Rahatullah Muslem

Derivation and Validation of a Novel Right-Sided Heart Failure Model After Implantation of Continuous Flow Left Ventricular Assist Devices:The EUROMACS (European Registry for Patients with Mechanical Circulatory Support) Right-Sided Heart Failure Risk Score

Background: The aim of the study was to derive and validate a novel risk score for early right-sided heart failure (RHF) after left ventricular assist device implantation. Methods: The EUROMACS (European Registry for Patients with Mechanical Circulatory Support) was used to identify adult patients undergoing continuous-flow left ventricular assist device implantation with mainstream devices. Eligible patients (n=2988) were randomly divided into derivation (n=2000) and validation (n=988) cohorts. The primary outcome was early (<30 days) severe postoperative RHF, defined as receiving short- or long-term right-sided circulatory support, continuous inotropic support for ≥14 days, or nitric oxide ventilation for ≥48 hours. The secondary outcome was all-cause mortality and length of stay in the intensive care unit. Covariates found to be associated with RHF (exploratory univariate P<0.10) were entered into a multivariable logistic regression model. A risk score was then generated using the relative magnitude of the exponential regression model coefficients of independent predictors at the last step after checking for collinearity, likelihood ratio test, c index, and clinical weight at each step. Results: A 9.5-point risk score incorporating 5 variables (Interagency Registry for Mechanically Assisted Circulatory Support class, use of multiple inotropes, severe right ventricular dysfunction on echocardiography, ratio of right atrial/pulmonary capillary wedge pressure, hemoglobin) was created. The mean scores in the derivation and validation cohorts were 2.7±1.9 and 2.6±2.0, respectively (P=0.32). RHF in the derivation cohort occurred in 433 patients (21.7%) after left ventricular assist device implantation and was associated with a lower 1-year (53% versus 71%; P<0.001) and 2-year (45% versus 58%; P<0.001) survival compared with patients without RHF. RHF risk ranged from 11% (low risk score 0–2) to 43.1% (high risk score >4; P<0.0001). Median intensive care unit stay was 7 days (interquartile range, 4–15 days) versus 24 days (interquartile range, 14–38 days) in patients without versus with RHF, respectively (P<0.001). The c index of the composite score was 0.70 in the derivation and 0.67 in the validation cohort. The EUROMACS-RHF risk score outperformed (P<0.0001) previously published scores and known individual echocardiographic and hemodynamic markers of RHF. Conclusions: This novel EUROMACS-RHF risk score outperformed currently known risk scores and clinical predictors of early postoperative RHF. This novel score may be useful for tailored risk-based clinical assessment and management of patients with advanced HF evaluated for ventricular assist device therapy.

Pre-operative proteinuria in left ventricular assist devices and clinical outcome

BACKGROUND This study evaluated the association of pre-operative proteinuria before continuous flow left ventricular assist device (CF-LVAD) implantation in relation to mortality and the need for renal replacement therapy (RRT) during the first year of follow-up. METHODS This retrospective, multicenter cohort study evaluated all patients (n = 241) who underwent CF-LVAD implantation in the 2 participating tertiary referral centers. Patients were included if a urine dipstick was performed within 7 days before CF-LVAD implantation. Proteinuria was defined as trace or higher. RESULTS In total, 173 patients (72%) were included (78% men; mean age, 52.3 ± 13.3; mean estimated glomerular filtration rate, 60.1 ± 25.9 mL/min/1.73 m2), and 42 patients (24%) had pre-operative proteinuria. The observed survival in patients with proteinuria vs without proteinuria was 57% vs 86% at 3 months and 52% vs 78% at 1 year (log-rank p < 0.001), respectively. In addition, during the first year after implantation, 32% of the patients with proteinuria and 15% of the patients without proteinuria required RRT (log-rank p = 0.02). Multivariate Cox regression analysis confirmed that pre-operative proteinuria was an independent predictor for mortality (adjusted hazard ratio, 2.09; 95% confidence interval, 1.10-3.80, p = 0.02) and for the need of RRT during the first year (adjusted hazard ratio, 2.23; 95% confidence interval, 1.13-4.84; p = 0.02). CONCLUSIONS Proteinuria, which was present in 25% of all tested LVAD patients, predicts worse outcome in all-cause mortality and need of RRT in patients with a CF-LVAD. This warrants the use of proteinuria in risk stratification when selecting patients for CF-LVAD therapy.

