Sirtaz Adatya

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.

Anti-factor Xa and activated partial thromboplastin time measurements for heparin monitoring in mechanical circulatory support.

OBJECTIVES This study investigated the relationship between anti-factor Xa (anti-FXa) and activated partial thromboplastin time (aPTT) for monitoring intravenous unfractionated heparin (IV-UFH) in patients with continuous-flow left ventricular assist devices (CF-LVADs). BACKGROUND CF-LVADs have become mainstream therapy for patients with advanced heart failure. Thromboembolic events, device thrombosis, and bleeding continue to be a challenge with this technology. Adequate anticoagulation is required to prevent these adverse events. METHODS A prospective study of consecutive patients implanted with a CF-LVAD was conducted. Paired samples were considered concordant if aPTT values fell into expected ranges for subtherapeutic, therapeutic, and supratherapeutic anti-FXa levels. Heparin dosing was on the basis of anti-Xa levels. RESULTS A total of 340 paired values from 38 patients were evaluated. Anti-FXa and aPTT were discordant in 253 samples (74.4%), with a high degree of variability in aPTT for any given anti-FXa level (r(2) = 0.57). Results were discordant in 104 samples (63.8%) from patients undergoing bridging therapy with warfarin and in 149 samples (84.2%) from patients with device obstruction and/or hemolysis (p < 0.001). The most common pattern of discordance was a supratherapeutic aPTT value despite a therapeutic anti-FXa level (49.1% for bridging vs. 75.8% for device obstruction and/or hemolysis; p < 0.001). CONCLUSIONS Levels of aPTT were disproportionately prolonged relative to the corresponding anti-FXa levels in CF-LVAD patients, particularly those with device obstruction. Hemolysis and warfarin administration may falsely elevate aPTT, resulting in overestimation of heparin concentration and under-anticoagulation. Use of aPTT and anti-FXa to guide heparin therapy may lead to different estimates of heparin concentration in the same patient.

Echocardiographic Ramp Test for Continuous-Flow Left Ventricular Assist Devices : Do Loading Conditions Matter?

OBJECTIVES This study investigated whether continuous AI and/or elevated mean arterial pressure (MAP) were associated with false positive results for flow obstruction in echocardiographic ramp speed tests in patients with a continuous-flow left ventricular assist device. BACKGROUND Failure to reduce the left ventricular end-diastolic diameter (LVEDD) with increasing device speeds in a ramp test is predictive of pump obstruction. Aortic insufficiency (AI) or increased MAP can diminish the ability to unload the left ventricle. METHODS LVEDD was plotted against device speed, and a linear function slope was calculated. A flat LVEDD slope (≥-0.16) was considered abnormal (suggestive of obstruction). Ramp test results were compared in patients with or without either AI or increased MAP at baseline speed, and receiver-operator characteristic (ROC) curves were constructed for predictors of device obstruction. Device thrombosis was confirmed by direct visualization of clot at explantation or on inspection by the manufacturer. RESULTS Of 78 ramp tests (55 patients), 36 were abnormal (18 true positive, 18 false positive), and 42 were normal (37 true negative, 5 false negative). In patients with AI, LVEDD slope was -0.14 ± 0.17, which was consistent with device obstruction (vs. -0.25 ± 0.11 in patients without AI; p < 0.001), despite no difference in mean lactate dehydrogenase concentration between the 2 groups (1,301 ± 1,651 U/l vs. 1,354 ± 1,365 U/l; p = 0.91). Area under the ROC curve (AUC) for LVEDD slope was 0.76 and improved to 0.88 after removal of patients with AI from the study. LVEDD slope in patients with MAP ≥85 mm Hg was similar to that for device obstruction (-0.18 ± 0.07) and was abnormal in 6 of the 12 ramp tests performed. Combining LVEDD slope with lactate dehydrogenase concentration increased the AUC to 0.96 as an indicator of device obstruction. CONCLUSIONS Abnormal loading conditions due to AI or elevated MAP may result in false positive ramp tests.

Survival in elderly patients supported with continuous flow left ventricular assist device as bridge to transplantation or destination therapy.

