Predictors of paravalvular aortic regurgitation following self-expanding Medtronic CoreValve implantation: the role of annulus size, degree of calcification, and balloon size during pre-implantation valvuloplasty and implant depth.

OBJECTIVES: We sought to investigate the role of balloon size during pre-implantation valvuloplasty in predicting AR and optimal Medtronic CoreValve (MCS) implantation depth. BACKGROUND: Paravalvular aortic regurgitation (AR) is common following MCS implantation. A number of anatomical and procedural variables have been proposed as determinants of AR including degree of valve calcification, valve undersizing and implantation depth. METHODS: We conducted a multicenter retrospective analysis of 282 patients who had undergone MCS implantation with prior cardiac CT annular sizing between 2007 and 2011. Native valve minimum (Dmin), maximum (Dmax) and arithmetic mean (Dmean) annulus diameters as well as agatston calcium score were recorded. Nominal and achieved balloon size was also recorded. AR was assessed using contrast angiography at the end of each procedure. Implant depth was measured as the mean distance from the nadir of the non- and left coronary sinuses to the distal valve frame angiographically. RESULTS: 29 mm and 26 mm MCS were implanted in 60% and 39% of patients respectively. The majority of patients (N=165) developed AR <2 following MCS implantation. AR ≥3 was observed in 16% of the study population. High agatston calcium score and Dmean were found to be independent predictors of AR ≥3 in multivariate analysis (P<0.0001). Nominal balloon diameter and the number of balloon inflations did not influence AR. However a small achieved balloon diameter-to-Dmean ratio (≤0.85) showed modest correlation with AR ≥3 (P=0.04). This observation was made irrespective of the degree of valve calcification. A small MCS size-to-Dmean ratio is also associated with AR ≥3 (P=0.001). A mean implantation depth of ≥8+2mm was also associated with AR ≥3. Implantation depth of ≥12 mm was associated with small MCS diameter-to-Dmean ratio and increased 30-day mortality. CONCLUSION: CT measured aortic annulus diameter and agatston calcium score remain important predictors of significant AR. Other procedural predictors include valve undersizing and low implantation depth. A small achieved balloon diameter-to-Dmean ratio might also predict AR ≥3. Our findings confirm that a small achieved balloon size during pre-implantation valvuloplasty predicts moderate-severe AR in addition to previously documented factors.

Permanent pacemaker insertion after CoreValve transcatheter aortic valve implantation: incidence and contributing factors (the UK CoreValve Collaborative).

BACKGROUND: Permanent pacemaker (PPM) requirement is a recognized complication of transcatheter aortic valve implantation. We assessed the UK incidence of permanent pacing within 30 days of CoreValve implantation and formulated an anatomic and electrophysiological model. METHODS AND RESULTS: Data from 270 patients at 10 centers in the United Kingdom were examined. Twenty-five patients (8%) had preexisting PPMs; 2 patients had incomplete data. The remaining 243 were 81.3±6.7 years of age; 50.6% were male. QRS duration increased from 105±23 to 135±29 milliseconds (P<0.01). Left bundle-branch block incidence was 13% at baseline and 61% after the procedure (P<0.001). Eighty-one patients (33.3%) required a PPM within 30 days. Rates of pacing according to preexisting ECG abnormalities were as follows: right bundle-branch block, 65.2%; left bundle-branch block, 43.75%; normal QRS, 27.6%. Among patients who required PPM implantation, the median time to insertion was 4.0 days (interquartile range, 2.0 to 7.75 days). Multivariable analysis revealed that periprocedural atrioventricular block (odds ratio, 6.29; 95% confidence interval, 3.55 to 11.15), balloon predilatation (odds ratio, 2.68; 95% confidence interval, 2.00 to 3.47), use of the larger (29 mm) CoreValve prosthesis (odds ratio, 2.50; 95% confidence interval, 1.22 to 5.11), interventricular septum diameter (odds ratio, 1.18; 95% confidence interval, 1.10 to 3.06), and prolonged QRS duration (odds ratio, 3.45; 95% confidence interval, 1.61 to 7.40) were independently associated with the need for PPM. CONCLUSION: One third of patients undergoing a CoreValve transcatheter aortic valve implantation procedure require a PPM within 30 days. Periprocedural atrioventricular block, balloon predilatation, use of the larger CoreValve prosthesis, increased interventricular septum diameter and prolonged QRS duration were associated with the need for PPM.

