Comparing Donor Heart Assessment Strategies During Ex Situ Heart Perfusion to Better Estimate Posttransplant Cardiac Function.

BACKGROUND: Ex situ heart perfusion (ESHP) limits ischemic periods and enables continuous monitoring of donated hearts; however, a validated assessment method to predict cardiac performance has yet to be established. We compare biventricular contractile and metabolic parameters measured during ESHP to determine the best evaluation strategy to estimate cardiac function following transplantation. METHODS: Donor pigs were assigned to undergo beating-heart donation (n = 9) or donation after circulatory death (n = 8) induced by hypoxia. Hearts were preserved for 4 hours with ESHP while invasive and noninvasive (NI) biventricular contractile, and metabolic assessments were performed. Following transplantation, hearts were evaluated at 3 hours of reperfusion. Spearman correlation was used to determine the relationship between ESHP parameters and posttransplant function. RESULTS: We performed 17 transplants; 14 successfully weaned from bypass (beating-heart donation versus donation after circulatory death; P = 0.580). Left ventricular invasive preload recruitable stroke work (PRSW) (r = 0.770; P = 0.009), NI PRSW (r = 0.730; P = 0.001), and NI maximum elastance (r = 0.706; P = 0.002) strongly correlated with cardiac index (CI) following transplantation. Right ventricular NI PRSW moderately correlated to CI following transplantation (r = 0.688; P = 0.003). Lactate levels were weakly correlated with CI following transplantation (r = -0.495; P = 0.043). None of the echocardiography measurements correlated with cardiac function following transplantation. CONCLUSIONS: Left ventricular functional parameters, especially ventricular work and reserve, provided the best estimation of myocardial performance following transplantation. Furthermore, simple NI estimates of ventricular function proved useful in this setting. Right ventricular and metabolic measurements were limited in their ability to correlate with myocardial recovery. This emphasizes the need for an ESHP platform capable of assessing myocardial contractility and suggests that metabolic parameters alone do not provide a reliable evaluation.

Ramping Up the Delivery of Cardiac Surgery During the COVID-19 Pandemic: A Guidance Statement From the Canadian Society of Cardiac Surgeons.

The coronavirus disease 2019 (COVID-19) has had a profound global effect. Its rapid transmissibility has forced whole countries to adopt strict measures to contain its spread. As part of necessary pandemic planning, most Canadian cardiac surgical programs have prioritized and delayed elective procedures in an effort to reduce the burden on the health care system and to mobilize resources in the event of a pandemic surge. While the number of COVID-19 cases continue to increase worldwide, new cases have begun to decline in many jurisdictions. This "flattening of the curve" has inevitably prompted discussions around reopening of the economy, relaxing some public health restrictions, and resuming nonurgent health care delivery. This document provides a template for cardiac surgical programs to begin to ramp-up the delivery of cardiac surgery in a deliberate and graded fashion as the COVID-19 pandemic burden begins to ease that is guided by 3 principles. First, all recommendations from public health authorities regarding COVID-19 containment must continue to be followed to minimize disease spread, ensure patient safety, and protect health care personnel. Second, patients awaiting elective cardiac surgery need to be proactively managed, reprioritizing those with high-risk anatomy or whose clinical status is deteriorating. Finally, case volumes should be steadily increased in a mutually agreed upon fashion and must balance the clinical needs of patients awaiting surgery against the overall requirements of the health care system.

Cardiac Surgery in Canada During the COVID-19 Pandemic: A Guidance Statement From the Canadian Society of Cardiac Surgeons.

On March 11, 2020, the World Health Organization declared that COVID-19 was a pandemic.1 At that time, only 118,000 cases had been reported globally, 90% of which had occurred in 4 countries.1 Since then, the world landscape has changed dramatically. As of March 31, 2020, there are now nearly 800,000 cases, with truly global involvement.2 Countries that were previously unaffected are currently experiencing mounting rates of the novel coronavirus infection with associated increases in COVID-19-related deaths. At present, Canada has more than 8000 cases of COVID-19, with considerable variation in rates of infection among provinces and territories.3 Amid concerns over growing resource constraints, cardiac surgeons from across Canada have been forced to make drastic changes to their clinical practices. From prioritizing and delaying elective cases to altering therapeutic strategies in high-risk patients, cardiac surgeons, along with their heart teams, are having to reconsider how best to manage their patients. It is with this in mind that the Canadian Society of Cardiac Surgeons (CSCS) and its Board of Directors have come together to formulate a series of guiding statements. With strong representation from across the country and the support of the Canadian Cardiovascular Society, the authors have attempted to provide guidance to their colleagues on the subjects of leadership roles that cardiac surgeons may assume during this pandemic: patient assessment and triage, risk reduction, and real-time sharing of expertise and experiences.

