Sensitization in Heart Transplantation: Emerging Knowledge: A Scientific Statement From the American Heart Association.

Sensitization, defined as the presence of circulating antibodies, presents challenges for heart transplant recipients and physicians. When present, sensitization can limit a transplantation candidate's access to organs, prolong wait time, and, in some cases, exclude the candidate from heart transplantation altogether. The management of sensitization is not yet standardized, and current therapies have not yielded consistent results. Although current strategies involve antibody suppression and removal with intravenous immunoglobulin, plasmapheresis, and antibody therapy, newer strategies with more specific targets are being investigated.

Late Surgical Bleeding Following Total Artificial Heart Implantation.

INTRODUCTION: Mechanical circulatory support for heart failure, including the Total Artificial Heart (TAH, Syncardia, Tucson, AZ, USA) has increased in recent years. This report describes bleeding complications associated with the device. METHODS: A single institution prospectively maintained quality improvement database was reviewed encompassing the first year of clinical experience with the TAH. Patients who underwent TAH implantation were identified, and a review of complications and outcomes was undertaken. RESULTS: Ten patients underwent TAH implant. Four patients experienced delayed postoperative bleeding. In three patients the manifestation of bleeding was tamponade and evidenced by TAH decreased cardiac output. In two patients, at postoperative days 31 and 137, there was a partial disruption of the aortic anastomosis along the outer curvature with pseudoaneurysm formation. Both were repaired by primary suture closure, without use of cardiopulmonary bypass. There was no mortality attributable to bleeding. CONCLUSIONS: TAH patients are at risk for delayed postoperative bleeding, often manifest as an acute decrease in cardiac output. Due to pulsatility and high dP/dT, bleeding from the aortic anastomosis should be considered in the differential of a patient with low flow and/or tamponade.

Relationship of TAPSE Normalized by Right Ventricular Area With Pulmonary Compliance, Exercise Capacity, and Clinical Outcomes.

BACKGROUND: While tricuspid annular plane systolic excursion (TAPSE) captures the predominant longitudinal motion of the right ventricle (RV), it does not account for ventricular morphology and radial motion changes in various forms of pulmonary hypertension. This study aims to account for both longitudinal and radial motions by dividing TAPSE by RV area and to assess its clinical significance. METHODS: We performed a retrospective analysis of 71 subjects with New York Heart Association class II to III dyspnea who underwent echocardiogram and invasive cardiopulmonary exercise testing (which defined 4 hemodynamic groups: control, isolated postcapillary pulmonary hypertension, combined postcapillary pulmonary hypertension, and pulmonary arterial hypertension). On the echocardiogram, TAPSE was divided by RV area in diastole (TAPSE/RVA-D) and systole (TAPSE/RVA-S). Analyses included correlations (Pearson and linear regression), receiver operating characteristic, and survival curves. RESULTS: On linear regression analysis, TAPSE/RVA metrics (versus TAPSE) had a stronger correlation with pulmonary artery compliance (r=0.48-0.54 versus 0.38) and peak VO2 percentage predicted (0.23-0.30 versus 0.18). Based on the receiver operating characteristic analysis, pulmonary artery compliance ≥3 mL/mm Hg was identified by TAPSE/RVA-D with an under the curve (AUC) of 0.79 (optimal cutoff ≥1.1) and by TAPSE/RVA-S with an AUC of 0.83 (optimal cutoff ≥1.5), but by TAPSE with only an AUC of 0.67. Similarly, to identify peak VO2 <50% predicted, AUC of 0.66 for TAPSE/RVA-D and AUC of 0.65 for TAPSE/RVA-S. Death or cardiovascular hospitalization at 12 months was associated with TAPSE/RVA-D ≥1.1 (HR, 0.38 [95% CI, 0.11-0.56]) and TAPSE/RVA-S ≥1.5 (HR, 0.44 [95% CI, 0.16-0.78]), while TAPSE was not associated with adverse outcomes (HR, 0.99 [95% CI, 0.53-1.94]). Among 31 subjects with available cardiac magnetic resonance imaging, RV ejection fraction was better correlated with novel metrics (TAPSE/RVA-D r=0.378 and TAPSE/RVA-S r=0.328) than TAPSE (r=0.082). CONCLUSIONS: In a broad cohort with suspected pulmonary hypertension, TAPSE divided by RV area was superior to TAPSE alone in correlations with pulmonary compliance and exercise capacity. As a prognostic marker of right heart function, TAPSE/RVA-D <1.1 and TAPSE/RVA-S <1.5 predicted adverse cardiovascular outcomes.

Increased RV:LV ratio on chest CT-angiogram in COVID-19 is a marker of adverse outcomes.

