Heparin-Induced Thrombocytopenia in Patients Undergoing Venoarterial Extracorporeal Membrane Oxygenation.

Background: Heparin-induced thrombocytopenia (HIT) is a serious, immune-mediated adverse drug reaction to unfractionated heparin (UFH) affecting also patients undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO). Although the association between VA-ECMO support and the development of thrombocytopenia has long been known and discussed, HIT as one underlying cause is still insufficiently understood. Therefore, the purpose of this study was to further investigate the epidemiology, mortality, diagnosis, and clinical management of HIT occurring in VA-ECMO patients treated with UFH. Methods: We conducted a retrospective single-center study including adult patients (≥18 years) with VA-ECMO support in the cardiac intensive care unit (ICU) of the University Hospital of Munich (LMU) between January 2013 and May 2022, excluding patients with a known history of HIT upon admission. Differences in baseline characteristics and clinical outcome between excluded HIT (positive anti-platelet factor 4 (PF4)/heparin antibody test but negative functional assay) and confirmed HIT (positive anti-PF4/heparin antibody test and positive functional assay) VA-ECMO patients as well as diagnosis and clinical management of HIT were analysed. Results: Among the 373 patients included, anti-PF4/heparin antibodies were detected in 53/373 (14.2%) patients. Functional HIT testing confirmed HIT in 13 cases (3.5%) and excluded HIT in 40 cases (10.7%), corresponding to a prevalence of confirmed HIT of 13/373 (3.5%) [1.6, 5.3] and a positive predictive value (PPV) of 24.5% for the antibody screening test. The platelet course including platelet recovery following argatroban initiation was similar between all groups. One-month mortality in patients with excluded HIT was 14/40 (35%) and 3-month mortality 17/40 (43%), compared to 5/13 (38%) (p > 0.999), and 6/13 (46%) (p > 0.999) in patients with confirmed HIT. Neurological outcome in both groups measured by the cerebral performance category of survivors on hospital discharge was similar, as well as adverse events during VA-ECMO therapy. Conclusions: With a prevalence of 3.5%, HIT is a non-frequent complication in patients on VA-ECMO and was not associated with a higher mortality rate. HIT was ultimately excluded by functional essay in 75% of VA-ECMO patients with clinical suspicion of HIT and positive anti-PF4/heparin antibody test. Argatroban seems to be an appropriate and safe therapeutic option for confirmed HIT-positive patients on VA-ECMO support.

Smoking and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients: a substudy from the randomized TROPICAL-ACS trial.

AIMS: Prior analyses disclosed variations in antiplatelet drug response and clinical outcomes between smokers and non-smokers, thus the safety and efficacy of any dual antiplatelet therapy (DAPT) de-escalation strategy may differ in relation to smoking status. Hence, we assessed the impact of smoking on clinical outcomes and adenosine diphosphate-induced platelet aggregation following guided de-escalation of DAPT in invasively managed acute coronary syndrome (ACS) patients. METHODS AND RESULTS: The multicentre TROPICAL-ACS trial randomized 2610 biomarker-positive ACS patients 1:1 to standard treatment with prasugrel for 12 months (control group) or a platelet function testing guided de-escalation of DAPT. Current smokers (n = 1182) showed comparable event rates between study groups [6.6% vs. 6.6%; hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.64-1.56, P > 0.99]. In non-smokers (n = 1428), a guided DAPT de-escalation was associated with a lower 1-year incidence of the primary endpoint [cardiovascular death, myocardial infarction, stroke, or bleeding ≥ Grade 2 according to Bleeding Academic Research Consortium (BARC) criteria] compared with control group patients (7.9% vs. 11.0%; HR 0.71, 95% CI 0.50-0.99, P = 0.048). This reduction was mainly driven by a lower rate of BARC ≥ Grade 2 bleedings (5.2% vs. 7.7%; HR 0.68, 95% CI 0.45-1.03, P = 0.066). There was no significant interaction of smoking status with treatment effects of guided DAPT de-escalation (Pint = 0.23). Adenosine diphosphate-induced platelet aggregation values were higher in current smokers [median 28 U, interquartile range (IQR: 20-40)] vs. non-smoker [median 24 U (16-25), P < 0.0001] in the control group and in current smokers [median 42 U, IQR (27-68)] vs. non-smoker [median 37 U, IQR (25-55), P < 0.001] in the monitoring group. CONCLUSION: Guided DAPT de-escalation appears to be equally safe and effective in smokers and non-smokers. Regardless of smoking status and especially for those patients deemed unsuitable for 1 year of potent platelet inhibition this DAPT strategy might be used as an alternative antiplatelet treatment regimen.

Diabetes and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients undergoing percutaneous coronary intervention: a pre-specified analysis from the randomised TROPICAL-ACS trial.

