Effect of Valvular Surgery in Carcinoid Heart Disease: An Observational Cohort Study.

CONTEXT: Carcinoid heart disease (NET-CHD) is associated with the development of symptom-limited exercise capacity and high rates of morbidity and mortality. OBJECTIVE: This study sought to determine the survival, cardiac function, and functional class following surgery. DESIGN AND SETTING, AND PATIENTS: This was a retrospective observational cohort study between 2005 and 2015 at a European Centre of Excellence for Neuroendocrine Tumours, Queen Elizabeth Hospital Birmingham. England consisting of 62 consecutive patients referred to the NET-Cardiology Service. INTERVENTIONS: Subjects were assessed at referral using transthoracic echocardiography (with saline contrast) and transesophageal echocardiography, and 77% with confirmed NET-CHD underwent cardiovascular magnetic resonance imaging. Symptomatic patients with concomitant severe valvular dysfunction were referred for surgery with stable NET disease. MAIN OUTCOME MEASURE: Survival of patients with proven NET-CHD following medical and surgical treatments was measure. RESULTS: In total, 47/62 patients were diagnosed with NET-CHD. Thirty-two patients (68%) underwent surgery with bioprosthetic valve replacements in all subjects; tricuspid, n = 31; pulmonary, n = 30; mitral, n = 3; and aortic, n = 3. Four patients underwent concomitant coronary artery bypass grafting. There were 4 (13%) early post-operative deaths. One- and 2-y survival rates after surgery were 75 and 69% compared with 45 and 15% in un-operated patients. Post-operatively, functional class was improved (pre-New York Heart Association Classification [NYHA], 2.6 [0.5] vs post-NYHA, 1.7 [1.1]), P < .05, right-ventricular (RV) size was reduced (136 ml/m(2) [25] vs 71 ml/m(2) [7]; P < .01) with preserved RV ejection fraction (61% ± 9 vs 55% ± 10; P = .26). CONCLUSION: Valve surgery improved functional class and resulted in RV reverse remodelling with improved survival rates at 2 y compared with those not proceeding to operation. These data highlight the importance of close collaboration between NET clinicians, cardiology, and cardiothoracic surgery teams. Early referral can improve functional capacity but more research is needed to define the selection of appropriate candidates and randomized data are needed to define the effect of surgery on prognosis.

Clinical and patho-anatomical factors affecting expansion of thoracic aortic aneurysms.

OBJECTIVE: To examine the expansion of aneurysmal aortic segments (> or = 35 mm) and to assess the impact of clinical and patho-anatomical factors on aneurysm expansion. DESIGN: 87 consecutive patients (mean age 63.6 years, range 22-84 years) were studied using serial (six month intervals) computed tomographic or magnetic resonance imaging to monitor progression of thoracic aortic aneurysms. Aortic diameter was measured at seven predetermined segments and at the site of maximum aortic dilatation (MAX). RESULTS: 780 segment intervals were identified. The median overall aneurysm expansion rate was 1.43 mm/year. This increased exponentially with incremental aortic diameter (p < 0.01) and varied by anatomical segment (p < 0.05). The presence of intraluminal thrombus (p < 0.01) but not dissection or calcification was associated with accelerated growth. Univariate analysis identified thrombus (p < 0.001), previous stroke (p < 0.002), smoking (p < 0. 01), and peripheral vascular disease (p < 0.05) as factors associated with accelerated growth in MAX. Dissection, wall calcification, and history of hypertension did not affect expansion. beta Blocker treatment was not associated with protection. Multivariate analysis confirmed the positive effect of intraluminal thrombus and previous cerebral ischaemia, and the negative effect of previous aortic surgery on aneurysm growth. These findings translated into a mathematical equation describing exponential aneurysm expansion. CONCLUSIONS: Aneurysmal thoracic aortic segments expand exponentially according to their initial size and their anatomical position within the aorta. The presence of intraluminal thrombus, atherosclerosis, and smoking history is associated with accelerated growth and may identify a high risk patient group for close surveillance.