Epithelioid angiomyolipoma: imaging appearances.

Epithelioid angiomyolipoma is a recently described rare variant of renal angiomyolipoma. It can occur in patients with or without tuberous sclerosis, and may potentially be malignant. We report the imaging findings from two cases of epithelioid angiomyolipoma: the first in a patient with tuberous sclerosis complex, arising in a horse-shoe kidney and growing into the inferior vena cava and right atrium; the second in a 62-year-old hypertensive man.

Risks of elective cardiac surgery: what do patients want to know?

OBJECTIVE: To examine patients' individual requirements for risk disclosure before surgery. DESIGN: Structured interview and questionnaire. SETTING: 50 patients interviewed following coronary artery bypass grafting or valve replacement or repair. MAIN OUTCOME MEASURES: Patient assessment of the nature and probability of risks they would have wished to be informed of from a pool comprising death and 13 postoperative complications. RESULTS: Out of 50 patients, 21 (42%) wanted no risk information at all, 25 (50%) did not want to be advised of the risk of death, and 27 (54%) did not want information about the risk of permanent stroke. This contrasts with standard practice of routinely informing patients of the risk of death and stroke. However, there were pronounced individual patient preferences. Three groups of patients emerged: those requiring little or no risk information, those requiring information about major risks, and those requiring full risk disclosure. Patients were not generally concerned about the specific probabilities of any risk. CONCLUSIONS: Clinicians counselling patients before operation should routinely discuss patient preferences before risk disclosure, distinguishing among a preference for "no risk information", "all potentially relevant risks", and "those risks considered significant or likely to occur". The fact of individual patient preferences may undermine the concept of the "reasonable patient" in determination of the legal requirements for risk disclosure. Future studies, in addition to replicating the present findings, should examine the reasons underlying individual patient preferences and the long term implications of degrees of risk disclosure, particularly when adverse outcomes occur.

Effects of storage solutions on in vitro vasoreactivity of radial artery conduits.

OBJECTIVES: Surgical preparation of coronary conduits for coronary artery bypass grafting may affect their early and long-term patency; one mechanism may involve endothelial damage. We investigated the effect of 3 commonly used solutions-Ringer's solution, normal saline solution, and heparinized whole blood-on in vitro endothelial and contractile functions of the human radial artery. METHODS: Radial artery segments were harvested, cut into 3-mm rings, and stored in unoxygenated Ringer's solution, normal saline solution, or heparinized whole blood for 45 minutes. Rings stored in Krebs solution were used as controls. The rings were then mounted and stretched to an optimal resting tension in oxygenated Krebs solution at 37 degrees C. Contraction responses to potassium, norepinephrine, and serotonin and relaxation responses to acetylcholine, verapamil, and nitroprusside were evaluated. RESULTS: Fifty-six radial artery ring segments from 14 patients (n = 7 rings for each contraction-relaxation curve) were studied. Equilibrated resting tension was 9.6 +/- 0.3 mN (5.9 +/- 0.2 g), and resting internal circumference was 6.4 +/- 0.2 mm. Absolute maximum contraction to potassium was significantly less in rings stored in normal saline solution than in rings stored in control solution (10.7 +/- 0.6 g vs 14.5 +/- 0.6 g, P <.01; 95% confidence intervals, 0.9-6.9). There was no difference in the contraction to norepinephrine (P =.11) and serotonin (P =.25) among the 3 solutions compared with the control solution. Rings stored in heparinized whole blood had significantly greater endothelium-dependent relaxation to acetylcholine (P <.007), whereas those stored in normal saline solution had reduced responses. Endothelium-independent relaxation to verapamil and nitroprusside were similar among the 3 solutions. CONCLUSION: Heparinized whole blood is a better physiologic medium for preservation of radial artery endothelial and contractile functions during storage before grafting.