Acute kidney injury and 1-year mortality after left ventricular assist device implantation

BACKGROUND Data on the consequences of acute kidney injury (AKI) after continuous-flow left ventricle assist device (LVAD) implantation are scarce and inconsistent. In this study, we evaluated the incidence, predictors and the impact of AKI on mortality and renal function in the first year after LVAD implantation. METHODS A retrospective, multicenter cohort study was conducted, including all patients (age ≥18 years) undergoing LVAD implantation (91% with a HeartMate II device and 9% with a HeartWare device). The definition proposed by the Kidney Disease Improving Global Outcome (KDIGO) criteria was used to define AKI. RESULTS Overall, 241 patients (mean age 52.4 ± 12.9 years, 76% males) were included in the study. AKI criteria were met in 169 (70%) patients, of whom 109 (45%) were in AKI Stage I, 22 (9%) in Stage II and 38 (16%) in Stage III. Two factors, the need for pre-operative inotropic support and pre-existent chronic kidney disease Stage ≤II (estimated glomerular filtration rate [eGFR] <30 ml/min/1.73 m2), were independently associated with the development of AKI and the severity of AKI stages. One-year mortality rates in patients without AKI and AKI Stages I, II and III were 18.7%, 26.4%, 23%, and 51%, respectively (log rank, p = 0.001). In the multivariable analysis, AKI Stage ≥II was independently associated with mortality (hazard ratio 2.2 [95% confidence interval 1.1 to 4.5], p = 0.027) and worse renal function (β = -7.4 [95% confidence interval -12.6 to -2.1], p < 0.01) at 1 year. CONCLUSION AKI is highly frequent after LVAD implantation. More severe AKI stages are associated with higher mortality rates and impaired renal function at 1 year after LVAD implantation.

Acquired coagulopathy in patients with left ventricular assist devices

Chronic heart failure (HF) is a major emerging healthcare problem, associated with a high morbidity and mortality. Left ventricular assist devices (LVADs) have emerged as a successful treatment option for patients with end‐stage HF. Despite its great benefit, the use of LVAD is associated with a high risk of complications. Bleeding, pump thrombosis and thromboembolic events are frequently observed complications, with bleeding complications occurring in over a third of the patients. Although the design of the third‐generation LVAD has improved greatly, these hemostatic complications still occur. The introduction of an LVAD into the circulatory system results in an altered hematological balance as a consequence of blood–pump interactions, changes in hemodynamics, the rheology, and the concomitant need for anticoagulation while implanted with an LVAD. The majority, if not all, LVAD patients experience a form of platelet dysfunction and impaired von Willebrand factor activity, leading to acquired coagulopathy disorders. Different diagnostic tools and treatment strategies have been reported; however, they require validation in LVAD patients. The present review focuses on acquired coagulopathies, describing the incidence, impact and underlying mechanism of acquired coagulopathy disorders in patients supported by LVADs. In addition, we will discuss diagnostic and management strategies for these acquired coagulopathies.

Tricuspid Valve Disease: A Computed Tomographic Assessment

Current cardiovascular computed tomography (CT) scanners provide a three-dimensional full volumetric dataset that covers the entire heart and its vascular connections at one or more time points. Cardiovascular CT plays an increasingly important role in the era of transcatheter aortic and mitral valve therapy. Likewise, it has a potential importance in planning of transcatheter tricuspid valve (TV) interventions. Advantages in the CT assessment of the TV include its ability to show a complete overview of the complex anatomy, its submillimetre isotropic spatial resolution and a temporal resolution as low as 66 ms. In addition, CT measurements are generally simple and accurate on good-quality images. It allows for precise anatomic measurements, which is needed for optimal valve sizing and successful valve placement. However, the use of cardiovascular CT has certain limitations. In detail visualization of the right atrioventricular junction can be challenging. It is associated with ionizing radiation, and it has other related risks, especially in dynamic imaging, and with the use of potentially nephrotoxic contrast agents. New TV therapies are evolving, although, evidence for the efficacy and safety is limited to case reports and small series. In this chapter, we will provide an overview of current and potential future applications of CT in the assessment of right heart disease with a focus on perioperative assessment of patients undergoing transcatheter TV therapy.

