Transcatheter Aortic Valve Implantation - Yesterday, Today and Tomorrow.

Since the first transcatheter aortic valve implantation (TAVI) was performed by Alain Cribier and colleagues in 2002 [1], the technology has garnered global support with more than 200,000 devices implanted. The rapid adoption of this technology has been driven by the need for a less invasive treatment modality in a cohort of patients often denied conventional surgical valve replacement due to an unacceptably high perioperative risk, whether real or perceived [2]. This, together with evidence that the technology confers morbidity and mortality advantages compared to medical therapy [3,4] and at least equivalent outcomes to surgical valve replacement [5,6] in select cohorts, has seen clinical approval in more than 50 countries. The last 13 years has seen an evolution of practises and equipment affecting almost every aspect of the TAVI procedure from pre-procedural assessment to device design and post-procedural care. The almost exponential rate of change has both benefits and risks. Benefits, in that impactful changes are translated into clinical practice very rapidly, but risks, in that meaningful comparative research studies potentially lag behind and can be outmoded by the time they are published. This instability may in turn delay regulatory review and approval processes that are based on such studies. The aim of this review is to provide an overview of the evolution of TAVI, its current clinical position and likely future directions.

The significance of pre-arrest factors in out-of-hospital cardiac arrests witnessed by emergency medical services: a report from the Victorian Ambulance Cardiac Arrest Registry.

BACKGROUND: The significance of pre-arrest factors in out-of-hospital cardiac arrests (OHCA) witnessed by emergency medical services (EMS) is not well established. The purpose of this study was to assess the association between prodromal symptoms and pre-arrest clinical observations on the arresting rhythm and survival in EMS witnessed OHCA. METHODS: Between 1st January 2003 and 31st December 2011, 1056 adult EMS witnessed arrests of a presumed cardiac aetiology were identified from the Victorian Ambulance Cardiac Arrest Registry. Pre-arrest prodromal features and clinical characteristics were extracted from the patient care record. Backward elimination logistic regression was used to identify pre-arrest factors associated with an initial shockable rhythm and survival to hospital discharge. RESULTS: The median age was 73.0 years, 690 (65.3%) were male, and the rhythm of arrest was shockable in 465 (44.0%) cases. The most commonly reported prodromal symptoms prior to arrest were chest pain (48.8%), dyspnoea (41.8%) and altered consciousness (37.8%). An unrecordable systolic blood pressure was observed in 34.4%, a respiratory rate <13 or >24min(-1) was present in 43.1%, and 45.5% had a Glasgow coma score <15. In the multivariable analysis, the following pre-arrest factors were significantly associated with survival: age, public location, aged care facility, chest pain, arm or shoulder pain, dyspnoea, dizziness, vomiting, ventricular tachycardia, pulse rate, systolic blood pressure, respiratory rate, Glasgow coma score, aspirin and inotrope administration. CONCLUSION: Pre-arrest factors are strongly associated with the arresting rhythm and survival following EMS witnessed OHCA. Potential opportunities to improve outcomes exist by way of early recognition and management of patients at risk of OHCA.

Direction of first bystander call for help is associated with outcome from out-of-hospital cardiac arrest.

BACKGROUND: Preventable bystander delays following out-of-hospital cardiac arrest (OHCA) are common, and include bystanders inappropriately directing their calls for help. METHODS: We retrospectively extracted Utstein-style data from the Victorian Ambulance Cardiac Arrest Registry (VACAR) for adult OHCA occurring in Victoria, Australia, between July 2002 and June 2012. Emergency medical service (EMS) witnessed events were excluded. Cases were assigned into two groups on the basis of the first bystander call for help being directed to EMS. Study outcomes were: likelihood of receiving EMS treatment; survival to hospital, and; survival to hospital discharge. RESULTS: A total of 44499 adult OHCA cases attended by EMS were identified, of which first bystander calls for help were not directed to EMS in 2842 (6.4%) cases. Calls to a relative, friend or neighbour accounted for almost 60% of the total emergency call delays. Patient characteristics and survival outcomes were consistently less favourable when calls were directed to others. First bystander call to others was independently associated with older age, male gender, arrest in private location, and arrest in a rural region. The risk-adjusted odds of treatment by EMS (OR 1.33, 95% CI 1.20-1.48), survival to hospital (OR 1.64, 95% CI 1.37-1.96) and survival to hospital discharge (OR 1.64, 95% CI 1.13-2.36) were significantly improved if bystanders called EMS first. CONCLUSION: The frequency of inappropriate bystander calls following OHCA was low, but associated with a reduced likelihood of treatment by EMS and poorer survival outcomes.

