Association of Angiopoetin-2 and TNF-α With Bleeding During Left Ventricular Assist Device Support: Analysis From the PREVENT Biorepository.

The purpose of this study was to describe the changes in plasma levels of angiogenic and inflammatory biomarkers, specifically Ang-2 and TNF-α, in patients receiving HeartMate II (HMII) left ventricular assist device (LVAD) and correlate them with nonsurgical bleeding. It has been shown that angiopoietin-2 (Ang-2) and tissue necrosis factor-α (TNF-α) may be linked to bleeding in LVAD patients. This study utilized biobanked samples prospectively collected from the PREVENT study, a prospective, multicenter, single-arm, nonrandomized study of patients implanted with HMII. Paired serum samples were obtained in 140 patients before implantation and at 90 days postimplantation. Baseline demographics were as follows: age 57 ± 13 years, 41% had ischemic etiology, 82% male, and 75% destination therapy indication. In the 17 patients with baseline elevation of both TNF-α and Ang-2, 10 (60%) experienced a significant bleeding event within 180 days postimplant compared with 37 of 98 (38%) patients with Ang-2 and TNF-α below the mean ( p = 0.02). The hazard ratio for a bleeding event was 2.3 (95% CI: 1.2-4.6) in patients with elevated levels of both TNF-α and Ang-2. In the PREVENT multicenter study, patients with elevations in serum Angiopoietin-2 and TNF-α at baseline before LVAD implantation demonstrated increased bleeding events after LVAD implantation.

Percutaneous MitraClip Device or Surgical Mitral Valve Repair in Patients With Primary Mitral Regurgitation Who Are Candidates for Surgery: Design and Rationale of the REPAIR MR Trial.

Background The current standard of care for the treatment of patients with primary mitral regurgitation (MR) is surgical mitral valve repair. Transcatheter edge-to-edge repair with the MitraClip device provides a less invasive treatment option for patients with both primary and secondary MR. Worldwide, >150 000 patients have been treated with the MitraClip device. However, in the United States, MitraClip is approved for use only in primary patients with MR who are at high or prohibitive risk for mitral valve surgery. The REPAIR MR (Percutaneous MitraClip Device or Surgical Mitral Valve Repair in Patients With Primary Mitral Regurgitation Who Are Candidates for Surgery) trial is designed to compare early and late outcomes associated with transcatheter edge-to-edge repair with the MitraClip and surgical repair of primary MR in older or moderate surgical risk patients. Methods and Results The REPAIR MR trial is a prospective, randomized, parallel-controlled, open-label multicenter, noninferiority trial for the treatment of severe primary MR (verified by an independent echocardiographic core laboratory). Patients with severe MR and indications for surgery because of symptoms (New York Heart Association class II-IV), or without symptoms with left ventricular ejection fraction ≤60%, pulmonary artery systolic pressure >50 mm Hg, or left ventricular end-systolic diameter ≥40 mm are eligible for the trial provided they meet the moderate surgical risk criteria as follows: (1) ≥75 years of age, or (2) if <75 years of age, then the subject has a Society of Thoracic Surgeons Predicted Risk Of Mortality score of ≥2% for mitral repair (or Society of Thoracic Surgeons replacement score of ≥4%), or the presence of a comorbidity that may introduce a surgery-specific risk. The local surgeon must determine that the mitral valve can be surgically repaired. Additionally, an independent eligibility committee will confirm that the MR can be reduced to mild or less with both the MitraClip and surgical mitral valve repair with a high degree of certainty. A total of 500 eligible subjects will be randomized in a 1:1 ratio to receive the MitraClip device or to undergo surgical mitral valve repair (control group). There are 2 co-primary end points for the trial, both of which will be evaluated at 2 years. Each subject will be followed for 10 years after enrollment. The study has received approval from both the Food and Drug Administration and the Centers for Medicare and Medicaid Services, and enrolled its first subject in July 2020. Conclusions The REPAIR MR trial will determine the safety and effectiveness of transcatheter edge-to-edge repair with the MitraClip in patients with primary MR who are at moderate surgical risk and are candidates for surgical MV repair. The trial will generate contemporary comparative clinical evidence for the MitraClip device and surgical MV repair. Registration https://clinicaltrials.gov/ct2/show/NCT04198870; NCT04198870.

Outcomes in HeartMate II Patients With No Antiplatelet Therapy: 2-Year Results From the European TRACE Study.

