Impact of gender, ethnicity and social deprivation on access to surgical or transcatheter aortic valve replacement in aortic stenosis: a retrospective database study in England.

OBJECTIVE: To assess gender, ethnicity, and deprivation-based differences in provision of aortic valve replacement (AVR) in England for adults with aortic stenosis (AS). METHODS: We retrospectively identified adults with AS from the English Hospital Episode Statistics (HES) between April 2016 and March 2019 and those who subsequently had an AVR. We separately used HES-linked Clinical Practice Research Datalink (CPRD) to identify people with AVR and evaluate the timeliness of their procedure (CPRD-AVR cohort). ORs for AVR in people with an AS diagnosis were estimated using multivariable logistic regression adjusted for age, region and comorbidity. AVR was considered timely if performed electively and without evidence of cardiac decompensation before AVR. RESULTS: 183 591 adults with AS were identified in HES; of these, 31 436 underwent AVR. The CPRD-AVR cohort comprised 10 069 adults. Women had lower odds of receiving AVR compared with men (OR 0.65; 95% CI 0.63 to 0.66); as did people of black (OR 0.70; 95% CI 0.60 to 0.82) or South Asian (OR 0.75; 95% CI 0.69 to 0.82) compared with people of white ethnicities. People in the most deprived areas were less likely to receive AVR than the least deprived areas (OR 0.8; 95% CI 0.75 to 0.86). Timely AVR occurred in 65% of those of white ethnicities compared with 55% of both those of black and South Asian ethnicities. 77% of the least deprived had a timely procedure compared with 58% of the most deprived; there was no gender difference. CONCLUSIONS: In this large, national dataset, female gender, black or South Asian ethnicities and high deprivation were associated with significantly reduced odds of receiving AVR in England. A lower proportion of people of minority ethnicities or high deprivation had a timely procedure. Public health initiatives may be required to increase clinician and public awareness of unconscious biases towards minority and vulnerable populations to ensure timely AVR for everyone.

'Valve for Life': tackling the deficit in transcatheter treatment of heart valve disease in the UK.

Transcatheter aortic valve implantation (TAVI) is a proven treatment for life-threatening aortic valve disease, predominantly severe aortic stenosis. However, even among developed nations, access to TAVI is not uniform. The Valve for Life initiative was launched by the European Association of Percutaneous Cardiovascular Interventions in 2015 with the objective of improving access to transcatheter valve interventions across Europe. The UK has been identified as a country with low penetration of these procedures and has been selected as the fourth nation to be included in the initiative. Specifically, the number of TAVI procedures carried out in the UK is significantly lower than almost all other European nations. Furthermore, there is substantial geographical inequity in access to TAVI within the UK. As a consequence of this underprovision, waiting times for TAVI are long, and mortality among those waiting intervention is significant. This article reviews these issues, reports new data on access to TAVI in the UK and presents the proposals of the UK Valve for Life team to address the current problems in association with the British Cardiovascular Intervention Society.

Periluminal expression of a secreted transforming growth factor-ß type II receptor inhibits in-stent neointima formation following adenovirus-mediated stent-based intracoronary gene transfer.

Transforming growth factor-ß1 (TGF-ß1) has been shown unequivocally to enhance neointima formation in carotid and ileo-femoral arteries. In our previous studies, however, TGF-ß1 expression in coronary arteries actually reduced neointima formation without affecting luminal loss postangioplasty, while expression of a TGF-ß1 antagonist (RIIs) in balloon-injured coronary arteries reduced luminal loss without affecting neointima formation. These observed effects may be a consequence of the mode of coronary artery gene transfer employed, but they may also represent differences in the modes of healing of coronary, carotid, and ileo-femoral arteries after endoluminal injury. To help clarify whether a gene therapy strategy to antagonize TGF-ß might have application within the coronary vasculature, we have investigated the effect of high-level periluminal expression of RIIs using stent-based adenovirus-mediated intracoronary gene transfer. Porcine coronary arteries were randomized to receive a custom-made CoverStent preloaded with saline only, or with 1×10(9) infectious units of adenovirus expressing RIIs or ß-galactosidase (lacZ). Vessels were analyzed 28 days poststenting, at which time angiographic in-stent diameter was significantly greater in RIIs-treated arteries, and in-stent luminal loss significantly reduced. Computerized morphometric minimum in-stent lumen area was ~300% greater in RIIs-exposed vessels than in lacZ or saline-only groups. This was because of significantly reduced neointima formation in the RIIs group. RIIs had no demonstrable effect on cellular proliferation or apoptosis, but greater normalized neointimal/medial collagen content was observed in RIIs-exposed arteries. These data highlight the qualitatively similar effect of TGF-ß antagonism on neointima formation in injured coronary and noncoronary arteries, and suggest that since cellular proliferation is unaffected, TGF-ß1 antagonism might prevent in-stent restenosis without the delayed healing that is associated with drug-eluting stents in current clinical use.