The SADRA Lotus Valve System: a fully repositionable, retrievable prosthesis.

Transcatheter aortic valve implantation (TAVI) has become the preferred treatment option for patients with severe aortic stenosis at extreme surgical risk and an acceptable alternative to surgical aortic valve replacement in patients at high risk. Despite a growing amount of evidence in support of TAVI there remain important limitations and recognized complications. The SADRA Lotus Valve System is a novel TAVI device capable of allowing full repositionability and retrievability, which may address some of the first generation limitations.

New DES: a new step forward?

Despite the benefits of first generation drug eluting stents (DES), concerns have been raised over their long term safety in particular the risk of stent thrombosis. As a result, the current generation and novel DES have been developed, the latter includes DES with biocompatible and biodegradable polymers, polymer free DES and completely bioresorbable stent platforms. Many of these stents are currently under evaluation in clinical trials, and early results are promising. This paper reviews the progress thus far in DES technology and aims to highlight the impact of recent DES innovations on clinical efficacy and safety.

Spontaneous coronary artery dissection in a female with antiphospholipid syndrome.

We report a case of spontaneous coronary artery dissection occurring in a young female who had been diagnosed with antiphospholipid syndrome. Coronary angiography revealed extensive dissection in the proximal to mid LAD. She was treated conservatively with an excellent result. Follow-up coronary angiography at two months failed to reveal any evidence of the previous dissection.

Cellular adhesion molecules and cardiovascular disease. Part II. Their association with conventional and emerging risk factors, acute coronary events and cardiovascular risk prediction.

The role of cellular adhesion molecules in the patho-genesis of atherosclerosis has now been clearly demonstrated. Plasma levels of adhesion molecules, which have been shed from the cell surface, have also been associated with the presence of clinical atherosclerotic disease, cardiovascular risk factors and acute coronary syndromes. However, there is little consensus in the literature, including between the large well-designed population studies. This may be explained either by unrecognized confounding factors or, alternatively, by the unpredictable relationship between cell surface expression and activity of cellular adhesion molecules and their shedding into the plasma under different circumstances. Probably for the latter reasons, there is at present little evidence that the measurement of circulating adhesion molecules is likely to offer any additional benefit for individual patients above the assessment of conventional cardiovascular risk factors in the assessment of either the extent of, or future risk from, cardiovascular disease.

Cellular adhesion molecules and cardiovascular disease. Part I. Their expression and role in atherogenesis.

Atherosclerosis is now recognized to be an inflammatory disease, and several inflammatory markers have been shown to be associated with both the presence and future risk of symptomatic cardiovascular disease. Cellular adhesion molecules, particularly members of the selectin family and immunoglobulin superfamily, are intimately involved in the recruitment of leucocytes to sites of inflammation, including developing atherosclerotic lesions. Their role in the pathogenesis of atherosclerosis has been clearly demonstrated using knockout mice models. Plasma levels of adhesion molecules, which have been shed from the cell surface, have been associated with the presence of clinical atherosclerotic disease, although published studies differ in their findings. This limited consensus in the literature may be explained either by unrecognized confounding factors, or perhaps by the unpredictable relationship between cell surface expression and activity of cellular adhesion molecules and their shedding into the plasma. While cell surface activity of adhesion molecules appears critical in the development of atherosclerotic lesions, the measurement of plasma levels of soluble adhesion molecules may offer little additional benefit for individual patients in the prediction of the extent of atherosclerotic disease above the assessment of conventional cardiovascular risk factors.

Impact of final coronary flow velocity reserve on late outcome following stent implantation.

