GI bleeding in patients with continuous-flow left ventricular assist devices: a systematic review and meta-analysis

doi:10.1016/j.gie.2014.03.040

Gastrointestinal Endoscopy

Volume 80, Issue 3, September 2014, Pages 435-446.e1

https://doi.org/10.1016/j.gie.2014.03.040 Get rights and content

Background

Patients with left ventricular assist devices (LVADs) are at increased risk of GI bleeding (GIB), primarily from GI angiodysplastic lesions (GIAD).

Objective

To perform meta-analysis of the medical literature in order to determine prevalence and risk factors for GIB.

Design

A literature search was performed to identify studies reporting GIB in LVAD patients. We extracted rates of prevalence, rebleeding, and overall mortality from each study. Pooled event rates and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

Setting

Meta-analysis of 17 case-control and cohort studies.

Patients

A total of 1839 LVAD patients of whom 1697 (92%) had continuous-flow LVADs.

Results

The pooled prevalence of GIB in LVAD patients was 23% (95% CI, 20.5%-27%). Subgroup analysis demonstrated that older age (standard difference in means (SDm), 0.69; 95% CI, 0.23-1.15), and elevated creatinine (SDm, 0.65; 95% CI, 0.12-1.18, P = .02) were associated with GIB. Risk factors not associated with GIB included LVAD as destination therapy (OR 1.85; 95% CI, 0.8-4.3), prior history of GIB (OR 2.22; 95% CI, 0.83-5.96), hypertension (OR 1.6; 95% CI, 0.87-2.97), and/or the presence of a continuous-flow LVAD (OR 4.5; 95% CI, 2.1-9.5). Recurrence of GIB occurred in 9.3% (95% CI, 7%-12%), with a GIB mortality rate of 23% (95% CI, 16%-32%). The pooled event rates were 48% (95% CI, 39%-57%) for upper GIB, 22% (95% CI, 16%-31%) for lower GIB, and 15% (95% CI, 8%-25%) for small-bowel bleeding. GIAD in the proximal GI tract were the most common cause of GIB (29%).

Limitations

Lack of information regarding endoscopic therapy and follow-up in most studies.

Conclusions

The prevalence of GIB is increased in patients with continuous-flow LVADs, primarily secondary to the presence of GIAD.

Section snippets

Data sources and search strategy

We performed a literature search by using PubMed, SCOPUS, and the Cochrane Central Register of Clinical Trials (1990-2013) to identify full articles reporting the prevalence of GIB in patients with LVADs. We identified studies using the following medical subject headings (MeSH) and keywords including “left ventricular assist device” or “cardiac assist device” or “heart-assist device” and “gastrointestinal bleeding” or “gastrointestinal hemorrhage” or “complications” or “adverse events.” The

Study characteristics and quality

The literature search resulted in 2573 articles. After exclusion of duplicates, case reports, and review articles, 63 papers were assessed via full text for eligibility. Of these, 46 articles were excluded for various reasons (Fig. 1), leaving 17 papers describing the prevalence of GIB in continuous-flow LVAD patients included. The study cohort included 1839 patients, 1697 (92%) of whom had continuous-flow LVADs (Fig. 1). The characteristics of the patients enrolled in each study are shown in

Discussion

GIB is an astoundingly common occurrence in the post-LVAD implantation patient. In particular, GIAD appear to be the predominant cause of bleeding, especially in patients with continuous-flow devices. There is some preliminary evidence that shows that bleeding events cease after heart transplantation and LVAD device removal, although this was noted in only 12 patients in our study. The increased risk of bleeding is thought to be a combination of several factors. First, it has been demonstrated

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Cited by (137)

