Hypothermic oxygenated perfusion (HOPE) safely and effectively extends acceptable donor heart preservation times: Results of the Australian and New Zealand trial.

BACKGROUND: Cold static storage preservation of donor hearts for periods longer than 4 hours increases the risk of primary graft dysfunction (PGD). The aim of the study was to determine if hypothermic oxygenated perfusion (HOPE) could safely prolong the preservation time of donor hearts. METHODS: We conducted a nonrandomized, single arm, multicenter investigation of the effect of HOPE using the XVIVO Heart Preservation System on donor hearts with a projected preservation time of 6 to 8 hours on 30-day recipient survival and allograft function post-transplant. Each center completed 1 or 2 short preservation time followed by long preservation time cases. PGD was classified as occurring in the first 24 hours after transplantation or secondary graft dysfunction (SGD) occurring at any time with a clearly defined cause. Trial survival was compared with a comparator group based on data from the International Society of Heart and Lung Transplantation (ISHLT) Registry. RESULTS: We performed heart transplants using 7 short and 29 long preservation time donor hearts placed on the HOPE system. The mean preservation time for the long preservation time cases was 414 minutes, the longest being 8 hours and 47 minutes. There was 100% survival at 30 days. One long preservation time recipient developed PGD, and 1 developed SGD. One short preservation time patient developed SGD. Thirty day survival was superior to the ISHLT comparator group despite substantially longer preservation times in the trial patients. CONCLUSIONS: HOPE provides effective preservation out to preservation times of nearly 9 hours allowing retrieval from remote geographic locations.

Graft function and incidence of cardiac allograft vasculopathy in donation after circulatory-determined death heart transplant recipients.

Experience in donation after circulatory-determined death (DCD) heart transplantation (HTx) is expanding. There is limited information on the functional outcomes of DCD HTx recipients. We sought to evaluate functional outcomes in our cohort of DCD recipients. We performed a single-center, retrospective, observational cohort study comparing outcomes in consecutive DCD and donation after brain death (DBD) HTx recipients between 2015 and 2019. Primary outcome was allograft function by echocardiography at 12 and 24 months. Secondary outcomes included incidence of cardiac allograft vasculopathy, treated rejection, renal function, and survival. Seventy-seven DCD and 153 DBD recipients were included. There was no difference in left ventricular ejection fraction at 12 months (59% vs 59%, P = .57) and 24 months (58% vs 58%, P = .87). There was no significant difference in right ventricular function at 12 and 24 months. Unadjusted survival between DCD and DBD recipients at 5 years (85.7% DCD and 81% DBD recipients; P = .45) was similar. There were no significant differences in incidence of cardiac allograft vasculopathy (odds ratio 1.59, P = .21, 95% confidence interval 0.77-3.3) or treated rejection (odds ratio 0.60, P = .12, 95% confidence interval 0.32-1.15) between DBD and DCD recipients. Post-transplant renal function was similar at 1 and 2 years. In conclusion, cardiac allografts from DCD donors perform similarly to a contemporary population of DBD allografts in the medium term.

Comparing Cardiac Mechanics and Myocardial Fibrosis in DBD and DCD Heart Transplant Recipients.

BACKGROUND: Heart transplantation (HTx) after donation after circulatory death (DCD) is an expanding practice but is associated with increased warm ischemic time. The impact of DCD HTx on cardiac mechanics and myocardial fibrosis has not been reported. We aimed to compare cardiac mechanics and myocardial fibrosis using cardiovascular magnetic resonance (CMR) imaging in donation after brain death (DBD) and DCD HTx recipients and healthy controls. METHODS AND RESULTS: Consecutive HTx recipients between March 2015 and March 2021 who underwent routine surveillance CMR imaging were included. Cardiac mechanics were assessed using CMR feature tracking to compute global longitudinal strain, global circumferential strain, and right ventricular free-wall longitudinal myocardial strain. Fibrosis was assessed using late gadolinium enhancement imaging and estimation of extracellular volume. There were 82 (DBD n = 42, DCD n = 40) HTx recipients (aged 53 years, interquartile range 41-59 years, 24% female) who underwent CMR imaging at median of 9 months (interquartile range 6-14 months) after transplantation. HTx recipients had increased extracellular volume (29.7 ± 3.6%) compared with normal ranges (25.9%, interquartile range 25.4-26.5). Myocardial strain was impaired after transplantation compared with controls (global longitudinal strain -12.6 ± 3.1% vs -17.2 ± 1.8%, P < .0001; global circumferential strain -16.9 ± 3.1% vs -19.2 ± 2.0%, P = .002; right ventricular free-wall longitudinal strain -15.7 ± 4.5% vs -21.6 ± 4.7%, P < .0001). There were no differences in fibrosis burden (extracellular volume 30.6 ± 4.4% vs 29.2 ± 3.2%; P = .39) or cardiac mechanics (global longitudinal strain -13.1 ± 3.0% vs -12.1 ± 3.1%, P = .14; global circumferential strain -17.3 ± 2.9% vs -16.6 ± 3.1%, P = .27; right ventricular free-wall longitudinal strain -15.9 ± 4.9% vs -15.5 ± 4.1%, P = .71) between DCD and DBD HTx. CONCLUSIONS: HTx recipients have impaired cardiac mechanics compared with controls, with increased myocardial fibrosis. There were no differences in early CMR imaging characteristics between DBD and DCD heart transplants, providing further evidence that DCD and DBD HTx outcomes are comparable.

