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.

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.

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.

Complex coronary arterial anatomy in transposition of the great arteries. Arterial switch procedure without coronary relocation.

Translocation of the coronary arteries remains a technical problem in anatomic correction of transposition of the great arteries. Myocardial ischemia related to difficulties with coronary relocation is a significant factor in perioperative morbidity and mortality, particularly in those patients with complex coronary anatomy. Two neonates with transposition of the great arteries and intact ventricular septum are described in whom the coronary arteries arose from multiple ostia, all lying within sinus 1, with one of the ostia in each instance being severely eccentric. An anatomic switch of the great vessels was done without coronary relocation. This was achieved by means of an aortopulmonary fenestration with a bovine pericardial tunnel to allow coronary artery perfusion with blood from the neoaorta. An additional pericardial patch was placed to the contralateral wall of the proximal neopulmonary artery. Both infants had an uneventful postoperative recovery with no evidence of myocardial ischemia, although both have a mild gradient across the proximal pulmonary artery. This operative technique may be appropriate in those patients in whom there is concern over the feasibility of translocating the coronary arteries without producing myocardial ischemia.

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.

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.

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.

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.

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.

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.

Single dose mezlocillin versus three dose cefuroxime plus metronidazole for the prophylaxis of wound infection after large bowel surgery.

A prospective, randomized, controlled trial was conducted in 116 consecutive patients undergoing colorectal surgery to compare single dose prophylaxis with mezlocillin to cefuroxime plus metronidazole in three doses. Patients were randomized to receive either a single dose of iv mezlocillin (5.0 g) or three doses of iv cefuroxime plus metronidazole at 8-hourly intervals. The first dose was given on the operating table. The overall wound infection rate in the mezlocillin treated patients (n = 54) was 30% and in the patients treated with cefuroxime plus metronidazole (n = 56) 25%. This difference is not statistically significant. When trivial wound infections were disregarded the wound infection rates were 11% and 16% respectively, which again was not statistically significant.

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.

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)

Circulatory support in infants with post-cardiopulmonary bypass left ventricular dysfunction using a left ventricular assist device.

Extracorporeal membrane oxygenation has been advocated as the most appropriate mode of circulatory support in the paediatric age group for post-cardiopulmonary bypass ventricular dysfunction. The results in infants who have predominantly left ventricular failure, or who require such support in order to be weaned off bypass, have been disappointing. Three infants with severe left ventricular dysfunction following cardiopulmonary bypass for correction of congenital heart defects have been managed with a left ventricular assist device. Two required this form of circulatory support in order to be weaned from full bypass while in the third infant it was instituted for progressive left ventricular dysfunction postoperatively. All three were less than 10 kg in weight. Left atrial appendage to aortic bypass was effected using a closed loop circuit with a constrained vortex pump (Biomedicus). Duration of support ranged between 40 and 146 h. One infant made a complete recovery and was able to be discharged home 20 days postoperatively. Another made a circulatory recovery such that both mechanical and inotropic support could be discontinued but had sustained massive neurological damage. The third died of progressive left ventricular dysfunction. This experience with a left ventricular assist device demonstrates that it is technically feasible in small infants, and can be performed to good effect in infants with predominant left ventricular dysfunction following cardiac surgery. It may well be more appropriate than extracorporeal membrane oxygenation in this group of patients.

Induced hypothermia in the management of refractory low cardiac output states following cardiac surgery in infants and children.

Post-operative low cardiac output states remain a major cause of mortality following cardiac surgery in infants and children. Since 1979 we have used moderate induced whole-body hypothermia in the management of low-output states refractory to conventional modes of therapy. This is based not only upon the relationship between body temperature and oxygen consumption, but also on experimental work showing a beneficial effect of cooling upon myocardial contractility, particularly when there is pre-existing impairment of ventricular function. Between July 1986 and June 1990, 20 children with refractory low-output states were cooled by means of a thermostatically controlled water blanket to a rectal temperature of 32-33 degrees C. The median age was 12 months (1 week-11 years) with a median weight of 6 kg (3.5-33 kg). Ten children survived to leave hospital while a further two made a haemodynamic recovery. There was a marked reduction in heart rate (P < 0.001). The mean arterial pressure rose (P = 0.037) while there was a fall in mean atrial pressure (P < 0.001). There was a significant improvement in the urine output (P = 0.002). A fall in the platelet count (P < 0.001) was not accompanied by any change in the white cell count (P = 0.15). Although it is impossible to say whether cooling influenced the outcome in any of these children, it was usually effective in stabilising their clinical condition. The technique is simple and has a sound theoretical basis.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.