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.

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.

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.

Effects of S-nitroso-glutathione in the human forearm circulation: evidence for selective inhibition of platelet activation.

OBJECTIVE: Nitric oxide (NO) is a vasodilator and inhibitor of platelet function. The clinical use of NO donors as inhibitors of platelet activation is limited by their concomitant hypotensive effect. S-nitroso-glutathione (GSNO) has a significant antiplatelet effect at doses that cause only a small decrease in blood pressure in rats. The aim of this study was to examine the antiplatelet and vasodilator properties of this nitrosothiol in the human forearm. METHODS: Forearm blood flow was measured by forearm occlusion plethysmography in five healthy males. Ex vivo platelet aggregation to ADP was performed in a platelet ionised calcium lumi-aggregometer. RESULTS: Intra-arterial infusion of GSNO (0.2, 1, and 5 nmol.min-1) resulted in inhibition of ADP (1-10 microM) induced platelet aggregation. This inhibition was submaximal for 0.2 and maximal for 1 and 5 nmol.min-1. However, the antiaggregatory effect observed at the lowest dose of GSNO was accompanied only by a threshold increase in forearm blood flow. CONCLUSIONS: These results show that GSNO is more effective as an inhibitor of platelet activation than as a vasodilator, suggesting that it is possible to achieve selective antiplatelet and potentially antithrombotic effects with NO donors.

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.

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.

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.

Cardiomyopathy: a role for nitric oxide?

The negative inotropism, myocardial dilatation and cytotoxicity in inflammatory heart disorders may be due to increased generation of nitric oxide (NO) by immunological induction of a high output NO pathway. This short review discusses the initial experiments which lead to this hypothesis, and evaluates data that this pathway exists in animal and human cardiomyopathic disorders. It is proposed that manipulation of this pathway may prove to be beneficial in patients with these disorders.

Preparation and properties of fluorescein-labelled hyaluronate.

Hyaluronate has been labelled with fluorescein groups by two procedures. Products with degrees of substitution ((d.s.) between 0.05 and 0.001 were obtained. Physico-chemical analysis (viscometry, gel chromatography, and measurements of sedimentation and diffusion coefficients) of the parent compound and the products showed that the labelling procedures caused only a limited degradation of the polysaccharide.

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 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.

Traumatic rupture of the thoracic aorta diagnosed by transoesophageal echocardiography.

Transoesophageal echocardiography is a safe and rapid means of obtaining anatomical and dynamic information about the descending aorta. It was used to confirm a suspected diagnosis of ruptured descending aorta.

Antibodies against hydroxyethylstarch produced in rabbits by immunization with a protein-hydroxyetylstarch conjugate.

Antibodies (ABS) against hydroxyethylstarch (HES) were raised in rabbits by immunization with HES-bovine serum albumin conjugate. ABS against HES were demonstrable by gel diffusion, passive hemagglutination (PH) and passive cutaneous anaphylaxis (PCA); specificity was confirmed by inhibition of PH and neutralization of PCA. No ABS against starch could be induced in comparative experiments. Non-immunogenicity of starch was attributed to its structural similarity with glycogen, widely distributed in animal species. Absence of cross-reactivity of anti-HES ABS with starch, amylopectin and glycogen and strong reactivity with 2-hydroxypropylstarch (DS = 0.65) and HES (DS = 0.7-1.2) indicate that hydroxyethyl substitution created antigenic determinants and conferred new immunochemical identity on the modified starch molecule. Anti-HES ABS represent specific analytical tools for the identification and quantitation of HES in biological material.