BACKGROUND: Current recommendations of antithrombotic therapy for HeartMate II (HMII) patients include the use of both an anticoagulant and an antiplatelet agent. Because bleeding is still the most frequent adverse event, the TRACE (STudy of Reduced Anti-Coagulation/Anti-platelet Therapy in Patients with the HeartMatE II) study was initiated to evaluate the incidence of adverse events in HMII patients on reduced antithrombotic (RT) therapy. METHODS: HMII patients (n = 101) from nine centers were enrolled in the European arm of TRACE and were managed on a single anticoagulant (vitamin K antagonist) with no antiplatelet agents. An analysis of bleeding and thrombotic adverse events from all 101 patients with 2-year follow-up after initiation of RT therapy is reported here. RESULTS: Median age was 56 years (range, 18 to 72 years), 93% were men, 70% had an Interagency Registry for Mechanically Assisted Circulatory Support profile 1 to 3, and 82% received the HMII as a bridge to transplantation. Ninety-two percent were placed on RT therapy as a center standard of care or due to physician preference and 6% as a response to bleeding. Median HMII support duration on RT therapy was 25 months (range, 1 to 93 months). Median international normalized ratio was 2.31 [quartile 1 to quartile 3: 2.07 to 2.60]. At 2 years, freedom from bleeding, ischemic stroke, hemorrhagic stroke, and pump thrombosis after initiation of RT therapy was 81% ± 6%, 96% ± 2%, 94% ± 3%, and 94% ± 3%, respectively. CONCLUSIONS: The 2-year analysis of the observational European TRACE study suggests that managing HMII patients with a vitamin K antagonist with a target international normalized ratio of 2.3 without antiplatelet therapy may help to reduce the incidence of major bleeding without increasing the risk of thromboembolic events, including ischemic stroke and pump thrombosis.

Incidence, risk, and consequences of atrial arrhythmias in patients with continuous-flow left ventricular assist devices.

BACKGROUND: Although atrial arrhythmias (AAs) are common in heart failure, the incidence of AAs subsequent to the placement of left ventricular assist devices (LVADs) has not been elucidated. METHODS: Patients receiving a HeartMate II LVAD in the bridge to transplant (n = 490) and destination therapy (n = 634) trials were included (n = 1125). AAs requiring treatment were recorded, regardless of symptoms. Using Cox models with and without a 60-day blanking period, risk factors for early and late AAs were determined. RESULTS: In total, there were 271 AAs in 231 patients (21%), most of which occurred within the first 60 days. Patients with and without AAs had similar survival (p = 0.16). Serum creatinine (hazard ratio [HR] = 1.49 per unit increase, 1.18 to 1.88; p < 0.001) and ejection fraction (HR = 0.98 per 1% increase, 0.95 to 0.999; p = 0.04) were associated with AAs in a multivariable model. Although quality of life (QoL) and functional status improved in all patients, those with AAs had worse unadjusted QoL (p < 0.001) and a decreased rate of improvement in six-minute walk distance over six to 24 months postimplant (p = 0.016). CONCLUSIONS: Approximately one-fifth of LVAD patients have AAs, most commonly within the first 60 days of support. Preoperative creatinine is a strong risk factor for early and late AAs. Although AAs do not impact survival, they are associated with decreased functional status and QoL improvements during LVAD support.

Fontan hemodynamics from 100 patient-specific cardiac magnetic resonance studies: a computational fluid dynamics analysis.

OBJECTIVES: This study sought to quantify average hemodynamic metrics of the Fontan connection as reference for future investigations, compare connection types (intra-atrial vs extracardiac), and identify functional correlates using computational fluid dynamics in a large patient-specific cohort. Fontan hemodynamics, particularly power losses, are hypothesized to vary considerably among patients with a single ventricle and adversely affect systemic hemodynamics and ventricular function if suboptimal. METHODS: Fontan connection models were created from cardiac magnetic resonance scans for 100 patients. Phase velocity cardiac magnetic resonance in the aorta, vena cavae, and pulmonary arteries was used to prescribe patient-specific time-averaged flow boundary conditions for computational fluid dynamics with a customized, validated solver. Comparison with 4-dimensional cardiac magnetic resonance velocity data from selected patients was used to provide additional verification of simulations. Indexed Fontan power loss, connection resistance, and hepatic flow distribution were quantified and correlated with systemic patient characteristics. RESULTS: Indexed power loss varied by 2 orders of magnitude, whereas, on average, Fontan resistance was 15% to 20% of published values of pulmonary vascular resistance in single ventricles. A significant inverse relationship was observed between indexed power loss and both systemic venous flow and cardiac index. Comparison by connection type showed no differences between intra-atrial and extracardiac connections. Instead, the least efficient connections revealed adverse consequences from localized Fontan pathway stenosis. CONCLUSIONS: Fontan power loss varies from patient to patient, and elevated levels are correlated with lower systemic flow and cardiac index. Fontan connection type does not influence hemodynamic efficiency, but an undersized or stenosed Fontan pathway or pulmonary arteries can be highly dissipative.

