David S. Raymer

Systolic blood pressure on discharge after left ventricular assist device insertion is associated with subsequent stroke

BACKGROUND Stroke is a significant complication in patients supported with continuous-flow left ventricular assist devices (CF-LVAD) and hypertension is a significant risk factor for stroke, but the association between blood pressure and stroke in LVAD patients is not well characterized. METHODS We identified 275 consecutive patients who survived implant hospitalization between January 2005 and April 2013. Patients were grouped according to systolic blood pressure (SBP) as above a median and below a median of 100 mm Hg by their averaged systolic blood pressure during the 48 hours before discharge from implantation hospitalization. The groups were compared for the primary outcome of time to stroke. RESULTS The above-median SBP group had mean SBP of 110 mm Hg and the below-median SBP group had mean SBP of 95 mm Hg. There were no significant between-group differences in body mass index, smoking, vascular disease, hypertension, atrial fibrillation, or prior stroke. During a mean follow-up of 16 months, stroke occurred in 16% of the above-median SBP group vs in 7% of the below-median SBP group (hazard ratio, 2.38; 95% confidence interval, 1.11-5.11), with a similar proportion of hemorrhagic and ischemic strokes in each group. In Cox proportional hazard models adjusting for age, diabetes, or prior stroke, the hazard ratio remained statistically significant. SBP as a continuous variable predictor of stroke had an area under the curve of 0.64 in a receiver operating characteristic curve analysis. CONCLUSIONS In this large, CF-LVAD cohort, elevated SBP was independently associated with a greater risk of subsequent stroke. These results identify management of hypertension as a potential modifiable risk factor for reducing the incidence of stroke in patients supported by CF-LVAD.

Risk model for estimating the 1-year risk of deferred lesion intervention following deferred revascularization after fractional flow reserve assessment

AIMS Although lesions deferred revascularization following fractional flow reserve (FFR) assessment have a low risk of adverse cardiac events, variability in risk for deferred lesion intervention (DLI) has not been previously evaluated. The aim of this study was to develop a prediction model to estimate 1-year risk of DLI for coronary lesions where revascularization was not performed following FFR assessment. METHODS AND RESULTS A prediction model for DLI was developed from a cohort of 721 patients with 882 coronary lesions where revascularization was deferred based on FFR between 10/2002 and 7/2010. Deferred lesion intervention was defined as any revascularization of a lesion previously deferred following FFR. The final DLI model was developed using stepwise Cox regression and validated using bootstrapping techniques. An algorithm was constructed to predict the 1-year risk of DLI. During a mean (±SD) follow-up period of 4.0 ± 2.3 years, 18% of lesions deferred after FFR underwent DLI; the 1-year incidence of DLI was 5.3%, while the predicted risk of DLI varied from 1 to 40%. The final Cox model included the FFR value, age, current or former smoking, history of coronary artery disease (CAD) or prior percutaneous coronary intervention, multi-vessel CAD, and serum creatinine. The c statistic for the DLI prediction model was 0.66 (95% confidence interval, CI: 0.61-0.70). CONCLUSION Patients deferred revascularization based on FFR have variation in their risk for DLI. A clinical prediction model consisting of five clinical variables and the FFR value can help predict the risk of DLI in the first year following FFR assessment.

Relationship Between Anticoagulation Intensity and Thrombotic or Bleeding Outcomes Among Outpatients With Continuous-Flow Left Ventricular Assist Devices

