Short-term outcome after transcatheter aortic valve replacement with a novel balloon-expandable valve.

OBJECTIVES: Transcatheter aortic valve replacement (TAVR) has been expanding rapidly with numerous transcatheter heart valve (THV) systems currently available. The Myval balloon-expandable (BE) valve (Meril Life Sciences Pvt. Ltd., India) is a novel THV system indicated for the treatment of patients with severe aortic stenosis. The primary objective of this study is to assess the safety and performance of the Myval BE valve. METHODS: In this prospective single-centre study, 120 consecutive patients who underwent TAVR with the Myval BE valve were included. Clinical outcomes were evaluated at 30 days and 6 months using Valve Academic Research Consortium­2 criteria. All-cause mortality, stroke, acute kidney injury, major vascular complications, moderate or severe paravalvular leakage (PVL) and need for a permanent pacemaker implantation (PPI) were investigated. RESULTS: At 6­month follow-up, all-cause death and cardiac death were seen in 5.8% and 0.8% of the patients respectively. Periprocedural stroke and need for PPI were both seen in 3.3% of the patients. Access-site-related vascular and bleeding complications were absent. Improved valve haemodynamics and no moderate to severe PVL could be seen at 30 days. An intermediate valve size was selected in 51% of the patients. CONCLUSIONS: The Myval BE valve demonstrates improved valve haemodynamics, absence of moderate to severe PVL and good safety outcomes at 6­month follow-up with low cardiac death rate and acceptable rates of permanent pacemaker implantation and periprocedural stroke. Future randomised controlled trials will further establish the clinical utility of the Myval BE valve.

Transcatheter aortic valve implantation amid the COVID-19 pandemic: a nationwide analysis of the first COVID-19 wave in the Netherlands.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has put tremendous pressure on healthcare systems. Most transcatheter aortic valve implantation (TAVI) centres have adopted different triage systems and procedural strategies to serve highest-risk patients first and to minimise the burden on hospital logistics and personnel. We therefore assessed the impact of the COVID-19 pandemic on patient selection, type of anaesthesia and outcomes after TAVI. METHODS: We used data from the Netherlands Heart Registration to examine all patients who underwent TAVI between March 2020 and July 2020 (COVID cohort), and between March 2019 and July 2019 (pre-COVID cohort). We compared patient characteristics, procedural characteristics and clinical outcomes. RESULTS: We examined 2131 patients who underwent TAVI (1020 patients in COVID cohort, 1111 patients in pre-COVID cohort). EuroSCORE II was comparable between cohorts (COVID 4.5 ± 4.0 vs pre-COVID 4.6 ± 4.2, p = 0.356). The number of TAVI procedures under general anaesthesia was lower in the COVID cohort (35.2% vs 46.5%, p < 0.001). Incidences of stroke (COVID 2.7% vs pre-COVID 1.7%, p = 0.134), major vascular complications (2.3% vs 3.4%, p = 0.170) and permanent pacemaker implantation (10.0% vs 9.4%, p = 0.634) did not differ between cohorts. Thirty-day and 150-day mortality were comparable (2.8% vs 2.2%, p = 0.359 and 5.2% vs 5.2%, p = 0.993, respectively). CONCLUSIONS: During the COVID-19 pandemic, patient characteristics and outcomes after TAVI were not different than before the pandemic. This highlights the fact that TAVI procedures can be safely performed during the COVID-19 pandemic, without an increased risk of complications or mortality.

The history of transcatheter aortic valve implantation: The role and contribution of an early believer and adopter, the Netherlands.

This paper describes the history of transcatheter aortic valve implantation (TAVI) from its preclinical phase during which visionary pioneers developed its concept and prototype valves against strong head wind to first application in clinical practice (2002) and the clinical and scientific role of an early believer and adopter, the Netherlands (2005).

