Fenestrated-branched endovascular repair for distal thoracoabdominal aortic pathology after total aortic arch replacement with frozen elephant trunk.

OBJECTIVE: To report the outcomes of fenestrated-branched endovascular repair (FBEVAR) for thoracoabdominal aortic pathology after total aortic arch replacement with frozen elephant trunk (TAR+FET). METHODS: Interrogation of prospectively maintained databases from four high-volume aortic centers identified consecutive patients treated with distal FBEVAR after prior TAR+FET between August 2013 and September 2020. The primary end point was 30-day/in-hospital mortality. Secondary end points were technical success, early clinical success, midterm survival, and freedom from reintervention. Data are presented as median (interquartile range). RESULTS: A total of 39 patients (21 men; median age, 73 years [67-75 years]) with degenerative (n = 22) and postdissection thoracoabdominal aortic aneurysms (n = 17) (median diameter, 71 mm [61-78 mm]) were identified. Distal FBEVAR was intended in 27 patients (median interval, 9.8 months [6.2-16.6 months]), anticipated in 7, and unexpected in 5. A total of 31 patients had a two- (n = 24) or three-stage (n = 7) distal FBEVAR. Renovisceral target vessel preservation was 99.3% (145 of 146). Early primary and secondary technical success was 92% and 97%, respectively. Thirty-day mortality was 2.6% (n = 1; respiratory failure and spinal cord ischemia [SCI]). Six survivors also developed SCI, which was associated with complete (n = 4) or partial recovery (n = 2) at hospital discharge. No patients required renal replacement therapy or suffered a stroke. Early clinical success was 95%. Median follow-up was 30.5 months (23.7-49.7 months). Eleven patients required 16 late reinterventions. Estimated 3-year survival and freedom from reintervention were 84% ± 6% and 63% ± 10%, respectively. CONCLUSIONS: Distal FBEVAR after prior TAR+FET is associated with high technical success and low early mortality. The risk of SCI is significant although the majority of patients demonstrate full or partial recovery before hospital discharge. Midterm patient survival is favorable, but there remains a high requirement for late reintervention. FBEVAR represents an acceptable alternative to distal open thoracoabdominal aortic aneurysm repair.

Impact of clinical factors and surgical techniques on early outcome of patients treated with frozen elephant trunk technique by using EVITA open stent-graft: results of a multicentre study.

OBJECTIVES: The treatment of patients with extensive thoracic aortic disease involving the arch and descending aorta is often performed, using the frozen elephant trunk (FET) technique. We retrospectively analysed early outcomes with this technique, using a prospective database. METHODS: A total of 509 patients (mean age: 61 ± 11 years) were registered between January 2005 and January 2014 in a multicentre database after FET surgery. Acute or chronic aortic dissection (AD) was the indication for surgery in 350 (68.8%) patients and degenerative or atherosclerotic aneurysm (DA) accounted for 159 (31.2%) patients. A logistic regression model was created to identify independent predictors of in-hospital mortality and neurological complications. RESULTS: The average in-hospital mortality was 15.9% (n = 81) with 17.1% for AD patients and 13.2% for DA patients (P = 0.2). Independent predictors of in-hospital mortality were haemodynamic instability [odds ratio (OR): 2.7, P = 0.005], peripheral vascular disease (OR: 2.6, P = 0.002), diabetes (OR: 2.1, P = 0.05) and selective cerebral perfusion time >60 min (OR: 2.2, P = 0.005). Patients under 60 years of age and the use of guide wire during FET implantation were protective for early survival. Stroke occurred in 7.7% (n = 39) of patients. Paraplegia or paraparesis occurred in 7.5% (n = 38) of patients. A distal landing zone lower than T10 was an independent predictor for spinal cord injury (OR: 2.3, P = 0.03). CONCLUSIONS: Techniques for faster arch replacement and controlled FET placement should be considered in order to reduce the early mortality and neurological complications after FET surgery. For distal aortic lesions, a two-staged approach is suggested, rather than the FET landing lower than T10.