BACKGROUND Published data on mechanical circulatory support for elderly patients in continuous flow devices are sparse and suggest relatively poor survival. This study investigated whether LVADs can be implanted in selected patients over the age of 65 years with acceptable survival compared with published outcomes. METHODS AND RESULTS A single-center retrospective analysis was conducted in 64 consecutive patients ≥65 years of age implanted with a continuous-flow left ventricular assist device (CF-LVAD) as either bridge to transplantation or destination therapy from August 2005 to January 2012. Baseline laboratory and hemodynamic characteristics and follow-up data were obtained. Median survival was 1,090 days. Survival was 85%, 74%, 55%, and 45% at 6 months and 1, 2, and 3 years, respectively. Our cohort had a baseline mean Seattle Heart Failure Model (SHFM) score of 2.6 ± 0.9. Observed survival was significantly better than SHFM-predicted medical survival. Stratification by age subsets, renal function, SHFM, implantation intention, or etiology did not reveal significant differences in survival. The most common cause of death was sepsis and nonlethalcomplication was bleeding. CONCLUSIONS Our experience with patients over the age of 65 receiving CF-LVADs suggests that this group demonstrates excellent survival. Further research is needed to discern the specific criteria for risk stratification for LVAD support in the elderly.

Clinical hemodynamic evaluation of patients implanted with a fully magnetically levitated left ventricular assist device (HeartMate 3)

BACKGROUND The HeartMate 3 (HM3) is a Conformiteé Européenne (CE) mark-approved left ventricular assist device (LVAD) with a fully magnetically levitated rotor with features consisting of a wide range of operational speeds, wide flow paths and an artificial pulse. We performed a hemodynamic and echocardiographic evaluation of patients implanted with the HM3 LVAD to assess the speed range for optimal hemodynamic support. METHODS Sixteen HM3 patients underwent pump speed ramp tests with right heart catheterization (including central venous pressure [CVP], pulmonary artery pressure, pulmonary capillary wedge pressure [PCWP] and blood pressure [BP]) and 3-dimensional echocardiography (3DE). Data were recorded at up to 13 speed settings. Speed changes were in steps of 100 revolutions per minute (rpm), starting at 4,600 rpm and ramping up to 6,200 rpm. RESULTS Mean original speed was 5,306 ± 148 rpm, with a majority of patients (10 of 16, 62.5%) having normal CVPs and PCWPs at their original rpm settings. Going from lowest to highest speeds, cardiac output improved at the rate of 0.08 ± 0.08 liter/min per 100 rpm (total change 1.25 ± 1.20 liters/min) and PCWP decreased at the rate of -0.48 ± 0.27 mm Hg per 100 rpm (total change -6.13 ± 3.72 mm Hg). CVP and systolic BP did not change significantly with changes in rpm. Left ventricular end-diastolic dimension (LVEDD) decreased at a rate of -0.15 ± 0.09 cm per 100 rpm. Number of rpm was adjusted based on test results to achieve CVPs and PCWPs as close to normal limits as possible, which was feasible in 13 (81.3%) patients. For the remaining 3 patients, medical management was pursued to optimize hemodynamic support. CONCLUSION Hemodynamic normalization of pressures was achieved in the majority of patients implanted with the HM3 pump within a narrow speed range.

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.

HAS-BLED and CHA2DS2-VASc Scores as Predictors of Bleeding and Thrombotic Risk After Continuous-Flow Ventricular Assist Device Implantation