Incidence and outcome of prosthetic valve endocarditis after transcatheter aortic valve replacement in the Netherlands.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is increasingly being used as an alternative to conventional surgical valve replacement. Prosthetic valve endocarditis (PVE) is a rare but feared complication after TAVR, with reported first-year incidences varying from 0.57 to 3.1%. This study was performed to gain insight into the incidence and outcome of PVE after TAVR in the Netherlands. METHODS: A multicentre retrospective registry study was performed. All patients who underwent TAVR in the period 2010-2017 were screened for the diagnosis of infective endocarditis in the insurance database and checked for the presence of PVE before analysis of general characteristics, PVE parameters and outcome. RESULTS: A total of 3968 patients who underwent TAVR were screened for PVE. During a median follow-up of 33.5 months (interquartile range (IQR) 22.8-45.8), 16 patients suffered from PVE (0.4%), with a median time to onset of 177 days (IQR 67.8-721.3). First-year incidence was 0.24%, and the overall incidence rate was 0.14 events per 1000 person-years. Overall mortality during follow-up in our study was 31%, of which 25% occurred in hospital. All patients were treated conservatively with intravenous antibiotics alone, and none underwent a re-intervention. Other complications of PVE occurred in 5 patients (31%) and included aortic abscess (2), decompensated heart failure (2) and cerebral embolisation (1). CONCLUSION: PVE in patients receiving TAVR is a relatively rare complication and has a high mortality rate.

The rationale of using cerebral embolic protection devices during transcatheter aortic valve implantation.

Aortic valve stenosis is one of the most common valvular abnormalities, which can manifest as angina, syncope, dyspnoea and sudden cardiac death. Transcatheter aortic valve implantation (TAVI) has been introduced as an alternative to surgical valve replacement in patients with severe aortic valve stenosis, resulting in less morbidity, shorter time to recovery and similar mortality rates. Progress in this field has reduced complication rates. However, the incidence of peri-procedural stroke remains relatively high (around 4%). To fully utilise the potential of TAVI, cerebral embolic protection devices (CEPD) have been developed and introduced. In this position paper, we aim to summarise the available data on several CEPD.

Treatment decision for transcatheter aortic valve implantation: the role of the heart team : Position statement paper of the Dutch Working Group of Transcatheter Heart Interventions.

The current paper presents a position statement of the Dutch Working Group of Transcatheter Heart Valve Interventions that describes which patients with aortic stenosis should be considered for transcatheter aortic valve implantation and how this treatment proposal/decision should be made. Given the complexity of the disease and the assessment of its severity, in particular in combination with the continuous emergence of new clinical insights and evidence from physiological and randomised clinical studies plus the introduction of novel innovative treatment modalities, the gatekeeper of the treatment proposal/decision and, thus, of qualification for cost reimbursement is the heart team, which consists of dedicated professionals working in specialised centres.

Recommendations for the use of bioresorbable vascular scaffolds in percutaneous coronary interventions : 2017 revision.

BACKGROUND: To eliminate some of the potential late limitations of permanent metallic stents, the bioresorbable coronary stents or 'bioresorbable vascular scaffolds' (BVS) have been developed. METHODS: We reviewed all currently available clinical data on BVS implantation. RESULTS: Since the 2015 position statement on the appropriateness of BVS in percutaneous coronary interventions, several large randomised trials have been presented. These have demonstrated that achieving adequate 1 and 2 year outcomes with these first-generation BVS is not straightforward. These first adequately powered studies in non-complex lesions showed worse results if standard implantation techniques were used for these relatively thick scaffolds. Post-hoc analyses hypothesise that outcomes similar to current drug-eluting stents are still possible if aggressive lesion preparation, adequate sizing and high-pressure postdilatation are implemented rigorously. As long as this has not been confirmed in prospective studies the usage should be restricted to experienced centres with continuous outcome monitoring. For more complex lesions, results are even more disappointing and usage should be discouraged. When developed, newer generation scaffolds with thinner struts or faster resorption rates are expected to improve outcomes. In the meantime prolonged dual antiplatelet therapy (DAPT, beyond one year) is recommended in an individualised approach for patients treated with current generation BVS. CONCLUSION: The new 2017 recommendations downgrade and limit the use of the current BVS to experienced centres within dedicated registries using the updated implantation protocol and advise the prolonged usage of DAPT. In line with these recommendations the manufacturer does not supply devices to the hospitals without such registries in place.

Antithrombotic therapy in patients undergoing TAVI: an overview of Dutch hospitals.

PURPOSE: To assess current antithrombotic treatment strategies in the Netherlands in patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: For every Dutch hospital performing TAVI (n = 14) an interventional cardiologist experienced in performing TAVI was interviewed concerning heparin, aspirin, thienopyridine and oral anticoagulation treatment in patients undergoing TAVI. RESULTS: The response rate was 100 %. In every centre, a protocol for antithrombotic treatment after TAVI was available. Aspirin was prescribed in all centres, concomitant clopidogrel was prescribed 13 of the 14 centres. Duration of concomitant clopidogrel was 3 months in over two-thirds of cases. In 2 centres, duration of concomitant clopidogrel was based upon type of prosthesis: 6 months versus 3 months for supra-annular and intra-annular prostheses, respectively. CONCLUSIONS: Leaning on a small basis of evidence and recommendations, the antithrombotic policy for patients undergoing TAVI is highly variable in the Netherlands. As a standardised regimen might further reduce haemorrhagic complications, large randomised clinical trials may help to establish the most appropriate approach.