Aims To assess whether coronary flow velocity reserve following stent implantation is predictive of the subsequent need of target lesion revascularization. Methods and Results The outcome was examined of 417 patients enrolled in a multicentre prospective randomized study (DESTINI), who received a successful single vessel stent implantation in native coronary arteries and in whom coronary flow velocity reserve was measured. Logistic regression analysis and the receiver operator characteristic curve were used. When compared with 358 patients not requiring target lesion revascularization, 59 patients (14%) who underwent target lesion revascularization had a lower final coronary flow velocity reserve (2.33 +/- 0.87 vs 2.48+/- 0.80, P= 0.20) and smaller final minimal lumen diameter (2.62 +/- 0.66 mm vs 2.73+/- 0.60, P= 0.19); however, those differences were not statistically significant. Patients with a coronary flow velocity reserve of < 2.0 (n=109, 26%) exhibited a significantly higher target lesion revascularization rate than patients with a coronary flow velocity reserve of > or = 2.0 (22% vs 11%, P= 0.010). This difference remained significant (odds ratio=2.01, 95% CI=1.11 to 3.66) after adjustment for other variables that were also correlated with the incidence of target lesion revascularization. Conclusion The presence of a final coronary flow velocity reserve of < 2.0 is an independent predictor of the need for target lesion revascularization after stent implantation in native coronary artery lesions.

Comparison of effects of diabetes mellitus on an EDHF-dependent and an EDHF-independent artery.

The hypothesis tested in this study is that diabetes has a different impact on an artery in which endothelium-dependent responses derive from both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) compared with responses in which NO predominates and EDHF is absent. The streptozotocin-treated rat model of diabetes was used, and the arteries were mounted on a wire myograph. In mesenteric arteries depolarized and constricted with phenylephrine, acetylcholine evoked hyperpolarization (31 +/- 2 mV) and complete relaxation; these responses were attributed to EDHF and NO. In femoral arteries, acetylcholine evoked a small, NO-mediated hyperpolarization (5 +/- 1 mV) and incomplete relaxation. Bradykinin evoked NO-dependent responses in mesenteric arteries. Whereas diabetes significantly impaired the EDHF-dependent hyperpolarization and relaxation in mesenteric arteries, NO-dependent responses in femoral and mesenteric arteries were preserved. 1-Ethyl-2-benzimidazolinone evoked hyperpolarization and relaxation in mesenteric arteries, and this was impaired in diabetes. In conclusion, NO-dependent responses are preserved in diabetes, whereas endothelial responses-dependent upon EDHF appear to be impaired. The putative channels responsible for mediating the EDHF response may be altered in diabetes.

Effect of anti-oxidant treatment and cholesterol lowering on resting arterial tone, metabolic vasodilation and endothelial function in the human forearm: a randomized, placebo-controlled study.

1. The aim of the present study was to determine whether anti-oxidant therapy with vitamin E and/or cholesterol-lowering therapy with simvastatin would augment resting forearm blood flow (FBF) and metabolic vasodilation in response to exercise and improve endothelial function in young patients with hypercholesterolaemia. 2. Endothelium-dependent and -independent, nitric oxide (NO)-mediated vasodilation have been shown to be impaired in young, otherwise healthy subjects with hypercholesterolaemia. Recent experimental and clinical studies suggest that vascular function may be improved with anti-oxidant or cholesterol- lowering therapy, although these treatments may be synergistic. 3. We compared FBF at rest, in response to isotonic exercise, the endothelium-dependent vasodilator acetylcholine (ACh), the endothelium-independent vasodilator sodium nitroprusside (SNP) and the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) in 26 young, otherwise healthy volunteers (mean (+/-SD) age 29+/-7 years; 14 female, 12 male) with hypercholesterolaemia, before and after 6 months treatment with vitamin E, simvastatin and/or placebo. Treatment was randomized, double-blinded in a 2 x 2 factorial design. Forearm blood flow was measured using venous occlusion plethysmography. 4. Vitamin E therapy increased plasma alpha-tocopherol from 39.5+/-9.6 to 75.7+/-33.8 micromol/L (P < 0.001). Simvastatin reduced total cholesterol from 6.9+/-1.7 to 4.9+/-0.8 mmol/L and low- density lipoprotein (LDL) from 4.8+/-1.7 to 3.0+/-0.7 mmol/L (both P < 0.001), although total and LDL-cholesterol also decreased slightly in the placebo group. Vitamin E increased resting FBF from 2.1+/-0.3 to 2.4+/-0.3 mL/100 mL per min (P = 0.04) and decreased resting forearm vascular resistance from 42.1+/-4.2 to 36.1+/-3.4 units (P = 0.01), but the reduction in resting FBF with L-NMMA was not affected. Vasodilation in response to isotonic exercise, ACh and SNP was similar before and after treatment in the placebo, vitamin E, simvastatin and in the combined vitamin E-simvastatin groups. NG-Monomethyl-L-arginine infusion reduced resting FBF and functional hyperaemia in response to exercise and these responses were not altered by treatment. 5. These data suggest that while vitamin E therapy augments resting FBF and reduces forearm vascular resistance in young hypercholesterolaemic subjects, these effects may not be via NO-dependent pathways. Metabolic vasodilation and responses to the NO-mediated vasodilators ACh and SNP were not favourably affected by anti-oxidant or cholesterol-lowering therapy, either alone or in combination.

