4.5 L/min with Sn 73% and Sp 79% (AUC 0.81). SVR could be predicted by MAP, VTI, and HR (SVRpred = 15.44MAP - 5.453VTI - 6.349HR + 856.15; R = 0.84) with Sn 84% and Sp 79% (AUC 0.91) to predict SVR ≥1200 dyn-s/cm5. CONCLUSIONS: Doppler-TTE variables derived from the LVAD outflow cannula can reliably predict PCWP, CO, and SVR in patients supported with LVADs and may mitigate the need for invasive testing.

3D Morphological Changes in LV and RV During LVAD Ramp Studies.

OBJECTIVES: The purpose of this study was to investigate the differential impact of the 2 most commonly available left ventricular assist device (LVAD) types on the right ventricle (RV) and left ventricle (LV) using 3-dimensional (3D) echocardiography-based analysis of ventricular morphology. BACKGROUND: LVADs have emerged as common therapy for advanced heart failure. Recent data suggest that the heart responds differently to speed settings in the 2 main devices available (HeartMate II [HMII], St Jude Medical, Pleasanton, California, and HVAD, HeartWare International, Framingham, Massachusetts). The authors hypothesized that 3D echocardiographic assessment of LV and RV volumes and shape would help describe the differential impact of the 2 LVAD types on the heart. METHODS: Simultaneous 3D echocardiography, ramp test, and right heart catheterization were performed in 31 patients with LVADs (19 with HMII and 12 with HVAD). Device speed was increased stepwise (8,000 to 12,000 for HMII and 2,300 to 3,200 revolutions per minute for HVAD). 3D echocardiographic full-volume LV and RV datasets were acquired, and endocardial surfaces were analyzed using custom software to calculate LV sphericity, conicity (perfect sphere/cone = 1) and RV septal and free-wall curvature (0 = flat; <0 = concave; >0 = convex). RESULTS: For both devices, cardiac output increased and wedge pressure decreased with increasing speed. In HMII, LV volumes progressively decreased (meanΔ = 127 ml) as the LV became less spherical and more conical, whereas the RV volume initially remained stable, but subsequently increased at higher speeds (meanΔ = 60 ml). Findings for the HVAD were similar, but less pronounced (LV:meanΔ = 51 ml, RV:meanΔ = 22 ml), and the LV remained significantly more spherical even at high speeds. On average, in HMII patients, the RV septum became more convex (bulging into the LV) at the highest speeds whereas in HVAD patients, there was no discernable change in the RV septum. CONCLUSIONS: The heart responds differently to pump speed changes with the 2 types of LVAD, as reflected by the volume and shape changes of both the LV and RV. Our study suggests that adding RV assessment to the clinical echo-ramp study may better optimize LVAD speed. Further study is needed to determine whether this would have an impact on patient outcomes.

Repeated Ramp Tests on Stable LVAD Patients Reveal Patient-Specific Hemodynamic Fingerprint.

Hemodynamic speed ramp tests are used in left ventricular assist device (LVAD) patients to guide speed adjustment and medical therapies. However, the reproducibility of these tests is unknown. In this prospective study, clinically stable LVAD patients underwent echocardiography and right heart catheterization ramp tests followed by a repeat test within 2 years as per institutional protocol. Sixteen patients (61.8 ± 10.5 years old, 50% male, eight with HeartMate II and eight with HVAD) underwent repeated ramp testing. The first test was performed 187 (42-1857) days from LVAD implant and the second test was performed 278 (126-560) days from the first test. All hemodynamic variables measured at the baseline speed remained statistically unchanged between the first and second ramp test (p > 0.05 for all). Changes in hemodynamic parameters, as assessed by the slopes of their changes over the range of speeds tested, were also the same at the two timepoints (p > 0.05 for all). Stable LVAD patients had similar hemodynamic profiles over the course of years including similar responses to speed changes. This suggests that ramp tests may represent a hemodynamic fingerprint; deviations from a baseline test can aid diagnosis at times of clinical deterioration or device malfunction.

Cannula and Pump Positions Are Associated With Left Ventricular Unloading and Clinical Outcome in Patients With HeartWare Left Ventricular Assist Device.