Antiplatelet therapy in patients undergoing coronary stenting: The risk of late stent thrombosis.

BACKGROUND: Anticoagulation after coronary stenting is essential to prevent stent thrombosis. Drug-eluting stents, which are the preferred therapy, may be associated with a higher tendency for stent thrombosis. METHODS: Patients who underwent coronary stent placement and presented with late stent thrombosis are described. RESULTS: Eight patients with stent thrombosis are presented. Early discontinuation of the antithrombotic medication is associated with the occurrence of these complications. CONCLUSION: Long-term antithrombotic therapy seems essential to prevent stent thrombosis, especially for patients treated with drug-eluting stents.

Histopathologic validation of in-vivo angioscopic observation of coronary thrombus after angioplasty in a porcine model.

BACKGROUND: Coronary angioscopy has been reported to be superior to angiography and intravascular ultrasound for detecting intracoronary thrombus. However, in-vivo histopathologic validation of angioscopic detection of intracoronary thrombus had not been performed. OBJECTIVE: To perform histopathologic validation of in-vivo angioscopic detection of coronary thrombus. DESIGN: An experimental, blinded comparison of angioscopy and histopathology. METHODS: Coronary angioscopy was performed from 0 to 14 days after angioplasty in 39 porcine coronary arteries. When thrombus was detected by angioscopy, it was subclassified into white, mixed red-white, or red thrombus according to color. By histopathology the presence of thrombus was determined and subclassified into platelet-rich, mixed platelet-erythrocyte, or erythrocyte-rich thrombus. RESULTS: Angioscopy correctly classified 19 of 21 coronary thrombi (sensitivity 90%) but incorrectly classified nine of 18 arteries without formation of thrombus as having a thrombus (specificity 50%). Positive and negative predictive values were 68 and 82%, respectively. The angioscopic subclassification of thrombus into white, mixed red-white, or red thrombi was not correlated to the corresponding histopathologic morphology (platelet-rich, mixed platelet-erythrocyte, or erythrocyte-rich) of the observed thrombi (chi2 test: P = 0.5). CONCLUSIONS: Angioscopic detection of thrombus in vivo had high sensitivity and negative predictive value but low-to-moderate specificity and positive predictive value. Visual assessment of color of angioscopically detected thrombi seemed not to reflect histopathologic morphology of thrombus according to the definitions used in the present study.

Hemodynamic effects of iodixanol and iohexol during ventriculography in patients with compromised left ventricular function.

A crossover study was performed to compare the hemodynamic effects of the iso-osmolar contrast agent iodixanol (Visipaque) 320 mg I/ml to those of the low-osmolar iohexol (Omnipaque) 350 mg I/ml. The main hypothesis was that iodixanol and iohexol would affect left ventricular end-diastolic pressure (LVEDP) to different degrees. In 48 patients with reduced cardiac function (mean ejection fraction 33. 4%), one ventricular injection was performed with each contrast medium. Ventricular, aortic and right atrial pressures and heart rate were measured continuously. Cardiac output (using Fick's principle) and systemic vascular resistance were calculated. LVEDP increased with both agents, but significantly less after iodixanol than after iohexol (P < 0.01), also in subgroups of patients in whom baseline LVEDP was severely increased and in whom 3-vessel disease was present. Immediate changes in variables reflecting vasodilatation were similar with both agents. In conclusion, both contrast agents influenced hemodynamics during ventriculography, but iodixanol had significantly less influence on LVEDP than did iohexol.

Myocardial "hybrid" revascularisation with minimally invasive direct coronary artery bypass grafting combined with coronary angioplasty: preliminary results of a multicentre study.