Replacement of the proximal aorta and aortic valve using a composite bileaflet prosthesis and gelatin-impregnated polyester graft (Carbo-Seal): early results in 143 patients.

OBJECTIVE: We report the combined early results from two centers in the United Kingdom using a composite conduit consisting of a bileaflet mechanical valve incorporated into a gelatin-impregnated, ultra-low porosity, woven polyester graft (Carbo-Seal; Sulzer Carbomedics, Inc, Austin, Tex). METHODS: Between August 1992 and March 1997, 143 patients underwent aortic root replacement with the Carbo-Seal composite prosthesis. The indication for surgery was acute type A dissection in 31 (22%), chronic type A dissection in 9 (6%), ascending aortic aneurysm without dissection in 100 (70%), and false aneurysm of the ascending aorta in 3 (2%). Twenty-seven patients (19%) had undergone previous sternotomy, and 40 (28%) were seen as emergencies. Concomitant procedures were performed in 38 (27%), including 18 aortic arch or hemiarch replacements. Total follow-up is 270 patient-years. Follow-up is 100% complete. RESULTS: The early (30-day) mortality was 7% (10 patients). Permanent neurologic events occurred in 2%. At a mean follow-up of 23 months, 94% of survivors were in New York Heart Association functional class I. Freedom from reoperation was 97.2% +/- 1.6% (1 standard error [1 SE]) at 12 months and 95.7% +/- 2.2% at 48 months. Including early mortality, survival was 90.1% +/- 2.6% at 12 months and 83.1% +/- 3. 5% at 48 months. CONCLUSIONS: Aortic root replacement with use of the Carbo-Seal prosthesis can be undertaken with a relatively low early mortality and morbidity. A low reoperation rate and high intermediate-term survival can be expected, but continued follow-up is needed to determine the long-term efficacy of this prosthesis.

Reproducibility of thoracic aortic diameter measurement using computed tomographic scans.

OBJECTIVES: Decisions to recommend elective surgical repair of thoracic aortic aneurysms (TAA) may be based on size or expansion rate, which are used as indices of the risk of rupture. Measurement error may thus affect clinical decision-making. In order to evaluate the reproducibility of aortic diameter measurements of TAA, we assessed departmental inter- and intra-observer variability of measurement of pre-selected computed tomographic scan images of aneurysmal segments of the thoracic aorta. METHODS: We compared measurements of minimum aortic diameter made by four observers in 50 pre-selected scans and at different times by two observers using a calliper method and a measurement tool within the scan. Differences in measured dimension were analysed using Wilcoxon's signed ranks test and the repeatability assessed using the method of Bland and Altman. RESULTS: There were no significant inter-observer differences among three observers but there were significant differences between another observer and two other observers (P < 0.05). No significant intra-observer differences existed. The best intra-observer repeatability was 2.25 while the worst inter-observer repeatability was 4.37. The mean and maximum difference in measurement were +/-0.88 mm and +/-8.0 mm, respectively. Variability of measurement increased with aortic diameter. CONCLUSIONS: Calliper measurement of TAA is an acceptable measurement method for surveillance of TAA but appears most accurate with a single observer. Increasing error is seen with increasing diameter which may compound error in estimation of expansion rate. Standardisation of technique is advisable for multiple observers and aortic units should adopt quality assurance protocols to minimise error.

S-100beta release in hypothermic circulatory arrest and coronary artery surgery.

