Transcatheter aortic valve replacement in Europe: adoption trends and factors influencing device utilization

OBJECTIVES The authors sought to examine the adoption of transcatheter aortic valve replacement (TAVR) in Western Europe and investigate factors that may influence the heterogeneous use of this therapy. BACKGROUND Since its commercialization in 2007, the number of TAVR procedures has grown exponentially. METHODS The adoption of TAVR was investigated in 11 European countries: Germany, France, Italy, United Kingdom, Spain, the Netherlands, Switzerland, Belgium, Portugal, Denmark, and Ireland. Data were collected from 2 sources: 1) lead physicians submitted nation-specific registry data; and 2) an implantation-based TAVR market tracker. Economic indexes such as healthcare expenditure per capita, sources of healthcare funding, and reimbursement strategies were correlated to TAVR use. Furthermore, we assessed the extent to which TAVR has penetrated its potential patient population. RESULTS Between 2007 and 2011, 34,317 patients underwent TAVR. Considerable variation in TAVR use existed across nations. In 2011, the number of TAVR implants per million individuals ranged from 6.1 in Portugal to 88.7 in Germany (33 ± 25). The annual number of TAVR implants performed per center across nations also varied widely (range 10 to 89). The weighted average TAVR penetration rate was low: 17.9%. Significant correlation was found between TAVR use and healthcare spending per capita (r = 0.80; p = 0.005). TAVR-specific reimbursement systems were associated with higher TAVR use than restricted systems (698 ± 232 vs. 213 ± 112 implants/million individuals ≥ 75 years; p = 0.002). CONCLUSIONS The authors' findings indicate that TAVR is underutilized in high and prohibitive surgical risk patients with severe aortic stenosis. National economic indexes and reimbursement strategies are closely linked with TAVR use and help explain the inequitable adoption of this therapy.

Future perspectives in transcatheter aortic valve implantation

Transcatheter aortic valve replacement (TAVR) constitutes a relatively new treatment option for the patients with severe symptomatic aortic stenosis. Evidence from registries and randomized control trials has underscored the value of this treatment in inoperable and high risk populations, while new developments in valve technology and TAVR enabling devices have reduced the risk of complications, simplified the procedure, and broadened the applications of this therapy. The initial promising clinical results and the potential of an effective less invasive treatment of aortic stenosis has not only created high expectations but also the need to address the pitfalls of TAVR technology. The evolving knowledge concerning the groups of patients who would benefit from this treatment, the limited long term follow-up data, the concerns about devices' long term durability, and the severity of complications remain important caveats which restrict the widespread clinical adoption of TAVR. The aim of this review article is to present the recent advances, highlight the limitations of TAVR technology, and discuss the future perspectives in this rapidly evolving field.

New approach to direct stenting using a novel "all-in-one" coronary stent system via 5 French diagnostic catheters: a pilot study

OBJECTIVES We sought to evaluate the strategy success and short term clinical outcomes of direct stenting via 5 French (F) diagnostic catheters using a novel bare metal stent with integrated delivery system (IDS) (Svelte Medical Systems, New Providence, NJ) and compare the results to a conventionally treated matched group. METHODS Fifteen consecutive patients with lesions deemed suitable for direct stenting using a bare metal stent were included. The primary endpoint was the strategy success defined as the ability to successfully treat a target lesion via a 5 F diagnostic catheter with a good angiographic result (TIMI III flow, residual stenosis ≤20%). Procedure and fluoroscopy times, contrast agent use, cost, and short-term clinical outcomes were compared to a matched group treated via conventional stenting. RESULTS The primary endpoint was reached in 14/15 patients (93%). There were no significant differences in procedural (58.6 min ± 12.7 vs. 57.4 min ± 14.2) or fluoroscopy times (10.0 min ± 4.3 vs.10.1 min ± 3.9) or contrast agent use (193.7 ml ± 54.8 vs. 181.4 ml ± 35.6). However, there were significant reductions in materials used in the study group compared to the control group equating to cost savings of almost US $600 per case (US $212.44 ± 258.09 vs. US $804.69 ± 468.11; P = 0.001). CONCLUSIONS Direct stenting using a novel bare metal stent with an IDS via 5 F diagnostic catheters is a viable alternative to conventional stenting in selected patients and is associated with significant cost savings.

Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document

OBJECTIVES The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection. BACKGROUND A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous. METHODS AND RESULTS Two in-person meetings (held in September 2011 in Washington, DC, and in February 2012 in Rotterdam, The Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and noninterventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiographic recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for several recommended composite endpoints. CONCLUSIONS This VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement. This initiative and document can furthermore be used as a model during current endeavors of applying definitions to other transcatheter valve therapies (for example, mitral valve repair).

Transcatheter aortic valve implantation: patient selection

Transcatheter aortic valve implantation (TAVI) is a disruptive technology as it satisfies a previously unmet need which is associated with a profound therapeutic benefit. In randomized clinical trials, TAVI has been shown to improve survival compared with medical treatment among patients considered not suitable candidates for surgical aortic valve replacement (SAVR), and to provide similar outcomes as SAVR in selected high-risk patients. Currently, TAVI is limited to selected elderly patients with symptomatic severe aortic stenosis. As this patient population frequently suffers from comorbid conditions, which may influence outcomes, the selection of patients to undergo TAVI underlies a complex decision process. Several clinical risk score algorithms are routinely used, although they fall short to fully appreciate the true risk among patients currently referred for TAVI. Beyond traditional risk scores, the clinical assessment by an interdisciplinary Heart Team as well as detailed imaging of the aortic valve, aortic root, descending and abdominal aorta as well as peripheral vasculature are important prerequisites to plan a successful procedure. This review will familiarize the reader with the concepts of the interdisciplinary Heart team, risk scores as well as the most important imaging algorithms suited to select appropriate TAVI patients.

Transcatheter aortic valve implantation: the transfemoral access route is the default access

Transcatheter aortic valve implantation (TAVI) is a widely accepted alternative to surgical aortic valve replacement (SAVR) among non-operable patients or selected high-risk patients with degenerative, severe aortic stenosis. TAVI is considered less invasive when compared with SAVR; however, there remain significant differences between different TAVI access routes. The transfemoral approach is considered the least invasive access route, and can be performed as a fully percutaneous procedure in a spontaneously breathing patient under local anaesthesia and mild sedation only. Moreover, transfemoral TAVI patients are typically transferred to coronary care rather than to an intensive care unit after the procedure, and benefit from early ambulation and a reduction in overall length of hospital stay. Considering these patient-specific and health-economic advantages, several TAVI centres follow the least invasive strategy for their patients and have implemented the transfemoral access route as the default access in their institutions. This article provides an overview on the prerequisites for a successful transfemoral TAVI procedure, describes the procedural advantages compared to alternative access routes, and highlights differences in clinical outcomes.

Idiopathic ventricular outflow tract arrhythmias from the great cardiac vein: Challenges and risks of catheter ablation

INTRODUCTION Catheter ablation for idiopathic ventricular arrhythmia is well established but epicardial origin, proximity to coronary arteries, and limited accessibility may complicate ablation from the venous system in particular from the great cardiac vein (GCV). METHODS Between April 2009 and October 2010 14 patients (56 ± 15 years; 9 male) out of a total group of 117 patients with idiopathic outflow tract tachycardias were included undergoing ablation for idiopathic VT or premature ventricular contractions (PVC) originating from GCV. All patients in whom the PVC arose from the GCV were subject to the study. In these patients angiography of the left coronary system was performed with the ablation catheter at the site of earliest activation. RESULTS Successful ablation was performed in 6/14 (43%) and long-term success was achieved in 5/14 (36%) patients. In 4/14 patients (28.6%) ablation was not performed. In another 4 patients (26.7%), ablation did not abolish the PVC/VT. In the majority, the anatomical proximity to the left coronary system prohibited effective RF application. In 3 patients RF application resulted in a coronary spasm with complete regression as revealed in repeat coronary angiography. CONCLUSION A relevant proportion idiopathic VT/PVC can safely be ablated from the GCV without significant permanent coronary artery stenosis after RF application. Our data furthermore demonstrate that damage to the coronary artery system is likely to be transient.

Anatomical eligibility of the renal vasculature for catheter-based renal denervation in hypertensive patients.