BACKGROUND: Cannula and pump positions are associated with clinical outcomes such as device thrombosis in patients with HeartMate II; however, clinical implications of HVAD (HeartWare International, Framingham, Massachusetts) cannula position are unknown. This study aims to assess the relationship among cannula position, left ventricular (LV) unloading, and patient prognosis. METHODS AND RESULTS: Twenty-seven HVAD patients (60.0 ± 12.6 years of age and 19 males [70%]) underwent ramp test. Device position was quantified from chest X-ray parameters obtained at the time of the hemodyamic ramp test: (1) cannula coronal angle, (2) pump depth, (3) cannula sagittal angle, and (4) pump area. Lower cannula coronal angle was associated with LV unloading (as measured by smaller LV diastolic dimension and lower pulmonary capillary wedge pressure). Smaller pump area was associated with LV dynamic unloading, as assessed by steeper negative slopes of LV diastolic dimension and pulmonary capillary wedge pressure during incremental rotational speed change. Cannula coronal angle ≤65° was associated with reduced heart failure readmission rate (hazard ratio, 10.33; P = .007 by log-rank test). CONCLUSION: HVAD cannula and pump positions are associated with LV unloading and improved clinical outcomes. Prospective studies evaluating surgical techniques to ensure optimal device positioning and its effects on clinical outcomes are warranted.

HVAD Waveform Analysis as a Noninvasive Marker of Pulmonary Capillary Wedge Pressure: A First Step Toward the Development of a Smart Left Ventricular Assist Device Pump.

Flow waveforms are an important feature of the HVAD left ventricular assist device (LVAD) that provides information about HVAD function and patient hemodynamics. We assessed the properties of one specific aspect of the waveform, the slope of the ventricular filling phase (VFP), and its correlation with pulmonary capillary wedge pressure (PCWP). A total of 101 screenshots from the HVAD monitor and simultaneous hemodynamic measurements were obtained simultaneously during sequential stages of invasive hemodynamic ramp studies. Each screenshot was digitized (IGOR Pro, WaveMetrics Inc., Oswego, OR) and properties of the flow waveforms including instantaneous flow and rate of change of flow were analyzed. Ventricular filling phase slope (VFPS) was calculated for each screenshot and correlated to PCWP. Ventricular filling phase slope was significantly higher in patients with PCWP ≥ 18 mm Hg than in patients with PCWP < 18 mm Hg [6.25 (5.84-7.37) L/min/s vs. 3.27 (2.00-4.69) L/min/s, p ≤ 0.0001]. A VFPS threshold of 5.8 L/min/s predicted a PCWP ≥ 18 mm Hg with a sensitivity of 87% and specificity of 95% (AUC 0.95). Ventricular filling phase slope of the HVAD flow waveform is a novel noninvasive parameter that correlates with PCWP and can discriminate elevated versus normal or low PCWP. Automated reporting of this parameter may help clinical assessment and management of patients supported by an HVAD and may serve as the basis of a smart LVAD pump that can adapt in response to changes in a patient's physiology.

Quality of life and functional capacity outcomes in the MOMENTUM 3 trial at 6 months: A call for new metrics for left ventricular assist device patients.