Invasive investigations and revascularisation.

Invasive investigation of coronary artery disease is relatively expensive, and carries risks including a mortality of approximately 1 in 2000. It would not be practical or appropriate to perform invasive investigation in all patients with a clinical diagnosis of coronary artery disease, still less in the large numbers with chest pain and possible angina. Clinicians will refer for invasive investigation those: (i) with a high level of angina, needing revascularisation on symptomatic grounds; and (ii) who are likely to have a poor prognosis with medical treatment, and thus likely to benefit from revascularisation. Not all of these patients will have a high level of symptoms.

Expression of soluble endothelial adhesion molecules in clinical cardiopulmonary bypass.

Soluble endothelial adhesion molecule expression in clinical cardiopulmonary bypass (CPB) was investigated. Neutrophil-mediated endothelial injury plays an important role in CPB-induced organ dysfunction. The adhesion of neutrophil to the endothelium is central to this process. It has been well documented that CPB induces neutrophil activation and changes in neutrophil adhesion molecule expression, but the effect of CPB on endothelial cell activation is not known. This study was designed to measure soluble endothelial adhesion molecules during CPB. We made serial measurements (by specific enzyme-linked immunoabsorbent assay) of plasma levels of the soluble endothelial adhesion molecules, ICAM-1 and E-selectin in patients undergoing routine CPB (n = 7) and in a control group (thoracotomy, n = 3). The results show an initial significant decrease during CPB followed by an increase in plasma E-selectin from 29.3 +/- 5.1 ng/ml (mean +/- SEM) prebypass to 34.0 +/- 5.4 ng/ml at 48 h postbypass. Likewise, plasma ICAM-1 significantly decreased during CPB and then increased from 246.3 +/- 38.0 ng/ml before bypass to 324.8 +/- 25.0 ng/ml and 355.0 +/- 23.0 ng/ml at 24 and 48 h after bypass, respectively. The rise in levels is statistically significant (p < 0.05). This study shows a decrease in circulating ICAM-1 and soluble E-selectin during CPB and an increase in their levels at 48 h after CPB.

Validation of a new intraoperative technique to evaluate load-independent indices of right ventricular performance in patients undergoing cardiac operations.

BACKGROUND: Assessment of right ventricular performance in the perioperative period is difficult because there is no generally accepted method of measuring right ventricular volume. We set out to determine whether conductance technology could provide a valuable technique for the investigation of intraoperative right ventricular function. METHODS AND RESULTS: Three validating studies were performed in 25 patients undergoing routine coronary revascularization. Study 1: The influence of conductance catheter position in the right ventricle was examined in 10 patients. Insertion of the conductance catheter through the outflow tract was associated with a larger gain constant and a smaller parallel conductance compared with insertion through the tricuspid valve. Study 2: The reproducibility of contractility measurements with the use of a conductance catheter was examined in 7 additional patients. Removal and reinsertion of the conductance catheter was not associated with any significant difference in right ventricular volume or contractile function. Study 3: Right ventricular performance before and after cardiopulmonary bypass was compared in 8 additional patients. There was a fall in the slope of the right ventricular preload recruitable stroke work from 15.6 (3.8) to 11.0 (5.1) mm Hg (P=.01) and an increase in the slope of the end-diastolic pressure-volume relations from 0.05 (0.02) to 0.11 (0.05) mm Hg/mL (P=.001). CONCLUSIONS: The conductance technique can be used to study perioperative changes in right ventricular performance. Insertion of the conductance catheter through the outflow tract provides stable and reproducible data. There is significant impairment of right ventricular contractility in the early postoperative period.

Predicting operative risk for coronary artery surgery in the United Kingdom: a comparison of various risk prediction algorithms.