Impact of concurrent surgical valve procedures in patients receiving continuous-flow devices.

BACKGROUND: Preexisting valve pathology is common in patients with end-stage heart failure undergoing left ventricular assist device (LVAD) placement. The indications and subsequent benefits of performing valvular procedures in these patients are unclear. The objective of this study was to determine the impact of performing concurrent surgical valve procedures in a large cohort of patients receiving LVADs. METHODS: One thousand one hundred six patients received the HeartMate II (HMII) LVAD in the bridge to transplant (n = 470) and destination therapy (n = 636) clinical trials. Of these, 374 patients (34%) had concurrent cardiac surgery procedures as follows: 242 patients (21%) with 281 concurrent valve procedures (VP) (aortic 80, mitral 45, and tricuspid 156), and 641 patients had only HMII LVAD. The focus of this study was to determine the clinical outcomes of patients undergoing HMII + VP compared with those who received HMII alone. RESULTS: Patients undergoing HMII + VP were significantly older, had higher blood urea nitrogen levels and central venous pressure, and decreased right ventricular stroke work index; intraoperatively, the median cardiopulmonary bypass times were also longer. The unadjusted 30-day mortality was significantly higher in patients undergoing HMII + VP (10.3% vs 4.8% for LVAD alone, P = .005). Subgroup analysis of individual VPs showed that higher mortality occurred in patients with HMII plus 2 or more VPs (13.5%, P = .04) followed by trends for increased mortality with HMII plus mitral alone (11.5%, P = NS), HMII plus aortic alone (10.9%, P = NS), and HMII plus tricuspid (8.9%, P = NS) procedures. Of these various groups, only patients undergoing HMII + isolated aortic VP (P = .001) and HMII + multiple VPs (P = .046) had significantly worse long-term survival compared with patients undergoing HMII alone. Right heart failure and right ventricular assist device use was increased in patients undergoing VPs, but there was no difference in the incidence of bleeding or stroke. CONCLUSIONS: Patients frequently require concurrent VPs at the time of LVAD placement; these patients are sicker and have higher early mortality. Furthermore, right ventricular dysfunction is increased in these patients. Further studies to develop selection criteria for concurrent valve interventions are important to further improve clinical outcomes.

Pre-operative risk factors of bleeding and stroke during left ventricular assist device support: an analysis of more than 900 HeartMate II outpatients.

OBJECTIVES: This study sought to determine the pre-operative risk factors related to late bleeding, stroke, and pump thrombosis in patients with HeartMate II (HMII) left ventricular assist devices (LVADs) (Thoratec Corporation, Pleasanton, California) that might influence tailored improvements in patient management. BACKGROUND: Adverse events in LVAD patients remain high. It is unclear whether pre-operative characteristics influence the likelihood of the development of post-operative hemorrhagic or thrombotic complications. Knowing which patients are at greater risk might assist in tailoring anticoagulation therapy for certain patients. METHODS: Advanced heart failure patients (n = 956) discharged from the hospital after LVAD implantation in the HMII bridge to transplantation (n = 405) and destination therapy (n = 551) clinical trials were retrospectively evaluated. Bleeding requiring surgery or transfusion of >2 U of packed red blood cells, stroke (hemorrhagic and ischemic), and pump thrombosis were tracked from hospital discharge until patient outcome. RESULTS: Adverse event rates for post-discharge bleeding (0.67 events/patient-year) were higher than those for hemorrhagic stroke (0.05), ischemic stroke (0.04), and pump thrombosis (0.03). The main sites of bleeding included gastrointestinal (45% of events), wound (12%), and epistaxis (4%). Older age (>65 years) (hazard ratio [HR]: 1.31), lower pre-operative hematocrit (≤31%) (HR: 1.31), ischemic etiology (HR: 1.35), and female (HR: 1.45) were statistically significant multivariable risk factors for bleeding. Female (HR: 1.92) and 65 years of age and younger (HR: 1.94) were multivariable risk factors for hemorrhagic stroke, whereas female (HR: 1.84) and history of diabetes (HR: 1.99) were risk factors for ischemic stroke. Female (HR: 1.90) and higher body mass index (HR: 1.71/10 kg/m(2) increase) were also multivariable risk factors for pump thrombosis. CONCLUSIONS: The risk of bleeding and thrombotic events during LVAD support differs by patient demographics, including sex, age, body mass index, and etiology of heart failure. Further studies should focus on the potential of tailored anticoagulation strategies in these subgroups.