Spontaneous Coronary Artery Dissection in an Orthotopic Heart Transplant Recipient.

We present the case of acute myocardial infarction secondary to spontaneous coronary artery dissection in a patient 2 weeks post orthotopic heart transplantation. (Level of Difficulty: Advanced.).

Validation of predicted heart mass equations by measurement of donor heart mass at time of heart transplantation.

Predicted heart mass (PHM) equations may be used in donor-recipient size matching in heart transplantation. We compared PHM and actual heart mass in 25 consecutive DBD heart transplants. There was a moderate positive correlation between actual heart mass and PHM. There was a similar moderate correlation between actual heart mass and donor weight or donor body surface area but not donor height. PHM was lower than actual heart mass for all donor hearts. Bland-Altman analysis showed a systematic bias between PHM and actual heart mass, with a mean difference of 190.9 ± 66.4 g. The utility of PHM equations is likely to be part of a multi-parametric assessment of the relative differences between donor and recipient, so the absolute difference is likely to be unimportant.

Size matching in heart transplantation: Is predicted heart mass the optimal method in a United Kingdom cohort?

Predicted heart mass (PHM) equations have been proposed as an alternative method for size matching in heart transplantation. We assessed association between donor-recipient size mismatch, defined using PHM equations, and survival post-heart transplant in the United Kingdom. Data from all adult patients who received a heart transplant between 1995 and 2017 were obtained from the United Kingdom Transplant Registry. PHM was calculated using published equations. Primary outcome was 1-year survival post-heart transplantation. Recipients of undersized organs had reduced 1-year survival (HR 1.31, 95% CI 1.03-1.67, p = .03). Oversizing had no impact on survival (HR 0.99, 95% CI 0.78-1.26, p = .96). Gender mismatching had no impact on survival in the cohort matched by PHM (HR 1.12, 95% CI 0.86-1.47, p = .4). In recipients without pulmonary hypertension, undersizing by PHM had no impact on 1-year survival (HR 0.95, 95% CI 0.61-1.49, p = .83). In recipients with pulmonary hypertension, oversizing donor RV by using PHM RV equation (PHMRV ) results in improved survival at 1 year (HR 0.65, 95% CI 0.5-0.83, p = .001). In conclusion, receiving an organ undersized by PHM was associated with decreased 1-year survival. Subgroup analyses demonstrated that undersizing only impacted survival in recipients with pulmonary hypertension and that these recipients had improved outcomes if they received an organ with an RV oversized by >10% by PHMRV .

A 5-year single-center early experience of heart transplantation from donation after circulatory-determined death donors.

BACKGROUND: In an effort to address the increasing demand for heart transplantation within the United Kingdom (UK), we established a clinical program of heart transplantation from donation after circulatory-determined death (DCD) donors in 2015. After 5 years, we report the clinical early outcomes and impact of the program. METHODS: This is a single-center, retrospective, matched, observational cohort study comparing outcomes of hearts transplanted from DCD donors from March 1, 2015 to February 29, 2020 with those from matched donation after brain death (DBD) donors at Royal Papworth Hospital (RPH) (Cambridge, UK). DCD hearts were either retrieved using thoracoabdominal normothermic regional perfusion or the direct procurement and perfusion technique. All DBD hearts were procured using standard cold static storage. The primary outcomes were recipient 30-day and 1-year survival. RESULTS: During the 5-year study, DCD heart donation increased overall heart transplant activity by 48% (79 for DCD and 164 for DBD). There was no difference in survival at 30 days (97% for DCD vs 99% for DBD, p = 1.00) or 1 year (91% for DCD vs 89% for DBD, p = 0.72). There was no difference in the length of stay in the intensive care unit (7 for DCD vs 6 for DBD days, p = 0.24) or in the hospital (24 for DCD vs 25 for DBD days, p = 0.84). CONCLUSIONS: DCD heart donation increased overall heart transplant activity at RPH by 48%, with no difference in 30-day or 1-year survival in comparison with conventional DBD heart transplantations. DCD heart donation is set to make a dramatic difference in the number of patients who can benefit from heart transplantation.