OBJECTIVE: To compare the ability of four risk models to predict operative mortality after coronary artery bypass graft surgery (CABG) in the United Kingdom. DESIGN: Prospective study. SETTING: Two cardiothoracic centres in the United Kingdom. SUBJECTS: 1774 patients having CABG. MAIN OUTCOME MEASURES: Risk factors were recorded for all patients, along with in-hospital mortality. Predicted mortality was derived from the American Society of Thoracic Surgeons (STS) risk program, Ontario Province risk score (PACCN), Parsonnet score, and the UK Society of Cardiothoracic Surgeons risk algorithm. RESULTS: There were significant differences (p < 0.05) between the British and American populations from which the STS risk algorithm was derived with respect to most variables. The observed mortality in the British population was 3.7% (65 of 1774). The mean predicted mortality by STS score, PACCN, Parsonnet score, and UK algorithms were 1.1%, 1.6%, 4.6%, and 4.7% respectively. The overall predictive ability of the models as measured by the area under the receiver operating characteristic curve were 0.64, 0.60, 0.73, and 0.75, respectively. CONCLUSIONS: There are differences between the British and American populations for CABG and the North American algorithms are not useful for predicting mortality in the United Kingdom. The UK Society of Cardiothoracic Surgeons algorithm is the best of the models tested but still only has limited predictive ability. Great care must be exercised when using methods of this type for comparisons of units and surgeons.

Pulmonary surfactant composition early in development of acute lung injury after cardiopulmonary bypass: prophylactic use of surfactant therapy.

Cardiopulmonary bypass surgery (CPB) causes lung injury and at least 2% of adult patients and more children develop the most severe from acute respiratory distress syndrome (ARDS). Pulmonary surfactant deficiency contributes to the pathogenesis of ARDS. It has been proposed that surfactant therapy immediately after CPB might arrest progression to ARDS. However, many patients develop only mild lung injury after CPB. Thus early markers are needed to identify those patients at highest risk to guide selection for treatment. The aim of this study was to determine whether changes in surfactant phospholipids occur, and reflect severity of lung injury within the first few hours after bypass. Because of the relatively low incidence of ARDS in adult patients, this study was conducted using young pigs highly susceptible to bypass-induced lung injury. Eight pigs were given 2 hours bypass. Six controls underwent 'sham' bypass. At 3 h after bypass pulmonary vascular endothelial permeability was assessed by transcapillary leakage of radiolabelled transferrin. A 4 hour broncho-alveolar lavage (BAL) was used to assess intra-alveolar levels of surfactant, inflammatory cells and oedema protein. Bypass caused falls in arterial oxygenation and lung compliance (P < 0.01), but at this early stage in progression of lung injury BAL surfactant phospholipid and albumin levels were within the control range indicating that the alveolar epithelium had not yet suffered major damage. The main abnormalities were increases in vascular endothelial permeability (P < 0.01), BAL neutrophils (P < 0.01), total protein and sphingomyelin (SM) (P < 0.05). Lung histology showed that the main damage was interstitial oedema located around the bronchioles and their associated vessels. A single instilled dose of surfactant phospholipids in 5 animals caused excess in vivo supplementation and did not reduce the early pathophysiologic changes. Our findings suggest that surfactant phospholipid deficiency does not make a major contribution in the initial stages of lung injury after CPB, and that excessive phospholipid supplementation at this stage can be deleterious.

Plasma brain natriuretic peptide concentrations in patients with chronic mitral regurgitation.