OBJECTIVE: To expand the benefits of the minimally invasive direct coronary artery bypass (MIDCAB) concept to patients with multivessel disease, a hybrid procedure combining surgical revascularisation of the left anterior descending artery with interventional procedures for additional coronary lesions has recently been introduced. Preliminary results in patients undergoing this hybrid procedure are presented. DESIGN AND PATIENTS: Since December 1996, 35 patients (29 male, 6 female, mean (SD) age 56.7 (17) years) underwent a hybrid revascularisation performed as a primary MIDCAB procedure for grafting of the left anterior descending artery with the left internal mammary artery, followed by staged angioplasty and stenting of additional coronary lesions. RESULTS: After MIDCAB grafting the postoperative course was uneventful in all patients. Coronary reangiography after a median of seven days revealed patent and functioning left internal mammary artery grafts in all patients. Applying subsequent percutaneous transluminal coronary angioplasty and occasional stenting (n = 14), a total of 47 lesions were treated successfully. Procedure related complications did not occur. All patients remained free from angina and no stress ECG changes were recorded. CONCLUSIONS: The preliminary results of this hybrid approach to myocardial revascularisation suggest that this is a safe and effective procedure for complete revascularisation in selected patients with multivessel disease. Elderly and reoperative patients with significant comorbidity may benefit especially from such hybrid procedures by avoiding cardiopulmonary bypass and mid sternotomy.

Coronary angioplasty induces rise in Chlamydia pneumoniae-specific antibodies.

Chlamydia pneumoniae is frequently found in atherosclerotic lesions, and high titers of specific antibodies are associated with increased risk for acute myocardial infarction. However, a causative relation has not been established yet. We performed a prospective study of 93 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) to investigate whether angioplasty influences Chlamydia-specific antibody titers and whether there is an association with restenosis. Blood samples were obtained before and 1 and 6 months after angioplasty. Antibodies against chlamydial lipopolysaccharide and against purified C. pneumoniae elementary bodies were measured by enzyme-linked immunosorbent assay (ELISA). After angioplasty, the prevalence of antibodies to lipopolysaccharide rose from 20 to 26% for immunoglobulin A (IgA), from 53 to 64% for IgG, and from 2 to 7% for IgM (P = 0.021, 0.004, and 0.046, respectively). There was a rapid increase of mean antibody titers of all antibody classes within 1 month of PTCA. During the following 5 months, antibody titers decreased slightly but were still higher than baseline values. Results of the C. pneumoniae-specific ELISA were essentially the same. The rise of anti-Chlamydia antibodies was not caused by unspecific reactivation of the immune system, as levels of antibodies against cytomegalovirus did not change. Neither seropositivity nor antibody titers were related to restenosis. However, increases in mean IgA and IgM titers were restricted to patients who had suffered from myocardial infarction earlier in their lives. In conclusion, we show that PTCA induces a stimulation of the humoral immune response against C. pneumoniae. These data support the idea that plaque disruption during angioplasty might make hidden chlamydial antigens accessible to the immune system.

Humoral immune response to human cytomegalovirus in patients undergoing percutaneous transluminal coronary angioplasty.

Possible causal relations between prior human cytomegalovirus (HCMV) infection and atherosclerosis and between HCMV reactivation and restenosis after coronary angioplasty have been suggested. We investigated patterns of antibodies directed to HCMV in 112 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) and in a group of sex- and age-matched controls (blood donors without evidence of atherosclerosis). Levels of antibodies to HCMV were measured by enzyme-linked immunosorbent assay (ELISA) of serum samples drawn before and 5 weeks after PTCA. To further differentiate the humoral immune response, we specifically tested antibody reactivity towards four single HCMV proteins (IE2, p52, pp150, and pp65) by recombinant ELISAs. We found that 73% of PTCA patients and 69% of sex- and age-matched controls were seropositive for HCMV (odds ratio, 1.2 [not significant]). The corresponding odds ratios for matched pairs ranged in the recombinant ELISAs from 1.2 to 1.4. Patients had more often high titers of anti-HCMV antibodies (11 versus 4%; odds ratio = 3.3 [0.9 to 15.2]; P = 0.052) and high titers of anti-pp150 antibodies (13 versus 4%; odds ratio = 6.0 [1.3 to 38.8]; P = 0.008). Anti-HCMV immunoglobulin M antibodies were not detected in any patient. There was no evidence of acute HCMV reactivation after PTCA, since the titers of antibodies to the investigated recombinant proteins did not increase at 5 weeks after PTCA. Our results show a limited association between prior HCMV infection and coronary artery disease. We infer that positive anti-HCMV titers are not a major risk factor at the time of disease manifestation. However, this study cannot rule out a possible role of HCMV at earlier stages of the atherosclerotic process. Recombinant ELISAs provide a valuable tool for investigating the antiviral immune response.