BACKGROUND: Right ventricular (RV) dilation has been used to predict adverse outcomes in acute pulmonary conditions. It has been used to categorize the severity of novel coronavirus infection (COVID-19) infection. Our study aimed to use chest CT-angiogram (CTA) to assess if increased RV dilation, quantified as an increased RV:LV (left ventricle) ratio, is associated with adverse outcomes in the COVID-19 infection, and if it occurs out of proportion to lung parenchymal disease. RESULTS: We reviewed clinical, laboratory, and chest CTA findings in COVID-19 patients (n = 100), and two control groups: normal subjects (n = 10) and subjects with organizing pneumonia (n = 10). On a chest CTA, we measured basal dimensions of the RV and LV in a focused 4-chamber view, and dimensions of pulmonary artery (PA) and aorta (AO) at the PA bifurcation level. Among the COVID-19 cohort, a higher RV:LV ratio was correlated with adverse outcomes, defined as ICU admission, intubation, or death. In patients with adverse outcomes, the RV:LV ratio was 1.06 ± 0.10, versus 0.95 ± 0.15 in patients without adverse outcomes. Among the adverse outcomes group, compared to the control subjects with organizing pneumonia, the lung parenchymal damage was lower (22.6 ± 9.0 vs. 32.7 ± 6.6), yet the RV:LV ratio was higher (1.06 ± 0.14 vs. 0.89 ± 0.07). In ROC analysis, RV:LV ratio had an AUC = 0.707 with an optimal cutoff of RV:LV ≥ 1.1 as a predictor of adverse outcomes. In a validation cohort (n = 25), an RV:LV ≥ 1.1 as a cutoff predicted adverse outcomes with an odds ratio of 76:1. CONCLUSIONS: In COVID-19 patients, RV:LV ratio ≥ 1.1 on CTA chest is correlated with adverse outcomes. RV dilation in COVID-19 is out of proportion to parenchymal lung damage, pointing toward a vascular and/or thrombotic injury in the lungs.

Left Ventricular Assist Device Inflow Cannula Insertion Depth Influences Thrombosis Risk.

Left ventricular assist device (LVAD) use has continued to grow. Despite recent advances in technology, LVAD patients continue to suffer from devastating complications, including stroke and device thrombosis. Among several variables affecting thrombogenicity, we hypothesize that insertion depth of the inflow cannula into the left ventricle (LV) influences hemodynamics and thrombosis risk. Blood flow patterns were studied in a patient-derived computational model of the LV, mitral valve (MV), and LVAD inflow cannula using unsteady computational fluid dynamics (CFD). Hundreds of thousands of platelets were tracked individually, for two inflow cannula insertion depth configurations (12 mm-reduced and 27 mm-conventional) using platelet-level (Lagrangian) metrics to quantify thrombogenicity. Particularly in patients with small LV dimensions, the deeper inflow cannula insertion resulted in much higher platelet shear stress histories (SH), consistent with markedly abnormal intraventricular hemodynamics. A larger proportion of platelets in this deeper insertion configuration was found to linger in the domain for long residence times (RT) and also accumulated much higher SH. The reduced inflow depth configuration promoted LV washout and reduced platelet SH. The increase of both SH and RT in the LV demonstrates the impact of inflow cannula depth on platelet activation and increased stroke risk in these patients. Inflow cannula depth of insertion should be considered as an opportunity to optimize surgical planning of LVAD therapy.

Impact of the New Pulmonary Hypertension Definition on Heart Transplant Outcomes: Expanding the Hemodynamic Risk Profile.

BACKGROUND: At the recent 6th World Symposium on Pulmonary Hypertension (PH), the definition of PH was redefined to include lower pulmonary artery pressures in the setting of elevated pulmonary vascular resistance (PVR). However, the relevance of this change to subjects with PH due to left-heart disease as well as the preoperative assessment of heart transplant (HT) recipients is unknown. METHODS: The United Network for Organ Sharing database was queried to identify adult recipients who underwent primary HT from 1996 to 2015. Recipients were subdivided into those with mean pulmonary artery pressure (mPAP) < 25 mm Hg and ≥ 25 mm Hg. Exploratory univariable analysis was undertaken to identify candidate risk factors associated with 30-day and 1-year survival (conditional on 30-day survival) in recipients with mPAP < 25 mm Hg, and subsequently, parsimonious multivariable Cox proportional hazards models were constructed to assess the independent association with PVR. RESULTS: Over the study period, 32,465 patients underwent HT, including 12,257 (38%) with mPAP < 25 mm Hg. The median age was 55 years (interquartile range, 47-62) and the median PVR was 1.5 Wood units (WU) (interquartile range, 1-2.2) in recipients with mPAP < 25 mm Hg. After controlling for confounders, PVR was independently associated with increased risk for 30-day mortality (hazard ratio, 1.16; 95% CI, 1.05-1.27; P < .01), but not conditional 1-year mortality (hazard ratio, 1.03; 95% CI, 0.94-1.12; P = .55). PVR ≥ 3 WU was associated with an absolute 1.9% increase in 30-day mortality in those with mPAP < 25 mm Hg, a similar risk to recipients with PVR ≥ 3 WU and mPAP ≥ 25 mm Hg. CONCLUSIONS: Elevated PVR remains associated with a significant increase in the hazard for 30-day mortality after cardiac transplantation, even in the setting of lower pulmonary artery pressures. These data support the validity of the new definition of pulmonary hypertension.

Pulmonary Arterial Compliance Improves Rapidly After Left Ventricular Assist Device Implantation.