AIMS: A guided de-escalation of P2Y12 inhibitor treatment is considered an alternative treatment strategy in ACS patients undergoing PCI. However, the safety and efficacy of this strategy may differ in diabetic vs non-diabetic patients. The aim of this study was to compare the outcomes of platelet function testing (PFT)-guided de-escalation of dual antiplatelet therapy (DAPT) in ACS patients with and without diabetes mellitus. METHODS AND RESULTS: The TROPICAL-ACS trial randomised 2,610 biomarker-positive ACS patients 1:1 to either standard treatment with prasugrel for 12 months (control group) or PFT-guided DAPT de-escalation. The association and interaction of diabetes on clinical endpoints across treatment groups and on platelet reactivity was investigated. In diabetic patients (n=527, 20.2%), the overall event rates were high and the one-year incidence of the primary endpoint (cardiovascular death, myocardial infarction, stroke or bleeding ≥grade 2) did not differ between guided de-escalation and control group patients (12.5% vs 10.8%; HR 1.17, 95% CI: 0.71-1.93, p=0.55). In non-diabetic patients (n=2,083, 79.8%), the one-year incidence of the primary endpoint was lower in the guided de-escalation vs control group (6.1% vs 8.5%; HR 0.71, 95% CI: 0.52-0.99, p=0.04, pint=0.10). Diabetic patients showed higher platelet reactivity levels in both control (=on prasugrel, p=0.01) and guided de-escalation group (=on clopidogrel, p=0.005) patients. CONCLUSIONS: Although diabetic status did not significantly interfere with the treatment effects of guided DAPT de-escalation, our results suggest that this approach might be safe and effective in non-diabetic patients. Further investigation is definitely warranted in diabetic patients.

Transcatheter aortic valve implantation (TAVI) by centres with and without an on-site cardiac surgery programme: preliminary experience from the German TAVI registry.

AIMS: To analyse patient characteristics, decision-making processes, and outcomes of TAVI performed in hospitals with versus those without on-site cardiac surgery (CS). METHODS AND RESULTS: Current guidelines mandate transcatheter aortic valve implantation (TAVI) to be performed at hospitals with both cardiology and on-site CS departments. Some hospitals in Germany perform TAVI without CS departments in-house. We analysed the data of 1,432 patients enrolled in the German TAVI registry at 27 hospitals between January 2009 and June 2010. Nineteen of these had on-site CS (group 1), while eight centres performed TAVI with no CS department at their institution (group 2). Patients in group 2 (n=178, 12% of the overall study population) were older than in group 1 (mean age 82.6±6.3 years vs. 81.6±6.2 years) with similar logistic EuroSCORE (average: 21%). Patients in group 2 were haemodynamically more stable (higher blood pressures, better ejection fraction, less low-flow or low-gradient aortic stenosis, and less urgent procedures). Procedure times and use of contrast were higher in group 2. The procedural success rate was higher in group 1 (98% vs. 95%). Post-procedural complications were similar in the two groups with 30-day mortality of 6.2% in group 2 compared with 8.3% in group 1 patients. CONCLUSIONS: Only 12% of patients enrolled in the German TAVI registry underwent TAVI at hospitals without an on-site CS department. Overall patient characteristics appeared to be similar, although patients in non-CS centres appeared to be haemodynamically more stable and more often had a history of previous heart surgery. Despite longer procedures, complication rates were similar. These preliminary data in a modest number of patients suggest the feasibility of performing TAVI in appropriately selected patients at hospitals without CS but this requires confirmation in future studies involving a large number of patients.

Outcome of patients after emergency conversion from transcatheter aortic valve implantation to surgery.

AIMS: To evaluate: 1) the causes of emergency conversion from transcatheter aortic valve implantation (TAVI) to surgery, 2) procedural settings, and 3) short-term outcome of converted patients. METHODS AND RESULTS: The prospective German TAVI registry was used to identify patients who underwent bail-out surgery during TAVI. Additionally, standardised questionnaires were developed and used to assess more detailed periprocedural and postprocedural data. Emergency conversion from TAVI to open cardiac surgery was required in 24 of 1,975 patients (1.2%). Primary conversion causes were aorto-valvular complications (i.e., aortic annulus rupture, aortic perforation, or thoracic aortic dissection). This was followed by prosthesis embolisation, myocardial perforation, severe aortic regurgitation, and coronary obstructions. The mean time interval between abortions of TAVI to surgery was 19 minutes (SD ± 17 min, range 5-80 min). Four of 24 patients (16.7%) died during the initial surgery, seven of 24 (29.2%) within the first 72 hours and the 30-day mortality was 45.8%. The highest mortality was observed in patients with aortic perforation or dissection (4/5, 80%). Mortality rates for other entities were: prosthesis embolisation 40% (2/5), myocardial perforation 50% (2/4), annulus rupture 67% (2/3), severe aortic regurgitation 33% (1/3), and coronary impairment 0% (0/3). CONCLUSIONS: Emergency conversion from TAVI to surgery is a rare event carrying a mortality of around 45% after 30 days. Outcome of converted patients with prior injury of aortic, aorto-valvular, or myocardial tissue during TAVI was poor, whereas patients with severe aortic regurgitation and those with coronary complications had a more favourable outcome after 30 days. Collected procedural and outcome data demand on-site cardiac surgery as a prerequisite for TAVI and constant process optimisation efforts regarding such emergency scenarios.