BACKGROUND: Aortic surgery utilizing profound hypothermic circulatory arrest (HCA) has a higher incidence of neurological injury than coronary artery bypass grafting (CABG). S-100beta is a potential marker of cerebral ischemic injury. The aim of this study is to assess its use in investigating cerebral injury during HCA. METHODS: We studied 40 patients (10 CABG, 30 HCA). The mean cardiopulmonary bypass (CPB) times were 72 and 158 minutes, respectively. Mean HCA duration was 27.6 min, with retrograde cerebral perfusion (RCP) used in 18 patients (mean 28.5 minutes, 95% CI 16-25). Perioperative venous blood samples were subjected to S100beta assay. RESULTS: S100beta levels with HCA (peak: 2.68 microg/L, 95% CI 1.99-3.38 microg/L; calculated area under the curve [AUC]: 1596 microg/L/min, 95% CI 825-2368 microg/L/min) were significantly higher (peak, p = 0.028 and AUC, p = 0.007) than with CABG (peak: 1.16 microg/L, 95% CI 0.25-2.1 microg/L and AUC: 53.4 microg/L/min 95% CI 3.0-103.8). Peak S100beta correlated with CPB time in CABG cases (r = 0.76, p < 0.05), and with both CPB and HCA time in HCA cases: without RCP (r = 0.46 and 0.21, respectively, p > 0.05) and with RCP (r = 0.88 and 0.33, respectively, p < 0.05). There was no significant difference in the S100beta levels between HCA groups with and without RCP, but HCA time was longer in the RCP group (p = 0.05). CONCLUSIONS: S100beta release correlates with duration of CPB and HCA. Elevated serum S100 indicates astrocyte death or activation, and suggests blood-brain barrier dysfunction. The continuing release of S100 after the end of operation suggests that HCA may be associated with greater injury than CABG. RCP did not influence S-100beta release in this study.

Prediction of thoracic aortic aneurysm expansion: validation of formulae describing growth.

BACKGROUND: The expansion rate of thoracic aortic aneurysms may be an important and clinically relevant index of the risk of rupture. The aims of this study were to assess the validity of three published exponential equations that predict expansion rate in a separate sample population, and to calculate an expansion rate formula for this cohort of patients. METHODS: We studied 88 consecutive patients undergoing serial computed tomographic or magnetic resonance imaging scanning to monitor thoracic aortic aneurysm progression. In interval scans of at least 6 months, we measured minimum coronal aortic diameter at seven set levels and maximal diameter, yielding 780 segment-intervals. RESULTS: The linear expansion rate (mean 2.6 mm/year) increased with incremental aortic diameter (aortic diameter < 40 mm: 2.0; 40-49 mm: 2.3; 50-59 mm: 3.6; > or = 60 mm: 5.6 mm/year; p < 0.01). Regression analysis showed close correlation between predicted and sample data, but there were significant differences between observed and expected measurements. The Yale formula underestimated growth by 0.8 mm, while Mt. Sinai and Osaka formulae overestimated actual change by 1.5 and 0.2 mm, respectively. The expansion rate derived from our population was: last diameter = initial diameter x e(0.00367 x time) (r = 0.617). CONCLUSIONS: Although formulae derived from one thoracic aortic aneurysm sample population may not extrapolate exactly to others, there is close concordance of results for patient populations in three different continents.

The management of bleeding following surgery requiring hypothermic circulatory arrest.

BACKGROUND: Hemostasis is a significant problem in aortic surgery requiring profoundly hypothermic techniques. Aprotinin, a serine protease inhibitor, reduces blood loss in high-risk coronary and valve surgery, but its use in profound hypothermia is controversial. METHODS: To evaluate the role of a modified protocol of aprotinin administration we have retrospectively reviewed our results in 73 procedures when hypothermic circulatory arrest was necessary. Thirty-seven (51%) were emergencies. Aprotinin was not administered until bypass had been recommenced after the period of circulatory arrest, and was then given as a bolus of 280 mg into the bypass machine followed by an intravenous infusion of 70 mg/hour. RESULTS: In this series the 30-day mortality was 12.3% (9/73), and the in-hospital mortality 13.7% (10/73). Mortality in the elective group was 11.1% and 16.2% in the emergency group. The mean blood loss over the first 12 hours after surgery was 542 mL; the mean transfusion requirement during surgery and this 12 hour period was 3.6 units of blood. Six patients (8.2%) developed transient renal dysfunction which did not require intervention. CONCLUSIONS: This data does not support the adverse effect of aprotinin upon early survival. Although early reports were of concern, the role of aprotinin as an adjunct to hemostasis requires further investigation.

Aprotinin in aortic surgery requiring profound hypothermia and circulatory arrest.

