Pre-procedural pacing bias among transcatheter aortic valves with higher post-procedure pacing rates: evidence from the UK TAVI Registry.

Rates of permanent pacemaker (PPM) implantation following transcatheter aortic valve implantation (TAVI) are higher than following surgery and are dependent on patient factors and valve type. There is an increasing trend towards pre-emptive PPM insertion in patients with significant conduction disease prior to TAVI. We report results from the British Cardiovascular Intervention Society (BCIS) on pre- and post-procedural PPM implantation in the TAVI population. All centres in the United Kingdom performing TAVI are required to submit data on all TAVI procedures to the National database which are then reported annually. During 2015, there were 2373 TAVI procedures in the UK. 22.4% of TAVI patients had a PPM implanted either pre-procedure (including the distant past), or during the in-hospital procedural episode. Of these, 7.9% were pre-procedure and 14.5% post-procedure. Overall PPM rates were Edwards Sapien (13.5%), Medtronic CoreValve (28.2%) and Boston Lotus (42.1%; p < 0.01). Pre-procedure pacing rates were Edwards Sapien (6.0%), Medtronic CoreValve (9.1%) and Boston Lotus (12.3%; p < 0.01). Pre-procedural pacing rates for the Boston Lotus valve have risen year-on-year from 5.8% (2013) to 8.6% (2014) to 12.3% (2015). The UK TAVI Registry demonstrates a pre-procedural permanent pacing bias amongst patients receiving transcatheter valves with higher post-procedure pacing rates. Pre-emptive permanent pacing is likely to be responsible for this difference.

Changing the coronary bifurcation angles after stenting procedures: the relevance to the technique and unfavorable outcome (Three-dimensional analysis).

AIM: Percutaneous transluminal balloon co-ronary angioplasty (PTCA) of coronary bifurcations is associated with a low success rate, higher rate of complications and need for revascularazation. We sought to analyze: 1) the change in 3D measurement of angles following stenting of coronary bifurcations; and 2) if changes in these angles might predict unfavourable outcomes. METHODS: Coronary angiograms of 102 patients with bifurcation lesions were analyzed with 3D software (CardiOp-B) before and after stenting. The change in angle between the proximal main artery and side branch (BA), and between the distal main artery and side branch (BS) were measured. A change of ≥ 5° after stenting was considered significant. The results were compared with clinical follow-up. RESULTS: Bifurcation lesions included 66 left anterior descending/first diagonal (LAD/D1) lesions, 15 left main stem (LMS) lesions, 19 atrioventricular circumflex/obtuse marginal (AVCx/OM) lesions, and 2 coronary artery (RCA) crux lesions. BA and BS measured 138.3° ± 17.2° and 64.3° ± 20.6° respectively. Stent deployment altered BA and BS significantly in 80-90% of cases. Furthermore, BS correlated positively with the magnitude of change in BS after stenting. BA was unaffected by the complexity of the stenting procedure, whereas BS increased significantly in complex versus simple stenting strategies (P<0.05). Procedure related complications occurred in 15.6% of patients. The incidence of in-hospital complications was lower when BA was increased (P<0.05). The one year incidence of the composite of in-hospital complications and late complications was also significantly lower when BA was increased by ≥ 5° (P=0.027). A decrease of BA was associated with 80% more complications compared to cases where BA was increased. No correlation was found between the change of BS and procedural or late complications. CONCLUSION: 3D measurements of coronary bifurcation angles prior to stenting can predict changes in bifurcation geometry after stenting. A decrease in BA after stenting is a strong predictor for less favourable outcomes of coronary bifurcation stenting procedures.

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.

Transradial coronary intervention without pre-screening for a dual palmar blood supply.