Pre-operative health status and outcomes after continuous-flow left ventricular assist device implantation.

BACKGROUND: Health status predicts adverse outcomes in heart failure and cardiac surgery patients, but its prognostic value in left ventricular assist device (LVAD) placement is unknown. METHODS: We examined the association of pre-operative health status, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), with survival and hospitalization after LVAD using the KCCQ score as a continuous variable and stratified by KCCQ score quartile plus missing KCCQ in 1,125 clinical trial participants who received the HeartMate II (Thoratec Corp, Pleasanton, CA) as destination therapy (n = 635) or bridge to transplantation (n = 490). RESULTS: The mean pre-operative KCCQ score was 29.4 ± 18.7 among survivors (n = 719), and 27.1 ± 18.3 (n = 406) in those who died. In time-to-event analysis for all available follow-up using health status as a continuous variable, the pre-operative KCCQ score did not correlate with overall mortality after LVAD implantation (p = 0.178). Small absolute differences were seen between the pre-operative KCCQ quartile and 30-day survival (Q4 95% vs. Q1 89% vs. missing 87%; p = 0.0009 for trend), 180-day survival (Q4 83% vs. Q1 76% vs missing 79%; p = 0.060 for trend), and days hospitalized at 180 days (Q4 29.8 ± 25.6 vs. Q1 34.1 ± 27.1 vs. missing 36.5 ± 29.9 days; p = 0.009 for trend). CONCLUSION: Our findings suggest that pre-operative health status has limited association with outcomes after LVAD implantation. Although these data require further study in a diverse population, mechanical circulatory support may represent a relatively unique clinical situation, distinct from heart failure and other cardiac surgeries, in which heart failure-specific health status measures may be largely reversed.

Power loss and right ventricular efficiency in patients after tetralogy of Fallot repair with pulmonary insufficiency: clinical implications.

OBJECTIVES: To quantify right ventricular output power and efficiency and correlate these to ventricular function in patients with repaired tetralogy of Fallot. This might aid in determining the optimal timing for pulmonary valve replacement. METHODS: We reviewed the cardiac catheterization and magnetic resonance imaging data of 13 patients with tetralogy of Fallot (age, 22 ± 17 years). Using pressure and flow measurements in the main pulmonary artery, cardiac output and regurgitation fraction, right ventricular (RV) power output, loss, and efficiency were calculated. The RV function was evaluated using cardiac magnetic resonance imaging. RESULTS: The RV systolic power was 1.08 ± 0.62 W, with 20.3% ± 8.6% power loss owing to 41% ± 14% pulmonary regurgitation (efficiency, 79.7% ± 8.6%; 0.84 ± 0.73 W), resulting in a net cardiac output of 4.24 ± 1.82 L/min. Power loss correlated significantly with the indexed RV end-diastolic and end-systolic volume (R = 0.78, P = .002 and R = 0.69, P = .009, respectively). The normalized RV power output had a significant negative correlation with RV end-diastolic and end-systolic volumes (both R = -0.87, P = .002 and R = -0.68, P = .023, respectively). A rapid decrease occurred in the RV power capacity with an increasing RV volume, with the curve flattening out at an indexed RV end-diastolic and end-systolic volume threshold of 139 mL/m(2) and 75 mL/m(2), respectively. CONCLUSIONS: Significant power loss is present in patients with repaired tetralogy of Fallot and pulmonary regurgitation. A rapid decrease in efficiency occurs with increasing RV volume, suggesting that pulmonary valve replacement should be done before the critical value of 139 mL/m(2) and 75 mL/m(2) for the RV end-diastolic and end-systolic volume, respectively, to preserve RV function.

Visualization of flow structures in Fontan patients using 3-dimensional phase contrast magnetic resonance imaging.