OBJECTIVE: The use of aprotinin in cardiac surgery to improve haemostasis and reduce blood loss particularly in patient groups at increased risk of bleeding is well established. Previous retrospective studies in profound hypothermic surgery have highlighted concerns that in this circumstances aprotinin may paradoxically cause increased bleeding and intravascular thrombosis. We therefore adopted a modified protocol for administering aprotinin, which was not started until cardiopulmonary bypass had been reinstituted after circulatory arrest. METHODS: Between April 1993 and June 1995, 45 patients underwent 46 thoracic aortic procedures which required hypothermic circulatory arrest; 25 of these were emergencies. All of these patients received aprotinin. RESULTS: There were five deaths (10.8%) in hospital. Two patients with preoperative oliguric renal failure required postoperative dialysis, and a further six (13%) developed transient renal dysfunction with complete recovery. Two patients suffered postoperative stroke; one from embolisation of a severely diseased aorta, while the other had signs of an acute evolving stroke before surgery. None of the patients suffered acute Q-wave perioperative myocardial infarction. The mean blood loss was 575 ml in the first 12 h, with a mean postoperative transfusion requirement of 1 U blood. CONCLUSIONS: We cannot implicate aprotinin in increased postoperative blood loss, renal dysfunction or mortality when used with hypothermic circulatory arrest according to this protocol. Elucidating the role of aprotinin in hypothermic circulatory arrest requires a randomised prospective study.

Arterial risk factors and ischemic cerebrovascular events after aortic valve replacement.

To assess the association of possible risk factors with ischemic cerebrovascular events after aortic valve replacement (AVR), 619 consecutive patients undergoing AVR with a Medtronic Hall valve between the beginning of December 1979 and the end of December 1992 and surviving the immediate postoperative period were analyzed. Possible risk factors examined were valve lesion, prosthesis size, postoperative functional status, systemic hypertension, cigarette smoking, diabetes, coronary artery disease and atrial fibrillation. There were 53 ischemic cerebrovascular events in 38 patients during 3,174 follow up years, yielding a linearized event rate of 1.7%/patient-year. Significant risk factors in terms of odds ratios (OR) were postoperative hypertension (OR 8.0), postoperative NYHA class III or IV (OR 5.5), postoperative smoking (OR 4.0), diabetes (OR 3.5), preoperative hypertension (OR 2.7) and preoperative smoking (OR 1.8). There was highly significant interaction between postoperative hypertension and postoperative smoking (OR 54.0). Eighty-one percent of patients who suffered events were hypertensive or smoking postoperatively or both. These findings have important implications for postoperative management and for the reporting of ischemic cerebrovascular events after valve replacement.

The role of risk factors and trigger factors in cerebrovascular events after mitral valve replacement: implications for antithrombotic management.

To determine the effect of risk factors and trigger factors on cerebrovascular events, 622 patients who survived mitral valve replacement between December 1979 and December 1992 were analyzed. Ninety-six patients suffered 139 nonhemorrhagic cerebrovascular events. Data were available on 138 events in 95 patients. There were 32 transient ischemic attacks (TIAs), 57 reversible ischemic neurological deficits (RINDs), and 49 strokes. Age, sex, atrial fibrillation, left atrial size, systemic hypertension, and abnormal body mass index did not discriminate between patients who suffered events and those who did not. In contrast, smoking status differed significantly between patients who suffered events and those who did not. Among current or recent ex-smokers, the risk of stroke or RIND was significantly higher than in non-smokers (p < < 0.001). The odds ratio of suffering any type of event in patients who smoked at any time postoperatively versus those who did not smoke was 2.9 (95% confidence interval: 1.8 to 4.6). Of 61 patients contacted directly, 30% recalled an infective episode immediately prior to their event. A diurnal and seasonal influence on events was also detected with peaks in the morning and in the winter months, respectively (both p < 0.001). It is concluded that there is persuasive evidence for the involvement of several nonprosthetic factors in the incidence of cerebrovascular events after mitral valve replacement. This has implications for patient management and for future analysis of prosthetic heart valve series.