It is usual practice to determine the presence of collateral blood supply to the hand prior to radial artery cannulation. We propose that pre-screening for a dual palmar vascular supply is not necessary and the presence of a palpable radial pulse is sufficient to allow successful radial artery cannulation. We retrospectively analysed our interventional PTCA registry, including only patients who had a transradial procedure without being pre-screened with an Allen's test or plethysmography. We report our data including complications the day after the procedure and at 30 days, and provide an up to date discussion on the need to assess patients for a dual palmar blood supply prior to transradial intervention.

Should primary angioplasty be available for all patients with an ST elevation myocardial infarction?

For the acute myocardial infarction patient, percutaneous coronary intervention is clearly superior to thrombolysis for many clinical end points, yet widespread availability of PCI services is still far from being realised.

Successful percutaneous transluminal coronary angioplasty for acute myocardial infarction in von Willebrand's disease.

An elderly woman with mild von Willebrand's disease presented with acute myocardial infarction. Percutaneous transluminal coronary angioplasty, to mechanically disrupt the thrombus without anticoagulation, was successfully undertaken. Haemostatic cover was also avoided.

A randomised trial of endoluminal reconstruction comparing the NIR stent and the Wallstent in angioplasty of long segment coronary disease: results of the RENEWAL Study.

BACKGROUND: The role of coronary stents in reducing the incidence of acute complications and late restenosis after angioplasty has been established in randomized studies focusing on simple, short coronary lesions. The development of long coronary stents has provided a safe and predictable means of treating long coronary lesions, but this carries with it a higher risk of restenosis. By comparing the outcome of treating long lesions with two different stent types, we aimed to assess the influence of stent design rather than the nature of long lesions per se on the relatively high restenosis rates in this subgroup. METHODS: This study was designed to assess procedural complications and 6-month restenosis rates in a randomized trial comparing a slotted tube stent with a self-expanding stent for the treatment of long coronary lesions. Randomization of vessels to either stent occurred after successful balloon angioplasty. Intravascular ultrasound (IVUS) was used to assess and optimize stent deployment. The patients were restudied angiographically and by IVUS at 6 months. RESULTS: A total of 82 patients (85 vessels) were recruited (slotted tube stent, n = 44 vessels; self-expanding stent, n = 41 vessels). Successful deployment occurred in 41 (100%) of 41 of the self-expanding stent group and 41 (93%) of 44 of the slotted tube stent group. There was no difference in lesion length between the two groups (slotted tube stent, 26.6 +/- 6.9 [SD] mm; self-expanding stent, 28.7 +/- 9.8 [SD] mm; P = .2), but the mean length of the self-expanding stent was greater than that of the slotted tube stent (41.6 +/- 18.8 [SD] mm vs 35.4 +/- 16.2 [SD] mm, respectively; P < .05). There was no significant difference in the rate of major events between the two groups at 6-month follow-up. The angiographic restenosis rate at follow-up was less in the slotted tube stent group, but this did not reach statistical significance (26% vs 46%, respectively; P = .1) and the target lesion revascularization rate was similar for both groups (7.9% vs 7.7%, respectively; P = .8). IVUS assessment of plaque/stent ratios suggested a greater plaque burden in the self-expanding stent compared with the slotted tube stent at follow-up (0.42 +/- 1.2 [SD] vs 0.3 +/- 0.08 [SD]), but this was not statistically significant (P = .1). CONCLUSIONS: Long stents can be safely and successfully deployed in long segment coronary disease, with an acceptable 6-month target lesion revascularization rate. Our results showed a trend toward lower angiographic restenosis and a lesser in-stent plaque burden at follow-up in the slotted tube stent compared with the self-expanding stent. This suggests that stent design may influence the restenotic process in long coronary lesions.

Development and validation of a Bayesian index for predicting major adverse cardiac events with percutaneous transluminal coronary angioplasty.

