T. Imamura

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.

Long-Acting Octreotide Reduces the Recurrence of Gastrointestinal Bleeding in Patients With a Continuous-Flow Left Ventricular Assist Device

BACKGROUND Recurrent gastrointestinal bleeding is one of the most significant adverse events in patients with left ventricular assist devices (LVADs). METHODS We enrolled LVAD patients who had received an intramuscular injection of 20 mg octreotide every 4 weeks as secondary prevention for recurrent gastrointestinal bleeding despite conventional medical therapies and repeated transfusions. The frequency of gastrointestinal bleeding and other associated clinical outcomes before and during octreotide therapy were compared. RESULTS Thirty LVAD patients (66.4 ± 8.8 years old, 16 men [53%]) received octreotide therapy for 498.8 ± 356.0 days without any octreotide-associated adverse events. The frequency of gastrointestinal bleeding was decreased significantly during octreotide therapy (from 3.4 ± 3.1 to 0.7 ± 1.3 events/year; P < .001), accompanied by significant reductions in red blood cell and flesh frozen plasma transfusions, days in hospital, and need for endoscopic procedures (P < .05 for all). CONCLUSIONS Octreotide therapy reduced the frequency of recurrent gastrointestinal bleeding and may be considered for secondary prevention.

Clinical implications of hemodynamic assessment during left ventricular assist device therapy

Left ventricular assist devices (LVADs) significantly improve outcomes of advanced heart failure patients. However, patients continue to have high readmission rates due to complications ranging from bleeding, thrombosis, heart failure, and infection. Considering that the hallmark benefit of LVAD therapy is improvement in hemodynamics (cardiac unloading and increased cardiac output), hemodynamic assessment on LVAD support is key to better understand these difficult complications and may serve as a tool to resolving them. In this review, we will discuss the hemodynamic changes following LVAD implantation, and the implications and prognostic impact of hemodynamic optimization on outcomes and complications.

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.

Increase in short-term risk of rejection in heart transplant patients receiving granulocyte colony-stimulating factor

BACKGROUND Neutropenia is a significant adverse event after heart transplantation (HT) and increases infection risk. Granulocyte colony-stimulating factor (G-CSF) is commonly used in patients with neutropenia. In this work, we assessed the adverse effects of G-CSF treatment in the setting of a university hospital. METHODS Data on HT patients from January 2008 to July 2016 were reviewed. Patients who received G-CSF were identified and compared with patients without a history of therapy. Baseline characteristics, rejection episodes, and outcomes were collected. Data were analyzed by incidence rates, time to rejection and survival were analyzed using Kaplan-Meier curves, and odds ratios were generated using logistic regression analysis. RESULTS Two hundred twenty-two HT patients were studied and 40 (18%) received G-CSF for a total of 85 total neutropenic events (0.79 event/patient year). There were no differences in baseline characteristics between the groups. In the 3 months after G-CSF, the incidence rate of rejection was 0.067 event/month. In all other time periods considered free of G-CSF effect, the incidence rate was 0.011 event/month. This rate was similar to the overall incidence rate in the non-GCSF group, which was 0.010 event/month. There was a significant difference between the incidence rates in the G-CSF group at 0 to 3 months after G-CSF administration and the non-GCSF group (p = 0.04), but not for the other time periods (p = 0.5). Freedom from rejection in the 3 months after G-CSF administration was 87.5% compared with 97.5% in the non-GCSF group (p = 0.006). CONCLUSIONS G-CSF administration was found to be associated with significant short-term risk of rejection. This suggests the need for increased surveillance during this time period.

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.

Decoupling Between Diastolic Pulmonary Arterial Pressure and Pulmonary Arterial Wedge Pressure at Incremental Left Ventricular Assist Device (LVAD) Speeds Is Associated With Worse Prognosis After LVAD Implantation

BACKGROUND Decoupling between diastolic pulmonary arterial pressure (dPAP) and pulmonary arterial wedge pressure (PAWP) is an index of pulmonary vasculature remodeling and provides prognostic information. Furthermore, decoupling may change during incremental left ventricular assist device (LVAD) speed changes. METHODS AND RESULTS In this prospective study, patients underwent an echocardiographic and hemodynamic ramp test after LVAD implantation and were followed for 1 year. The change in decoupling (dPAP - PAWP) between the lowest and highest LVAD speeds during the ramp test was calculated. Survival and heart failure admission rates were assessed by means of Kaplan-Meier analysis. Eighty-seven patients were enrolled in the study: 54 had a Heartmate II LVAD (60.8 ± 9.3 years of age and 34 male) and 33 had an HVAD LVAD (58.6 ± 13.2 years of age and 20 male). Patients who experienced greater changes in decoupling (Δdecoupling >3 mm Hg) had a persistently elevated dPAP at incremental LVAD speed and had worse 1-year heart failure readmission-free survival compared with the group without significant changes in the degree of decoupling (41% vs 75%; P = .001). CONCLUSIONS An increase in decoupling between dPAP and PAWP at incremental LVAD speed changes was associated with worse prognosis in LVAD patients.