In-hospital outcomes of very elderly patients (85 years and older) undergoing percutaneous coronary intervention.

OBJECTIVE: To compare in-hospital outcomes of a large cohort of very elderly patients (age ≥ 85 years) with younger patients (age < 85 years) undergoing percutaneous coronary intervention (PCI) for all indications at our institution. BACKGROUND: Interventionist cardiologists are often reluctant to undertake PCI in very elderly patients due to the perception of poor outcome in this high-risk cohort. However, the prognostic significance of advanced age itself is not clear. METHODS: Baseline clinical, angiographic and procedural variables, and in-hospital outcome data were entered into a prospective registry of 17,572 consecutive patients undergoing PCI at the University Health Network between April 2000 and December 2008. Patients were stratified according to age (< 85 years, n = 17,168, or ≥ 85 years, n = 404) and in-hospital mortality, major adverse cardiac events (MACE), and complication rates were calculated. Logistic regression-analysis identified independent predictors of unadjusted mortality and MACE. Very elderly patients were propensity matched with younger patients (1:2 ratio), and the analysis repeated. RESULTS: Very elderly patients had a mean age of 87.5 ± 2.9 (range, 85-97 years) vs. 62.8 ± 11.1 years for the younger cohort and had a greater number of comorbid conditions. This cohort were more likely to present as an urgent or primary PCI, underwent more complex interventions, and achieved less angiographic success. Unadjusted mortality and post procedure myocardial infarction were significantly higher in very elderly patients (6.93% vs. 1.20%, P < 0.0001 and 4.46% vs. 2.74%, P = 0.04). Renal, neurological, and access-site complications were all greater in the very elderly cohort. Although age ≥ 85 years was a significant independent predictor of both mortality (OR, 2.62; CI, 1.44-4.78, P = 0.0016) and MACE (OR, 1.94; CI, 1.25-3.01, P = 0.003), other variables such as cardiogenic shock were more potent predictors of adverse outcomes. CONCLUSION: Very elderly patients represent a high-risk cohort, with significantly increased in-hospital mortality and complication rates after PCI. Death occurred predominantly in very elderly patients undergoing nonelective PCI. Decisions to proceed with PCI in very elderly patients should be based on other prognostic variables in combination with advanced age, and these patients should not be excluded from revascularization based on age alone.

Double stenting: a method for treating acute stent recoil and luminal filling defects.

AIMS: Acute stent recoil and luminal filling defects can result in a suboptimal angiographic result following stent deployment and are associated with an increased risk of adverse outcomes. We aimed to evaluate the effect of double stenting, deployment of a second stent within the first, in the treatment of these conditions and to review the literature on this procedure. METHODS AND RESULTS: Thirteen cases of double stenting performed by a single operator at the Manchester Royal Infirmary over a three year period were identified and quantitative coronary angiography was performed. The indication for double stenting was acute stent recoil in eight cases, luminal filling defects in three cases and a combination of recoil and filling defects in two cases. There was a high frequency of target vessel calcification (77%) and ostial lesions (23%). Following double stenting, mean minimum lumen diameter increased significantly from 2.5 mm to 3.5 mm (p <0.001). There were no procedural complications. At mean clinical follow-up of 19 months (range six to 37 months), there were no major adverse cardiac events. CONCLUSIONS: Double stenting can significantly improve angiographic outcome in cases of acute stent recoil and luminal filling defects, with excellent clinical results in the medium term.

Drug eluting stents for the treatment of bare metal in-stent restenosis: long-term outcomes in real world practice.