Safety and feasibility of contrast echocardiography for the evaluation of patients with HeartMate 3 left ventricular assist devices

Aims Patients with a left ventricular assist device (LVAD) are challenging to evaluate using conventional imaging techniques, such as standard echocardiography (SE). The aim of this pilot study was to evaluate the potential of contrast echocardiography (CE) for the evaluation of the left ventricle (LV). Methods and results This prospective study included 14 ambulatory patients (mean age 58 ± 9 years, 79% male) with a LVAD (all HeartMate 3, Abbott Laboratories, Chicago, IL, USA). Nine (64%) patients had an ischaemic cardiomyopathy, and 5 (36%) had a non-ischaemic cardiomyopathy. All patients underwent SE and CE using intravenous administration of Sonovue contrast agent (Bracco, Milan, Italy). The echocardiograms were assessed by three observers, using a standard 17-segment model of the LV. Left ventricular end-diastolic volume (LVEDV) was assessed using the biplane Simpson method. The contrast agent was well tolerated by all patients, without any side effects. Overall, SE allowed visualization of 57% of LV segments (135/238) and CE allowed visualization of 79% of LV segments (187/238), P < 0.001. Per patient, SE resulted in visualization of 9.6 ± 5.2 segments and CE was able to visualize 13.4 ± 5.8 segments (P < 0.001). Administration of contrast agent significantly improved the assessment of LVEDV (feasibility SE: 36% vs. CE: 79%, P < 0.05). Conclusion Routine use of a contrast agent appears safe when used in patients having a new third generation LVAD and may enhance the diagnostic accuracy of transthoracic echocardiography in these patients. LV size determination can be obtained more often due to improved LV visualization using contrast agent.

Left ventricular assist device implantation with and without concomitant tricuspid valve surgery: a systematic review and meta-analysis

OBJECTIVES Moderate-to-severe tricuspid regurgitation is common in end-stage heart disease and is associated with an impaired survival after left ventricular assist device (LVAD) surgery. Controversy remains whether concomitant tricuspid valve surgery (TVS) during LVAD implantation is beneficial. We aimed to provide a contemporary overview of outcomes in patients who underwent LVAD surgery with or without concomitant TVS. METHODS A systematic literature search was performed for articles published between January 2005 and March 2017. Studies comparing patients undergoing isolated LVAD implantation and LVAD + TVS were included. Early outcomes were pooled in risk ratios using random effects models, and late survival was visualized by a pooled Kaplan-Meier curve. RESULTS Eight publications were included in the meta-analysis, including 562 undergoing isolated LVAD implantation and 303 patients with LVAD + TVS. Patients undergoing LVAD + TVS had a higher tricuspid regurgitation grade, central venous pressure and bilirubin levels at baseline and were more often female. We found no significant differences in early mortality and late mortality, early right ventricular failure and late right ventricular failure, acute kidney failure, early right ventricular assist device implantation or length of hospital stay. Cardiopulmonary bypass time was longer in patients undergoing additional TVS [mean difference +35 min 95% confidence interval (16-55), P = 0.001]. CONCLUSIONS Adding TVS during LVAD implantation is not associated with worse outcome. Adding TVS, nevertheless, may be beneficial, as baseline characteristics of patients undergoing LVAD + TVS were suggestive of a more progressive underlying disease, but with comparable short-term outcome and long-term outcome with patients undergoing isolated LVAD.

Incidence, predictors and clinical outcome of early bleeding events in patients undergoing a left ventricular assist device implant