OBJECTIVES This study sought to determine the vascular anatomical eligibility for catheter-based renal artery denervation (RDN) in hypertensive patients. BACKGROUND Arterial hypertension is the leading cardiovascular risk factor for stroke and mortality globally. Despite substantial advances in drug-based treatment, many patients do not achieve target blood pressure levels. To improve the number of controlled patients, novel procedure- and device-based strategies have been developed. RDN is among the most promising novel techniques. However, there are few data on the vascular anatomical eligibility. METHODS We retrospectively analyzed 941 consecutive hypertensive patients undergoing coronary angiography and selective renal artery angiography between January 1, 2010, and May 31, 2012. Additional renal arteries were divided into 2 groups: hilar (accessory) and polar (aberrant) arteries. Anatomical eligibility for RDN was defined according to the current guidelines: absence of renal artery stenosis, renal artery diameter ≥4 mm, renal artery length ≥20 mm, and only 1 principal renal artery. RESULTS A total of 934 hypertensive patients were evaluable. The prevalence of renal artery stenosis was 10% (n = 90). Of the remaining 844 patients without renal artery stenosis, 727 (86%) had nonresistant hypertension and 117 (14%) had resistant hypertension; 62 (53%) of the resistant hypertensive and 381 (52%) of the nonresistant hypertensive patients were anatomically eligible for sympathetic RDN. CONCLUSIONS The vascular anatomical eligibility criteria of the current guidelines are a major limiting factor for the utilization of RDN as a therapeutic option. Development of new devices and/or techniques may significantly increase the number of candidates for these promising therapeutic options.

Secondary arterial hypertension: when, who, and how to screen?

Secondary hypertension refers to arterial hypertension due to an identifiable cause and affects ∼5-10% of the general hypertensive population. Because secondary forms are rare and work up is time-consuming and expensive, only patients with clinical suspicion should be screened. In recent years, some new aspects gained importance regarding this screening. In particular, increasing evidence suggests that 24 h ambulatory blood pressure (BP) monitoring plays a central role in the work up of patients with suspected secondary hypertension. Moreover, obstructive sleep apnoea has been identified as one of the most frequent causes. Finally, the introduction of catheter-based renal denervation for the treatment of patients with resistant hypertension has dramatically increased the interest and the number of patients evaluated for renal artery stenosis. We review the clinical clues of the most common causes of secondary hypertension. Specific recommendations are given as to evaluation and treatment of various forms of secondary hypertension. Despite appropriate therapy or even removal of the secondary cause, BP rarely ever returns to normal with long-term follow-up. Such residue hypertension indicates either that some patients with secondary hypertension also have concomitant essential hypertension or that irreversible vascular remodelling has taken place. Thus, in patients with potentially reversible causes of hypertension, early detection and treatment are important to minimize/prevent irreversible changes in the vasculature and target organs.

Clinical parameters associated with collateral development in patients with chronic total coronary occlusion

OBJECTIVE Well-developed collaterals provide survival benefit in patients with obstructive coronary artery disease (CAD). Therefore, in this study we sought to determine which clinical variables are associated with arteriogenesis. DESIGN Clinical and laboratory variables were collected before percutaneous coronary intervention. Multivariate analysis was performed to determine which variables are associated with the collateral flow index (CFI). PATIENTS Data from 295 chronic total occlusion (CTO) patients (Bern, Switzerland, Amsterdam, the Netherlands and Jena, Germany) were pooled. In earlier studies, patients had varying degrees of stenosis. Therefore, different stages of development of the collaterals were used. In our study, a unique group of patients with CTO was analysed. INTERVENTIONS Instead of angiography used earlier, we used a more accurate method to determine CFI using intracoronary pressure measurements. CFI was calculated from the occlusive pressure distal of the coronary lesion, the aortic pressure and central venous pressure. RESULTS The mean CFI was 0.39 ± 0.14. After multivariate analysis, β blockers, hypertension and angina pectoris duration were positively associated with CFI (B: correlation coefficient β=0.07, SE=0.03, p=0.02, B=0.040, SE=0.02, p=0.042 and B=0.001, SE=0.000, p=0.02). Furthermore also after multivariate analysis, high serum leucocytes, prior myocardial infarction and high diastolic blood pressure were negatively associated with CFI (B=-0.01, SE=0.005, p=0.03, B=-0.04, SE=0.02, p=0.03 and B=-0.002, SE=0.001, p=0.011). CONCLUSIONS In this unique cohort, high serum leucocytes and high diastolic blood pressure are associated with poorly developed collaterals. Interestingly, the use of β blockers is associated with well-developed collaterals, shedding new light on the potential action mode of this drug in patients with CAD.

