Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation.

BACKGROUND: Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. METHODS: CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR- and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR- or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. RESULTS: Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P=0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P=0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P=0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. CONCLUSIONS: A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. REGISTRATION: HREC/13/SVH/66 and HREC/17/SVH/80. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12618000672257.

Vasoplegia in patients following ventricular assist device explant and heart transplantation.

BACKGROUND: Vasoplegia has been shown to be associated with increased morbidity and mortality in patients undergoing cardiac surgery. It has been previously stated that low pulsatile states as seen with current left ventricular assist devices (LVADs) may contribute to vasoplegia post LVAD-explant and heart transplant. We sought to examine the literature regarding vasoplegia in the post-operative setting for patients undergoing LVAD explant and heart transplant. METHOD: A literature review was conducted to firstly define vasoplegia in the setting of LVAD patients, and secondly to better understand the relationship between vasoplegia and LVAD explantation in the postoperative heart transplant patient cohort. A keyword search of 'vasoplegia' OR 'vasoplegic' AND 'transplant' was used. Search engines used were PubMed, Cochrane Library, ClinicalTrials.gov, Ovid, Scopus and grey literature. RESULTS: 17 studies met the selection criteria for review. Three key themes emerged from the literature. Firstly, there is limited consensus regarding the definition of vasoplegia. Secondly, patients with LVADs experienced higher rates of vasoplegia following heart transplant than their counterparts and thirdly, increased cardiopulmonary bypass time was associated with a higher rate of vasoplegia. CONCLUSION: Vasoplegia is not clearly defined in the literature as it pertains to the LVAD patient cohort. Patients bridged with LVADs appear to have higher rates of vasoplegia, however the aetiology of this is unclear and may be associated with continuous flow physiology or prolonged cardiopulmonary bypass time. A universal definition will aid in risk stratification, early recognition and management.

Prevention and Reversal of Frailty in Heart Failure　- A Systematic Review.

BACKGROUND: Frailty is prevalent in patients with heart failure (HF) and associated with increased morbidity and mortality. Hence, there has been increased interest in the reversibility of frailty following treatment with medication or surgery. This systematic review aimed to assess the reversibility of frailty in patients with HF before and after surgical interventions aimed at treating the underlying cause of HF. It also aimed to assess the efficacy of cardiac rehabilitation and prehabilitation in reversing or preventing frailty in patients with HF.Methods and Results:Searches of PubMed, MEDLINE and Academic Search Ultimate identified studies with HF patients undergoing interventions to reverse frailty. Titles, abstracts and full texts were screened for eligibility based on the PRISMA guidelines and using predefined inclusion/exclusion criteria in relation to participants, intervention, control, outcome and study design. In total, 14 studies were included: 3 assessed the effect of surgery, 7 assessed the effect of rehabilitation programs, 2 assessed the effect of a prehabilitation program and 2 assessed the effect of program interruptions on HF patients. CONCLUSIONS: Overall, it was found that frailty is at least partially reversible and potentially preventable in patients with HF. Interruption of rehabilitation programs resulted in deterioration of the frailty status. Future research should focus on the role of prehabilitation in mitigating frailty prior to surgical intervention.

Incidence of early diaphragmatic dysfunction after lung transplantation: results of a prospective observational study.

BACKGROUND: Diaphragmatic dysfunction is common after cardiothoracic surgery, but few studies report its incidence and consequences after lung transplantation. We aimed to estimate the incidence of diaphragmatic dysfunction using ultrasound in lung transplant patients up to 3 months postoperatively and evaluated the impact on clinical outcomes. METHODS: This was a single-center prospective observational cohort study of 27 lung transplant recipients using diaphragmatic ultrasound preoperatively, at 1 day, 1 week, 1 month, and 3 months postoperatively. Diaphragmatic dysfunction was defined as excursion < 10 mm in men and < 9 mm in women during quiet breathing. Clinical outcomes measured included duration of mechanical ventilation, length of stay (LOS) in Intensive Care (ICU), and hospital LOS. RESULTS: Sixty-two percentage of recipients experienced new, postoperative diaphragmatic dysfunction, but the prevalence fell to 22% at 3 months. No differences in clinical outcomes were found between those with diaphragmatic dysfunction compared to those without. Patients who experienced diaphragmatic dysfunction at 1 day postoperatively were younger and had a lower BMI than those who did not. CONCLUSIONS: Diaphragmatic dysfunction is common after lung transplant, improves significantly within 3 months, and did not impact negatively on duration of mechanical ventilation, LOS in ICU or hospital, or discharge destination.