Open aortic arch replacement in high-risk patients: the gold standard.

OBJECTIVES: Open total aortic arch replacement (TAR) in high-risk patients is considered by some to be associated with a prohibitively perioperative risk. Recent reports describe hybrid techniques to treat this group. We reviewed our outcomes of open surgery in a 'high-risk' group of patients. METHODS: All patients who underwent open TAR between 2000 and 2013 were identified from our prospectively maintained database. Patients comparable with the ones who underwent hybrid repair in previous studies (logistic EuroSCORE between 20 and 60 without intervention on the aortic root or on the mitral/tricuspid valve) were selected for analysis. RESULTS: Fifty-eight patients were identified. Median logistic EuroSCORE was 27.4 (range 20-57) and median age was 76 years (34.5% male). There were 11 resternotomies (18.9%) and 20 procedures were urgent/emergency (34.5%). Preoperative comorbidities included chronic obstructive pulmonary disease (31%), coronary artery disease (22.4%), peripheral vascular disease (48.3%), previous stroke (5.2%), previous myocardial infarction (3.4%) and left ventricular dysfunction (12%). Concomitant procedures included aortic valve replacement/resuspension (58.7%), coronary artery bypass grafting (22.4%), open descending aorta replacement (10.3%) and frozen elephant trunk (19%). Overall in-hospital mortality, permanent stroke and spinal cord injury rate were 6.9, 1.7 and 0%, respectively. There were no deaths or stroke in the elective group. One-year, 5-year and 10-year estimates of survival were 82.7, 70.0 and 37.8%, respectively. CONCLUSIONS: Open TAR can be performed with low mortality and morbidity and excellent long-term results even in high-risk patients. Total endovascular repair may represent an option for patients not suitable for open surgery.

The effect of perhexiline on myocardial protection during coronary artery surgery: a two-centre, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Perhexiline is thought to modulate metabolism by inhibiting mitochondrial carnitine palmitoyltransferase-1, reducing fatty acid uptake and increasing carbohydrate utilization. This study assessed whether preoperative perhexiline improves markers of myocardial protection in patients undergoing coronary artery bypass graft surgery and analysed its effect on the myocardial metabolome. METHODS: In a prospective, randomized, double-blind, placebo-controlled trial, patients at two centres were randomized to receive either oral perhexiline or placebo for at least 5 days prior to surgery. The primary outcome was a low cardiac output episode in the first 6 h. All pre-specified analyses were conducted according to the intention-to-treat principle with a statistical power of 90% to detect a relative risk of 0.5 and a conventional one-sided α-value of 0.025. A subset of pre-ischaemic left ventricular biopsies was analysed using mass spectrometry-based metabolomics. RESULTS: Over a 3-year period, 286 patients were randomized, received the intervention and were included in the analysis. The incidence rate of a low cardiac output episode in the perhexiline arm was 36.7% (51/139) vs 34.7% (51/147) in the control arm [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.56-1.50, P = 0.74]. Perhexiline was associated with a reduction in the cardiac index at 6 h [difference in means 0.19, 95% CI 0.07-0.31, P = 0.001] and an increase in inotropic support in the first 12 h (OR 0.55, 95% CI 0.34-0.89, P = 0.015). There were no significant differences in myocardial injury with troponin-T or electrocardiogram, reoperation, renal dysfunction or length of stay. No difference in the preischaemic left ventricular metabolism was identified between groups on metabolomics analysis. CONCLUSIONS: Preoperative perhexiline does not improve myocardial protection in patients undergoing coronary surgery and in fact reduced perioperative cardiac output, increasing the need for inotropic support. Perhexiline has no significant effect on the mass spectrometry-visible polar myocardial metabolome in vivo in humans, supporting the suggestion that it acts via a pathway that is independent of myocardial carnitine palmitoyltransferase inhibition and may explain the lack of clinical benefit observed following surgery. CLINICALTRIALSGOV ID: NCT00845364.