OBJECTIVE: To create a risk model for predicting major adverse complicating events of percutaneous transluminal coronary angioplasty (PTCA), and to test the accuracy of the model on a prospective cohort of patients SETTING: Tertiary cardiac centre METHODS: Available software can predict probabilities of events using Bayes's theorem. To establish the accuracy of these predictive tools, a Bayes table was created to evaluate major adverse complicating events (MACE)-death, emergency coronary artery bypass grafting (CABG), or Q wave infarct occurring during the in-patient episode-on the first 1500 patients in the department PTCA database (development group); the predictive value of this model was then tested with the subsequent 1000 patients (evaluation group). The following probabilities were assessed to determine their association with MACE: age, sex, left ventricular function, American Heart Association lesion morphology classification, cardiogenic shock, previous CABG, diabetes, hypertension, multivessel PTCA. MAIN OUTCOME MEASURES: To establish the discriminatory ability of the predictive index, calibration plots and receiver operating characteristic (ROC) curves were obtained to compare the development and evaluation groups. RESULTS: The ROC curve plotted to determine the discriminatory value of the Bayesian table created from the development group (n = 1500) in predicting MACE in the evaluation group (n = 1000) showed a moderately predictive area under the curve of 0.76 (SEM 0.07). This predictive accuracy was confirmed with separately constructed calibration plots. CONCLUSIONS: Accurate predictions of MACE can be identified in populations undergoing percutaneous intervention. The database used allows operators to obtain consent from patients appropriately from their own experience rather than from other published data. If a national PTCA database existed along similar lines, individual operators and interventional centres could compare themselves with nationally available data.

Intravascular ultrasound-guided stenting in long lesions: an insight into possible mechanisms of restenosis and comparison of angiographic and intravascular ultrasound data from the MUSIC and RENEWAL trials.

The high restenosis rates in long stents may be related to suboptimal stent deployment. In an attempt to understand the potential components associated with restenosis in long stents, this study compares angiographic and intravascular ultrasound (IVUS) data from the MUSIC and RENEWAL studies where IVUS was used to optimize stent deployment in short (< 15 mm) and long (> 20 mm) coronary lesions, respectively. The RENEWAL study, a randomized trial, compared the NIR stent and Wallstent in long (> 20 mm) coronary lesions and used on-line visual IVUS criteria to optimize stent expansion. Detailed analysis of IVUS data was performed off line. Angiographic and IVUS data from this study was compared to that from the MUSIC study. Initial stent deployment was deemed optimal by the operator after visual angiographic and IVUS assessment in 50 of 70 lesions. In the remaining 20 lesions further balloon inflations were required to optimize stent apposition that led to an average gain in minimal in-stent luminal area (MISA) of 15.9% (P < 0.01). Off-line IVUS data analysis showed that the number reaching "MUSIC criteria" for optimal stent deployment preredilatation was 8 (11.4%) of 70 and 14 (20%) of 70 postredilatation. The ratio of MISA/MRAprox (mean proximal reference area) was 0.69 in RENEWAL. At 6-month follow-up, the angiographic restenosis rate in RENEWAL was 36% and target lesion revascularization (TLR) rate was 7.8%, compared with MUSIC's 9.7% and 4.5%, respectively. In conclusion, angiographic assessment of stent deployment in long lesions is limited. On-line visual IVUS with further balloon inflations to improve stent apposition led to a significant gain in MISA, but the MISA/MRAprox ratio remained suboptimal. Therefore, suboptimal stent deployment due to constraint by lesion resistance may be an important mechanism underlying the high restenosis rates in long stents.

Induction of myocardial nitric oxide synthase by Coxsackie B3 virus in mice.