Improved right ventricular function following transapical transcatheter mitral valve implantation for severe mitral regurgitation.

BACKGROUND: Transapical transcatheter mitral valve implantation (TMVI) may be a therapeutic option for patients with severe mitral regurgitation (MR) excluded from cardiac surgery due to excessive risk. Exclusion criteria frequently include pulmonary hypertension and right ventricular (RV) dysfunction. The effect of TMVI on RV function has not previously been well-characterized. The aim of this study was to examine the procedural and 3-month impact of TMVI on RV hemodynamics and function. METHODS: This was a multi-center, retrospective, observational cohort study of patients with >3+MR undergoing TMVI. Pre- and post-TMVI hemodynamics were assessed with right heart catheterization. RV function was assessed at baseline, pre-discharge and at 3-months by echocardiography. RESULTS: Forty-six patients (age 72±9 years; 34 men) with ≥3+MR underwent TMVI over a 5-year period. Successful device implantation was achieved in all patients with abolition of MR (p < 0.001) and reduction in left-ventricular end-diastolic volume (p = 0.001). RV stroke work index (RVSWI) increased intra-operatively (7 ± 4 g/m/beat/m2 vs 11 ± 5 g/m/beat/m2; p < 0.001). At 3-months there were reductions in severity of tricuspid regurgitation (TR) (p < 0.001) and pulmonary artery systolic pressure (PASP) (49 ± 16 mmHg vs 36 ± 12 mmHg; p < 0.001), and improvements in RV fractional area change (28 ± 7% vs 34 ± 9%, p<0.001), tricuspid annular plane systolic excursion (TAPSE) (1.0 ± 0.3 vs 1.5 ± 0.5cm, p = 0.03), and RV free wall longitudinal strain (-14.2±5.0 vs -17.6±7.3, p = 0.05). CONCLUSIONS: Transapical TMVI results in significant improvement of RV function that is sustained to 3-months as evidenced by improvements in RVSWI and RV fractional area change, as well as reductions in PASP and TR severity.

Reviewing the clinical utility of ventricular assist device log files.

BACKGROUND: Ventricular assist devices (VADs) have provided a temporising solution to many individuals with refractory heart failure (HF) while awaiting a suitable donor for heart transplantation which remains the gold standard in treatment. Many of the discussions around VADs involve ongoing morbidity; however, one aspect of VADs that is often overlooked is the utility of their log files. We decided to review the literature for mentions of the clinical utility of VAD log files. METHODS: A keyword search was utilised on PUBMED using the terms 'Ventricular Assist Device' and 'Log files'. Perhaps unsurprisingly, this search only yielded 4 results with further articles being discovered through the bibliography of these publications. RESULTS: The 4 identified articles provided basic information on log files, particularly with reference to the HVAD. Logs can be categorised into three types-data (pump parameters), events (changes in parameters) and alarms (abnormal function). Using a combination of these logs, we can readily identify abnormal pump operation such as the development and progression of pump thrombosis, suction events and gastrointestinal bleeding. However, the research potential of log files was not discussed in these publications, particularly as it pertains to areas such as studying speed modulation and pulsatility in VADs. CONCLUSIONS: VADs are an important staple in the treatment of patients with refractory HF. Log files provide a treasure-trove of information and knowledge that can be utilised for clinical benefit. Furthermore, log files provide an excellent tool for conducting research into device functionality. Current literature on the clinical utility of log files is sparse with much untapped potential.

Macrophage inhibitory cytokine-1/growth differentiation factor-15 in premalignant and neoplastic tumours in a high-risk pancreatic cancer cohort.