Evaluation of a weight-adjusted single-bolus plasminogen activator in patients with myocardial infarction: a double-blind, randomized angiographic trial of lanoteplase versus alteplase.

BACKGROUND: Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. METHODS AND RESULTS: InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P<0. 001). Similar results were observed at 90 minutes (26.1% to 57.1%, P<0.001). At 90 minutes, coronary patency (TIMI 2 or 3) increased across the dose range up to 83% of subjects at 120 kU/kg lanoteplase compared with 71.4% with alteplase. Thus, at this dose, lanoteplase was superior to alteplase in restoring coronary patency (difference, 12%; 95% CI, 1% to 23%). The early safety experience in this study suggests that lanoteplase was well tolerated at all doses with safety comparable to that of alteplase. CONCLUSIONS: Lanoteplase, a single-bolus, weight-adjusted agent, increased coronary patency at 60 and 90 minutes in a dose-dependent fashion. Coronary patency at 90 minutes was achieved more frequently with 120 kU/kg lanoteplase than alteplase. In this study, safety with lanoteplase and alteplase was comparable. InTIME-II, a worldwide mortality trial, will evaluate efficacy and safety with this promising new agent.

Coronary blood flow dynamics during transcutaneous electrical nerve stimulation for stable angina pectoris associated with severe narrowing of one major coronary artery.

To study the effect of transcutaneous electrical nerve stimulation (TENS) on coronary vasomotion, patients with New York Heart Association class III angina pectoris and significant single-vessel left coronary artery disease and who were also scheduled for elective percutaneous transluminal coronary angioplasty, were allocated to a study group (precordial actual TENS, n = 10) and a control group (precordial simulated TENS, n = 5, and TENS on the back, n = 3). Coronary volumetric flow was assessed in the stenotic and nonstenotic coronary artery before and after neurostimulation. The diameter (in millimeters) of the stenotic coronary artery was reduced in the study group after actual TENS (from 2.73 +/- 0.55 by 0.12 +/- 0.11; p = 0.008). In the nonstenotic coronary artery, the diameter increased in the study group (from 2.64 +/- 0.43 by 0.24 +/- 0.15; p = 0.01). In both the stenotic and nonstenotic coronary arteries, no effect was shown on the average peak velocity (centimeters per second) in the study group. The coronary volumetric flow (milliliters per minute) was reduced in the stenotic artery of the study group (from 62 +/- 18 by 8 +/- 7; p = 0.007). In the nonstenotic coronary artery, volumetric flow increased in the study group (from 57 +/- 18 by 11 +/- 10; p = 0.007). In the control group, simulated TENS and TENS on the back had no effect on the diameter of the artery, average peak velocity, or volumetric flow. In addition, in all patients, TENS had no effect on the total volumetric flow of the left coronary artery and hemodynamic variables during the study period. This observation suggests that TENS modulates regional coronary vasomotion in patients with coronary artery disease.

Prior cytomegalovirus infection does not predict clinical outcome after percutaneous transluminal coronary angioplasty.

BACKGROUND: A direct association between human cytomegalovirus (HCMV) infection and the development of restenosis after coronary angioplasty has been suggested. The aim of this prospective study was to evaluate the value of HCMV serology in predicting the clinical outcome after percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS: 112 patients undergoing elective PTCA were included in the study. HCMV antibody levels were measured by ELISA. Cardiac events within a follow-up period of 6 months after PTCA were defined as (1) progression or recurrence of anginal complaints and/or a positive exercise test; (2) restenosis that required repeat revascularization. 73% of PTCA patients were seropositive for HCMV. Successful PTCA was achieved in a total of 94 patients, who were followed for 6 months. In 31/94 patients (33%) cardiac events occurred and in 15/94 (16%), this could be related to restenosis. We found no statistically significant difference between seropositive and negative patients with respect to anginal complaints or the need for revascularization. There was no evidence of acute reactivation, since titers of anti-HCMV antibodies did not increase after PTCA. CONCLUSION: This study shows that the clinical outcome after PTCA is not related to the HCMV serostatus of the patient. Therefore, our data do not support the hypothesis that serological markers of HCMV infection are of clinical importance for the assessment of a patient's individual risk after PTCA. This does not preclude a role for local reactivation of HCMV at the site of angioplasty.