Background—We evaluated thrombotic and bleeding outcomes in patients with continuous-flow left ventricular assist devices (CF-LVADs), stratified by anticoagulation intensity. Previous studies of outpatients with CF-LVADs have suggested that target international normalized ratio (INR) values <2.5 (range, 2–3) may be used. However, recent studies reported an increase in pump thrombosis among CF-LVADs, especially within the first 6 months of implant. Methods and Results—We retrospectively reviewed 249 outpatients at our center who received a CF-LVAD between January 2005 and August 2013. Using Poisson models, we analyzed their 10 927 INRs to determine INR-specific rates of thrombotic (ischemic stroke and suspected pump thrombosis) and hemorrhagic (gastrointestinal bleeding and hemorrhagic stroke) events occurring outside of the hospital. In multivariate analyses, we adjusted for age, sex, atrial fibrillation, coronary disease, and LVAD type as time-dependent Cox proportional hazard models. During a mean follow-up of 17.6±13.6 months, thrombotic events occurred in 46 outpatients. The highest event rate (0.40 thrombotic events per patient-year) was in the INR range of <1.5, but INR values of 1.5 to 1.99 also had high rates (0.16 thrombotic events per patient-year). INR was inversely associated with thrombotic events (hazard ratio, 0.40; 95% confidence interval, 0.22–0.72; P=0.002). The optimal INR based on weighted mortality of thrombotic and bleeding events was 2.6. Conclusions—INR is inversely related to thrombotic events occurring outside of the hospital among patients supported with CF-LVADs. INR values <2.0 increase the rate of thrombotic events occurring outside of the hospital among patients supported with CF-LVADs.

Association of Lower Fractional Flow Reserve Values With Higher Risk of Adverse Cardiac Events for Lesions Deferred Revascularization Among Patients With Acute Coronary Syndrome

Background The safety of deferring revascularization based on fractional flow reserve (FFR) during acute coronary syndrome (ACS) is unclear. We evaluated the association of FFR and adverse cardiac events among patients with coronary lesions deferred revascularization based on FFR in the setting of ACS versus non-ACS. Methods and Results The study population (674 patients; 816 lesions) was divided into ACS (n=334) and non-ACS (n=340) groups based on the diagnosis when revascularization was deferred based on FFR values >0.80 between October 2002 and July 2010. The association and interaction between FFR and clinical outcomes was evaluated using Cox proportional hazards models within each group (mean follow-up of 4.5±2.1 years). Subsequent revascularization of a deferred lesion was classified as a deferred lesion intervention (DLI), whereas the composite of DLI or myocardial infarction (MI) attributed to a deferred lesion was designated as deferred lesion failure (DLF). In the non-ACS group, lower FFR values were not associated with any increase in adverse cardiac events. In the ACS group, every 0.01 decrease in FFR was associated with a significantly higher rate of cardiovascular death, MI, or DLI (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03 to 1.12), MI or DLI (HR, 1.09; 95% CI: 1.04 to 1.14), DLF (HR, 1.12; 95% CI, 1.06 to 1.18), MI (HR, 1.07; 95% CI, 1.00 to 1.14), and DLI (HR, 1.12; 95% CI, 1.06 to 1.18). Conclusion Lower FFR values among ACS patients with coronary lesions deferred revascularization based on FFR are associated with a significantly higher rate of adverse cardiac events. This association was not observed in non-ACS patients.

Outcomes of Coronary Stenoses Deferred Revascularization for Borderline Versus Nonborderline Fractional Flow Reserve Values

Current evidence supports deferral of revascularization for lesions with fractional flow reserve (FFR) values >0.80. The natural history after deferral of revascularization of lesions with borderline FFR values is unknown. This study evaluated the outcomes of patients after deferred revascularization of coronary stenoses based on a borderline FFR value. We retrospectively studied 720 patients with 881 intermediate-severity coronary stenoses who underwent FFR assessment from October 2002 to July 2010 and were deferred revascularization. Patients were divided into gray zone (0.75 to 0.80), borderline (0.81 to 0.85), and nonborderline (>0.85) FFR groups. Any subsequent percutaneous coronary intervention or coronary artery bypass grafting of a deferred stenosis during follow-up was classified as a deferred lesion intervention (DLI). Patient and/or lesion characteristics and clinical outcomes were compared between the FFR groups using univariate and propensity score-adjusted inverse probability of weighting Cox proportional hazards analyses. During a mean follow-up of 4.5 ± 2.1 years, 157 deferred lesions (18%) underwent DLI by percutaneous coronary intervention (n = 117) or coronary artery bypass grafting (n = 40). No statistically significant differences were observed in clinical outcomes between the gray zone and borderline FFR groups. Lesions with a borderline FFR were associated with a significantly higher risk of DLI compared with lesions with nonborderline FFR values (hazard ratio 1.63, 95% confidence interval 1.14 to 2.33, p = 0.007). Lesions deferred revascularization because of a borderline FFR (0.81 to 0.85) were associated with a higher risk of DLI compared with lesions with a nonborderline FFR (>0.85). Further study is needed to determine the optimal management of coronary stenoses with a borderline FFR value.