AIMS: Drug eluting stents (DES) have had a great impact in reducing in-stent restenosis (ISR) in de novo lesions. However, long-term data regarding effectiveness and safety of these stents in treating bare metal stent (BMS) ISR are limited. We report long-term clinical outcomes in a cohort of patients with BMS-ISR treated with DES between April 2002 and December 2003 at our institution. METHODS AND RESULTS: Sixty-nine consecutive patients with significant BMS-ISR were treated with DES implantation. Sirolimus DES were used in 43 patients and paclitaxel DES in 26. All patients were followed up to determine the incidence of major adverse cardiac event (MACE) rates (all-cause death, myocardial infarction, or target vessel revascularisation [TVR]), angina class and the need for clinically driven angiography. The mean age of the cohort was 58.6 ± 10.8 years; 68% were male, 33% were diabetic, 50% had hypertension, 78% were on statin therapy and 59% were current (19%) or previous (41%) smokers. The clinical presentation of ISR was with chronic stable angina in 54 patients, 12 had a non-ST elevation acute coronary syndrome and three presented with ST-elevation myocardial infarction. Multivessel stenting was performed in 21 patients and bifurcation stenting in seven patients. Over a mean follow period of 4.9 years, the first event MACE rate was 20% (17 events in 14 patients - eight deaths of which three were cardiac, two non-fatal myocardial infarctions and seven TVR). Excluding non-cardiac death, the adjusted MACE rate was 14.5% (12 events in 10 patients). At long-term follow-up, mean Canadian angina class decreased from 2.3 ± 0.7 pre-procedure to 1.2 ± 0.4, 65% of patients were angina free and 80% were free of MACE. No differences in long-term outcomes were observed between patients receiving paclitaxel and sirolimus DES. CONCLUSIONS: The use of DES for the treatment of BMS-ISR is safe and effective over a mean follow-up period of nearly five years. To our knowledge, this represents the longest follow-up data of real world patients treated in a single interventional centre.

Late outcomes following percutaneous coronary interventions: results from a large, observational registry.

BACKGROUND: Randomized controlled trials report short- and medium- term outcomes following percutaneous coronary intervention (PCI), but their applicability to the general population is not known. Data regarding the long-term clinical outcomes of patients undergoing PCI are lacking. OBJECTIVE: To determine the long-term outcomes of 'all-comers' undergoing PCI at a large-volume tertiary cardiac referral centre. METHODS: A total of 12,662 consecutive patients undergoing an index procedure and entered into the University Health Network's (Toronto, Ontario) prospective registry between April 2000 and September 2007 were identified. In-hospital outcomes were assessed. Follow-up data were obtained through linkage to a provincial registry. Kaplan-Meier analysis was performed to calculate unadjusted survival rates, and Cox multiple regression analysis identified independent predictors of late mortality, major adverse cardiac events and all cardiovascular events. RESULTS: The population included a relatively high-risk patient cohort, with 19% older than 75 years of age, 28% with diabetes, 61% with multivessel disease and 1.3% in cardiogenic shock. Urgent procedures comprised 53% of all cases. The all-cause mortality rate at seven years follow-up was 10.6%. Repeat PCI occurred in 14.2% of patients, and coronary artery bypass grafting in 4.2%. Men showed a significant unadjusted survival advantage compared with women. Procedural characteristics such as incomplete revascularization and residual stenosis, in addition to established risk factors, were predictors of poorer long-term outcomes. Cardiogenic shock was the strongest predictor of late mortality. CONCLUSION: In the present large registry of 'all-comers' for PCI, longterm major adverse cardiac event rates were low and consistent with outcomes from randomized controlled trials. These data reflect a large cohort in real-world clinical practice, and may help clinicians further characterize and better treat high-risk patients who are undergoing PCI.

Selective use of embolic protection devices during saphenous vein grafts interventions: a single-center experience.