BACKGROUND AND AIMS OF THE STUDY: Patients with chronic mitral regurgitation (MR) are often referred for surgery only after irreversible left ventricular (LV) dysfunction has developed. Our aim was to determine whether plasma brain natriuretic peptide (BNP) concentrations could serve as a marker for early LV dysfunction in this condition. METHODS: Twenty-two patients with isolated chronic MR and echocardiographic evidence of at least moderate regurgitation were studied. RESULTS: Plasma BNP concentrations were significantly higher in patients than in normal volunteers (20.85 +/- 16.9 versus 3.37 +/- 0.9 pmol/l; p = 0.007). Concentrations increased with increasing severity of symptoms and were highest in those in NYHA class IV, but did not correlate with LV dimensions, fractional shortening or left atrial size. Of note, two asymptomatic patients with high BNP concentrations were referred for surgery within the 12-month follow up period due to symptom progression. CONCLUSIONS: Plasma BNP concentrations are elevated in most patients with isolated chronic MR, including those who are asymptomatic with normal LV dimensions. The significance of these findings is uncertain, but they suggest that changes in ventricular physiology occur early in the disease process and before they can be detected echocardiographically. Longitudinal studies are required to determine if patients with high BNP levels have an adverse prognosis and if this can be altered by earlier surgical intervention.

Effects of inhibition of complement activation using recombinant soluble complement receptor 1 on neutrophil CD11b/CD18 and L-selectin expression and release of interleukin-8 and elastase in simulated cardiopulmonary bypass.

The inflammatory response to cardiopulmonary bypass includes activation of complement and induction of several neutrophil activation pathways. A recombinant soluble form of complement receptor 1 was used as a specific inhibitor of complement activation in simulated cardiopulmonary bypass circuits. Substantial complement activation was observed in these circuits with progressive accumulation of both plasma C3a and terminal complement complex. Soluble complement receptor 1 resulted in a significant reduction in C3a levels (p < 0.01) but did not inhibit terminal complement complex generation. A marked rise in neutrophil CD11b/CD18 expression, simultaneous loss of L-selectin expression, and a progressive accumulation of plasma elastase-alpha 1-antitrypsin occurred and were not affected by soluble complement receptor. However, generation of interleukin-8 in the circuits was inhibited (p < 0.05) by pretreatment with soluble complement receptor. These data suggest that changes in neutrophil activation seen during cardiopulmonary bypass may not be induced directly by anaphylatoxin generation.

Cytokine production and hemofiltration in children undergoing cardiopulmonary bypass.

Multiorgan dysfunction still occurs after cardiopulmonary bypass and remains a major cause of morbidity and mortality, especially in the pediatric age group. This is consequent upon the so-called systemic inflammatory response to bypass with an increase in inflammatory mediators. Hemofiltration may be able to attenuate the effects of this response by elimination of some or all of these mediators. We undertook a prospective, randomized study to investigate the effect of hemofiltration on plasma levels of the cytokines tumor necrosis factor alpha, interleukin-8, and interleukin 6 in 18 infants and children undergoing deep hypothermic bypass. Serial plasma samples were taken before, during, and after bypass. Assay of the plasma samples revealed presence of the cytokines in a number of subjects in both groups, in some cases before operation. There were significant reductions in levels of tumor necrosis factor after hemofiltration, with no reduction noted in the group not undergoing hemofiltration. A similar difference (p < 0.05) was detected in the levels of interleukin-6 between the two groups after bypass, although this was largely due to changes in 2 subjects. Interleukin-8 was detected in a small number of subjects insufficient for statistical analysis, but with higher values in the group undergoing hemofiltration. We conclude that hemofiltration has the potential to remove cytokines from the circulation, with consequent beneficial effects.

Humoral and cellular activation in a simulated extracorporeal circuit.

Endothelial injury consequent upon widespread humoral and cellular activation is probably a major contributor to the phenomenon of cardiopulmonary bypass-induced organ dysfunction. This article reviews some of the mechanisms by which complement and neutrophil activation and interleukin-8 may be involved in this inflammatory response. In a model consisting of a simulated extracorporeal circulation we were able to demonstrate complement activation, profound and specific changes in neutrophil adhesion molecule expression, and interleukin-8 generation. The importance of these changes and their potential interactions are discussed.

Chelatable iron and copper can be released from extracorporeally circulated blood during cardiopulmonary bypass.