Current results of endovascular repair of thoraco-abdominal aneurysms†.

OBJECTIVES: Fenestrated and branch endografts represent a totally endovascular solution for high-risk patients with atherosclerotic thoraco-abdominal aortic aneurysms (TAAAs). This study reports the early outcome of endovascular TAAA repair. METHODS: Interrogation of a prospective database of consecutive patients who underwent endovascular repair (EVAR) for TAAA between June 2007 and October 2012. RESULTS: Sixty-two high-risk patients (55 men; median age 72, range 54-84 years) underwent fenestrated (n = 39) or branch (n = 23) EVAR for non-ruptured TAAA [extent I-III (n = 26) and IV (n = 36)]. Twenty patients had undergone 22 previous aortic procedures. A total of 221 target vessels (coeliac 50, superior mesenteric 61, renal 106, left subclavian 1 and hypogastric 3) were preserved with scallops (n = 17), fenestrations (n = 140) or branches (n = 62) and 201 of these vessels were stent-grafted (coeliac 34, superior mesenteric 58, renal 105, left subclavian 1 and hypogastric 3). The 30-day mortality was 1.6% (n = 1) and one further patient died on postoperative day 62 from respiratory complications. Spinal cord injury (SCI) developed in 5 (8%) patients (3 women and 2 men). Two patients required temporary renal replacement therapy and a further two commenced planned postoperative dialysis. CONCLUSIONS: In high-risk patients with TAAA, fenestrated and branch EVAR is associated with low early mortality and requirement for renal support, but the risk of SCI is not insignificant despite the use of cerebrospinal fluid drainage and blood pressure manipulation. Our current practice is to stage the repair of extent I-III aneurysms and this has significantly reduced the incidence of SCI.

Glucose-insulin-potassium reduces the incidence of low cardiac output episodes after aortic valve replacement for aortic stenosis in patients with left ventricular hypertrophy: results from the Hypertrophy, Insulin, Glucose, and Electrolytes (HINGE) trial.

BACKGROUND: Patients undergoing aortic valve replacement for critical aortic stenosis often have significant left ventricular hypertrophy. Left ventricular hypertrophy has been identified as an independent predictor of poor outcome after aortic valve replacement as a result of a combination of maladaptive myocardial changes and inadequate myocardial protection at the time of surgery. Glucose-insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection. This study was designed to evaluate the effects of GIK infusion in patients undergoing aortic valve replacement surgery. METHODS AND RESULTS: Patients undergoing aortic valve replacement for aortic stenosis with evidence of left ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was double-blind and conducted at a single center. The primary outcome was the incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed to assess changes in 5' adenosine monophosphate-activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked ß-N-acetylglucosamination (O-GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control, 110 GIK). GIK treatment was associated with a significant reduction in the incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval, 0.10 to 0.47; P=0.0001) and a significant reduction in inotrope use 6 to 12 hours postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60; P=0.0007). These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands. CONCLUSIONS: Perioperative treatment with GIK was associated with a significant reduction in the incidence of low cardiac output state and the need for inotropic support. This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow-up will determine whether routine use of GIK improves patient prognosis.

Remote ischemic preconditioning in human coronary artery bypass surgery: from promise to disappointment?