BACKGROUND: Inducible nitric oxide synthase (iNOS) expression is regulated by cytokines. This study investigated whether Coxsackie group B virus (CVB) myocarditis resulted in an environment suitable for induction of NOS in the murine heart. MATERIALS AND METHODS: Myocardium was removed from mice infected with CVB3 and from controls. Histology, reverse transcriptase polymerase reaction (RT-PCR) for murine iNOS, NOS enzyme activity and immunohistochemistry were assessed. RESULTS: Histology revealed severe myocarditis 7 days after infection with CVB3 but not in controls. RT-PCR using primers for murine iNOS detected iNOS mRNA in infected mice but not in controls. Calcium-independent NOS activity increased by day 5 after infection with a peak at day 7. Calcium-dependent NOS activity was present throughout, with a trend to lower levels during peak calcium-independent activity. Immunohistochemistry revealed iNOS to be localized to inflammatory cells rather than to myocytes. CONCLUSION: This study demonstrates the development of calcium-independent NOS activity and de novo gene transcription for iNOS in the murine myocardium in response to CVB3 infection. The nitric oxide produced at such high output may act at times as part of the immune defence as an antiviral agent and may be toxic to host tissue.

S-nitrosoglutathione inhibits platelet activation and deposition in coronary artery saphenous vein grafts in vitro and in vivo.

OBJECTIVE: To investigate platelet activation and deposition in human saphenous vein and internal mammary artery grafts following coronary artery bypass in vitro and in vivo, as well as inhibition of activation by the platelet selective nitric oxide donor S-nitrosoglutathione (GSNO). DESIGN: Controlled in vitro and in vivo studies. SETTING: Tertiary cardiac centre. PATIENTS: 24 patients undergoing coronary artery bypass surgery requiring vein and artery grafts. INTERVENTIONS: In vitro: human platelet rich plasma was perfused through segments of vein and artery, with or without GSNO 10(-6) M, and the platelet count was measured in the effluent. In vivo: indium-111 labelled antibody against the platelet alpha granule protein GMP-140 was injected at the end of coronary bypass grafting and gamma counts were compared between vein and artery grafts with or without systemic infusion of GSNO (40 nmol/min). RESULTS: In vitro: platelet count in perfused vein (< 70% of baseline) decreased more than in artery segments (89-94% of baseline) (p < 0.001). The platelet count was unchanged with GSNO in vein and artery segments. In vivo: gamma counts were greater at all time points over vein than artery grafts (p < 0.05), and were reduced by infusion of GSNO (p < 0.05). CONCLUSIONS: Platelet activation is greater in vein than in artery grafts in vitro and in vivo. Activation, which contributes to early vein graft failure, was inhibited by GSNO.

Megakaryocyte ploidy and platelet changes in human diabetes and atherosclerosis.

Altered platelet morphology and function have been reported in patients with diabetes. They are likely to be associated with the pathological processes and increased risk of vascular disease seen in these patients. Mean platelet volume (MPV), platelet count, and megakaryocyte (MK) ploidy (DNA content) were measured in (1) nondiabetics with normal coronary arteries, (2) nondiabetics with coronary artery atherosclerosis, (3) diabetics without evidence of vascular complications, and (4) diabetics with vascular disease. The platelet count (+/- SD) was increased in all groups but only significantly in the diabetics with vascular disease (236 +/- 65 versus 250 +/- 54 versus 257 +/- 64 versus 295 +/- 90 [P < or = .05] x 10(9)/L, for groups, I, II, II, and IV, respectively). The MPV was significantly increased in patients with atherosclerosis (7.0 +/- 0.4 versus 8.0 +/- 1.2 [P < or = .05] versus 7.2 +/- 0.9 versus 8.1 +/- 0.9 [P < or = .05] IL). Geometric mean MK ploidy was significantly increased in all groups compared with controls (16 +/- 1.5 versus 18.7 +/- 1.8 [P < or = .05] versus 19.8 +/- 1.6 [P < or = .05] versus 20.1 +/- 2.7 [P < or = .05]). Furthermore, some patients with vascular disease and/or diabetes had a modal ploidy shift from 16 (the normal mammalian modal ploidy) to 32, with a concomitant reduction of MKs in the 8 and 16 ploidy classes. This shift was seen particularly in the diabetics with vascular disease (P = .007). Interleukin-6 (IL-6) levels were measured and were elevated in patients with atherosclerosis; the highest levels were found in the diabetic patients (0.7 +/- 0.9 versus 5.3 +/- 5.5 [P < or = .05] versus 2.5 +/- 2.8 versus 6.7 +/- 5.5 [P < or = .05] ng/L). In the diabetic patients with atherosclerosis, fibrinogen levels were also increased (2.85 +/- 0.76 versus 3.34 +/- 1.32 versus 2.43 +/- 1.50 versus 5.59 +/- 1.72 [P < or = .05] g/L). Furthermore, IL-6 levels correlated with MK ploidy (r = .45, P = .009) and fibrinogen levels (r = .5, P = .0001). This study demonstrates that patients with vascular disease, particularly diabetics, have an altered MK ploidy distribution, showing a shift toward higher ploidy in association with an increased platelet mass (count x volume). Changes in platelets in diabetes probably reflect MK changes, which themselves are a response to systemic change.