During cardiopulmonary bypass surgery blood is extracorporeally oxygenated and circulated before returning to the systemic arterial circulation. Blood undergoing extracorporeal dilution and circulation is exposed to non-physiological surfaces, which cause the activation of several regulatory cascades. Cells are also subjected to damaging shear stresses. Under such conditions neutrophils can be 'activated' to release reactive oxygen intermediates such as O2- and H2O2, and other cells can release proteolytic enzymes and metalloproteins. Collectively, these events can result in the release of micromolar quantities of redox active iron and copper. Bleomycin-detectable iron and phenanthroline-detectable copper were found in two out of four mock bypass experiments. However, there was no correlation between the presence of chelatable iron and copper and the activation of neutrophils measured as elastase.

Changes in neutrophil CD11b/CD18 and L-selectin expression and release of interleukin 8 and elastase in paediatric cardiopulmonary bypass.

Children undergoing cardiopulmonary bypass (CPB) surgery for congenital heart defects develop an acute post-operative capillary leak which may be due to endothelial injury inflicted by adherent neutrophils (PMN). Direct immunofluorescence and flow cytometry were used to measure CD11a/CD18, CD11b/CD18 and L-selectin (L-s) expression on circulating PMN in CPB circuits containing human blood and in children undergoing CPB. In vitro, a general rise in CD11b/CD18 expression over 2 h contrasted with complete loss of L-s in a small but progressively increasing proportion of PMN. Marked but inconsistent changes in CD11b/CD18 and L-s were observed in vivo, in conjunction with fluctuations in circulating PMN count. Circulating IL-8 was detected starting at rewarming from hypothermia and reperfusion of the heart and lungs with a simultaneous, closely correlated rise in both PMN count and circulating elastase. IL-1 and TNF were not detected. These studies demonstrate changes in the pathways of PMN-endothelial interaction during and after CPB.

Organ dysfunction and cardiopulmonary bypass: the role of complement and complement regulatory proteins.

Cardiopulmonary bypass-induced organ dysfunction remains a clinical problem in certain groups of patients. Although the pathogenesis is multifactorial, it is likely that a panendothelial injury consequent upon widespread humoral and cellular activation is a major contributor to this process. The biologically active products of complement activation are certainly capable of inducing many of the features of the post-perfusion syndrome. The complex interactions between complement and many of the other proposed mediators of this response also supports this contention. However, it is equally certain that many of the other proposed mediators have some role to play. Inhibition of one cell type or inflammatory cascade is therefore unlikely to abolish all the adverse effects of CPB but will, at least in experimental systems, permit a more precise determination of the pathogenesis of this problem. The temptation to simply measure elevated circulating levels of newly identified mediators must be resisted and more effort applied to examining the pathophysiological effects of specific inhibitors. This type of investigation should initially be effected in experimental models where reproducible conditions can be ensured. In conjunction with this, far more precise end-points are required in order to assess the effect of any potential therapeutic intervention in a clinical setting. In particular, new techniques of evaluating endothelial injury need to be developed. In clinical studies careful consideration must be given to the patient population studied. Whilst patients undergoing routine coronary artery surgery form a relatively homogeneous group, the magnitude of endothelial injury sustained is probably small and, especially in terms of lung function, the signal will be diluted by other non-bypass-related events. The study of high risk groups would seem more appropriate despite their heterogeneity. An important unanswered question is why certain sub-populations of patients are at increased risk of clinically relevant bypass-induced injury. The endothelium of these patients may be different: the neonatal pulmonary microcirculation is not the same as that of an adult (with increased fluid filtration pressure and a higher microvascular surface area per unit lung mass [5,6]), children with pulmonary hypertension have histological evidence of an altered/damaged endothelium (S.G. Haworth, Personal Communication) whilst pre-existing sepsis could clearly induce a degree of endothelial dysfunction. A further possibility is that the inflammatory response in these patients is already "primed". Some patients with heart failure have been shown to have elevated circulating TNF.(ABSTRACT TRUNCATED AT 400 WORDS)