OBJECTIVES: To report on outcomes with selective use of embolic protection devices (EPD) during percutaneous coronary intervention (PCI) to saphenous vein grafts (SVG). BACKGROUND: PCI to SVG is associated with increased risk and the use of EPD is recommended in this setting. METHODS: Angiographic and clinical outcomes were prospectively obtained from 534 consecutive patients who underwent PCI to SVG with or without EPD at a tertiary cardiac centre. Long-term outcomes were obtained by linkage to a provincial registry. RESULTS: EPD, deployed in 198 of 373 SVGs (53%) suitable for deployment of a distal EPD, were used more often in ectatic (33% vs. 19%, P = 0.003), ulcerated (17% vs. 9%, P = 0.03), thrombotic (26% vs. 10%, P < 0.0001) vein grafts, with longer degenerated segments (P = 0.002), and in lesions involving the body of the graft (85% vs. 66%, P < 0.0001), and less with lesions involving the graft ostium (29% vs. 44%, P = 0.003). Patients suitable for but not receiving EPD tended to be more likely to have a periprocedural myocardial infarction. During 3 years of follow-up, 49% of the patients had a cardiovascular event. Cumulative mortality was 8.4%, 18.8% and 14.7% in patients unsuitable for distal EPD, suitable but without EPD, and with EPD (p = 0.11). Nonuse of EPD was an independent predictor of MACE at 3 years. (P = 0.02). CONCLUSIONS: Selective use of EPD is associated with low in-hospital cardiovascular event rates. Long-term outcomes are manifested by a high rate of events, especially in patients with SVG's suitable for but not receiving EPD. This suggests that routine use of distal EPD may be warranted in unselected patients with suitable SVG anatomy.

The adverse long-term impact of renal impairment in patients undergoing percutaneous coronary intervention in the drug-eluting stent era.

BACKGROUND: An observational study determining the long-term impact of chronic kidney disease (CKD) on patients undergoing percutaneous coronary intervention at a tertiary cardiac referral center. CKD is associated with poor in-hospital outcomes after percutaneous coronary intervention, but its effect beyond 1 year, particularly in the drug-eluting stent (DES) era, has not been reported. METHODS AND RESULTS: Baseline creatinine was available for 11,953 patients entered into a prospective registry (April 2000 to September 2007). Patients were stratified: those with or without at least moderate CKD (creatinine clearance, <60 mL/min). Follow-up data were obtained through linkage to a provincial registry. Kaplan-Meier analysis was performed. Cox multiple-regression analysis identified independent predictors of late mortality and major adverse cardiac events (MACE) and examined the association between DES use and late outcomes in the presence or absence of CKD. CKD was present in 3070 patients (25.7%). In-hospital mortality and MACE were significantly increased in CKD (3.34% versus 0.44%, P<0.001 and 5.73% versus 2.2%, P<0.001). Survival and MACE-free survival at 7 years were reduced (64.5+/-1.4% versus 89.4+/-0.5%, P<0.001; 44.0+/-1.4% versus 63.4+/-0.8%, P<0.001). CKD was an independent predictor of late mortality and MACE (hazard ratio [HR]: 2.18, CI: 1.90 to 2.49, P<0.0001; HR: 1.37, CI: 1.25 to 1.49, P<0.0001). DES use was associated with a significant reduction in both (HR: 0.71, CI: 0.60 to 0.83, P<0.0001; HR: 0.70, CI: 0.63 to 0.78, P<0.0001). In patients with CKD, DES use was associated with reduced revascularization (HR: 0.68, CI: 0.53 to 0.88, P=0.004) and reduced MACE (HR: 0.81, CI: 0.69 to 0.95, P=0.011) but not reduced mortality (HR: 0.85, CI: 0.69 to 1.05, P=0.1). CONCLUSIONS: In a large registry of "all comers" for percutaneous coronary intervention, CKD was an independent predictor of adverse late outcomes. DES use may be associated with improved long-term outcomes in this high-risk cohort, but further prospective studies are required.

Contemporary management of pregnancy-related coronary artery dissection: A single-centre experience and literature review.

Spontaneous coronary artery dissection (SCAD) is an infrequent event that is most commonly associated with pregnant women or those in the postpartum period. Because of its rarity, the literature describing this condition is confined to sporadic case reports, with few reporting long-term follow-up, and no clear consensus exists on the optimal treatment strategy for these patients. The present article reports a single-centre experience with SCAD, highlighting the issues surrounding its management with a brief description of five cases of pregnancy-associated coronary dissection. The treatment used in these cases ranged from a conservative medical approach to surgical and percutaneous intervention, with one patient proceeding to transplantation. Four of the cases have long-term angiographic follow-up.In addition, a comprehensive review of all previously published cases is presented, and temporal trends in the management strategy are highlighted. Possible pathophysiological mechanisms pertaining to this condition, and the complex diagnostic and therapeutic issues involved, which may affect both patient and fetus, are discussed. Finally, an optimal approach to patients with SCAD, informed by our experience and literature review, is described.

