Stage D advanced heart failure (HF) is characterized by abnormalities in cardiac structure that lead to tissue hypoperfusion, target-organ damage, cachexia, and limiting symptoms.
VAD is a surgically implanted mechanical pump that provides circulatory support in patients with severe systolic dysfunction, restoring cardiac output and reducing left ventricular (LV) work.
In the last decade, approximately 25 thousand patients have undergone VAD implantation.
Despite advances in the VAD design and in clinical treatment, 30-day adverse events still occur in 31% of patients.
Several measures should be taken to promote safety and minimize potential adverse treatment events for the patients using VADs.
Here we report a clinical case of a female patient, 54 years old, history of dilated cardiomyopathy and severe mitral insufficiency for Chagas disease, who underwent HMII implantation in 2018 due to inotrope dependence and immune hypersensitivity, which reduces the possibility of HT. The post-implantation was complicated with bleeding, sepsis, severe abdominal distension and difficult anticoagulation control. After about 10 months of follow-up, the patient developed sustained elevation of power and important VAD flow variations, clinical signs of hemolysis – hemoglobinuria and hemoglobin fall, requiring blood transfusion, peak lactate dehydrogenase (LDH) of 2557 U/L and loss of renal function. The patient underwent replacement of the VAD pump, due to clinical suspicion of thrombosis, which was confirmed intraoperatively. After two years with a good clinical course, persistent low-flow VAD alarms occurred, and the patient developed progressive signs of HF and cardiogenic shock. Due to clinical suspicion of subocclusive thrombus in the outflow cannula and aortic insufficiency (AoI), the patient underwent another surgery. Surgical findings revealed dense fibrous tissue around the Dacron and polytetrafluoroethylene (PTFE) patch of the outflow cannula, and presence of inflammatory exudate within the cannula, causing extrinsic compression (
We will now describe the main adverse events related to the use of VADs and a brief discussion of their management.
Devastating neurological events such as ischemic (thromboembolic) or hemorrhagic stroke affect nearly 10% of patients with VAD within one year.
The risk of stroke in patients with VADs is associated with several factors. Patient-related factors may be related to higher odds of cerebrovascular events, such as age, female sex, severity of HF, history of diabetes, hypertension, atrial fibrillation, hypercoagulability, and infections unrelated to the implant. Besides, perioperative (aortic clamping and cardiac arrest with cardioplegia) and postoperative (duration of mechanical support, infection, subtherapeutic anticoagulation and hypertension following VAD implantation) factors, and those related to the VAD (infection, hemolysis and pump thrombosis) also influence the rate of stroke.
During patient assessment, attention should be paid to the precise onset of neurologic manifestations and their course, using preferably the National Institute of Health and Stroke Scale (NIHSS),
A previous imaging test and a careful clinical examination can help in the diagnostic and decision-making processes. VAD parameters should be analyzed for signs of the VAD malfunction or thrombosis.
In cases where embolism is secondary to VAD thrombosis, systemic thrombolysis was shown to be safe in case reports.
Nearly 25% of patients that undergo VAD implantation develop severe-to-moderate AoI or aggravation of pre-existing AoI. This is a relatively high rate, considering that the prevalence of severe AoI prior to VAD implantation is 0.6%.
Elevations in the pump flow lead to intermittent or permanent closure of the aortic valve and eventual commissural fusion.
The assessment of the aortic valve is essential for determining AoI severity and the planning of treatment.
The degree of AoI may not be reduced by clinical treatment and requires surgical intervention. Although there is still not a consensus on the best surgical approach, the Park stitch (a central coaptation stitch for leaflets) and the aortic valve replacement stand out. Both procedures can be performed either concomitantly or after the VAD implantation, in the presence of hemodynamically important AoI. Percutaneous aortic valve replacement for this indication has been noted in case reports, further studies are still needed.
Previous right ventricular (RV) dysfunction, associated with pulmonary hypertension and acute hemodynamic changes, facilitate the occurrence of right HF in the post-left VAD implantation in approximately 15-25% of patients.