Consequences of Retained Defibrillator and Pacemaker Leads After Heart Transplantation—An Underrecognized Problem

BACKGROUND Cardiovascular implantable electronic devices (CIEDs) are common in patients undergoing heart transplantation (HT), and complete removal is not always possible at the time of transplantation. METHODS We retrospectively assessed the frequency of retained CIED leads and clinical consequences in consecutive HT patients from 2013 to 2016. Clinical outcomes included bacteremia, upper-extremity deep venous thrombosis (UEDVT), lead migration, and inability to perform magnetic resonance imaging (MRI). RESULTS A total of 138 patients (55 ± 11 years of age, 76% male) were identified; 37 (27%) had retained lead fragments (RLFs) at discharge. Patients with RLFs were older, had longer lead implantation time before HT, and a higher prevalence of dual-coil CIED leads compared with those without RLFs (P < .05 for all). Lead implantation time was identified as an independent predictor for RLFs (P < .05). Patients with RLFs had a higher frequency of DVT compared with the non-RLF group during the 1-year study period (42% vs 21%; P < .04). There was no difference in bacteremia. Fourteen patients (38%) could not undergo clinically indicated MRI. CONCLUSION RLFs after HT occur commonly and are associated with a higher rate of UEDVT and limit the use of MRI. Although no significant difference was found in the rates of bacteremia between the groups, this finding might be explained by the overall low incidence. Patients with risk factors for RLFs should be identified before transplantation, and complete lead removal should be considered with a multidisciplinary approach.

A Useful Scoring System For Predicting Right Ventricular Assist Device Requirement Among Patients with a Paracorporeal Left Ventricular Assist Device

Ventricular assist devices (VADs) have become an important therapy for advanced heart failure, however, the prognosis of those who receive a biventricular assist device (BiVAD) is still poor. We enrolled 70 patients who underwent paracorporeal VAD (Nipro-VAD®) implantation between 2004 and 2015 and studied the preoperative risk factors, including hemodynamic parameters for RVAD requirement. Furthermore, 2-year survival was compared between the BiVAD group and LVAD only group. Fourteen patients (20%) required RVAD. The BiVAD group had a significantly smaller left ventricular diastolic/systolic dimension, lower mean pulmonary artery wedge pressure (PAWP), lower cardiac index (CI), higher pulmonary vascular resistance (PVR), higher mean right atrial pressure (RAP), lower pulmonary artery pulsatility index (PAPi), lower right ventricular stroke work index (RVSWI), and higher mean RAP/mean PAWP ratio preoperatively. After multivariate analysis, only PVR > 4.5 Wood units: WU (P = 0.013, odds ratio: OR 7.9) and mean RAP/mean PAWP > 0.8 (P < 0.001, OR 14.4) were significant predictors for RVAD requirement. From these odds ratios, we assigned 1 point to PVR > 4.5 WU and 2 points to mean RAP/mean PAWP > 0.8. This simple scoring method adequately stratified the incidence of RVAD implantation (score 0: 4.4%, score 1: 28.6%, score 2: 41.7%, score 3: 83.3%). The cumulative survival rate at 2-year after VAD implantation was significantly worse among patients who required RVAD support compared to the LVAD only group (28.5% versus 74.4%, P = 0.009). RVAD requirement is associated with poor long-term survival, and this simple scoring system using PVR and mean RAP/mean PAWP may be useful for predicting RVAD requirement in such patients.

What is the Optimal Strategy for Adaptive Servo-Ventilation Therapy?

Clinical advantages in the adaptive servo-ventilation (ASV) therapy have been reported in selected heart failure patients with/without sleep-disorder breathing, whereas multicenter randomized control trials could not demonstrate such advantages. Considering this discrepancy, optimal patient selection and device setting may be a key for the successful ASV therapy. Hemodynamic and echocardiographic parameters indicating pulmonary congestion such as elevated pulmonary capillary wedge pressure were reported as predictors of good response to ASV therapy. Recently, parameters indicating right ventricular dysfunction also have been reported as good predictors. Optimal device setting with appropriate pressure setting during appropriate time may also be a key. Large-scale prospective trial with optimal patient selection and optimal device setting is warranted.