Journal of Heart and Lung Transplantation最新文献

Introduction: A common limitation to normothermic ex situ heart perfusion (ESHP) is functional decline. We previously designed a cardioprotective normothermic perfusion protocol, incorporating adenosine-lidocaine cardioplegia, subnormothermic reperfusion, pyruvate and methylprednisolone supplementation, and hemofiltration to prevent myocardial functional decline over 4 hours. In this study, we added continuous catecholamine infusion and protective loading conditions to assess the effectiveness of this enhanced cardioprotective perfusion protocol in preventing functional decline during extended normothermic perfusion in marginal porcine hearts.

Materials & methods: Six slaughterhouse pig hearts underwent 9 hours of normothermic ESHP using the enhanced cardioprotective protocol. Cardiac function was assessed at 90, 120, 240, 360, 480 and 540 minutes of ESHP. Subsequently, a preload-challenge was conducted after 9 hours to assess preload-responsiveness (mimicking the Frank-Starling principle) and suitability for transplantation.

Results: During perfusion, myocardial function remained stable, indicated by consistent mean cardiac index (9.2 L/min/kg at 90; 9.3 L/min/kg at 540 minutes of ESHP), left ventricular stroke work index (6258 mmHg*ml/kg at 90; 6707 mmHg*ml/kg at 540 minutes) and rate of ventricular pressure change over time. In response to a preload-challenge, there was a notable increase of 34% in mean cardiac index and 58% in mean stroke work.

Conclusion: Our study demonstrates that the implementation of a cardioprotective protocol enables (very) marginal porcine slaughterhouse hearts, subjected to both a warm and cold ischemic insult prior to ESHP, to sustain satisfactory cardiac function without notable decline during 9 hours of normothermic ESHP, while also preserving their preload-responsiveness. The latter finding might indicate suitability for transplantation. This study provides a groundwork for further extending normothermic ESHP, unlocking the full potential of this promising technology.

Background: Partial cardiac sympathetic reinnervation after cardiac transplant has been extensively investigated and evidenced. However, there have been no large-scale, long-term studies evaluating the prevalence, time-course, and association with long-term survival of sympathetic reinnervation of the heart.

Methods: Cardiac transplant recipients (n = 232) were recruited from outpatient clinic at a single transplant center in the United Kingdom. Participants were each tested once for the presence of sympathetic reinnervation of the sinus node using the low-frequency component of power spectral analysis of heart rate variability, with a cutoff defined as 2 standard deviations above the mean for denervated participants (those tested <56 days posttransplant). Time course was calculated based on the timing of testing posttransplant. Patients were then followed up over a period of up to 27 years after transplant for survival analysis.

Results: The overall prevalence of cardiac sympathetic reinnervation in the 225 patients tested >56 days posttransplant was 64.9%. Sympathetic reinnervation primarily occurred in the first 18 months after transplant, with a plateau thereafter. The prevalence in participants tested >18 months posttransplant was 69.6%. In Kaplan-Meier survival analysis, sympathetic reinnervation was associated with significantly improved survival (Log-rank p = 0.019), with a median survival time for reinnervated patients of 19.9 years compared with 14.4 years for the denervated group.

Conclusions: Sympathetic reinnervation of the sinus node occurs mostly within 18 months of transplant, is found in 70% of cardiac transplant recipients tested >18 months posttransplant, and is associated with significantly improved long-term survival.

Background: Infections after orthotopic heart transplantation (OHT) cause significant morbidity and mortality. Concurrent with increased pre-OHT temporary mechanical circulatory support (MCS), there have been recent concerns of a perceived increase in infections post-OHT. We examined the association between pre-OHT temporary versus durable MCS and post-OHT infection.

Methods: We performed a single-center retrospective review of patients who received OHT at Tufts Medical Center between January 2014 and April 2022. Our composite outcome was the occurrence of bacteremia, invasive fungal infections, opportunistic infections, or skin/soft tissue infections of device sites within 1-year post-OHT. We used Cox proportional hazards models to assess the relationship between the type of pre-OHT MCS and time to the first infection, treating death from other causes as a competing risk. We addressed confounding with 2 statistical methods: propensity score (PS) with inverse probability weighting (IPW) and an instrumental variable (IV) analysis.

Results: Of the 320 OHT recipients, 268 required MCS before OHT; 192 were managed with durable MCS and 76 with temporary MCS. Patients receiving pre-OHT temporary MCS had no difference in time to first infection (unadjusted hazard ratio [HR] 0.77, 95% CI 0.41-1.44) compared to durable MCS. Results were similar in the model employing PS with IPW (HR 0.61, 95% CI 0.29-1.27) and the IV analysis (HR 0.28, 95% CI 0.26-2.36).

Conclusions: Pre-OHT temporary MCS was not associated with the composite outcome of bacteremia, invasive fungal infections, opportunistic infections, or skin/device site infections post-OHT compared to durable MCS in this single-center cohort.

Right ventricular outflow tract (RVOT) function is not systematically quantified by three-dimensional (3D) echocardiography. We tested the hypothesis that loss of RVOT function in pulmonary hypertension (PH) is related to disease severity independently of other echocardiographic parameters. In this observational study, patients with PH, disease controls, and a matched healthy control group underwent 3D echocardiography and RVOT analysis using ReVISION software. The study included 43 patients (38 with PH, 5 disease controls) and 43 healthy controls. Median 3D RVOT-ejection fraction (EF) was 30.4% in the patients and 44.2% in the healthy controls (p < 0.001). Patients with low 3D RVOT-EF (<30.4%) were more frequently categorized in higher-risk groups and had a higher incidence of clinical worsening than those with high 3D RVOT-EF. Even in patients with RV-EF ≥35%, those with low 3D RVOT-EF had worse outcomes. Segmental RVOT analysis identifies high-risk patients even with normal overall RV function.

Background: Stroke remains a devastating complication of durable left ventricular assist device (LVAD) therapy. This study evaluated the incidence and risk factors for early stroke within 7 days following LVAD implantation investigating both traditional pre-implant and new intraoperative variables collected by The Society of Thoracic Surgeons (STS) Intermacs National Database.

Methods: STS Intermacs was queried for patients undergoing implantation of a fully magnetically levitated centrifugal LVAD between November 25, 2020 and June 30, 2023. STS Intermacs stroke definitions were used to identify patients who suffered a stroke within the first 7 postoperative days (POD). A multivariable logistic regression model was created to generate adjusted odd ratios (OR) for variables associated with early stroke.

Results: Among 6,950 patients in the study cohort, 5.9% (413/6950) developed a stroke after a median follow-up of 11 months, with 50% (205/413) of strokes occurring within 7 days after LVAD implantation. Of the strokes occurring during POD 0-7, 70% (144/205) occurred on POD 0-2. By multivariable analysis, the following factors were associated with early stroke: older age (70 vs 50; OR 1.4, p = 0.0129), white race (OR 1.5, p = 0.0078), pre-implant temporary mechanical circulatory support (MCS) bridge (temporary LVAD only: OR 1.6, extracorporeal membrane oxygenation [ECMO] only: OR 1.7, combination of both devices: OR 3.3; p = 0.0001) and presence of an unremoved left atrial clot (OR 8.0, p < 0.0001).

Conclusions: A significant proportion of strokes occur within the first 7 days following LVAD implantation, particularly within the first 2 days. In addition to pre-implant variables, we identified modifiable intraoperative factors associated with stroke that provide an opportunity for further risk mitigation and improvement in quality of care.