The adequate screening for candidates for the VAD implantation by risk prediction is essential to identify those patients with right HF that could benefit from a left VAD.
Although most patients with RV dysfunction respond to inotropic therapy and optimization of VAD parameters, the early implementation of temporary RV circulatory support shows prognostic benefit.
Patients with right HF may develop hemodynamic deterioration, implantable cardioverter defibrillator, and even cardiac arrest with ventricular tachycardia or fibrillation caused by impaired filling and inadequate flow in the VAD. Echocardiography should be performed to exclude cardiac tamponade and to analyze ventricular filling and dimensions. Clinical treatment includes vasoactive therapy, diuretics and inotropic support, preferably with milrinone, and should be guided by invasive hemodynamic monitoring with pulmonary artery catheterization. In case of significant pulmonary hypertension, pulmonary vasodilator therapy should be considered, and percutaneous RV support may be less relevant.
Pump thrombosis has an incidence of 8% in the first year after VAD implantation and consists one of the main causes (up to 50%) of replacement of the device. According to the INTERMACS, pump thrombosis affects 5.5% of patients with HMII. In this regard, magnetic levitation devices, like the HMIII, provide a safer design, with an incidence of only 1% in a 24-month follow-up.
Although the etiology of pump thrombosis has not been fully elucidated, it is known to be multifactorial and show variations depending on the device.
Patients with pump thrombosis usually present elevation in the pump speed and power, decreased flow, and different degrees of hemolysis and HF.
Therapeutical strategies include anticoagulation and antiplatelet agents, thrombolysis and/or device replacement. The selection of the initial therapy is a complex decision, based on several factors, including patient clinical presentation. While pump replacement has been associated with an increase in perioperative mortality, clinical treatment is more likely to be unsuccessful, and to higher rates of recurrence or need for pump replacement or HT. Also, mortality is found to increase with every pump replacement.
In case of improvement in clinical outcomes with unfractionated heparin and/or direct thrombin inhibitors, an increase in the antithrombotic regimen (AAS 200 mg or 325 mg/day and warfarin and target INR between 2.5 and 3.0), and eventually, dual antiplatelet therapy. If symptoms persist, aggressive antithrombotic therapy with direct thrombin inhibitors such as bivalirudin and argatroban should be considered, but data on their efficacy are still limited. Thrombolysis with recombinant tissue plasminogen activator (e.g. alteplase) should be considered only after cranial computed tomography to exclude eventual ischemic events and hemorrhagic transformation. It is important to mention that the evidence of the benefits of these therapies is still uncertain and based on case series, and the risk of severe hemorrhagic complications cannot be ruled out. For this reason, the therapies should be implemented with caution and be restricted to patients who are not candidates for surgical treatment.
Surgical replacement of the pump for thrombosis is considered the definite (and gold-standard) treatment. Preoperative evaluation by computed tomography scan of the chest with contrast and echocardiography can be performed to detect possible anatomical causes of thrombosis. Suggestive findings of malpositioning of the inflow cannula and dynamic obstruction, kinking or compression of the outflow cannula are indications for the replacement of the VAD by median sternotomy due to limited access via the subcostal approach. The subcostal approach is the preferred route as it allows better access to the LV apex for manipulation of the pump and inflow connection. It can be performed with extracorporeal circulation (ECC) via peripheral cannulation or without ECC, depending on the ventricular reserve and hemodynamic stability of the patient. Good results have been reported with the subcostal approach in experienced centers, with a 30-day mortality of 6.5% in patients with HMII.
Emergency HT is a therapeutical option for patients without contraindications, considering that the estimated waiting time is not long, the management of the HF is feasible, and that hemolysis does not have important repercussions, such as the need for multiple transfusions or severe renal insufficiency. Favorable results of the management of outflow cannula stenosis with percutaneous stent implantation and intravascular ultrasound to distinguish between thrombosis from external compression have been reported.