Non-invasive cardiac investigations in patients awaiting renal transplantation.

Patients with chronic renal failure undergoing renal transplantation have a high prevalence of cardiovascular disease. Invasive investigation may identify those at risk of cardiac death during or after renal transplantation, but which patients should undergo cardiac catheterization is currently not clear. In 95 patients awaiting renal transplantation we assessed the ability of echocardiography and exercise electrocardiography to identify patients at risk of cardiac death. Echocardiography identified impaired left ventricular (LV) systolic function in 20%, severe in 8%. Of the patients with severe LV dysfunction, 25% died before transplantation. Of those undergoing exercise electrocardiography, 44% did not achieve 85% of maximum predicted heart rate. No coronary artery disease requiring intervention was identified by exercise testing. These findings indicate that echocardiography, but not exercise electrocardiography, should be part of the assessment for renal transplantation.

Transradial artery coronary angiography and intervention in patients with severe peripheral vascular disease.

BACKGROUND: Traditionally, cardiac catheterization in patients with severe aorto-iliac disease has been performed using a brachial arteriotomy. This approach is associated with significant vascular and neuronal complications and requires considerable training to achieve an adequate level of expertise. Improvement and miniaturization of catheter equipment now allows the radial artery to be used for coronary investigation and intervention. The lack of important structures close to the radial artery, a good collateral ulnar artery circulation and its superficial position suggests that these procedures should have a low complication rate. The purpose of this study was to assess the efficacy and safety of percutaneous transradial diagnostic and interventional coronary catheterization in patients with severe peripheral vascular disease. PATIENTS AND METHODS: We undertook a non-randomized prospective analysis of 75 patients who had transradial artery diagnostic and interventional coronary catheterization in whom femoral angiography was impossible or relatively contraindicated (22 patients with severe claudication and absent femoral pulses, 24 patients with previous aorto-iliac surgery or intervention, 20 patients with a failed femoral approach, 9 patients with an aortic aneurysm). Three patients had an absent ulnar artery and were excluded. RESULTS: Radial artery cannulation was successful in 73/75 (97%) cases. Seventy-one (95%) patients had a successful diagnostic study. There was a high incidence of 3 vessel disease (73%), and the majority of patients (64%) were referred for coronary bypass surgery. Twelve patients underwent successful follow-on intervention including the insertion of 9 intracoronary stents. Adequate haemostasis was achieved within 20 min after diagnostic angiography and 60 min after interventional procedures. One patient had a forearm haematoma with paraesthesia of the hand which settled with conservative treatment. At 4-6 weeks, all patients had normal hand sensation and function (100%) with a palpable pulse present in 59/62 (96%). All patients undergoing diagnostic angiography were discharged on the same day, and patients undergoing intervention were discharged the following day. CONCLUSIONS: Transradial coronary investigation and intervention can be performed with a high degree of success and a low complication rate with early mobilization and discharge in patients with severe peripheral vascular disease. We suggest that the percutaneous transradial technique should be considered as an alternative to the Sones' technique in these patients.

A study of platelet activation during human cardiopulmonary bypass and the effect of S-nitrosoglutathione.