BACKGROUND: The Multicenter Study of MAGLEV Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) clinical trial demonstrated improved 6-month event-free survival, but a detailed analysis of health-related quality of life (HR-QOL) and functional capacity (FC) was not presented. Further, the effect of early serious adverse events (SAEs) on these metrics and on the general ability to live well while supported with a left ventricular assist system (LVAS) warrants evaluation. METHODS: FC (New York Heart Association [NYHA] and 6-minute walk test [6MWT]) and HR-QOL (European Quality of Life [EQ-5D-5L] and the Kansas City Cardiomyopathy [KCCQ]) assessments were obtained at baseline and 6 months after HeartMate 3 (HM3, n = 151; Abbott, Abbott Park, IL) or HeartMate II (HMII, n = 138; Abbott) implant as part of the MOMENTUM 3 clinical trial. Metrics were compared between devices and in those with and without events. The proportion of patients "living well on an LVAS" at 6 months, defined as alive with satisfactory FC (NYHA I/II or 6MWT > 300 meters) and HR-QOL (overall KCCQ > 50), was evaluated. RESULTS: Although the median (25th-75th percentile) patient KCCQ (change for HM3: +28 [10-46]; HMII: +29 [9-48]) and EQ-5D-5L (change for HM3: -1 [-5 to 0]; HMII: -2 [-6 to 0]) scores improved from baseline to 6 months (p < 0.05), there were no differences between devices (p > 0.05). Likewise, there was an equivalent improvement in 6MWT distance at 6 months in HM3 (+94 [1-274] meters] and HMII (+188[43-340 meters]) from baseline. In patients with SAEs (n = 188), 6MWTs increased from baseline (p < 0.001), but gains for both devices were less than those without SAE (HM3: +74 [-9 to 183] meters with SAE vs +140 [35-329] meters without SAE; HMII: +177 [47-356] meters with SAE vs +192 [23-337] meters without SAE, both p < 0.003). SAEs did not affect the 6-month HR-QOL scores. The "living well" end point was achieved in 145 HM3 (63%) and 120 HMII (68%) patients (p = 0.44). CONCLUSIONS: Gains in HR-QOL and FC were similar early after HM3 and HMII implant. 6MWT improvements were attenuated in patients experiencing SAEs, but HR-QOL metrics did not change. The development of left ventricular assist device-specific HR-QOL tools is needed to better characterize the effect of SAEs on a patient's well-being. CLINICAL TRIAL NO: MOMENTUM 3 clinical trial #NCT02224755.

Increased Risk of Bleeding in Left Ventricular Assist Device Patients Treated with Enoxaparin as Bridge to Therapeutic International Normalized Ratio.

Anticoagulation therapy is used to prevent thromboembolic events in patients with left ventricular assist devices (LVADs). This study aims to determine the safety of low molecular weight heparin (enoxaparin) for bridging subtherapeutic international normalized ratio (INR) in LVAD patients. In this retrospective single-center study, all patients who underwent LVAD implantation were examined between January 1, 2013, and December 31, 2014. Patients were divided into two groups: enoxaparin bridge and no bridge, with identification of major bleeding episodes (MBEs) and thrombotic events (TEs). Major bleeding episode and TE incidence was compared between the two groups, with subanalysis of incidence in the enoxaparin group between the periods on and off treatment. One hundred eighteen patients were included in this analysis. Fifty-five patients received enoxaparin, whereas 63 patients did not receive enoxaparin, with no significant difference between groups in all baseline characteristics. For the study period, enoxaparin patients had no increased incidence of MBEs (0.53 vs. 0.35 MBE per year; p = 0.12). However, there was a fourfold increase in MBEs during the bridged period in the enoxaparin group (2.02 vs. 0.45 MBE per year; p = 0.03). Major bleeding episodes on versus off enoxaparin had no major difference in transfusion requirements (2.7 ± 2.9 vs. 2.5 ± 3.4 units; p = 0.57) or mortality (p = 0.11). The enoxaparin group trended to a higher incidence of TEs (0.20 vs. 0.11 events per year; p = 0.08). Enoxaparin bridging in patients with subtherapeutic INR is associated with a significantly increased risk of MBEs. Prospective studies are needed to confirm these findings; however, until then, caution should be used with enoxaparin for bridging in LVAD patients.

Decoupling Between Diastolic Pulmonary Artery Pressure and Pulmonary Capillary Wedge Pressure as a Prognostic Factor After Continuous Flow Ventricular Assist Device Implantation.