BACKGROUND: Pancreatic cancer (PC) is a leading cause of cancer related mortality worldwide, with poor survival due to late diagnosis. Currently, biomarkers have limited use in early diagnosis of PC. Macrophage inhibitory cytokine-1 or growth differentiation factor-15 (MIC-1/GDF15) has been implicated as a potential serum biomarker in PC and other malignancies. AIM: To determine the role of MIC-1/GDF15 in detecting pre-malignant pancreatic lesions and neoplastic tumours in an asymptomatic high-risk cohort part of Australian Pancreatic Cancer Screening Program. METHODS: A feasibility prospective single centre cohort study was performed. Participants recruited for yearly surveillance with endoscopic ultrasound (EUS) had serial fasting blood samples collected before EUS for MIC-1/GDF15, C-reactive protein and carbohydrate antigen 19-9. Patients were stratified into five groups based on EUS findings: Normal; pancreatic cysts, branch-duct intraductal papillary mucinous neoplasm; diffuse non-specific abnormalities; and neoplastic tumours. MIC-1/GDF15 serum levels were quantified using ELISA. Participants in whom EUS demonstrated abnormalities but not malignancy were closely followed up with magnetic resonance imaging (MRI) or computed tomography. RESULTS: One hundred twenty participants were prospectively recruited from 2011-2018. Forty-seven participants (39.2%) had an abnormal EUS and five participants (4.2%) were diagnosed with neoplastic tumours, three by EUS (two pancreatic and one liver) and two by MRI/computed tomography (breast cancer, bladder cancer), which were performed for follow up of abnormal EUS. Baseline serum MIC-1/GDF15 was a significant predictor of neoplastic tumours on receiver operator characteristic curve analysis [area under curve (AUC) = 0.814, P = 0.023]. Baseline serum MIC-1/GDF15 had moderate predictive capacity for branch-duct intraductal papillary mucinous neoplasm (AUC = 0.644) and neoplastic tumours noted on EUS (AUC = 0.793), however this was not significant (P = 0.188 and 0.081 respectively). Serial serum MIC-1/GDF15 did not demonstrate a significant percentage change between a normal and abnormal EUS (P = 0.213). Median baseline MIC-1/GDF15 was greater in those with neoplastic tumours (Median = 1039.6, interquartile range = 727.0-1977.7) compared to those diagnosed with a benign lesion (Median = 570.1, interquartile range = 460.7-865.2) on EUS and MRI (P = 0.012). CONCLUSION: In this pilot study MIC-1/GDF15 has predictive capacity for neoplastic tumours in asymptomatic individuals with a genetic predisposition for PC. Further imagining may be warranted in patients with abnormal EUS and raised serum MIC-1/GDF15. Larger multicentric prospective studies are required to further define the role of MIC-1/GDF15 as a serological biomarker in pre-malignant pancreatic lesions and neoplastic tumours.

Pressure difference between radial and femoral artery pressure in minimally invasive cardiac surgery using retrograde perfusion.

OBJECTIVE: To investigate whether radial artery pressure is a reliable surrogate measure of central arterial pressure as approximated by femoral artery pressure in minimally invasive cardiac surgery with retrograde perfusion via femoral cannulation. METHOD: Fifty-two consecutive patients undergoing minimally invasive cardiac surgery were prospectively included in this study. Cardiopulmonary bypass was established via a femoral artery cannulation and femoral vein. Radial and femoral arterial pressures were recorded continuously, and the pressure differential between them was calculated for both systolic and mean arterial pressures. The agreement between measurements from the two arteries was compared using Bland-Altman plots. An interval of 95% limits of agreement of less than 20 mm Hg was set as satisfactory agreement. RESULTS: Average age was 65 ± 14 years. With respect to systolic arterial pressure, 28 patients (54%) had a peak pressure differential between radial and femoral arteries ⩾20 mm Hg. With respect to mean arterial pressure, only five patients (9%) had a peak pressure differential ⩾20 mm Hg. The pressure differential changed with time. Pressure differential in systolic arterial pressure was 5 ± 8 mm Hg until aortic declamping, then increased to a peak of 23 ± 16 mm Hg when cardiopulmonary bypass was turned off. The femoral systolic arterial pressures were significantly greater than radial systolic arterial pressures from time of aortic declamping to 20 min after cardiopulmonary bypass. The Bland-Altman plots revealed large biases and poor agreement in this period. CONCLUSION: Radial and femoral systolic artery pressure readings can differ significantly in minimally invasive cardiac surgery with retrograde perfusion. Intraoperative arterial pressure management based solely on radial systolic arterial pressure readings should be avoided.

Patients with HIV and coronary disease: are we meeting national guidelines?