OBJECTIVES Bleeding is a common complication following left ventricular assist device (LVAD) implantation. The goal of this study was to investigate the incidence, predictors and clinical outcome of early bleeding events in patients after LVAD implantation. METHODS A total of 83 patients (age 50 ± 13 years, 76% men) had an LVAD implanted [77% HeartMate II, 19% HeartMate 3 (Abbott, Chicago, IL, USA)] over a period of 11 years. Patients were included consecutively. An early bleeding event was defined as the need for thoracic surgical re-exploration or transfusion with >4 units of packed red blood cells before discharge. RESULTS Overall, 39 (47%) patients (age 50 ± 14 years, 77% men) experienced an early bleeding event [median time 6 days (interquartile range 1-9 days)]. Furthermore, 10 (26%) of these patients had ≥2 bleeding events. Twelve of the 14 (92%) patients with venoarterial extracorporeal membrane oxygenation (ECMO) support before LVAD implantation experienced an early bleeding event versus 27 of the 69 (39%) patients without ECMO support (P < 0.001). No difference was found in early bleeding rates between HeartMate II and HeartMate 3. Predictors for early bleeding events were lower pre- and postimplant platelet counts and ECMO support preimplantation. After multivariable adjustment, early bleeding events were associated with ECMO support preimplantation (odds ratio 6.3, 95% confidence interval 1.2-32.4; P = 0.03) and thrombocytopenia (<150 × 109/l) postimplant (odds ratio 5.9, 95% confidence interval 1.9-18.7; P = 0.002). Patients who experienced an early bleeding event had a significantly worse 90-day survival rate compared to patients who did not (79% vs 96%, P = 0.03). CONCLUSIONS An early bleeding event needing surgical exploration is highly prevalent after LVAD implantation, especially in patients bridged with ECMO and with pre- and postimplant thrombocytopenia.

Long-Term Mechanical Durability of Left Ventricular Assist Devices: An Urgent Call for Periodic Assessment of Technical Integrity.

Long-term durability and incidence of potential mechanical device failure (MDF) are largely unknown. In this study, we investigated the incidence and potential predictors of MDF in continuous flow left ventricular assist device (CF-LVAD) patients. We conducted a retrospective study of all CF-LVADs (type HeartMate II) implanted in our center. MDF was defined as a failure of driveline, inflow–outflow graft, electrical power, drive unit, or motor failure, excluding device failure because of a biologic complication (e.g., device thrombosis, hemolysis, or infections). A total of 69 CF-LVADs were implanted in 59 patients (median support time 344 days [interquartile range {IQR}, 149–712 days], mean age 50.1 ± 10.7 years, 75% male). MDF occurred in 9 (13%) CF-LVAD patients at a median follow-up time of 846 (IQR, 708–1337) days after implantation. Freedom of MDF through the first, second, and third year after LVAD implantation was 100%, 85%, and 64%, respectively. Patients who experienced MDF were significantly longer supported by their LVAD (median 846 [IQR, 708–1337] vs 268 [IQR, 103–481] days; p = 0.001) and were more frequently readmitted because of LVAD-related technical problems (p = 0.002), including a higher rate of LVAD controllers exchange (44% vs 12%, respectively; p = 0.03). The main reason for MDF was a damaged or fractured driveline (n=8, 89%). In 2 patients, sudden death was related to MDF. Patients needing extended CF-LVAD support are at increasing risk for MDF. Various technical problems precede the onset of MDF. Periodical extensive assessment of the technical integrity of the device is urgently needed during long-term LVAD support.

Effect of Age and Renal Function on Survival After Left Ventricular Assist Device Implantation

Left ventricular assist devices (LVAD) are increasingly used, especially as destination therapy in in older patients. The aim of this study was to evaluate the effect of age on renal function and mortality in the first year after implantation. A retrospective multicenter cohort study was conducted, evaluating all LVAD patients implanted in the 2 participating centers (age ≥18 years). Patients were stratified according to the age groups <45, 45-54, 55-64, and ≥65 years old. Overall, 241 patients were included (mean age 52.4 ± 12.9 years, 76% males, 33% destination therapy). The mean estimated Glomerular Filtration Rate (eGFR) at 1 year was 85, 72, 69, and 49 mL/min per 1.73 m2 in the age groups <45(n = 65, 27%), 45-54(n = 52, 22%), 55-64(n = 87, 36%), and ≥65 years (n = 37, 15%) p <0.001)), respectively. Older age and lower eGFR at baseline (p <0.01) were independent predictors of worse renal function at 1 year. The 1-year survival post-implantation was 79%,84%, 68%, and 54% for those in the age group <45, 45-54, 55-64 and ≥65 years (Log-rank p = 0.003). Older age, lower eGFR and, INTERMACS class I were independent predictors of 1-year mortality. Furthermore, older patients (age > 60 years) with an impaired renal function (eGFR <55 mL/min per 1.73 m2) had a 5-fold increased hazard ratio for mortality during the first year after implantation (p <0.001). In conclusion, age >60 years is an independent predictor for an impaired renal function and mortality. Older age combined with reduced renal function pre-implantation had a cumulative adverse effect on survival in patients receiving a LVAD.