Utility of the INTERMACS profile at the time of assessment for heart transplant.

The Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS) profiles are associated with mortality in heart failure patients undergoing ventricular assist device (VAD) implantation and heart transplantation (HTx). We assessed the prognostic value of the INTERMACS profile at the time of assessment for HTx or durable VAD implantation as bridge to candidacy (BTC). A total of 503 consecutive patients considered for HTx or VAD between 2006 and 2016 were included. The associations between INTERMACS profile and (a) waitlist mortality or delisting, (b) probability of HTx, and (c) overall mortality or delisting were evaluated using multivariable analysis. Median follow-up time was 2.9 years (IQR: 0.9-5.5) during which 184 received VAD, 347 received HTx, and 73 died (27 waitlist, 46 post-transplant). INTERMACS I-II profile was associated with higher waitlist mortality or delisting (HR: 3.83, 95% CI: 1.22-12.03), and this risk was reversed by VAD implantation (HR: 0.12, 95% CI: 0.03-0.50). INTERMACS III-IV profile was associated with a higher probability of HTx (HR: 1.82, 95% CI: 1.37-2.40). INTERMACS profile was not associated with the composite outcome of overall mortality or delisting. These results emphasize the prognostic utility of INTERMACS at time of decision for advanced therapies and its potential value in selecting patients for different interventions.

Longitudinal assessment of inflammation in recipients of continuous-flow left ventricular assist devices.

BACKGROUND: The long-term effects of continuous-flow left ventricular assist device (CF-LVAD) support on trends of inflammatory markers over time are unknown. We examined the hypothesis that the levels of inflammatory markers in CF-LVAD recipients are higher than in healthy controls and that these levels increase over time with long-term CF-LVAD support. METHODS: We examined the levels of inflammatory markers longitudinally at baseline before CF-LVAD implantation and at 3, 6, and 9 months after implantation. We then compared the levels of inflammatory markers to those in a healthy control group. RESULTS: Compared with baseline values before CF-LVAD implantation, left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) decreased significantly at 3, 6, and 9 months after CF-LVAD implantation. Brain natriuretic peptide (BNP) levels dropped significantly after CF-LVAD implantation but did not normalize. Improvements in ejection fraction at 3, 6, and 9 months after CF-LVAD implantation did not reach significance. Monocyte chemoattractant protein-1, interferon γ-induced protein, and C-reactive protein levels were higher in the CF-LVAD recipients at each of the time points (baseline before CF-LVAD implantation and 3, 6, and 9 months after implantation) compared with levels in healthy controls. In CF-LVAD recipients, serum interleukin-8, tumour necrosis factor-α, and macrophage inflammatory protein-ß increased significantly at 9 months, and macrophage-derived chemokine increased at 6 months after CF-LVAD implantation compared with baseline. CONCLUSIONS: Despite improvements in LV dimensions and BNP levels, markers of inflammation remained higher in CF-LVAD recipients. High levels of inflammation in CF-LVAD recipients may result from heart failure preconditioning or the long-term device support, or both. Because inflammation may be detrimental to CF-LVAD recipients, future studies should determine whether inflammatory pathways are reversible.

The THRIVE score predicts symptomatic intracerebral hemorrhage after intravenous tPA administration in SITS-MOST.

BACKGROUND: The Totaled Health Risks in Vascular Events (THRIVE) score is a clinical prediction score that predicts ischemic stroke outcomes in patients receiving intravenous tissue plasminogen activator, endovascular stroke treatment, or no acute therapy. We have previously found an association between THRIVE and risk of post-tissue plasminogen activator symptomatic intracranial hemorrhage in the National Institute of Neurological Disorders and Stroke (NINDS) tissue plasminogen activator trial and risk of radiographic hemorrhage in Virtual International Stroke Trials Archive. AIMS: The study aims to validate the relationship between THRIVE and symptomatic intracranial hemorrhage among tissue plasminogen activator-treated patients in the large Safe Implementation of Thrombolysis in Stroke - Monitoring Study (SITS-MOST). METHODS: This is a retrospective analysis of the prospective SITS-MOST to examine the relationship between THRIVE and symptomatic intracranial hemorrhage after tissue plasminogen activator treatment. Symptomatic intracranial hemorrhage after tissue plasminogen activator was defined according to each of three standard definitions: the NINDS, European Cooperative Acute Stroke Study (ECASS), and Safe Implementation of Thrombolysis in Stroke (SITS) criteria. Multivariable logistic regression was used to confirm the relationship of THRIVE and individual THRIVE components with the risk of symptomatic intracranial hemorrhage and to examine the relationship of THRIVE, symptomatic intracranial hemorrhage, and functional outcome. RESULTS: The odds ratio for symptomatic intracranial hemorrhage at each increased level of THRIVE score is 1·34 (95% CI 1·27 to 1·41, P < 0·001) for symptomatic intracranial hemorrhage by NINDS criteria, 1·36 (95% CI 1·27 to 1·46, P < 0·001) for symptomatic intracranial hemorrhage by ECASS criteria, and 1·21 (95% CI 1·09 to 1·36, P < 0·001) for symptomatic intracranial hemorrhage by SITS criteria. In receiver-operator characteristics analysis, the C-statistic for THRIVE prediction of symptomatic intracranial hemorrhage was 0·65 (95% CI 0·62 to 0·67) for symptomatic intracranial hemorrhage by NINDS criteria, 0·66 (95% CI 0·63 to 0·69) for symptomatic intracranial hemorrhage by ECASS criteria, and 0·61 (95% CI 0·56 to 0·66) for symptomatic intracranial hemorrhage by SITS criteria. Each component of the THRIVE score predicts the risk of symptomatic intracranial hemorrhage, with independent impact of each component in multivariable analysis. CONCLUSIONS: The THRIVE score predicts the risk of symptomatic intracranial hemorrhage after intravenous tissue plasminogen activator administration. This external validation of the relationship between THRIVE and symptomatic intracranial hemorrhage in a prospective study further strengthens the role of the THRIVE score in the prediction of poststroke outcomes.