Cardiovascular disease (CVD) has a higher incidence in patients with HIV infection. This study sought to determine whether HIV-infected patients with established CVD were being managed according to national guidelines. Data were collected from Australian general practitioners for 77 HIV-infected patients with a median age of 59 (range 54-64). There was good adherence to guidelines with regards to anti-platelet (84%; n=65; 95% confidence interval (CI) 74-92%) and statin therapy (97%; n=75; 95% CI 91-100%), despite a failure to meet cholesterol targets, with only 31% (n=24; 95% CI 21-42%) of the cohort meeting low-density lipoprotein target values. Similarly, there was limited adherence to guidelines regarding the prescriptions of medications for those with established hypertension (66%; n=51; 95% CI 55-77%), body mass index targets met (40%; n=31; 95% CI 29-52%), and depression screening (32%; n=25; 95% CI 22-44%). This Australian audit provides insight into adherence to guidelines for individuals with CVD and HIV, suggesting that current screening and management practices for these patients falls short of guidelines, particularly in relation to cholesterol management.

Minimally invasive aortic valve surgery.

Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease.

Outcomes of patients with spontaneous coronary artery dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an uncommon but serious condition presenting as an acute coronary syndrome (ACS) or cardiac arrest. The pathophysiology and outcomes are poorly understood. We investigated the characteristics and outcomes of patients presenting with SCAD. METHODS: In a retrospective study of a large cohort of patients with SCAD, data were collected regarding clinical presentation, patient characteristics, vascular screening, coronary artery involvement and clinical outcomes. RESULTS: 40 patients with SCAD (95% women, mean age 45±10 years) were included. At least 1 traditional cardiovascular risk factor was present in 40% of patients. Migraine was reported in 43% of patients. Events preceding SCAD included parturition (8%), physical stress (13%), emotional stress (10%) and vasoconstrictor substance-use (8%). 65% of patients had a non-ST elevation ACS (NSTEACS) at presentation, 30% had an ST elevation myocardial infarction (STEMI) and 13% had a cardiac arrest. The left anterior descending artery was most frequently involved (68% of patients), and 13% had involvement of multiple coronary territories. Fibromuscular dysplasia (FMD) was identified in 7 (37%) of 19 patients screened. 68% of patients were managed medically, 30% had percutaneous coronary intervention and 5% had coronary artery bypass grafting. Over a median 16-month follow-up period, 8% of patients had at least 1 recurrent SCAD event. There were no deaths. CONCLUSIONS: Patients with SCAD in this study often had multiple coronary territories involved (13%) and extracardiac vascular abnormalities, suggesting a systemic vascular process, which may explain the high incidence of migraine. All patients with SCAD should be screened for FMD and followed closely due to the possibility of recurrence.

The role of minimal access valve surgery in the elderly. A meta-analysis of observational studies.

BACKGROUND: Minimal access valve surgery, both mitral and aortic, may be related to improvement in specific post-operative outcomes, therefore may be beneficial for the subgroup of the elderly referred for valve surgery. METHODS: A systematic literature review identified several different studies, of which 6 fulfilled criteria for meta-analysis. Outcomes for a total of 1347 patients (675 conventional standard sternotomy and 672 minimally invasive valve surgery) were assessed with a meta-analysis using random effects modeling. Heterogeneity, subgroup analysis with quality scoring were also assessed. The primary endpoint was early mortality. Secondary endpoints included intra and post-operative outcomes. RESULTS: In the context of elderly patients, minimal access valve surgery conferred comparable early mortality to standard sternotomy (odd ratio (OR) 0.79, CI [0.40,1.56], p = 0.50) with no heterogeneity (p = 0.13); it was also associated with reduced mechanical intubation time (OR 0.48, CI [0.30,0.78], p = 0.003) and reduced post-operative length of stay (weighted mean difference (WMD) -2.91, CI [-3.09, -2.74] p < 0.00001), however both cardio-pulmonary bypass time and cross clamp time were longer (WMD 24.29, CI [22.97, 25.61] p < 0.00001 and WMD 8.61, CI [7.61, 9.61], p < 0.00001, respectively); subgroup analysis demonstrated statistically significant reduced post-operative length of stay for both minimally invasive aortic and mitral surgery (WMD -2.84, CI [-3.07, -2.60] p < 0.00001 and WMD -2.98, CI [-3.25, -2.71] p < 0.00001 respectively). CONCLUSIONS: Despite a prolonged cardiopulmonary bypass and cross clamp time, minimally invasive valve surgery is a safe alternative to standard sternotomy in the elderly, with similar early mortality, and improvements in intubation time as well as length of stay.