Combined heart-lung transplantation from a donation after circulatory death donor.

Combined heart-lung transplantation is the optimal treatment option for many patients with end-stage heart failure and fixed severe pulmonary hypertension. It offers the only possibility of long-term survival and a return to a normal quality of life. Unfortunately, it is rarely performed because of donor organ allocation policies. We present the case of a critically ill 24-year-old man, who after waiting for >100 days in-hospital on the urgent transplant list, deteriorated further and underwent the first successful heart-lung transplant with organs from a donation after circulatory death.

A review of the management of patients with advanced heart failure in the intensive care unit.

Despite progress in the medical and device therapy for heart failure (HF), the prognosis for those with advanced HF remains poor. Acute heart failure (AcHF) is the rapid development of, or worsening of symptoms and signs of HF typically leading to hospitalization. Whilst many HF decompensations are managed at a ward-based level, a proportion of patients require higher acuity care in the intensive care unit (ICU). Admission to ICU is associated with a higher risk of in-hospital mortality, and in those who fail to respond to standard supportive and medical therapy, a proportion maybe suitable for mechanical circulatory support (MCS). The optimal pre-operative management of advanced HF patients awaiting durable MCS or cardiac transplantation (CTx) is vital in improving both short and longer-term outcomes. This review will summarize the clinical assessment, hemodynamic profiling and management of the patient with AcHF in the ICU. The general principles of pre-surgical optimization encompassing individual systems (the kidneys, the liver, blood and glycemic control) will be discussed. Other factors impacting upon post-operative outcomes including nutrition and sarcopenia and pre-surgical skin decolonization have been included. Issues specific to durable MCS including the assessment of the right ventricle and strategies for optimization will also be discussed.

Validation of Cardiovascular Magnetic Resonance-Derived Equation for Predicted Left Ventricular Mass Using the UK Biobank Imaging Cohort: Tool for Donor-Recipient Size Matching.

BACKGROUND: Current guidance from International Society for Heart and Lung Transplantation recommends using body weight for donor-recipient size matching for heart transplantation. However, recent studies have shown that predicted heart mass, using body weight, height, age, and sex, may represent a better method of size matching. We aim to validate a cardiovascular magnetic resonance (CMR)-derived equation for predicted left ventricular mass (LVM) in a cohort of normal individuals in the United Kingdom. METHODS: This observational study was conducted in 5065 middle-aged (44-77 years old) UK Biobank participants who underwent CMR imaging in 2014 to 2015. Individuals with cancer diagnosis in the previous 12 months or history of cardiovascular disease were excluded. Predicted LVM was calculated based on participants' sex, height, and weight recorded at the time of imaging. Correlation analyses were performed between the predicted LVM and the LVM obtained from manual contouring of CMR cine images. The analysis included 3398 participants (age 61.5±7.5 years, 47.8% males). RESULTS: Predicted LVM was considerably higher than CMR-derived LVM (mean±SD of 138.8±28.9 g versus 86.3±20.9 g). However, there was a strong correlation between the 2 measurements (Spearman correlation coefficient 0.802, P<0.0001). CONCLUSIONS: Predicted LVM calculated using a CMR-derived equation that incorporates height, weight, and sex has a strong correlation with CMR LVM in large cohort of normal individuals in the United Kingdom. Our findings suggest that predicted heart mass equations may be a valid tool for donor-recipient size matching for heart transplantation in the United Kingdom.

Computed Tomographic Coronary Angiography-Derived Plaque Characteristics Predict Major Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis.

BACKGROUND: Computed tomographic coronary angiography is a noninvasive imaging modality that permits identification and characterization of coronary plaques. Despite consensus statements supporting routine reporting of computed tomographic coronary angiography plaque characteristics, there remains uncertainty whether these data convey prognostic information. We performed a systematic review and meta-analysis assessing the strength of association between computed tomographic coronary angiography-derived plaque characterization and major adverse cardiovascular events (MACE). METHODS AND RESULTS: Electronic databases were searched for studies reporting computed tomographic coronary angiography plaque characterization and MACE. Data were gathered on plaque morphology (noncalcified, partially calcified, and calcified) and high-risk plaque (HRP) features, including low-attenuation plaque, napkin-ring sign, spotty calcification, and positive remodeling. Of 5496 citations, 13 studies met inclusion criteria. Five hundred fifty-two (3.9%) MACE occurred in 13 977 patients with mean follow-up ranging between 1.3 and 8.2 years. In terms of plaque morphology, the strongest association was observed for noncalcified plaque (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.24-1.70; P<0.001), with weaker associations found for partially calcified (HR, 1.37; 95% CI, 1.18-1.60; P<0.001) and calcified plaques (HR, 1.23; 95% CI, 1.16-1.30; P<0.001). All HRP features were strongly associated with MACE, including napkin-ring sign (HR, 5.06; 95% CI, 3.23-7.94; P<0.001), low-attenuation plaque (HR, 2.95; 95% CI, 2.03-4.29; P<0.001), positive remodeling (HR, 2.58; 95% CI, 1.84-3.61; P<0.001), and spotty calcification (HR, 2.25; 95% CI, 1.26-4.04; P=0.006). The presence of ≥2 HRP features had highest risk of MACE (HR, 9.17; 95% CI, 4.10-20.50; P<0.001). CONCLUSIONS: These data demonstrate that HRP is most likely an independent predictor of MACE, which supports the inclusion of HRP reporting in clinical practice. However, at this point, it remains unclear whether HRP reporting has clinical implications.