BACKGROUND: We assessed whether remote ischemic preconditioning (RIPC) improves myocardial, renal, and lung protection after on-pump coronary surgery. METHODS AND RESULTS: This was a single-center, prospective, randomized (1:1), placebo-controlled trial. Patients, investigators, anesthetists, surgeons, and critical care teams were blinded to group allocation. Subjects received RIPC (or placebo) stimuli (×3 upper limb (or dummy arm), 5-minute cycles of 200 mm Hg cuff inflation/deflation) before aortic clamping. Anesthesia, perfusion, cardioplegia, and surgical techniques were standardized. The primary end point was 48-hour area under the curve (AUC) troponin T (cTnT) release. Secondary end points were 6-hour and peak cTnT, ECG changes, cardiac index, inotrope and vasoconstrictor use, renal dysfunction, and lung injury. Hospital survival was 99.4%. Comparing placebo and RIPC, median (interquartile range) AUC 48-hour cTnT (ng/mL(-1)/48 h(-1)); 28 (19, 39) versus 30 (22, 38), 6-hour cTnT (ng/mL(-1)); 0.93(0.59, 1.35) versus 1.01(0.72, 1.43), peak cTnT (ng/mL(-1)); 1.02 (0.74, 1.44) versus 1.04 (0.78, 1.51), de novo left bundle-branch block (4% versus 0%) and Q waves (5.3% versus 5.5%), serial cardiac indices, intraaortic balloon pump usage (8.5% versus 7.5%), inotrope (39% versus 50%) and vasoconstrictor usage (66% versus 64%) were not different. Dialysis requirement (1.2% versus 3.8%), peak creatinine (median [interquartile range], 1.2 mg/dL(-1) (1.1, 1.4) versus 1.2 (1.0, 1.4)), and AUC urinary albumin-creatinine ratios 69 (40, 112) versus 58 (32, 85) were not different. Intubation times; median (interquartile range), 937 minutes(766, 1402) versus 895(675, 1180), 6-hour; 278 (210, 338) versus 270 (218, 323) and 12-hour pO(2):FiO(2) ratios 255 (195, 323) versus 263 (210, 308) were similar. CONCLUSIONS: In contrast to prior smaller studies, RIPC did not reduce troponin release, improve hemodynamics, or enhance renal or lung protection. Clinical Trial Registration-URL: http://www.ukcrn.org.uk. Unique identifier: 4659.

N-terminal pro-brain-type natriuretic peptide: a biochemical surrogate of cardiac function in the potential heart donor.

OBJECTIVES: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is elevated in subarachnoid haemorrhage, brainstem death (BSD) and heart failure. We examined the relationship between NT-proBNP and cardiac functional status after BSD and left ventricular (LV) BNP precursor gene expression. METHODS: We assayed NT-proBNP in the serum of potential heart donors investigated with pulmonary artery flotation catheters, transthoracic echocardiography and cardiac troponin (cTn) I and T. After 6.9 h of optimisation, haemodynamic studies were repeated to determine haemodynamic functional suitability for transplantation. Median (interquartile range (IQR)) NT-proBNP levels are reported according to initially measured dichotomised pulmonary capillary wedge pressure (PCWP), cardiac index (CI), indexed cardiac power output (CPOi), left ventricular ejection fraction (LVEF), wall motion score (WMS), extravascular lung water index (EVLWI), cTnT and cTnI and end-management functional suitability. LV biopsies were snap-frozen, mRNA extracted and reverse-transcribed, allowing performance of Taqman real-time polymerase chain reaction assays of mRNA-BNP precursor. RESULTS: There were 79 subjects. Median NT-proBNP was 121 pg ml(-1) (range 5-4139) and levels correlated with time from coning (p<0.01, r=-0.379). Higher NT-proBNP was found in donors with PCWP >14 mmHg; 504 (120-1544) versus 101 (38-285); p=0.01; CI <2.4 l min(-1) m(-2) 410 (123-1511) versus 95 (37-264); p=0.001; CPOi <0.5 Wm(-2) 256 (78-694) versus 105 (37-315); p=0.02; LVEF <50% 231 (75-499) versus 72 (36-177); p=0.04; WMS >2; 343 (80-673) versus 99 (37-236); p=0.01; cTnT >0.1 microg ml(-1) 499 (127-967) versus 80 (36-173); p<0.001 and cTnI >1 mg ml(-1) 410 (97-684) versus 88 (36-190); p<0.01 and in hearts functionally unsuitable at end-optimisation; 189 (74-522) versus 85 (39-243); p=0.02. Hearts functionally suitable for transplantation expressed significantly less mRNA encoding for BNP precursor (0.19-fold; p=0.01). CONCLUSION: During or after BSD, NT-proBNP is released and the heart is a likely source. Higher NT-proBNP levels are associated with donor heart dysfunction and a failure to achieve haemodynamic functional suitability criteria. This supports the hypothesis that biomarkers, including NT-proBNP, may be useful in donor heart assessment.