OBJECTIVE: Our objective was to analyze 3-dimensional (3D) blood flow patterns within the total cavopulmonary connection (TCPC) using in vivo phase contrast magnetic resonance imaging (PC MRI). METHODS: Sixteen single-ventricle patients were prospectively recruited at 2 leading pediatric institutions for PC MRI evaluation of their Fontan pathway. Patients were divided into 2 groups. Group 1 comprised 8 patients with an extracardiac (EC) TCPC, and group 2 comprised 8 patients with a lateral tunnel (LT) TCPC. A coronal stack of 5 to 10 contiguous PC MRI slices with 3D velocity encoding (5-9 ms resolution) was acquired and a volumetric flow field was reconstructed. RESULTS: Analysis revealed large vortices in LT TCPCs and helical flow structures in EC TCPCs. On average, there was no difference between LT and EC TCPCs in the proportion of inferior vena cava flow going to the left pulmonary artery (43% ± 7% vs 46% ± 5%; P = .34). However, for EC TCPCs, the presence of a caval offset was a primary determinant of inferior vena caval flow distribution to the pulmonary arteries with a significant bias to the offset side. CONCLUSIONS: 3D flow structures within LT and EC TCPCs were reconstructed and analyzed for the first time using PC MRI. TCPC flow patterns were shown to be different, not only on the basis of LT or EC considerations, but with significant influence from the superior vena cava connection as well. This work adds to the ongoing body of research demonstrating the impact of TCPC geometry on the overall hemodynamic profile.

Individualized computer-based surgical planning to address pulmonary arteriovenous malformations in patients with a single ventricle with an interrupted inferior vena cava and azygous continuation.

OBJECTIVE: Pulmonary arteriovenous malformations caused by abnormal hepatic flow distribution can develop in patients with a single ventricle with an interrupted inferior vena cava. However, preoperatively determining the hepatic baffle design that optimizes hepatic flow distribution is far from trivial. The current study combines virtual surgery and numeric simulations to identify potential surgical strategies for patients with an interrupted inferior vena cava. METHODS: Five patients with an interrupted inferior vena cava and severe pulmonary arteriovenous malformations were enrolled. Their in vivo anatomies were reconstructed from magnetic resonance imaging (n = 4) and computed tomography (n = 1), and alternate virtual surgery options (intracardiac/extracardiac, Y-grafts, hepato-to-azygous shunts, and azygous-to-hepatic shunts) were generated for each. Hepatic flow distribution was assessed for all options using a fully validated computational flow solver. RESULTS: For patients with a single superior vena cava (n = 3), intracardiac/extracardiac connections proved dangerous, because even a small left or right offset led to a highly preferential hepatic flow distribution to the associated lung. The best results were obtained with either a Y-graft spanning the Kawashima to split the flow or hepato-to-azygous shunts to promote mixing. For patients with bilateral superior vena cavae (n = 2), results depended on the balance between the left and right superior inflows. When those were equal, connecting the hepatic baffle between the superior vena cavae performed well, but other options should be pursued otherwise. CONCLUSIONS: This study demonstrates how virtual surgery environments can benefit the clinical community, especially for patients with a single ventricle with an interrupted inferior vena cava. Furthermore, the sensitivity of the optimal baffle design to the superior inflows underscores the need to characterize both preoperative anatomy and flows to identify the best option.

Altered right ventricular papillary muscle position and orientation in patients with a dilated left ventricle.

OBJECTIVE: To investigate the impact of left ventricular dilatation on right ventricular papillary muscle displacement. METHODS: Thirteen patients underwent high-resolution cardiac magnetic resonance imaging at Emory University Hospital: Seven patients with congestive heart failure and a dilated left ventricle composed the dilated left ventricular group, and 6 normal subjects were used as a control. A total of 120 cardiac magnetic resonance imaging slices were acquired in a short-axis view at end diastole for each subject. Cardiac magnetic resonance imaging slices were used to identify the papillary muscle tip position in 3-dimensional coordinates for the septal, posterior, and anterior papillary muscles. The centroid of the papillary muscle coordinates was used as the reference point for comparison between subjects. The relative orientation between the right ventricular papillary muscles was evaluated and compared between the dilated left ventricular group and normal subjects. RESULTS: Dilatation of the left ventricle resulted in a significant (P = .05) displacement of the septal right ventricular papillary muscle toward the centroid: normal group, 0.0285 ± 0.036 mm/mm versus dilated left ventricular group, 0.1437 ± 0.026 mm/mm. More specifically, the septal papillary muscle significantly (P = .03) moved away from the septal wall (normal group: 0.61 ± 0.09 mm/mm, dilated left ventricular group: 0.379 ± 0.037 mm/mm). Specific locations of all 3 right ventricular papillary muscles were reported for normal subjects and patients with a dilated left ventricle. CONCLUSIONS: Patients with a dilated left ventricle have significantly increased displacement of the septal right ventricular papillary muscle away from the septum when compared with normal controls. This demonstrates pathophysiologic contribution of the left ventricle to specific papillary muscle alterations within the right ventricle.

Application of Computer Modeling in Systemic VAD Support of Failing Fontan Physiology.