BACKGROUND: A cohort of heart failure (HF) patients receiving left ventricular assist devices (LVADs) has decoupling of their diastolic pulmonary artery pressure and pulmonary capillary wedge pressure. However, the clinical implications of this decoupling remain unclear. METHODS AND RESULTS: In this prospective study, patients with LVADs underwent routine invasive hemodynamic ramp testing with right heart catheterization, during which LVAD speeds were adjusted. Inappropriate decoupling was defined as a >5 mm Hg difference between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure. The primary outcomes of survival and heart failure readmission rates after ramp testing were assessed. Among 63 LVAD patients (60±12 years old and 25 female [40%]), 27 patients (43%) had inappropriate decoupling at their baseline speed. After adjustment of their rotation speed during ramp testing, 30 patients (48%) had inappropriate decoupling. Uni/multivariable Cox analyses demonstrated that decoupling was the only significant predictor for the composite end point of death and heart failure readmission during the 1 year following the ramp study (total of 18 events; hazards ratio, 1.09; 95% confidence interval, 1.04-1.24; P<0.05). Furthermore, normalization of decoupling (n=8) during ramp testing was significantly associated with higher 1-year heart failure readmission-free survival rate compared with the non-normalized group (n=19, 100% versus 53%; P=0.035). CONCLUSIONS: The presence of inappropriate decoupling was associated with worse outcomes in patients with LVADs. Prospective, large-scale multicenter studies to validate the result are warranted.

The Hemodynamic Effects of Aortic Insufficiency in Patients Supported With Continuous-Flow Left Ventricular Assist Devices.

BACKGROUND: The impact of aortic insufficiency (AI) on the morbidity and mortality of left ventricular assist device (LVAD) patients remains controversial. This study's aim was to assess the hemodynamics of LVAD patients with at least mild AI, at baseline and in response to device speed changes. METHODS AND RESULTS: Asymptomatic LVAD patients were prospectively enrolled and underwent a hemodynamic and echocardiographic ramp study. Hemodynamics at rest and in response to device speed changes were compared between patients with at least mild AI at their baseline speed and patients without AI. Fift-five patients were enrolled in the study, and 42% had AI. The AI group had higher baseline central venous pressure (11 ± 5 vs 8 ± 5 mm Hg; P = .03), higher pulmonary capillary wedge pressure (PCWP) (16 ± 6 vs 12 ± 6 mm Hg; P = .02) and lower pulmonary artery pulsatility index (PAPI) (2.3 ± 1.3 vs 3.6 ± 2.4; P = .01). Cardiac index (CI) increased and PCWP decreased in both groups by similar degrees during the ramp study. AI worsened in 78% of patients during the ramp study. CONCLUSIONS: LVAD patients with at least mild AI have increased filling pressures and reduced PAPI. Normalization of filling pressures can be achieved by increasing LVAD speed; however, this concomitantly worsens AI severity. The long-term hemodynamic consequences of this approach are unknown.

Cardiac Output Assessment in Patients Supported with Left Ventricular Assist Device: Discordance Between Thermodilution and Indirect Fick Cardiac Output Measurements.

Cardiac output (CO) assessed by thermodilution (TD) and indirect Fick (iFK) methods is commonly employed in left ventricular assist device (LVAD) patients; however, no study has assessed agreement. This study assesses correlation between these methods and association with hemodynamic/echocardiographic data in LVAD patients. Discordance was defined as a 20% difference between TD and iFK CO measurements. Bias and agreement were determined via the Bland-Altman technique in both the overall sample and iFK-stratified tertiles. Correlation with each assessment of CO and right heart catheterization (RHC) hemodynamics was performed. Among 111 RHCs, the mean CO for TD and iFK were 4.65 ± 1.33 (range: 1.44-9.30) and 5.37 ± 1.51 (range: 3.07-11.80) L/min (p < 0.001), respectively, with a calculated discordance of 45.9%. A correlation coefficient of 0.66 with a bias of -0.72 L/min was found. The lower and upper limit of precision were -3.12 and 1.68 L/min, respectively. By tertile analysis, bias (lower and upper limit of precision) for the low, middle, and high tertile groups were -0.24 (-1.88 and 1.40), -0.48 (-2.50 and 1.53), and -1.39 (-4.18 and 1.39) L/min, respectively. No significant correlation was found between either method with right atrial pressure or pulmonary capillary wedge pressure or any valvular condition. Substantial discrepancies exist between TD and iFK CO in LVAD patients. Although fixed bias was small, the limits of agreement extend into the clinically relevant area, with larger bias being present at higher CO. Studies with flow probes are needed to define which method better represents CO in LVAD patients.