Comparison of three patent foramen ovale closure devices in a randomized trial (Amplatzer versus CardioSEAL-STARflex versus Helex occluder).

This randomized trial compared procedural complications and 30-day clinical outcomes of 3 patent foramen ovale (PFO) closure devices (Amplatzer, Helex, and CardioSEAL-STARflex). It examined 660 patients (361 men, 299 women, mean age 49.3+/-1.9 years), with 220 patients per group. All patients had a history of paradoxical embolism. All PFO closures were successful technically. Exchange of devices for others was most frequently required for the Helex occluder (7 of 220) and 2 of 220 in either of the other groups. Three device embolizations in the Helex group were retrieved and replaced successfully. One patient with a Helex occluder developed a transient ischemic attack and recovered without treatment. A hemopericardium in that group was punctured without affecting the device. One tamponade in the Amplatzer group required surgical device explantation. In 8 of 660 patients in the CardioSEAL-STARflex group, thrombi resolved after anticoagulation. Sixteen patients (11 in the CardioSEAL-STARflex group, 3 in the Amplatzer group, and 2 in the Helex group) had episodes of atrial fibrillation. PFOs were closed completely in 143 of 220 patients (65%) in the Amplatzer group, 116 of 220 patients (52.7%) in the Helex group, and 137 of 220 patients (62.3%) in the CardioSEAL-STARflex group at 30 days with significant differences between the Helex and Amplatzer occluders (p=0.0005) and the Helex and CardioSEAL-STARflex occluders (p=0.0003). PFO closure can be performed safely with each device. In conclusion, the Helex occluder embolized more frequently. Device thrombus formation and paroxysmal atrial fibrillation were more common with the CardioSEAL-STARflex occluder.

New concepts in transcatheter closure of paravalvular leaks.

New catheter techniques and a large variety of endovascular devices permit transcatheter treatment - not only of common atrial or ventricular septal defects - but also of rare intracardiac malformations such as postmyocardial infarction ventricular septal defects, sinus valsalva aneurysm or paravalvular leak. Owing to the variable anatomical nature of paravalvular leaks, closure may be one of the most challenging interventional procedures in the field of structural heart disease. Current literature documents ambiguous results and endorses the limitations of this procedure. In most cases these limitations are technical. Further efforts in the development of defect-specific devices and techniques may result in an improved patient outcome and extended patient selection.

Percutaneous devices for stroke prevention.

The most important approaches to prevent cerebral ischemia by catheter technique are patent foramen ovale (PFO) closure in patients with a history of cryptogenic stroke and left atrial appendage (LAA) occlusion in atrial fibrillation (AF) patients. Over the past years, several new devices have been developed for these procedures. Results of randomized trials comparing device therapy, antiplatelet, or anticoagulation therapy are still not available. However, several nonrandomized studies have shown promising results. This article gives a review on the current results and techniques of the most commonly used devices as well as on new developments and approaches to catheter-based stroke prevention.

Short- and long-term outcome after carotid artery stenting with neuroprotection: single-center experience within a prospective registry.

BACKGROUND: Carotid artery stenting is an alternative method to surgical endarterectomy for treatment of carotid artery stenosis. METHODS AND RESULTS: Three hundred and seventy-one consecutive patients (71+/-9 years) undergoing 405 carotid artery interventions at a single cardiologic center were studied prospectively within a therapy registry. In general, the interventional procedure was performed using neuroprotective devices to prevent distal embolization. Stents were used routinely whenever possible. Independent neurological assessment took place prior to and after carotid stenting. The neurological event rate was assessed in the early (<30 days) and late post interventional period. In asymptomatic patients, 286 interventions were done with a 30-day stroke rate of 1.3% (ipsilateral 1.0%). In symptomatic patients, strokes occurred in a significantly (p<0.005) higher rate of 5.0% after 119 interventions (all ipsilateral). At long-term follow-up (mean 728+/-548 days) additional strokes occurred ipsilateral to the side of carotid intervention in 0.4% of asymptomatic patients (1.7% of symptomatic patients); contralateral strokes were seen at long-term follow-up in 1.1% of asymptomatic (1.7% of symptomatic) patients. Due to their comorbidities, 1.6% of patients died early, and an additional 11.1% late after carotid stenting. CONCLUSION: Carotid artery stenting with the general use of neuroprotective devices yields acceptable shortterm results with respect to neurological events. Asymptomatic patients have significantly less periprocedural strokes than symptomatic patients. Neurological events during long-term follow-up are rare, in particular ipsilateral to the side of carotid stenting. Thus, carotid artery stenting with neuroprotection is a safe method for carotid revascularization, with acceptable periprocedural events, particularly in asymptomatic patients, and a good long-term neurologic outcome.