Clinical outcomes associated with INTERMACS-defined right heart failure after left ventricular assist device implantation

Background: Left Ventricular Assist Device (LVAD) pump thrombosis (PT) is a devastating complication of mechanical circulatory support. The diagnosis of LVAD thrombus is difficult in vivo, often only suggested by markers of hemolysis and echocardiographic features, which lack sensitivity. We sought to test a probe with high avidity anti-fibrin 99mTc to localize and quantify thrombus within the high shear environment of titanium axial-flow pumps. Methods: Monomeric bifunctional ligands with a fibrin-specific peptide, a short spacer, and technetium chelating amino acid sequence (F1A) were covalently inter-coupled via a 4-arm-PEG2000 tetramer to form F4A. Each was radiolabeled with 99mTc using the IsoLink procedure. We collected 20 explanted HeartMate II LVADs, of which 9 were explanted for suspected pump thrombosis and 11 were explanted during heart transplant or exchange for other complications. Ex-vivo imaging of explanted pumps was conducted in plasma using a mock circulatory loop running at 9400 RPM for 30 minutes as has previously been described. After imaging the devices were sent to the manufacturer for disassembly and thorough inspection for thrombus. Results: The majority of patients were male (85%) with a mean age of 54.1 6 9.8 and a median INTERMACS profile of 2. The median time of LVAD support prior to explant was 7.6 6 7.2 months. Of the 9 patients exchanged for suspected pump thrombosis all had undetectable haptoglobin levels and mean LDH levels of 3520 6 2596. All 9 had CT scans prior to LVAD exchange without any visualized thrombus or kinking of the inflow or outflow cannulas. Two of the pumps have been disassembled and inspected by the manufacturer. Both pumps were in patients with suspected pump thrombosis and both the pumps had thrombus found on SPECT imaging and on visual inspection (Figure 1A and 1B). Conclusions: A novel, fibrin-specific 99mTc small tetrameric probe offers the potential to detect, localize, and quantify intra-LVAD thrombus noninvasively. Once verified in a large cohort this agent offers the opportunity to diagnose LVAD pump thrombosis at an earlier stage. Definite and early diagnosis may confer therapeutic options to avoid pump failure and/or costly and morbid LVAD exchange.

Video capsule endoscopy in left ventricular assist device recipients with obscure gastrointestinal bleeding.

AIM To assess whether video capsule endoscopy (VCE) affects the outcomes of left ventricular assist devices (LVADs) recipients with gastrointestinal bleeding. METHODS This is a retrospective study of LVAD recipients with obscure gastrointestinal bleeding (OGIB) who underwent VCE at a tertiary medical center between 2005 and 2013. All patients were admitted and monitored with telemetry and all VCE and subsequent endoscopic procedures were performed as inpatients. A VCE study was considered positive only when P2 lesions were found and was regarded as negative if P1 or P0 were identified. All patients were followed until heart transplant, death, or the end of the study. RESULTS Between 2005 and 2013, 30 patients with LVAD underwent VCE. Completion rate of VCE was 93.3% and there was no capsule retention. No interference of VCE recording or the function of LVAD was found. VCE was positive in 40% of patients (n = 12). The most common finding was active small intestinal bleeding (50%) and small intestinal angiodysplasia (33.3%). There was no difference in the rate of recurrent bleeding between patients with positive and negative VCE study (50.0% vs 55.6%, P = 1.00) during an average of 11.6 ± 9.6 mo follow up. Among patients with positive VCE, the recurrent bleeding rate did not differ whether subsequent endoscopy was performed (50% vs 50%, P = 1.00). CONCLUSION VCE can be safely performed in LVAD recipients with a diagnostic yield of 40%. VCE does not affect recurrent bleeding in LVAD patients regardless of findings.