Agreement between coronary flow velocity reserve and stress echocardiography in intermediate-severity coronary stenoses.

Visual and quantitative assessments of percent diameter stenosis on coronary angiography correlate poorly with functional testing, particularly in intermediate-severity (40%-70%) lesions, yet are frequently relied on to make decisions regarding revascularization. Coronary flow velocity reserve (CFVR) and relative CFVR (RCFVR) are promising methods for on-line functional assessment of lesion severity in the catheterization laboratory. We sought to determine the agreement between maximal, mean, and relative CFVR and stress echocardiography in intermediate-severity stenoses. The results of exercise or dobutamine stress echocardiography and CFVR measured by intracoronary Doppler were compared in 28 patients referred for assessment of intermediate-severity stenoses, using 15 patients with either angiographically normal coronary arteries or diameter stenoses > 70% as reference groups. CFVR was measured at least three times in response to a bolus of adenosine in the target vessel distal to the stenosis. RCFVR (target/normal vessel CFVR) was also measured in 27 patients. Maximal, mean (of three measures), and relative CFVR were calculated. CFVR > or = 2.0 and RCFVR > or = 0.75 were accepted as normal. A minority (29%) of patients in the intermediate-severity stenosis group had a positive test by either method. There was good to very good agreement between stress echocardiography and maximal CFVR (84%, kappa = 0.62, P < 0.0001) and RCFVR (81%, kappa = 0.59, P < 0.001) across the entire patient cohort, though in the intermediate subgroup concordance was only fair. Using the mean (of three measures of) CFVR for the same comparison improved the agreement in the intermediate subgroup to good (86%, kappa = 0.58, P = 0.002), and in the entire cohort the agreement was very good (88%, kappa = 0.74, P < 0.0001). There was only fair correlation between measures of CFVR and percent coronary stenosis. CFVR improved from 1.8 +/- 0.8 to 2.7 +/- 0.7 after percutaneous intervention (n = 12, P < 0.0001). These results suggest that there is good agreement between CFVR and stress echocardiography across a wide range of coronary lesion severity. The mean of three CFVR measurements distal to the target vessel stenosis increases diagnostic accuracy. Intracoronary Doppler flow velocity measurements at the time of cardiac catheterization may facilitate improved decision-making by providing the ability to assess the functional significance of coronary stenoses on-line.

Soluble adhesion molecules, endothelial function and vitamin E in type 1 diabetes.