Although changes in the VAD design have caused a reduction in the incidence of bleeding, this is still one of the most common complications. The contemporary rate of bleeding is 1.4 events per patient-year within 90 days after the implantation, and 0.3 events per patient-year in the late follow-up period. According to INTERMACS, only 67% of patients are free from major bleeding in the first year of therapy. In addition, severe bleeding is the cause of 2% of deaths in patients with VADs.
Perioperative bleeding is the most common immediate complication after VAD implantation, affecting up to 80% of patients. Besides the sternum, the most common site of bleeding is the outflow cannula anastomosis. Its preoperative prevention includes nutritional and hemodynamic optimization (especially for reversal of hepatic and renal dysfunction and related coagulopathies), suspension of anticoagulant and antiplatelet therapy. The risk of bleeding may be reduced by improvements of surgical techniques, appropriate reversal of heparin anticoagulation, and use of pro-hemostatic agents and factor concentrates as appropriate.
In the postoperative period, gastrointestinal bleeding is the most prevalent, especially in elderly patients with a history of this condition.
The treatment of gastrointestinal bleeding includes volemic resuscitation, proton pump inhibitors and endoscopic approach. Either suspension or reversal of anticoagulation therapy yields modest benefits, with a recurrence rate of up to 9%, besides increasing the risk of severe thromboembolic events. Blood component transfusions may be required, but should be considered cautiously, as they add risk of immune hypersensitivity in candidates for HT.
Epistaxis is the second most common hemorrhagic complication in patients with VAD. Its initial management consists of local vasoconstriction, cautery and tamponade. Percutaneous intervention including arterial embolization should be needed in severe cases, and evaluation by an otorhinolaryngologist is recommended.
Infection is a common complication and an independent predictor of mortality in patients with VADs.
VAD-specific infections may occur in the pump, cannulas, pump pocket or driveline. An early identification and an aggressive treatment are essential in the infection control, which may require the removal of the device.
Gram-positive cocci, especially
Due to the smaller size and surface of contact, continuous-flow VADs are associated with lower rates of infection than pulsatile-flow VADs (e.g., 0.38 versus 0.62 driveline infections per patient-year with HMII and HeartMate XVE, respectively).
Regarding laboratory data, VAD infections are marked by high white blood cell counts, and increased C-reactive protein levels.
Controlling the source of the infection should be made whenever possible and includes drainage and debridement. Local debridement of the driveline exit site may be needed in the presence of fluctuant, hard, or necrotic tissue, and eventually, the driveline is relocated to another site, distant far from the infection. In patients with deep infection, surgical drainage and vacuum-assisted closure should be considered.
Infections of the surgical cavity refer to those in the pump pocket which, similar to the driveline infections, occur in the long term. First- and second-generation VADs required a large cavity between the abdominal wall or pericardium and the diaphragm and were more prone to therapeutic failure because of poor vascularization.
Bloodstream infections affect up to 30% of patients using VADs, especially in the first three months after the implant surgery.
Mechanical dysfunction of the VAD occurs in up to 6% of patients in the first year.
The
Periodic VAD interrogation is essential for identification of failures. Registries of critical alarms and flow changes, pulsatility index and peak circulatory power should be recorded. A member of the VAD team should send log files for analysis by clinical engineers whenever appropriate.
Standardized preclinical tests and medical device engineering have been developed to prevent these failures. Patients, caregivers and health care professionals should receive systematic instructions about how to care for the VADs. However, there are challenges in real life that cannot be predicted by laboratory tests, and devices may be less robust in the long term for reasons not necessarily related to lack of care.
In a relatively short time, VADs have become a well-established treatment for advanced HF, with an increasing number of adults being supported with VADs as destiny therapy, bridge to transplant, bridge to transplant eligibility and, less frequently, as bridge to recovery. Although the risks of adverse events are still significant, improvements in survival rates and reduction in morbidity tend to progress with advances in technology and patient selection and follow-up. Besides, there is a growing number of studies evaluating strategies for prevention, diagnosis and management of complications, despite the observational design in most of them. The continuous review of adverse events of VADs and the identification of unique aspects of their diagnosis and management become paramount as novel devices are developed and implemented in the clinical practice.