Although the Fontan procedure has been enormously successful in palliation of single-ventricle patients, many seem to experience progressive failure of the Fontan circulation over time. Ventricular assist devices (VADs) have developed into stable platforms for long-term support of adult patients with heart failure. Given the success of axial flow devices, it was hypothesized that the technology could provide clinical benefit to failing Fontan patients. The aim of this study was to use a computer model to evaluate VAD support in failing Fontan physiology. A computer model of Fontan circulation with heart failure was developed and the HeartMate II (HM II) (Thoratec Corp) axial flow ventricular assist device was connected to this model in a systemic configuration to examine its impact. Cardiac catheterization data from 7 patients (8 catheterization studies) with failing Fontan physiology were applied to this model to evaluate the impact of using the HM II in this manner. When the HM II was used in a systemic configuration at 8000 rpm, there was a 35% decrease in the systemic venous pressure in the Fontan circuit and a 63% decrease in pulmonary capillary wedge pressure with a resultant 41% increase in CI. The model also predicted patient-specific parameters where the VAD may not benefit the patient, such as fixed elevated pulmonary vascular resistance, low systemic ventricular end-diastolic pressure, and high unresponsive systemic vascular resistance. These data suggest a potential benefit from application of axial flow VAD technology in the management of failing Fontan physiology. Clinical correlation will allow for refinement of this model as a predictive tool in discerning which patients may benefit from placement of a VAD and what issues must be addressed prior to implanting the device.

Pulmonary hepatic flow distribution in total cavopulmonary connections: extracardiac versus intracardiac.

OBJECTIVE: Pulmonary arteriovenous malformations can occur after the Fontan procedure and are believed to be associated with disproportionate pulmonary distribution of hepatic venous effluent. We studied the effect of total cavopulmonary connection geometry and the effect of increased cardiac output on distribution of inferior vena caval return to the lungs. METHODS: Ten patients undergoing the Fontan procedure, 5 with extracardiac and 5 with intracardiac configurations of the total cavopulmonary connection, previously analyzed for power loss were processed for calculating the distribution of inferior vena caval return to the lungs (second-order accuracy). One idealized total cavopulmonary connection was similarly analyzed under parametric variation of inferior vena caval offset and cardiac output flow split. RESULTS: Streaming of the inferior vena caval return in the idealized total cavopulmonary connection model was dependent on both inferior vena caval offset magnitude and cardiac output flow-split ratio. For patient-specific total cavopulmonary connections, preferential streaming of the inferior vena caval return was directly proportional to the cardiac output flow-split ratio in the intracardiac total cavopulmonary connections (P < .0001). Preferential streaming in extracardiac total cavopulmonary connections correlated to the inferior vena caval offset (P < .05) and did not correlate to cardiac output flow split. Enhanced mixing in intracardiac total cavopulmonary connections is speculated to explain the contrasting results. Exercising tends to reduce streaming toward the left pulmonary artery in intracardiac total cavopulmonary connections, whereas for extracardiac total cavopulmonary connections, exercising tends to equalize the streaming. CONCLUSIONS: Extracardiac and intracardiac total cavopulmonary connections have inherently different streaming characteristics because of contrasting mixing characteristics caused by their geometric differences. Pulmonary artery diameters and inferior vena caval offsets might together determine hepatic flow streaming.

Post-operative heparin may not be required for transitioning patients with a HeartMate II left ventricular assist system to long-term warfarin therapy.

BACKGROUND: Anti-coagulation with heparin is often used after left ventricular assist device implantation as a transition to long-term warfarin therapy. We retrospectively evaluated the effects of heparin use on thromboembolic and bleeding complications after implantation of the HeartMate II left ventricular assist device (LVAD). METHODS: LVAD patients (n = 418) implanted as a bridge to transplant were divided into three groups: Group A patients (therapeutic, n = 118) received heparin and had a partial thromboplastin time (PTT) of >50 seconds on two or more occasions; Group B patients (sub-therapeutic, n = 178) had at least one PTT value in the range of 40 to 55 seconds; and Group C patients (no heparin, n = 122) had no PTT values >40 seconds. All patients were transitioned to warfarin and aspirin therapy. The following adverse events were evaluated: ischemic stroke; hemorrhagic stroke; pump thrombosis; bleeding requiring surgery; and bleeding requiring > or = 2 units of packed red blood cells in 24 hours. RESULTS: There was no difference in the percentages of patients with ischemic (5%, 4%, 3%) or hemorrhagic (3%, 3%, 5%) strokes or pump thrombosis (3%, 2%, 2%) after post-operative day (POD) 3 among Groups A, B and C, respectively. From PODs 3 to 30, the percentage of patients requiring transfusion for bleeding was significantly lower for Group C (18%) than for Groups A (32%) and B (26%) (p = 0.04); differences after 30 days were not significant. Multivariate analysis revealed that post-operative heparin use, low post-operative platelet count and low baseline hematocrit value were independent risk factors for bleeding events between PODs 3 and 30. CONCLUSIONS: In patients receiving the HeartMate II LVAD who were directly transitioned to warfarin and aspirin therapy without intravenous heparin there was no short-term increase in risk of thrombotic or thromboembolic events, and bleeding requiring transfusion was significantly reduced. Additional long-term follow-up is needed to evaluate possible late effects.

Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: incidence, risk factors, and effect on outcomes.

OBJECTIVE: The aim of this study was to evaluate the incidence, risk factors, and effect on outcomes of right ventricular failure in a large population of patients implanted with continuous-flow left ventricular assist devices. METHODS: Patients (n = 484) enrolled in the HeartMate II left ventricular assist device (Thoratec, Pleasanton, Calif) bridge-to-transplantation clinical trial were examined for the occurrence of right ventricular failure. Right ventricular failure was defined as requiring a right ventricular assist device, 14 or more days of inotropic support after implantation, and/or inotropic support starting more than 14 days after implantation. Demographics, along with clinical, laboratory, and hemodynamic data, were compared between patients with and without right ventricular failure, and risk factors were identified. RESULTS: Overall, 30 (6%) patients receiving left ventricular assist devices required a right ventricular assist device, 35 (7%) required extended inotropes, and 33 (7%) required late inotropes. A significantly greater percentage of patients without right ventricular failure survived to transplantation, recovery, or ongoing device support at 180 days compared with patients with right ventricular failure (89% vs 71%, P < .001). Multivariate analysis revealed that a central venous pressure/pulmonary capillary wedge pressure ratio of greater than 0.63 (odds ratio, 2.3; 95% confidence interval, 1.2-4.3; P = .009), need for preoperative ventilator support (odds ratio, 5.5; 95% confidence interval, 2.3-13.2; P < .001), and blood urea nitrogen level of greater than 39 mg/dL (odds ratio, 2.1; 95% confidence interval, 1.1-4.1; P = .02) were independent predictors of right ventricular failure after left ventricular assist device implantation. CONCLUSIONS: The incidence of right ventricular failure in patients with a HeartMate II ventricular assist device is comparable or less than that of patients with pulsatile-flow devices. Its occurrence is associated with worse outcomes than seen in patients without right ventricular failure. Patients at risk for right ventricular failure might benefit from preoperative optimization of right heart function or planned biventricular support.

Larger aortic reconstruction corresponds to diminished left pulmonary artery size in patients with single-ventricle physiology.

BACKGROUND: Pulmonary artery size is a crucial determinant of hemodynamic energy loss in total cavopulmonary connections. We investigated the effect of aortic arch reconstruction on left pulmonary artery size based on their anatomic proximity. METHODS: Thirty-two patients undergoing the Fontan operation, 16 with hypoplastic left heart syndrome and 16 with non-hypoplastic left heart syndrome, were selected from the multicenter Fontan magnetic resonance imaging database at the Georgia Institute of Technology. The 16 datasets were consecutive with full anatomic reconstructions of the total cavopulmonary connection and aortic arch with no artifacts. The size of the aorta along the transverse arch and left pulmonary artery size in the region below the aortic arch was quantified by using a previously validated skeletonization technique. RESULTS: The transverse aortic and left pulmonary artery measurements (median, maximum, and minimum, respectively) for non-hypoplastic left heart syndrome were 2.2, 3.1, and 1.5 cm/m and 1.2, 1.6, and 0.2 cm/m, respectively, compared with 2.5, 4.1, and 2.0 cm/m and 0.9, 1.5, and 0.4 cm/m for patients with hypoplastic left heart syndrome. Thus the transverse aortic diameter of patients with hypoplastic left heart syndrome was, on average, 24% greater than that for patients with non-hypoplastic left heart syndrome (P < .05), whereas the left pulmonary artery diameter of patients with hypoplastic left heart syndrome was smaller than that of patients with non-hypoplastic left heart syndrome (P < .05). Regression analysis showed a significant negative correlation (P < .05) between aortic and left pulmonary artery diameters in both the hypoplastic left heart syndrome and non-hypoplastic left heart syndrome groups. However, when the study population was regrouped into reconstructed aorta and nonreconstructed aorta groups, the negative correlation was only significant for patients with reconstructed aortas, regardless of ventricular pathology (P < .02). CONCLUSIONS: Stage 1 aortic reconstruction procedures that result in a large aorta limit left pulmonary artery size in patients undergoing the Fontan operation.