A calcified neointima--"stent" within a stent.

De novo atherosclerosis arising within a coronary stent is rare and generally occurs many years after stent deployment. We describe a case of restenosis in a patient presenting with angina 8 years after original stent deployment. Intravascular ultrasound greyscale imaging and virtual histology demonstrated that this "neointima" was calcified.

Beta-adrenoceptor blockade markedly attenuates transgene expression from cytomegalovirus promoters within the cardiovascular system.

OBJECTIVE: The major immediate-early cytomegalovirus enhancer/promoter (MIECMV), widely used in cardiovascular gene therapy, contains several positively regulatory cAMP response elements (CRE). Catecholamine signaling via beta-adrenoceptors might increase transgene expression from MIECMV, and if so, beta-blockers may have a detrimental effect on the efficacy of clinical cardiovascular gene therapy strategies. METHODS AND RESULTS: Cultured smooth muscle cells were exposed to isoprenaline, atenolol, or propranolol, alone and in combination before infection with adenoviruses expressing beta-galactosidase. beta-galactosidase expression was assayed 72 hours later. Isoprenaline increased transgene expression from MIECMV up to 8-fold (P<0.001), but had no effect on a promoter containing no CRE. The effect of isoprenaline was inhibited by beta-blockade and by specific CRE-decoy oligonucleotides. Beta-blockers did not reduce transgene expression below basal levels. After adenovirus-mediated porcine intracoronary gene transfer, however, beta-blockade reduced beta-galactosidase expression by up to 250-fold compared with non-beta-blocked animals (P<0.01). CONCLUSIONS: Enhancement of promoter activity by endogenous catecholamines is essential for high-level transgene expression from MIECMV within the vasculature. Beta-blocker-mediated suppression of transgene expression from MIECMV in vascular tissues has a significant bearing on clinical studies of cardiovascular gene transfer. This is the first described interaction to our knowledge between widely prescribed pharmaceuticals and a commonly used promoter of clinical transgene expression.

Adenovirus-mediated gene transfer of transforming growth factor-beta3, but not transforming growth factor-beta1, inhibits constrictive remodeling and reduces luminal loss after coronary angioplasty.

BACKGROUND: Extracellular matrix (ECM) remodeling is central to the development of restenosis after PTCA. Substantial evidence implicates transforming growth factor-beta1 (TGF-beta1), a regulator of ECM deposition by vascular cells, in its pathogenesis. TGF-beta3 reduces TGF-beta1-induced ECM deposition in cutaneous wounds. We therefore investigated the effects of intracoronary expression of TGF-beta3 and TGF-beta1 on luminal loss after angioplasty. METHODS AND RESULTS: Porcine coronary arteries received an adenovirus expressing TGF-beta3, TGF-beta1, or lacZ (beta-galactosidase), or PBS only, at the site of angioplasty. Morphometric analysis 28 days after angioplasty confirmed reduced luminal loss in TGF-beta3 vessels (-0.65+/-0.10 mm2) compared with lacZ (-1.18+/-0.19 mm2) or PBS only (-1.19+/-0.17 mm2; P=0.003). Luminal loss was not reduced in TGF-beta1 vessels (-1.02+/-0.19 mm2; P=0.48). An increase in the external elastic lamina area in TGF-beta3-treated vessels (+0.73+/-0.32 mm2) contrasted with decreases in control vessels (mean, -0.53+/-0.17 mm2; P=0.001) and TGF-beta1 vessels (-0.87+/-0.34 mm2; P=0.003). Collagen content increased at the site of injury in TGF-beta3-treated vessels (26.1+/-14.2%) but decreased in the lacZ (-22.8+/-6.6%) and PBS-only (-23.4+/-7.0%; P=0.002) groups and was not significantly changed in TGF-beta1-treated vessels. CONCLUSIONS: Expression of TGF-beta3 inhibits constrictive remodeling after PTCA and reduces luminal loss. This is accompanied by increased adventitial collagen, which may act as an external "scaffold" preventing vessel constriction. These findings confirm the potential of gene therapies that modify ECM remodeling for prophylaxis of restenosis.