The THRIVE score strongly predicts outcomes in patients treated with the Solitaire device in the SWIFT and STAR trials.

BACKGROUND: The Totaled Health Risks in Vascular Events (THRIVE) score strongly predicts clinical outcome, mortality, and risk of thrombolytic haemorrhage in ischemic stroke patients, and performs similarly well in patients receiving intravenous tissue plasminogen activator, endovascular stroke treatment, or no acute treatment. It is not known if the THRIVE score predicts outcomes with the Solitaire endovascular stroke treatment device. AIMS: To validate the relationship between the THRIVE score and outcomes after treatment with the Solitaire endovascular stroke treatment device. METHODS: The study conducted a retrospective analysis of the prospective SWIFT and STAR trials to examine the relationship between THRIVE and outcomes after treatment with the Solitaire device. We examined the relationship between THRIVE and clinical outcomes (good outcome or death at 90 days) among patients in SWIFT and STAR. Receiver-operator characteristics curve analysis was used to compare THRIVE score performance with other stroke prediction scores. Multivariable modeling was used to confirm the independence of the THRIVE score from procedure-specific predictors (successful recanalization or device used) and other predictors of functional outcome. RESULTS: The THRIVE score strongly predicts good outcome and death among patients treated with the Solitaire device in SWIFT and STAR (Mantel-Haenszel chi-square test for trend P < 0·001 for good outcome, P = 0·01 for death). In receiver-operator characteristics (ROC) curve comparisons, totaled health risks in vascular events score is superior to Stroke Prognostication using Age and NIH Stroke Scale score-100 (P < 0·001) and performed similarly to Houston Intra-Arterial Therapy score (HIAT) (P = 0·98) and HIAT-2 (P = 0·54). In multivariable models, THRIVE's prediction of good outcome is not altered after controlling for recanalization or after controlling for device used. The THRIVE score remains a strong independent predictor after controlling for the above predictors together with time to procedure, rate of symptomatic haemorrhage, and use of general anesthesia. Of note, use of general anesthesia was not an independent predictor of outcome in SWIFT + STAR after controlling for totaled health risks in vascular events and other factors. CONCLUSIONS: The THRIVE score strongly predicts clinical outcome and mortality in patients treated with the Solitaire device in the SWIFT and STAR trials. The lack of interaction between THRIVE and procedure-specific elements such as vessel recanalization or device choice makes the THRIVE score a reasonable candidate for use as a patient selection criterion in stroke clinical trials.

Cost-effectiveness of ventricular assist device therapy as a bridge to transplantation compared with nonbridged cardiac recipients.

BACKGROUND: Current available treatment options for advanced heart failure include heart transplantation and ventricular assist device (VAD) therapy. This project aimed to evaluate the cost-effectiveness of a bridge-to-transplantation (BTT)-VAD approach relative to direct heart transplantation in transplant-eligible patients. METHODS AND RESULTS: A Markov model was used to evaluate survival benefits and costs for BTT-VAD versus nonbridged heart transplant recipients. Three different scenarios were considered according to severity of patients' baseline hemodynamic status (high, medium, and low risk). Results are presented in terms of survival, costs, and cost-effectiveness ratio. Sensitivity analyses were used to analyze uncertainty in model estimates. Over a 20-year time horizon, BTT-VAD therapy increased survival at an increased cost relative to nonbridged heart transplant recipients: $100 841more in costs and 1.19 increased life years (LYs) in high-risk patients ($84 964/LY), $112 779 more in costs and 1.14 more LYs ($99 039/LY) in medium-risk patients, and an additional cost of $144 334 and incremental clinical benefit of 1.21 more LYs ($119 574/LY) in low-risk patients. The sensitivity analysis estimated a 59%, 54%, and 43% chance of BTT-VAD therapy being cost-effective for high-, medium-, and low-risk patients at a willingness-to-pay level of $100 000/LY. Subgroup analyses indicated that risk of post-VAD and transplantation complications, waiting time, renal dysfunction, and patient age substantially affected the cost-effectiveness ratio. CONCLUSIONS: BTT-VAD therapy is associated with improved survival and increased costs. On the basis of commonly accepted willingness-to-pay thresholds, BTT-VAD therapy is likely to be cost-effective relative to nonbridged heart transplantation in specific circumstances.