Extracardiac Conduit Fontan - Outcome Data in Early Adulthood.

BACKGROUND: To describe the survival and health outcome status of young adults with an extracardiac Fontan procedure performed either as a primary or conversion (secondary) Fontan surgery. METHODS: The database of the Adult Congenital Heart disease service at the Royal Melbourne Hospital was interrogated to identify all adults who had undergone a primary extracardiac conduit Fontan (n=29) or a Fontan conversion with this procedure (n=8). We then determined vital status, age, original anatomy and functional status in early adulthood in both groups. RESULTS: Adults with an ECC Fontan procedure report reasonable NYHA functional class (84% NYHA I or II) though, objectively, exercise testing demonstrates a reduced exercise capacity, and desaturation on exertion is frequent. The majority (86%) have completed secondary education. Most (78%) are managed on warfarin and there is a preponderance of ACE inhibition use (62%). Atrial arrhythmias have been documented in 5 of the 29 primary ECC groups (17%); in 3 patients this preceded primary ECC and 2 patients developed post primary ECC (between 6 and 14 years postoperatively). At a lesser time of follow-up [median 4.5 years (IQR 3.3-6)], conversion to an ECC as a secondary Fontan procedure has successfully treated atrial arrhythmias in the 7 (of 8) patients where this was the surgical indication for conversion. CONCLUSIONS: Though long-term data will require decades to establish, in young adulthood the functional outcomes of a primary ECC Fontan operation are encouraging. Secondary ECC conversion successfully mitigates atrial arrhythmias in the short to medium term.

Intravascular ultrasound guidance improves clinical outcomes during implantation of both first- and second-generation drug-eluting stents: a meta-analysis.

AIMS: Our aim was to assess whether intravascular ultrasound (IVUS) improves clinical outcomes during implantation of first- and second-generation drug-eluting stents (DES). IVUS guidance is associated with improved clinical outcomes during DES implantation, but it is unknown whether this benefit is limited to either first- or second-generation devices. METHODS AND RESULTS: MEDLINE, EMBASE and PubMed were searched for studies comparing outcomes between IVUS- and angiography-guided PCI. Among 909 potentially relevant studies, 15 trials met the inclusion criteria. The primary endpoint was MACE, defined as death, myocardial infarction, target vessel/lesion revascularisation (TVR/TLR) or stent thrombosis (ST). Summary estimates were obtained using Peto modelling. In total, 9,313 patients from six randomised trials and nine observational studies were included. First-generation DES were implanted in 6,156 patients (3,064 IVUS-guided and 3,092 angiography-guided) and second-generation in 3,157 patients (1,528 IVUS-guided and 1,629 angiography-guided). IVUS guidance was associated with a significant reduction in MACE (odds ratio [OR] 0.73, 95% CI: 0.64-0.85, p<0.001), across both first- (OR 0.79, 95% CI: 0.67-0.92, p=0.01) and second-generation DES (0.57, 95% CI: 0.43-0.77, p<0.001). For second-generation DES, IVUS guidance was associated with significantly lower rates of cardiac death (OR 0.33, 95% CI: 0.14-0.78, p=0.02), TVR (OR 0.47, 95% CI: 0.28-0.79, p=0.006), TLR (OR 0.61, 95% CI: 0.42-0.90, p=0.01) and ST (OR 0.31, 95% CI: 0.12-0.78, p=0.02). Cumulative meta-analysis highlighted progressive temporal benefit towards IVUS-guided PCI to reduce MACE (OR 0.60, 95% CI: 0.48-0.75, p<0.001). CONCLUSIONS: IVUS guidance is associated with a significant reduction in MACE during implantation of both first- and second-generation DES platforms. These data support the use of IVUS guidance in contemporary revascularisation procedures using second-generation DES.