Left Ventricular Assist Device Emergencies: Diagnosis and Management
2024, Critical Care Clinics
Patient-specific severity of von Willebrand factor degradation identifies patients with a left ventricular assist device at high risk for bleeding
2024, Journal of Thoracic and Cardiovascular Surgery
Continuous-flow left ventricular assist devices (LVADs) cause an acquired von Willebrand factor (VWF) deficiency and bleeding. Models to risk-stratify for bleeding are urgently needed. We developed a model of continuous-flow LVAD bleeding risk from patient-specific severity of VWF degradation.
In a prospective, longitudinal cohort study, paired blood samples were obtained from patients (n = 67) with a continuous-flow LVAD before and during support. After 640 ± 395 days, patients were categorized as all-cause bleeders, gastrointestinal (GI) bleeders, or nonbleeders. VWF multimers and VWF clotting function were evaluated to determine bleeding risk.
Of 67 patients, 34 (51%) experienced bleeding, 26 (39%) experienced GI bleeding, and 33 (49%) did not bleed. In all patients, LVAD support significantly reduced high-molecular-weight VWF multimers (P < .001). Bleeders exhibited greater loss of high-molecular-weight VWF multimers (mean ± standard deviation, –10 ± 5% vs –7 ± 4%, P = .008) and reduced VWF clotting function versus nonbleeders (median [interquartile range], –12% [–31% to 4%] vs 0% [–9 to 26%], P = .01). A combined metric of VWF multimers and VWF function generated the All-Cause Bleeding Risk Score, which stratified bleeders versus nonbleeders (86 ± 56% vs 41 ± 48%, P < .001) with a positive predictive value of 86% (95% confidence interval, 66%-95%) and diagnostic odds ratio of 11 (95% confidence interval, 2.9-44). A separate GI Bleeding Risk Score stratified GI bleeders versus nonbleeders (202 ± 114 vs 120 ± 86, P = .003) with a positive predictive value of 88% (64%-97%) and diagnostic odds ratio of 18 (3.1-140).
The severity of loss of VWF multimers and VWF clotting function generated Bleeding Risk Scores with high predictive value for LVAD-associated bleeding. This model may guide personalized antithrombotic therapy and patient surveillance.
Gastrointestinal bleeding and pro-angiogenic shift in the angiopoietin axis with continuous flow left ventricular assist device implantation
2023, American Journal of the Medical Sciences
Gastrointestinal bleeding (GIB) affects up to 40% of continuous-flow left ventricular assist device (CF-LVAD) recipients. A higher risk of GIB is seen in CF-LVAD recipients with lower device pulsatility without a known mechanism. One hypothesis is that the novel hemodynamics in CF-LVAD recipients affect angiogenesis signaling. We aimed to (1) measure serum levels of angiopoietin (Ang)-1, Ang-2, and VEGF-A in CF-LVAD recipients with and without GIB and in healthy controls and (2) evaluate correlations of those levels with hemodynamics.
We recruited 12 patients with CF-LVADs (six who developed GIB after device implantation) along with 12 age-matched controls without heart failure or GIB and measured Ang-1, Ang-2, and VEGF-A levels in serum samples from each patient.
CF-LVAD recipients had significantly higher Ang-2 and lower Ang-1 levels compared to controls with no difference in VEGF-A levels. CF-LVAD recipients with GIB had lower Ang-1 levels than those without GIB. There were trends for pulse pressure to be positively correlated with Ang-1 levels and negatively correlated with Ang-2 levels in CF-LVAD recipients with no correlation observed in healthy controls.
CF-LVAD recipients demonstrated a shift toward a pro-angiogenic phenotype in the angiopoietin axis that is significantly associated with GIB and may be linked to low pulse pressure.
Gastrointestinal Bleeding in Patients Supported with Left Ventricular Assist Devices: The Journey from Bridging to Destination
2023, American Journal of Cardiology
End-stage heart failure is a prevalent and fatal cardiovascular disease. Almost 1 in 4 cases of mortality in the United States is attributed to heart failure. Left ventricular assist devices (LVADs) have emerged as a safe destination therapy or bridge to transplant. Despite remarkable results, LVAD is associated with significant adverse events, such as gastrointestinal bleeding (GIB). In this review, we aimed to understand the incidence and prevalence, pathophysiologic mechanisms, predictors, diagnostic mechanisms, management, and preventative measures of GIB in patients with an LVAD. GIB is a common adverse event in patients with an LVAD with an incidence of 15% to 25%. The exact pathogenesis of GIB is poorly understood. However, different mechanisms of bleeding have been described, such as arteriovenous malformations, acquired von Willebrand syndrome, coagulopathy, and treatment with antithrombotic therapy. Upper GIB is the most common site of GIB in patients with an LVAD. The management of GIB in patients with LVAD includes ensuring hemodynamic stability, holding or reversing antithrombotic therapy, and investigating and controlling the source of GIB through diagnostic and interventional endoscopic and radiologic means. Prophylactic medication use (e.g., danazol, octreotide, and bevacizumab) can decrease the risk of GIB in patients with an LVAD by decreasing arteriovenous malformations. Despite that the overall risk of GIB has decreased with new advancements in LVAD technology, further studies are needed regarding predictors, risk stratification, and optimal antithrombotic therapy to minimize the morbidity and mortality in patients with an LVAD. In conclusion, prompt diagnosis and management in a multidisciplinary team approach are crucial and lifesaving in such a life-threatening condition.
HFSA Expert Consensus Statement on the Medical Management of Patients on Durable Mechanical Circulatory Support
2023, Journal of Cardiac Failure
The medical management of patients supported with durable continuous flow left ventricular assist device (LVAD) support encompasses pharmacological therapies administered in the preoperative, intraoperative, postoperative, and chronic LVAD support stages. As patients live longer on LVAD support, the risks of LVAD-related complications and progression of cardiovascular and other diseases increase. Using existing data from cohort studies, registries, randomized trials, and expert opinion, this Heart Failure Society of America Consensus Document on the Medical Management of Patients on Durable Mechanical Circulatory Support offers best practices on the management of patients on durable mechanical circulatory support, focusing on pharmacological therapies administered to patients on continuous flow LVADs. Although quality data in the LVAD population are few, the use of guideline-directed heart failure medical therapies and the importance of blood pressure management, right ventricular preload and afterload optimization, and antiplatelet and anticoagulation regimens are discussed. Recommended pharmacological regimens used to mitigate or treat common complications encountered during LVAD support, including arrhythmias, vasoplegia, mucocutaneous bleeding, and infectious complications, are addressed. Finally, this document touches on important potential pharmacological interactions from antidepressants and herbal and nutritional supplements of relevance to providers of patients on LVAD support.
An Institutional Overview of Gastrointestinal Bleeding Among 563 Continuous-Flow Left Ventricular Assist Device Recipients
2023, Techniques and Innovations in Gastrointestinal Endoscopy
Gastrointestinal bleeding (GIB) is a common morbidity among continuous-flow left ventricular assist device (CF-LVAD) recipients. The study objectives were to investigate the incidence, recurrence, risk factors, and medical and endoscopic management of GIB among CF-LVAD patients.
This is a single-center retrospective study analyzing 563 CF-LVAD recipients implanted at a large tertiary referral center from 2007 to 2018 with 619 bleeding events characterized. Patients with device exchanges or history of right ventricular assist devices were excluded. Chart review data pertaining to demographics, LVAD characteristics, endoscopic reports, and medications were collected.
The incidence of GIB was 44%, with a median time to first bleed of 133 days and a recurrence rate of 53%. Approximately 13% of patients had ≥5 GIB events. There is an association of reduced GIB among patients taking angiotensin-converting enzyme inhibitors (ACEis). There was no association with GIB and acid-reducing medications, antiplatelet medications, and history of GIB before device implantation. Arteriovenous malformations were the most common bleeding etiology. CF-LVAD patients that bled more frequently were older, had their CF-LVAD longer, and bled earlier after LVAD implantation.
This is the largest comprehensive single-center GIB study among CF-LVAD recipients. The incidence and recurrence of GIB among CF-LVAD recipients is underreported. Push enteroscopy improves diagnostic yield for upper GIB. Special attention should be given to CF-LVAD patients that bleed within the first 18 days of implantation. There is an associative, dose-dependent benefit of ACEi medications among CF-LVAD recipients. Further studies on this effect are warranted.