Cardiac surgery is complicated by the occurrence of post-operative bleeding due to platelet dysfunction. This is largely caused by platelet activation and consumption during cardiopulmonary bypass. Patients undergoing cardiac surgery requiring cardiopulmonary bypass were studied to determine whether early platelet changes due to bypass could be inhibited using the platelet-selective nitric oxide donor S-nitrosoglutathione (GSNO). Flow cytometry was used to measure platelet surface expression of P-selectin (an alpha-granule protein) and glycoproteins (GP) IIb/IIIa and Ib (mediators of aggregation and adhesion) before and 5 and 10 min after commencing cardiopulmonary bypass, in 6 controls and 6 patients receiving GSNO 50 microg/min. Platelet P-selectin expression increased during bypass both in controls and patients receiving GSNO. Glycoproteins IIb/IIIa and Ib fell during bypass in control and GSNO-treated patients. There was no difference between control and GSNO-treated groups. Thus no significant platelet inhibition by S-nitrosoglutathione was demonstrated under these conditions.

Expression of nitric oxide synthase in ulcerative colitis.

Nitric oxide (NO) is generated from L-arginine by a family of enzymes called the NO synthases. Previous investigators have proposed that the expression of this inducible enzyme (iNOS) may account for the characteristic vasodilatation, oedema and impairment of get motility seen in active ulcerative colitis. Using a specific antibody to iNOS, we have investigated the distribution of this enzyme in colonic tissue from patients with histologically proven ulcerative colitis. Eight patients with ulcerative colitis expressed calcium-independent citrulline activity (9.96 +/- 2.34 pmol citrulline mg-1 protein min-1) and showed immunoreactivity to the iNOS antibody within the inflammatory infiltrate of the lamina propria, and also within the cytoplasm of the epithelial cells lining the colon. Five age-matched controls showed no calcium-independent citrulline activity (0.2 +/- 0.08 pmol citrulline mg-1 protein min-1) and no immunoreaction to the antibody. We conclude that this enzyme is present in colonic tissue including the epithelium from patients with active colitis. Inhibition of this enzyme may provide a novel therapeutic option for patients with active ulcerative colitis.

The effects of S-nitrosoglutathione on platelet activation, hypertension, and uterine and fetal Doppler in severe preeclampsia.

OBJECTIVE: To determine the effects of the platelet-specific nitric oxide donor S-nitrosoglutathione on women with severe preeclampsia. METHODS: Ten women with severe preeclampsia or preeclampsia with severe fetal compromise at 21-33 weeks' gestation each received a 60-90-minute intravenous infusion of 50-250 micrograms/minute of S-nitrosoglutathione. Each was hypertensive, despite conventional oral antihypertensive therapy in eight. Maternal blood pressure, heart rate, platelet activation, uterine artery, and fetal Doppler indices were measured during the infusion. RESULTS: A dose-dependent reduction in mean arterial pressure from 125 mmHg (95% confidence interval [CI] 117-133) to 103.5 (95% CI 97-111) (P < .005) and an increase in pulse rate from 73.7 beats per minute (95% CI 64.3-84.5) to 89.1 (95% CI 81.2-97.8) (P < .02) was observed during the infusion. Mean uterine artery resistance index fell from 0.76 (95% CI 0.73-0.81) to 0.70 (95% CI 0.65-0.75) (P < .009). Platelet activation measured by P-selectin expression was reduced from 3.02% (95% CI 2.09-4.36) to 1.22% (95% CI 0.94-1.58) (P < .01). Fetal Doppler indices (umbilical artery, middle cerebral artery, and thoracic aorta) showed no significant changes during the infusion. CONCLUSION: S-nitrosoglutathione infusion reduced material mean arterial pressure, platelet activation, and uterine artery resistance without further compromising fetal Doppler indices. This study suggests that platelet-specific nitric oxide donors may prove beneficial in the management of severe preeclampsia.