N. Sarswat

Hemodynamic Ramp Tests in Patients With Left Ventricular Assist Devices

OBJECTIVES This study tested whether combined invasive hemodynamic and echocardiographic ramp tests can help optimize patient management. BACKGROUND Guidelines for optimizing speed and medications in continuous flow ventricular assist device (cfLVAD) patients are mainly based on expert opinion. METHODS Thirty-five cfLVAD patients (21 HeartMate II [Thoratec, Pleasanton, California] and 14 HVAD [HeartWare International, Framingham, Massachusetts]) underwent ramp tests with right heart catheterization (including central venous pressure [CVP], pulmonary artery pressure, pulmonary capillary wedge pressure [PCWP], and blood pressure) and echocardiography. Data were recorded at up to 9 speed settings. Speed changes were in steps of 400 revolutions per minute (RPM) for HeartMate II (8,000 to 12,000 RPM) and 100 RPM for HVAD (2,300 to 3,200 RPM) patients. RESULTS Only 42.9% of patients had normal CVPs and PCWPs at their original RPM settings. Going from lowest to highest speeds, cardiac output improved by 0.16 ± 0.19 l/min/step (total change 1.28 ± 1.41 l/min) and PCWP decreased by 1.23 ± 0.85 mm Hg/step (total change 9.9 ± 6.5 mm Hg). CVP and systolic blood pressure did not change significantly with RPM. RPM were adjusted based on test results to achieve CVPs and PCWPs as close to normal limits as possible, which was feasible in 56% of patients. For the remainder, results indicated which type of medical management should be pursued. CONCLUSIONS Use of combined hemodynamic and echocardiographic ramp tests in patients provides objective means of optimizing RPM, and has the potential to guide medical management. It remains to be tested whether this strategy has a beneficial impact on quality of life or clinical outcomes.

Novel echocardiographic parameters of aortic insufficiency in continuous-flow left ventricular assist devices and clinical outcome

BACKGROUND The aim of this study was to evaluate the prognostic performance of novel echocardiographic (transthoracic echocardiography, or TTE) parameters for grading aortic insufficiency (AI) severity in patients with continuous-flow left ventricular assist devices (CF-LVADs). The development of AI after CF-LVAD implantation is common, although the clinical significance remains unclear. We previously described novel TTE parameters that outperformed traditional TTE parameters in grading AI severity in these patients. METHODS CF-LVAD patients with varying degrees of AI (N = 57) underwent Doppler TTE of the LVAD outflow cannula. Patients had AI severity graded by the novel parameters (systolic/diastolic velocity ratio and the diastolic acceleration of the LVAD outflow cannula) and the traditional vena contracta. The prognostic performance of novel and traditional AI parameters was determined by comparing rates of congestive heart failure re-admission, need for aortic valve intervention, urgent transplantation and death (composite end-points) for each parameter. RESULTS Grading AI severity using novel AI parameters led to reclassification of 32% of patients from trace/mild AI to moderate or greater AI (N = 18). Using traditional AI parameters, there was no difference in the occurrence of the composite end-point between the moderate or greater group and the trace/mild group (1.50 vs 1.18 events/person, p = 0.46). With the novel AI parameters, there were significantly more events in the patients with moderate or greater AI compared to those with trace/mild AI (1.57 vs 0.13 events/person, p = 0.002). Novel parameters also better predicted the need for aortic valve intervention, urgent transplantation or death than traditional methods (p = 0.024 vs p = 0.343). CONCLUSIONS In patients with CF-LVADs, traditional parameters tend to underestimate AI severity and future cardiac events. Novel AI TTE parameters are better able to discriminate AI severity and predict clinically meaningful outcomes.

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 studys 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.

Screening for Outflow Cannula Malfunction of Left Ventricular Assist Devices (LVADs) With the Use of Doppler Echocardiography: New LVAD-Specific Reference Values for Contemporary Devices

BACKGROUND Echocardiographic assessment of left ventricular assist devices (LVADs) is used as a screening tool to evaluate the integrity and mechanics of the pump and circuit. We aimed to 1) establish the normal range and upper reference limit of peak velocity of the outflow cannula for the modern era of LVADs and 2) assess the clinical performance of the currently cited and newly proposed reference limits in patients with continuous-flow LVADs as a screening tool for cannula malfunction. METHODS LVAD outflow peak CW velocities were measured with the use of Doppler transthoracic echocardiography (TTE) in 57 patients with LVADs (44 with Heartmate II (HM2), 13 with Heartware (HW)). The average velocity and the upper and lower normal reference limits (defined as ±2 standard deviations from the mean) for each LVAD type was calculated. The upper reference limit was then used as a screening threshold for cannula malfunction. RESULTS The average outflow cannula peak velocity for the normal HM2 cohort was 1.86 ± 0.44 m/s with upper and lower reference limits of 2.73 m/s and 0.98 m/s, respectively. The average outflow cannula peak velocity for the normal HW cohort was 2.36 ± 0.53 m/s with upper and lower reference limits of 3.42 m/s and 1.3 m/s, respectively, which was significantly higher than the HM2 cohort (P = .004). CONCLUSIONS In both HM2 and HW LVADs, the average peak outflow velocity and reference limit for the normal population, as measured by Doppler TTE, was markedly higher than the currently used LVAD reference limits of 2 m/s and are significantly different between devices. Patients with peak outflow velocities above our upper reference limits should be evaluated for LVAD outflow cannula malfunction.

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.

Increased Risk of Bleeding in Left Ventricular Assist Device Patients Treated with Enoxaparin as Bridge to Therapeutic INR

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.

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.

Left Ventricular Assist Device Deactivation via Percutaneous Closure of the Outflow Graft.

• After LVAD pump stoppage, the outflow graft acts as a conduit for continuous regurgitation of blood