Echocardiography in the potential heart donor.

BACKGROUND: The relationship between echocardiographic left ventricular(LV) systolic function (E-function) and pulmonary artery catheter(PAC) assessment of hemodynamic function (H-function) in potential heart donors is ill defined. We investigated this and determined (a) whether optimization could improve abnormal E-function, (b) feasibility and usefulness of repeat transthoracic echocardiography (TTE), and (c) whether thyroid status and therapy affected E-function. MATERIALS AND METHODS: Transthoracic E-function imaging was performed at baseline and 4 hr in potential donors (enrolled in a randomized controlled trial of tri-iodothyronine+/-methylprednisolone [MP] therapy) undergoing PAC-guided algorithmic optimization. Images were analyzed post hoc for LV wall thickness, ejection fraction, and Tei index. RESULTS: The study comprised 66 donors. Both LV ejection fraction (LVEF) and LV-Tei correlated with cardiac index (CI; P<0.001), and LV Tei was most frequently measurable and repeatable(P=0.01). Normal LVEF independently predicted end-assessment H-functional suitability (odds ratio 1.05, 95% confidence interval 1.007-1.088 [P=0.021]) but had poor specificity. Initial subnormal E-function was identified in 29 of 66 of hearts, of which 58% (17/29) achieved H-function suitability criteria. In 52 hearts, repeat E-function assessment was possible. Nineteen of 52 had initially subnormal E-function, which improved in over half (53%). H-function could be manipulated to meet functional suitability criteria for transplant even without E-function change. Neither initial thyroid status nor hormonal therapy affected LV function. CONCLUSIONS: Echocardiography is possible in most potential heart donors. Normal E-function predicts hemodynamic suitability for transplantation but lacks specificity. More than 50% of hearts with subnormal E-function can attain hemodynamic transplantation criteria after donor management. Repeat echocardiography is feasible but has a limited role. Both initial echocardiography and PAC-guided management should be used routinely.

The proinflammatory environment in potential heart and lung donors: prevalence and impact of donor management and hormonal therapy.

BACKGROUND: Brain stem death can elicit a potentially manipulable cardiotoxic proinflammatory cytokine response. We investigated the prevalence of this response, the impact of donor management with tri-iodothyronine (T3) and methylprednisolone (MP) administration, and the relationship of biomarkers to organ function and transplant suitability. METHODS: In a prospective randomized double-blinded factorially designed study of T3 and MP therapy, we measured serum levels of interleukin-1 and -6 (IL-1 and IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein, and procalcitonin (PCT) levels in 79 potential heart or lung donors. Measurements were performed before and after 4 hr of algorithm-based donor management to optimize cardiorespiratory function and +/-hormone treatment. Donors were assigned to receive T3, MP, both drugs, or placebo. RESULTS: Initial IL-1 was elevated in 16% donors, IL-6 in 100%, TNF-alpha in 28%, CRP in 98%, and PCT in 87%. Overall biomarker concentrations did not change between initial and later measurements and neither T3 nor MP effected any change. Both PCT (P =0.02) and TNF-alpha (P =0.044) levels were higher in donor hearts with marginal hemodynamics at initial assessment. Higher PCT levels were related to worse cardiac index and right and left ventricular ejection fractions and a PCT level more than 2 ng x mL(-1) may attenuate any improvement in cardiac index gained by donor management. No differences were observed between initially marginal and nonmarginal donor lungs. A PCT level less than or equal to 2 ng x mL(-1) but not other biomarkers predicted transplant suitability following management. CONCLUSIONS: There is high prevalence of a proinflammatory environment in the organ donor that is not affected by tri-iodothyronine or MP therapy. High PCT and TNF-alpha levels are associated with donor heart dysfunction.