Neoatherosclerosis as reason for stent failures beyond 5 years after drug-eluting stent implantation

A 69-year-old male (case 1) was admitted due to acute non-ST-segment elevation myocardial infarction (NSTEMI). Eight years earlier, he had previously undergone treatment with a sirolimus-eluting stent (SES). Four years after stent implantation, a follow-up angiography was obtained showing a patent stent without obstructive in-stent restenosis (Panel A). Angiograms obtained at the time of NSTEMI (Panel B) disclosed subtotal occlusion in the middle of the SES (arrowheads). Optical coherence tomography revealed a signal intense luminal layer with an underlying, highly attenuating, diffusely demarcated area, suggestive for an instent fibroatheroma (Panel D) with a minimal cap thickness of 80 µm. Accordingly, ischaemia was caused by the high degree of stenosis (Panel E). Similarly, a 59-year-old male (case 2) was admitted due to STEMI. Nine years before, he had received a paclitaxel-eluting stent (PES). Five years after stent implantation, a follow-up angiography revealed a patent stent (Panel F). Angiograms obtained at the time of STEMI (Panel G) disclosed total occlusion in the proximal of PES (arrowheads). Optical coherence tomography showed a rupture of thin cap fibroatheroma within the stented segment (Panel I). The thin cap fibroatheroma caused a severe stenosis with superimposed thrombus (Panel J). Neoatherosclerosis has been recently described as particular disease entity being responsible for very late stent failures. These two cases illustrate that the presence of a favourable long-term angiographic result years after DES implantation does not exclude a future neoatherosclerosis-related event (restenosis or stent thrombosis). Large observational and long-term intracoronary imaging studies are required to fully elucidate the dynamics and clinical relevance of neoatherosclerosis.

Coronary collateral perfusion in patients with coronary artery disease: effect of metoprolol

BACKGROUND The use of ultrathin Doppler angioplasty guidewires has made it possible to measure collateral flow quantitatively. Pharmacologic interventions have been shown to influence collateral flow and, thus, to affect myocardial ischaemia. METHODS Twenty-five patients with coronary artery disease undergoing PTCA were included in the present analysis. Coronary flow velocities were measured in the ipsilateral (n = 25) and contralateral (n = 6; two Doppler wires) vessels during PTCA with and without i.v. adenosine (140 microg/kg.min) before and 3 min after 5 mg metoprolol i.v., respectively. The ipsilateral Doppler wire was positioned distal to the stenosis, whereas the distal end of the contralateral wire was in an angiographically normal vessel. The flow signals of the ipsilateral wire were used to calculate the collateral flow index (CFI). CFI was defined as the ratio of flow velocity during balloon inflation divided by resting flow. RESULTS Heart rate and mean aortic pressure decreased slightly (ns) after i.v. metoprolol. The collateral flow index was 0.25+/-0.12 (one fourth of the resting coronary flow) during the first PTCA and 0.27+/-0.14 (ns versus first PTCA) during the second PTCA, but decreased with metoprolol to 0.16+/-0.08 (p<0.0001 vs. baseline) during the third PTCA. CONCLUSIONS Coronary collateral flow increased slightly but not significantly during maximal vasodilatation with adenosine but decreased in 23 of 25 patients after i.v. metoprolol. Thus, there is a reduction in coronary collateral flow with metoprolol, probably due to an increase in coronary collateral resistance or a reduction in oxygen demand.