Correction of pulmonary arteriovenous malformation using image-based surgical planning.

The objectives of this study were to develop an image-based surgical planning framework that 1) allows for in-depth analysis of pre-operative hemodynamics by the use of cardiac magnetic resonance and 2) enables surgeons to determine the optimum surgical scenarios before the operation. This framework is tailored for applications in which post-operative hemodynamics are important. In particular, it is exemplified here for a Fontan patient with severe left pulmonary arteriovenous malformations due to abnormal hepatic flow distribution to the lungs. Patients first undergo cardiac magnetic resonance for 3-dimensional anatomy and flow reconstruction. After analysis of the pre-operative flow fields, the 3-dimensional anatomy is imported into an interactive surgical planning interface for the surgeon to virtually perform multiple surgical scenarios. Associated hemodynamics are predicted by the use of a fully validated computational fluid dynamic solver. Finally, efficiency metrics (e.g., pressure decrease and hepatic flow distribution) are weighted against surgical feasibility to determine the optimal surgical option.

Blood flow distribution in a large series of patients having the Fontan operation: a cardiac magnetic resonance velocity mapping study.

OBJECTIVES: Our goal was to determine flow distribution in the cavopulmonary connections of patients with and without bilateral superior venae cavae who had the Fontan procedure. No large series exists that establishes the flow distributions in Fontan patients, which would be an important resource for everyday clinical use and may affect future surgical reconstruction. METHODS: We studied 105 Fontan patients (aged 2-24 years) with through-plane phase contrast velocity mapping to determine flow rates in the inferior and superior venae cavae and left and right pulmonary arteries. Superior caval anastomosis type included 40 bidirectional Glenn shunts (of which 15 were bilateral) and 53 hemi-Fontan anastomoses; Fontan type included 69 intra-atrial baffles, 28 extracardiac conduits, and 4 atriopulmonary connections. RESULTS: Total caval flow was 2.9 +/- 1.0 L x min(-1) x m(-2), with an inferior vena cava contribution of 59% +/- 15%. Total pulmonary flow was 2.5 +/- 0.8 L x min(-1) x m(-2), statistically less than caval flow and not explained by fenestration presence. The right pulmonary artery contribution (55% +/- 13%) was statistically greater than the left. In patients with bilateral superior cavae, the right cava accounted for 52% +/- 14% of the flow, with no difference in pulmonary flow splits (50% +/- 16% to the right). Age and body surface area correlated with percent inferior caval contribution (r = 0.60 and 0.74, respectively). Superior vena cava anastomosis and Fontan type did not significantly affect pulmonary flow splits. CONCLUSIONS: Total Fontan cardiac index was 2.9 L x min(-1) x m(-2), with normal pulmonary flow splits (55% to the right lung). Inferior vena caval contribution to total flow increases with body surface area and age, consistent with data from healthy children.

Fontan hemodynamics: importance of pulmonary artery diameter.

OBJECTIVE: We quantify the geometric and hemodynamic characteristics of extracardiac and lateral tunnel Fontan surgical options and correlate certain anatomic characteristics with their hemodynamic efficiency and patient cardiac index. METHODS AND RESULTS: The study was conducted retrospectively on 22 patients undergoing Fontan operations (11 extracardiac and 11 lateral tunnel operations). Total cavopulmonary connection geometric parameters such as vessel areas, curvature, and offsets were quantified using a skeletonization method. Energy loss at the total cavopulmonary connection junction was available from previous in vitro experiments and computational fluid dynamic simulations for 5 and 9 patients, respectively. Cardiac index data were available for all patients. There was no significant difference in the mean and minimum cross-sectional vessel areas of the pulmonary artery between the extracardiac and lateral tunnel groups. The indexed energy dissipation within the total cavopulmonary connection was strongly correlated to minimum cross-sectional area of the pulmonary arteries (R(2) value of 0.90 and P < .0002), whereas all other geometric features, including shape characteristics, had no significant correlation. Finally, cardiac index significantly correlated with the minimum pulmonary artery area (P = .006), suggesting that total cavopulmonary connection energy losses significantly affect resting cardiac output. CONCLUSIONS: The minimum outlet size of the total cavopulmonary connection (ie, minimum cross section of pulmonary artery) governs the energy loss characteristics of the total cavopulmonary connection more strongly than variations in the shapes corresponding to extracardiac and lateral tunnel configurations. Differences in pulmonary artery sizes must be accounted for when comparing energy losses between extracardiac and lateral tunnel geometries.