A Case Series of Acute Myocardial Infarction in Left Ventricular Assist Device-Supported Patients.

Acute myocardial infarction (AMI) is an underrecognized phenomenon in patients with continuous-flow left ventricular assist devices (CF-LVAD). Previously, there has been an optimistic expectation of a benign clinical course; however, AMI in LVAD-supported patients can result in profound consequences and management remains controversial. We describe a case series of AMI in four CF-LVAD patients, each with a different presentation, clinical course, treatment, and outcome. The clinical variability and mixed outcomes of these patients highlights the unique challenges in diagnosis and management of AMI in this population, particularly the uncertain role of percutaneous intervention (PCI), and underscores the potentially poor prognosis of this entity. Several key points emerge from this review. First, LVAD-supported patients frequently have underlying abnormalities on the electrocardiogram (ECG) that obscure the diagnosis of AMI. Second, clinicians should have a high degree of suspicion for AMI in the presence of suggestive clinical features, elevated cardiac biomarkers, or new-onset ventricular arrhythmias. Third, the decision to proceed with PCI requires careful evaluation of the risk of hemorrhage, and strong consideration should be given to the use of bleeding avoidance strategies during and after PCI.

Coronary Stenting to Treat Dyspnea in a Patient With Severe Lung Disease: A Teachable Moment

Story From the Front Lines We were recently asked to provide cardiovascular consultation for a 51-year-old man with acute on chronic hypoxic respiratory failure due to severe and progressive pulmonary fibrosis. His pulmonary fibrosis was attributed to toxic effects from 6 cycles of a bleomycincontaining chemotherapeutic regimen and mediastinal radiation therapy for stage IIB Hodgkin lymphoma 3 years earlier that was curative. He was transferred to our institution for consideration of a lung transplant. Four months earlier, during admission at another hospital for worsening dyspnea, a cardiology consultant recommended for the same patient right and left heart catheterizations to evaluate the possibility that coronary artery disease was causing his shortness of breath. Right and left heart pressures were normal. Coronary angiography revealed a 70% stenosis of the distal right coronary artery (Figure 1) that was treated with a drug-eluting stent without any objective evidence of ischemia on prior stress testing. Fractional flow reserve was not assessed prior to stent placement. After evaluation at our institution, the lung transplant team concluded that the patient was at prohibitively high risk of both bleeding, if he were to remain on with aspirin and prasugrel, and cardiovascular complications from stent thrombosis if dual antiplatelet therapy was discontinued. Both conclusions were supported by a consensus statement from the International Society for Heart and Lung Transplantation.1 Aspirin alone was felt to be reasonable after 6 months of dual antiplatelet therapy, but, unfortunately, this required an additional 2 months of delay for the surgery. Thus, the lung transplant was denied and the patient had progressive respiratory failure and died during the hospitalization.

ECHO DERIVED RIGHT VENTRICULAR CONTRACTION PRESSURE INDEX PREDICTS RIGHT VENTRICULAR FAILURE AND MORTALITY IN PATIENTS WITH DURABLE LEFT VENTRICULAR ASSIST DEVICES

Right ventricular (RV) dysfunction is a major determinant of poor outcomes after continuous flow left ventricular assist device (CF-LVAD) implantation but can be difficult to evaluate prior to surgery. The simplified Right Ventricular Contraction Pressure Index (sRVCPI=TAPSE × RV-Right atrial