The haemodynamic effects of adjunctive hormone therapy in potential heart donors: a prospective randomized double-blind factorially designed controlled trial.

AIMS: The aim of this study was to assess the haemodynamic effects of tri-iodothyronine (T3) and methylprednisolone in potential heart donors. METHODS AND RESULTS: In a prospective randomized double-blind trial, 80 potential cardiac donors were allocated to receive T3 (0.8 microg kg(-1) bolus; 0.113 microg kg(-1) h(-1) infusion) (n = 20), methylprednisolone (1000 mg bolus) (n = 19), both drugs (n = 20), or placebo (n = 21) following initial haemodynamic assessment. After hormone or placebo administration, cardiac output-guided optimization was initiated, using vasopressin as a pressor and weaning norepinephrine and inotropes. Treatment was administered for 5.9 +/- 1.3 h until retrieval or end-assessment. Cardiac index increased significantly (P < 0.001) but administration of T3 and methylprednisolone alone or in combination did not affect this change or the heart retrieval rate. Thirty-five per cent (14/40) of initially marginal or dysfunctional hearts were suitable for transplant at end-assessment. At end-assessment, 50% of donor hearts fulfilled criteria for transplant suitability. CONCLUSION: Cardiac output-directed donor optimization improves donor circulatory status and has potential to increase the retrieval rate of donor hearts. Tri-iodothyronine and methylprednisolone therapy do not appear to acutely affect cardiovascular function or yield.

Early donor management increases the retrieval rate of lungs for transplantation.

BACKGROUND: Lung transplantation activity is frustrated by donor lung availability. We sought to examine the effect of active donor management and hormone administration on pulmonary function and yield in cadaveric heart-beating potential lung donors. METHODS: We studied 182 potential lung donors (arterial oxygen tension [PaO2]/fractional inspired oxygen [FIO2] ratio > or = 230). From this group, 60 patients (120 lungs) were allocated, within a randomized trial, to receive methylprednisolone (1 g), triiodothyronine (0.8 microg/kg bolus and 0.113 microg/kg/h infusion), both methylprednisolone and triiodothyronine, or placebo as soon as feasible after consent and initial assessment. Trial donors underwent protocol-guided optimization of ventilation and hemodynamics, lung water assessment, and bronchoscopy. Function was assessed by PaO2/FIO2 ratio, extravascular lung water index (EVLWI), and pulmonary vascular resistance (PVR). A nontrial group of 122 donors (244 lungs) received similar management without bronchoscopy, pulmonary artery flotation catheter monitoring, or lung water assessment. RESULTS: Within the trial, management commenced within a median of 2 hours (interquartile range, 0.5 to 3.5 hours) of consent and continued for an average of 6.9 +/- 1.2 hours. The PaO2/FIO2 ratio deteriorated (p = 0.028) from 397 +/- 78 (95% CL, 376 to 417) to 359 +/- 126 (95% CL, 328 to 390) and EVLWI from 9.7 +/- 4.5 mL/kg (95% CL, 8.6 to 10.9 mL/kg) to 10.8 +/- 5.2 mL/kg (95% CL, 9.4 to 12.2 mL/kg; p = 0.009). PVR remained unchanged (p = 0.28). At end management, 48 of 120 trial lungs (40%) were transplanted versus 66 of 244 nontrial lungs (27%; p = 0.016). Neither methylprednisolone and triiodothyronine nor T3 increased lung yield or affected PaO2/FIO2 or EVLWI; however, methylprednisolone attenuated the increase in EVLWI (p = 0.009). CONCLUSIONS: Early active management of lung donors increases yield. Steroid administration reduces progressive lung water accumulation.