BACKGROUND: Elevated levels of soluble adhesion molecules are found in subjects with vascular disease and inconsistently in subjects with conditions predisposing them to atherosclerosis, such as hypercholesterolaemia and diabetes. Oxidized low-density lipoprotein (LDL), protein kinase C and lower than normal levels of NO appear to be important for expression of adhesion molecules, raising the possibility that vitamin E is useful for downregulating levels. We have recently shown that administration of 1000 IU vitamin E for 3 months will improve endothelial vasodilator function (EVF) in uncomplicated type-1 diabetes. OBJECTIVE: To determine whether levels of soluble adhesion molecules in young subjects with uncomplicated diabetes are elevated, whether there is a relationship between levels of soluble adhesion molecule and EVF as well as parameters of diabetes and lipid levels and whether an improvement in EVF related to vitamin E therapy is also associated with a decrease in levels of soluble adhesion molecules. DESIGN: A randomized, placebo-controlled, study. RESULTS: There was no difference between levels of soluble vascular cell adhesion molecule-1 (VCAM-1; 621 +/- 17 versus 635 +/- 37 ng/ml) and P-selectin (59 +/- 2 versus 57 +/- 6 ng/ml) for the diabetic and control groups. For the diabetic cohort, levels of soluble VCAM-1 were inversely related to flow-mediated vasodilatation of the brachial artery (r = -0.41, P < 0.005) and directly related to levels of total cholesterol (r = 0.44, P < 0.005) and LDL cholesterol (r = 0.42, P < 0.01) and duration of diabetes (r = 0.55, P < 0.0005) but there was no relationship with susceptibility of LDL to oxidation or vitamin-E content of LDL. Levels of soluble P-selectin were directly related to duration of diabetes (r = 0.43, P < 0.05) and inversely related to size of LDL particles (r = 0.32, P < 0.05) but were not related to EVF. Vitamin E produced no change in levels of soluble P-selectin and VCAM-1. CONCLUSIONS: Levels of soluble VCAM-1 and P-selectin in young subjects with type-1 diabetes and no evidence of overt vascular disease do not appear to be elevated and are not influenced by vitamin-E supplementation.

Intravascular ultrasound assessment of ambiguous coronary lesions.

Accurate assessment of coronary lesions is essential for clinical decision-making. While angiography has long been accepted as the gold standard investigation, this technique provides only a planar 2-D silhouette of the arterial lumen and therefore has limited accuracy in the setting of vessel tortuosity or overlap, bifurcational and eccentric lesions, and diffusely diseased arteries. By providing high-resolution cross-sectional imaging through the arterial wall, intravascular ultrasound (IVUS) can overcome many of these limitations and accurately quantify angiographically indeterminate lesions. Angiographic evaluation of the left main coronary artery presents particular challenges that are ideally resolved with IVUS examination. The role of IVUS in the assessment of coronary stenoses of angiographically intermediate severity (50-70%) continues to evolve. Recent data correlating IVUS with intracoronary flow and pressure measurements suggest that epicardial coronary artery lesions with minimum lumen area of less than 3-4 mm2 may be haemodynamically significant. In addition to accurately quantifying minimum lumen diameter and area at the lesion site, IVUS can characterise coronary artery plaque morphology, and it may have the potential to predict plaque complications.

Percutaneous transluminal septal myocardial ablation: a new catheter-based therapy for patients with hypertrophic obstructive cardiomyopathy.

Hypertrophic obstructive cardiomyopathy is a complex disorder with serious clinical implications. Percutaneous transluminal septal myocardial ablation is a promising new addition to existing therapies for this condition. It is a catheter-based approach that involves instilling alcohol into the septal branches of the left anterior descending artery to induce a 'controlled' septal myocardial infarct. The result is a decrease in thickness of the hypertrophied interventricular septum and a reduction of the left ventricular outflow tract gradient. To date, the results from several series have been promising, with improvements in haemodynamic and clinical parameters without prohibitive complication rates. In this article, the indications, technique and outcomes of this procedure are reviewed.

Does unprotected left main-stem stenting have a role in current interventional practice?

Left main-stem disease is found in up to 5% of patients undergoing coronary angiography. Until recently, it has been regarded as an absolute indication for coronary bypass surgery, given the poor results of the early trials of balloon angioplasty for this condition. However, with rapidly advancing technology, including new generation stents and increasingly effective post-stenting anti-thrombotic regimens, there is now an increasing body of evidence to support the consideration of a percutaneous approach to left main-stem disease. Discerning patient selection, meticulous stent sizing and deployment, the routine use of intravascular ultrasound, aggressive anti-platelet regimes, and careful patient follow up are a few of the technical considerations required for a successful long-term outcome in this group.

Combination thrombolytic therapy and percutaneous coronary intervention: the future for revascularisation for acute myocardial infarction?

It seems theoretically sound to consider rescue percutaneous coronary intervention (PCI) in patients with failed thrombolysis. However, randomised controlled data in this setting are limited. In this brief review we will present those trials analysing the role of rescue PCI in patients with acute myocardial infarction and failed thrombolysis, and consider appropriate management strategies in this setting.