Pulmonary artery compliance (PAC) contributes to right ventricular (RV) afterload, is decreased in the setting of increased left ventricular (LV) filling pressures, and may be an important component of World Health Organization (WHO) group II pulmonary hypertension (PH). Left ventricular assist device (LVAD) implantation can rapidly change LV filling, but its relationship with PAC is unknown. Right heart catheterization was performed preoperatively, postoperatively (between 48 and 72 hours), and >30 days post-LVAD implantation in a cohort of 64 patients with end-stage systolic heart failure. Within 72 hours, LVAD implantation was associated with an increase in PAC (2.0-3.7 ml/mm Hg, p < 0.0001), a decrease in pulmonary vascular resistance (3.5-1.7 Wood units, p < 0.0001). Pulmonary arterial compliance did not increase further at the >30 post-LVAD time point (3.7 ± 1.7 to 3.6 ± 0.44 ml/mm Hg, p = 0.44). Pulmonary artery compliance improves rapidly after LVAD implantation. This suggests that more permanent changes in the pulmonary vascular bed may not be responsible for the abnormal PAC observed in WHO group II PH.

Pulmonary function tests do not predict mortality in patients undergoing continuous-flow left ventricular assist device implantation.

OBJECTIVES: To investigate the effect of pulmonary function testing on outcomes after continuous flow left ventricular assist device implantation. METHODS: A total of 263 and 239 patients, respectively, had tests of forced expiratory volume in 1 second and diffusing capacity of the lungs for carbon monoxide preoperatively for left ventricular assist device implantations between July 2005 and September 2015. Kaplan-Meier analysis and multivariable Cox regressions were performed to evaluate mortality. Patients were analyzed in a single cohort and across 5 groups. Postoperative intensive care unit and hospital lengths of stay were evaluated with negative binomial regressions. RESULTS: There is no association of forced expiratory volume in 1 second and diffusing capacity of the lungs for carbon monoxide with survival and no difference in mortality at 1 and 3 years between the groups (log rank P = .841 and .713, respectively). Greater values in either parameter were associated with decreased hospital lengths of stay. Only diffusing capacity of the lungs for carbon monoxide was associated with increased intensive care unit length of stay in the group analysis (P = .001). Ventilator times, postoperative pneumonia, reintubation, and tracheostomy rates were similar across the groups. CONCLUSIONS: Forced expiratory volume in 1 second and diffusing capacity of the lungs for carbon monoxide are not associated with operative or long-term mortality in patients undergoing continuous flow left ventricular assist device implantation. These findings suggest that these abnormal pulmonary function tests alone should not preclude mechanical circulatory support candidacy.

Periportal fibrosis without cirrhosis does not affect outcomes after continuous flow ventricular assist device implantation.

OBJECTIVE: This study investigates the relationship of periportal fibrosis on postoperative outcomes after ventricular assist device (VAD) implantation. METHODS: Between July 2005 and August 2014, a total of 233 patients were implanted with continuous flow VADs. Liver biopsy was performed on 16 patients with concern for liver disease. Survival was evaluated using the Kaplan-Meier method. The effect of fibrosis on length of stay (LOS) in the intensive care unit was modeled using Poisson regression. Adjustments were made for age, profile from the Interagency Registry for Mechanically Assisted Circulatory Support, biopsy, and model for end-stage liver disease score. RESULTS: Fourteen of the 16 patients who underwent biopsy had periportal fibrosis without cirrhosis. One-year survival for the groups with and without biopsy-proven fibrosis was 93% ± 7% and 86% ± 2% (P = .97), respectively. The intensive care unit LOS was not different for those with (median, 7 days; interquartile range: 3-14 days) versus without fibrosis (median, 6 days; interquartile range 4-10 days; P = .65). Fibrosis (P = .42), age (0.95), model for end-stage liver disease excluding internal normalized ratio-XI score (P = .64), performance of a biopsy (P = .28), and Interagency Registry for Mechanically Assisted Circulatory Support class (P = .70) were not associated with intensive care unit LOS. Risk was increased of gastrointestinal bleeding (14% vs 4%; P = .026) in the first year among patients with fibrosis. CONCLUSIONS: The presence of periportal fibrosis did not affect survival or outcomes in patients undergoing VAD implantation. These findings suggest that carefully selected patients with advanced heart failure and hepatic fibrosis without cirrhosis may achieve acceptable outcomes with VAD implantation.

Three-dimensional transesophageal echocardiography of a thrombus entrapped by a patent foramen ovale.

The substrate of paradoxic embolization is a patent foramen ovale allowing right-to-left passage of embolic material. A thrombus in transit entrapped by a patent foramen straddling an atrial septal aneurysm is an exceedingly transient condition rarely documented on imaging studies. We present the case of a 67-year-old man with acute pulmonary embolism and concomitant cerebral infarction found to have a large thrombus traversing a patent foramen ovale. Intraoperative real-time three-dimensional transesophageal echocardiography allowed accurate spatial characterization of the thrombus and correlated closely with surgical findings. It provided more realistic intraoperative guidance compared with conventional two-dimensional transesophageal echocardiography.