Stricture of the Afferent Isoperistaltic Tubular Segment: A Late and Rare Cause of Bilateral Dilation of the Upper Urinary Tract After Ileal Bladder Substitution

OBJECTIVE To evaluate the etiology and treatment of bilateral hydronephrosis not responding to bladder substitute drainage after ileal bladder substitution using an afferent isoperistaltic tubular segment. MATERIALS AND METHODS A retrospective analysis was performed of a consecutive series of 739 patients who had undergone bladder substitution from April 1985 to August 2012. RESULTS Of the 739 ileal bladder substitute patients, 10 (1.4%) developed bilateral hydronephrosis unresponsive to complete bladder substitute drainage. The etiology was stenosis of the afferent isoperistaltic tubular segment. The median interval to presentation was 131 months (range 45-192). The incidence of afferent tubular segment stenosis was significantly higher in the 61 ileal bladder substitute patients with recurrent urinary tract infection (9 [15%]) than in the 678 without recurrent urinary tract infection (1 [0.15%]; P <.001). Urine cultures revealed mixed infections (34%), Escherichia coli (18%), Staphylococcus aureus (13%), enterococci (11%), Candida (8%), Klebsiella (8%), and others (8%). Seven patients underwent 10 endourologic interventions, only 1 of which was successful (10%). After failed endourologic treatment, 7 open surgical revisions with resection of the stricture were performed, with all 7 (100%) successful. CONCLUSION Bilateral dilation of the upper urinary tract after ileal orthotopic bladder substitution unresponsive to complete bladder substitute drainage is likely to be caused by stenosis of the afferent isoperistaltic tubular segment. The stenosis occurs almost exclusively in patients with long-lasting, recurrent urinary tract infection and can develop many years after the ileal bladder substitution. Minimally invasive endourologic treatment is usually unsuccessful; however, open surgical revision offers excellent results.

Post-Mortem Cardiac 3T Magnetic Resonance Imaging. Visualization of Sudden Cardiac Death?

OBJECTIVES: This study aimed to investigate post-mortem magnetic resonance imaging (pmMRI) for the assessment of myocardial infarction and hypointensities on post-mortem T2-weighted images as a possible method for visualizing the myocardial origin of arrhythmic sudden cardiac death. BACKGROUND: Sudden cardiac death has challenged clinical and forensic pathologists for decades because verification on post-mortem autopsy is not possible. pmMRI as an autopsy-supporting examination technique has been shown to visualize different stages of myocardial infarction. METHODS: In 136 human forensic corpses, a post-mortem cardiac MR examination was carried out prior to forensic autopsy. Short-axis and horizontal long-axis Images were acquired in situ on a 3-T system. RESULTS: In 76 cases, myocardial findings could be documented and correlated to the autopsy findings. Within these 76 study cases, a total of 124 myocardial lesions were detected on pmMRI (chronic: 25; subacute: 16; acute: 30; and peracute: 53). Chronic, subacute, and acute infarction cases correlated excellently to the myocardial findings on autopsy. Peracute infarctions (age range: minutes to approximately 1 h) were not visible on macroscopic autopsy or histological examination. Peracute infarction areas detected on pmMRI could be verified in targeted histological investigations in 62.3% of cases and could be related to a matching coronary finding in 84.9%. A total of 15.1% of peracute lesions on pmMRI lacked a matching coronary finding but presented with severe myocardial hypertrophy or cocaine intoxication facilitating a cardiac death without verifiable coronary stenosis. CONCLUSIONS: 3-T pmMRI visualizes chronic, subacute, and acute myocardial infarction in situ. In peracute infarction as a possible cause of sudden cardiac death, it demonstrates affected myocardial areas not visible on autopsy. pmMRI should be considered as a feasible post-mortem investigation technique for the deceased patient if no consent for a clinical autopsy is obtained.

Sustained attention in children with two etiologies of early hydrocephalus.

Several studies have shown that children with spina bifida meningomyelocele (SBM) and hydrocephalus have attention problems on parent ratings and difficulties in stimulus orienting associated with a posterior brain attention system. Less is known about response control and inhibition associated with an anterior brain attention system. Using the Gordon Vigilance Task (Gordon, 1983), we studied error rate, reaction time, and performance over time for sustained attention, a key anterior attention function, in 101 children with SBM, 17 with aqueductal stenosis (AS; another condition involving congenital hydrocephalus), and 40 typically developing controls (NC). In SBM, we investigated the relation between cognitive attention and parent ratings of inattention and hyperactivity and explored the impact of medical variables. Children with SBM did not differ from AS or NC groups on measures of sustained attention, but they committed more errors and responded more slowly. Approximately one-third of the SBM group had attention symptoms, although parent attention ratings were not associated with task performance. Hydrocephalus does not account for the attention profile of children with SBM, which also reflects the distinctive brain dysmorphologies associated with this condition.