BACKGROUND HAS-BLED and CHA₂DS₂-VASc scores predict bleeding in patients on anticoagulation and thromboembolic (TE) risk in patients with atrial fibrillation, respectively. We hypothesized that these scores would be predictive of bleeding and TE complications following continuous-flow ventricular assist device (CF-VAD) implantation. METHODS AND RESULTS Baseline HAS-BLED and CHA2DS2-VASc scores were retrospectively determined for 173 consecutive patients who underwent HeartMate II CF-VAD implantation at a single center from 2005 to 2011. Forty-three patients had bleeding (24.9%) and 22 had TE (12.7%) events over a 290 patient-year follow-up period. The mean ± SD HAS-BLED scores were 2.7 ± 1.0 and 1.9 ± 1.1 (P < .0001) in patients with and without bleeding, respectively. The CHA₂DS₂-VASc scores were 3.6 ± 1.4 and 2.9 ± 1.5 (P = .03) in patients with and without TE events, respectively. A HAS-BLED score of ≥ 3 was associated with a significantly higher risk of bleeding events compared with a score of <3 (42% vs 15%, respectively; hazard ratio [HR] 3.40, 95% confidence interval [CI] 1.82-6.32; P < .001). A CHA₂DS₂-VASc score of ≥ 3 was associated with a higher risk of TE events compared with a score of <3 (18% vs 4%, respectively; HR 4.02, 95% CI 1.19-13.6; P = .025). CONCLUSIONS Baseline HAS-BLED and CHA₂DS₂-VASc scores of ≥ 3 conferred significantly higher risks of bleeding and TE, respectively, following HeartMate II implantation.

Substance abuse at the time of left ventricular assist device implantation is associated with increased mortality

BACKGROUND Advanced heart failure teams are often faced with the decision of whether or not to offer a left ventricular assist device (LVAD) to patients who have end-stage heart failure and recent or ongoing substance abuse. The outcomes of these patients after LVAD implantation are unknown. METHODS Baseline predictors and outcomes were collected and analyzed from patients with active substance abuse and a cohort of patients without active substance abuse matched for age, INTERMACS profile and year of implantation. The primary outcome was all-cause mortality. Secondary outcomes included rates of listing for cardiac transplantation, transplantation and chronic drive-line infection. RESULTS The cohort consisted of 20 consecutive LVAD recipients with active substance abuse and 40 recipients without active substance abuse. During a median follow-up period of 2.3 years (IQR 1.4 to 3.6), the substance abuse group had 3.2 times the rate (hazard) of death compared with a matched cohort (HR 3.2, 95% CI 1.2 to 8.0, p < 0.05). Furthermore, the rate of listing for transplant was 69% lower (rate ratio 0.31, p < 0.0005), rate of cardiac transplant was 89% lower (rate ratio 0.11, p < 0.0005), and risk of chronic drive-line infection was 5.4 times higher (rate ratio 5.4, p < 0.0005) in the substance abuse group. CONCLUSIONS Active substance abuse in patients who received an LVAD was associated with increased mortality and overall poor outcomes. Larger scale data will be needed to confirm these findings and to inform decision-making in this population.

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.

Use of a percutaneous temporary circulatory support device as a bridge to decision during acute decompensation of advanced heart failure

BACKGROUND Prognosis is poor for patients with decompensated advanced heart failure (HF) refractory to medical therapy. Evaluating candidacy for durable mechanical circulatory support (MCS), cardiac transplantation, or palliative care is complex, and time is often needed to stabilize the patient hemodynamically. The Impella 5.0 (Abiomed, Danvers, MA) is a minimally invasive axial-flow catheter capable of providing full temporary hemodynamic support. We report a multicenter series on the use of this device for bridge to decision (BTD) in decompensated advanced HF patients. METHODS In a retrospective evaluation at 3 centers of patients with advanced HF who acutely decompensated and received the Impella 5.0 for BTD, we analyzed demographics, procedural characteristics, in-hospital and intermediate-term outcomes, and in-hospital complications. RESULTS There were 58 patients who met inclusion criteria from 2010 to 2015. All were inotrope dependent. The mean ejection fraction was 13%, and median age was 59 years (interquartile range, 48-64 years). Mean duration of support was 7 days (range, 0-22 days). Thirty-nine patients survived to next therapy (67%), with most receiving durable MCS (n = 20) or heart transplantation (n = 15). In-hospital complications included bleeding (n = 9) and hemolysis (n = 4). Of patients who survived to the next therapy, 1-year survival was 65% for those who received durable MCS, 87% for those who received a transplant, and 75% for those who were stabilized and weaned. CONCLUSIONS The Impella 5.0 may provide a BTD strategy for patients with advanced HF and acute hemodynamic instability. Prospective studies are needed to evaluate the safety and effectiveness of this device in this patient population.