View all citing articles on Scopus

: DISCLOSURE: All authors disclosed no financial relationships relevant to this article.

: If you would like to chat with an author of this article, you may contact Dr Gerson at [email protected].

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Original articleClinical endoscopyGI bleeding in patients with continuous-flow left ventricular assist devices: a systematic review and meta-analysis

Background

Objective

Design

Setting

Patients

Results

Limitations

Conclusions

Section snippets

Data sources and search strategy

Study characteristics and quality

Discussion

Ann Thorac Surg

Transplant Proc

J Thorac Cardiovasc Surg

J Heart Lung Transplant

Ann Thorac Surg

J Am Coll Cardiol

Control Clin Trials

J Heart Lung Transplant

Gastrointest Endosc

J Heart Lung Transplant

Gastroenterology

J Am Coll Cardiol

J Am Coll Cardiol

Lancet

J Heart Lung Transplant

Heart transplantation and left ventricular assist device therapy: two comparable options in end-stage heart failure?

Clin Cardiol

Clinical differences between continuous flow ventricular assist devices: a comparison between HeartMate II and HeartWare HVAD

J Card Surg

Management options to treat gastrointestinal bleeding in patients supported on rotary left ventricular assist devices: a single-center experience

Artif Organs

Original article
Clinical endoscopy
GI bleeding in patients with continuous-flow left ventricular assist devices: a systematic review and meta-analysis