Percutaneous closure of perivalvular leaks with Amplatzer occluders: feasibility, safety, and shortterm results.

BACKGROUND AND AIM OF THE STUDY: Perivalvular leak (PVL) may have significant hemodynamic and/or hematological consequences, and re-do surgery is associated with considerable mortality and morbidity. Herein are reviewed the short-term results of percutaneous closure of PVLs using the Amplatzer occluder. METHODS: Eleven patients (five males, six females; mean age 59.7 +/- 7.3 years; range: 46-67 years) were referred for percutaneous closure of PVL using the Amplatzer occluder. Patients presented with congestive heart failure (n = 2), hemolysis (n = 1), or both (n = 8). The average number of previous heart operations was 2.4 +/- 1.3 per patient; seven patients had undergone two or more operations. The procedure was performed under general anesthesia, with fluoroscopic and transesophageal echocardiographic guidance. Antegrade and retrograde approaches were used for the mitral and aortic leaks, respectively. RESULTS: The PVLs were in the mitral position (n = 8), aortic position (n = 1), or both (n = 2). Device deployment was achieved in 11 (91.7%) of 12 attempted valves (10 patients, 90.9%). Failure to cross the leak with the wire occurred in one patient, and interruption of mitral leaflet movement occurred in two patients. Leakage was decreased in six patients (60%), but residual leak was observed at 10 of the 11 sites. Hemolysis was reduced in four patients, increased in four, and remained unchanged in two. An improved NYHA functional class of one grade was noted in five patients. One patient required a second operative session to seal a residual leak. CONCLUSION: Percutaneous closure of PVL using the Amplatzer occluder is feasible, but technically demanding. Although symptoms were improved, there was an inconsistent effect on hemolysis. At present, the Amplatzer occluder should be reserved for poor surgical candidates.

Catheter closure of paravalvular leak.

AIMS: The purpose of this study was to evaluate the feasibility and short-term efficacy of transcatheter paravalvular leak closure using different occlusion devices. METHODS AND RESULTS: Twenty-one patients underwent transcatheter closure of either aortic or mitral paravalvular leak from June 2002 to February 2006 using the Amplatzer PDA, ASD or VSD occluder. All patients had symptoms and signs of haemolysis and/or cardiac decompensation with dyspnoea.Implantation of a device was technically successful in twenty patients (95%). Immediate residual leak was found in seventeen patients (85%). Significant shunting persisted in nine cases during follow up (45%).Permanent leaflet obstruction was observed in one patient. Severe complications during follow up led to early death in one patient and surgical intervention in three. A successful second catheter treatment was performed in another three patients. The event-free survival from re-operation, death and stroke at the end of the observation period was 80%. CONCLUSION: Transcatheter closure of paravalvular leaks is a technically feasible, but demanding procedure. Residual leaks are common and may worsen pre-existing haemolysis. Due to the significant ongoing morbidity in this group of patients and the complexity of follow up individual patient results differ considerably. Nevertheless, it is possible to achieve some symptomatic relief, thus an interventional approach should be discussed as a potential treatment option for those patients with a limited defect and who are not deemed suitable for another operation.

Atrial and ventricular septal defects can safely be closed by percutaneous intervention.

Various transcatheter devices and methods to close congenital heart defects are currently available. Devices have been designed specifically for atrial septal defect (ASD), patent foramen ovale (PFO), and ventricular septal defect (VSD) closure. The trend in interventional treatment of intracardiac shunts shows toward defect-specific systems. The PFO is a tunnel defect requiring occluders that adapt to its length while common ASD strongly vary in their diameter, making a large scale of device sizes indispensable. VSDs are predominantly sealed by coils or tissue-adapted devices like muscular or perimembranous occluders. Since VSDs may occur with an aneurysm (VSA), a multi-perforated septum, an instable myocardial situation (postinfarction) or a high interventricular pressure gradient, closure of these defects is regarded sometimes as complicated. But during the last 30 years (since King and Mills implanted the first double-umbrella occluding system) several studies have proven procedure efficacy and safety of both ASD and VSD closure. This article reviews a large scale of studies and includes our single center data on 1,609 PFO, ASD, and VSD patients.