Sex differences in resource use after on-pump and off-pump coronary artery bypass surgery: a propensity score-matched cohort.

BACKGROUND: Previous studies have demonstrated that off-pump coronary artery bypass surgery (OPCAB) is associated with less use of hospital resources compared with on-pump coronary artery bypass surgery (ONCAB). OBJECTIVE: To determine whether there is a sex effect between the two procedures regarding resource utilization. METHODS: Between 1996 and 2004, 13,522 patients (10,637 men and 2885 women) underwent coronary artery bypass grafting surgery at the Toronto General Hospital (Toronto, Ontario). Among the men, 10,121 patients underwent ONCAB and 516 underwent OPCAB. The female population consisted of 2723 ONCAB and 162 OPCAB patients. Both groups were matched to standard preoperative risk factors. A propensity score macro-matched 471 OPCAB men to 471 ONCAB men, and 148 OPCAB women to 148 ONCAB women. RESULTS: The mean (+/- SD) postoperative length of stay (7.5+/-6.5 days versus 6.4+/-5.5 days; P<0.0001) was significantly higher in ONCAB compared with OPCAB in the male population. The mean length of stay in the intensive care unit and the mean ventilation time was similar between the groups. However, in the female population, there were no differences in mean postoperative length of stay (8+/-5.9 days versus 8+/-6 days; P=0.4), mean length of stay in the intensive care unit (43+/-38 h versus 53+/-81 h; P=0.4) or mean ventilation time (9.8+/-9.7 h versus 11+/-13 h; P=0.8). CONCLUSION: These results suggest that the benefits of OPCAB in terms of hospital resource use are influenced by sex. The potential beneficial effects are not demonstrated in the female population.

The dilemma of a left ventricular assist device explantation: a decision analysis.

BACKGROUND: Left ventricular assist devices (LVADs) are an important adjunct to the management of end-stage heart failure patients. Uncertainty remains regarding whether to remove an LVAD in a clinically stable, asymptomatic patient who displays signs of ventricular recovery. OBJECTIVES: To evaluate, from a patient's perspective, the quality-adjusted life expectancy of an LVAD explantation. METHODS: A Markov state transition model was used to assess the benefits of two strategies: remove an LVAD or continue the LVAD support. Effectiveness was measured in quality-adjusted life months. Utility and probability scores were derived from the literature and expert opinion. The base case focused on a 35-year-old man with dilated cardiomyopathy, an implantable LVAD and signs of ventricular recovery, with New York Heart Association class I heart failure symptoms. RESULTS: In the base case, continuing LVAD support was strongly preferred and improved quality-adjusted life expectancy by nine quality-adjusted life months. In sensitivity analyses for the utility post-transplant, removal of the device would have been preferred if the utility was less than 0.7. The model was also sensitive to the probability of late complications post-LVAD implantation. As the probability of complications increased (greater than 28%), the preferred strategy was to remove the LVAD. CONCLUSIONS: Continuing LVAD support in asymptomatic patients with signs of ventricular recovery appears to be the preferred strategy for conveying greater quality-adjusted life months compared with LVAD explantation. As the probability of complications after LVAD implantation increases, the preferred strategy is to remove the LVAD.

Explantation of a mechanical assist device: assessment of myocardial recovery.

Reliable predictors of myocardial recovery post-mechanical assist device implantation are not well defined. We report the case of a 29-year-old woman with refractory congestive heart failure due to acute myocarditis of unknown etiology. The patient was supported with a HeartMate (Thoratec Corp., Woburn, MI) left ventricular assist device for 100 days showing improvement in clinical status. Hemodynamic monitoring, dobutamine stress echocardiography, and cardiopulmonary testing were performed to identify myocardial recovery. Improvements in myocardial reserve, hemodynamic parameters, and myocardial oxygen consumption were identified prior to explantation. The patient was successfully explanted. This case confirms that myocardial recovery is feasible with the use of a mechanical assist device. This article describes our current left ventricular assist device weaning protocol.