Outcomes and predictors of left ventricle recovery in patients with severe left ventricular dysfunction undergoing transcatheter aortic valve implantation.

BACKGROUND: Data on the likelihood of left ventricle (LV) recovery in patients with severe LV dysfunction and severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and its prognostic value are limited. AIMS: We aimed to assess the likelihood of LV recovery following TAVI, examine its association with midterm mortality, and identify independent predictors of LV function. METHODS: In our multicentre registry of 17 TAVI centres in Western Europe and Israel, patients were stratified by baseline LV function (ejection fraction [EF] >/≤30%) and LV response: no LV recovery, LV recovery (EF increase ≥10%), and LV normalisation (EF ≥50% post-TAVI). RESULTS: Our analysis included 10,872 patients; baseline EF was ≤30% in 914 (8.4%) patients and >30% in 9,958 (91.6%) patients. The LV recovered in 544 (59.5%) patients, including 244 (26.7%) patients whose LV function normalised completely (EF >50%). Three-year mortality for patients without severe LV dysfunction at baseline was 29.4%. Compared to this, no LV recovery was associated with a significant increase in mortality (adjusted hazard ratio 1.32; p<0.001). Patients with similar LV function post-TAVI had similar rates of 3-year mortality, regardless of their baseline LV function. Three variables were associated with a higher likelihood of LV recovery following TAVI: no previous myocardial infarction (MI), estimated glomerular filtration rate >60 mL/min, and mean aortic valve gradient (mAVG) (expressed either as a continuous variable or as a binary variable using the standard low-flow, low-gradient aortic stenosis [AS] definition). CONCLUSIONS: LV recovery following TAVI and the extent of this recovery are major determinants of midterm mortality in patients with severe AS and severe LV dysfunction undergoing TAVI. Patients with no previous MI and those with an mAVG >40 mmHg show the best results following TAVI, which are at least equivalent to those for patients without severe LV dysfunction. (ClinicalTrials.gov: NCT04031274).

Comparison of different percutaneous revascularisation timing strategies in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: The optimal timing to perform percutaneous coronary interventions (PCI) in transcatheter aortic valve implantation (TAVI) patients remains unknown. AIMS: We sought to compare different PCI timing strategies in TAVI patients. METHODS: The REVASC-TAVI registry is an international registry including patients undergoing TAVI with significant, stable coronary artery disease (CAD) at preprocedural workup. In this analysis, patients scheduled to undergo PCI before, after or concomitantly with TAVI were included. The main endpoints were all-cause death and a composite of all-cause death, stroke, myocardial infarction (MI) or rehospitalisation for congestive heart failure (CHF) at 2 years. Outcomes were adjusted using the inverse probability treatment weighting (IPTW) method. RESULTS: A total of 1,603 patients were included. PCI was performed before, after or concomitantly with TAVI in 65.6% (n=1,052), 9.8% (n=157) or 24.6% (n=394), respectively. At 2 years, all-cause death was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (6.8% vs 20.1% vs 20.6%; p<0.001). Likewise, the composite endpoint was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (17.4% vs 30.4% vs 30.0%; p=0.003). Results were confirmed at landmark analyses considering events from 0 to 30 days and from 31 to 720 days. CONCLUSIONS: In patients with severe aortic stenosis and stable coronary artery disease scheduled for TAVI, performance of PCI after TAVI seems to be associated with improved 2-year clinical outcomes compared with other revascularisation timing strategies. These results need to be confirmed in randomised clinical trials.

Management of Myocardial Revascularization in Patients With Stable Coronary Artery Disease Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: The best management of stable coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI) is still unclear due to the marked inconsistency of the available evidence. METHODS: The REVASC-TAVI registry (Management of Myocardial Revascularization in Patients Undergoing Transcatheter Aortic Valve Implantation With Coronary Artery Disease) collected data from 30 centers worldwide on patients undergoing TAVI who had significant, stable CAD at preprocedural work-up. For the purposes of this analysis, patients with either complete or incomplete myocardial revascularization were compared in a propensity score matched analysis, to take into account of baseline confounders. The primary and co-primary outcomes were all-cause death and the composite of all-cause death, stroke, myocardial infarction, and rehospitalization for heart failure, respectively, at 2 years. RESULTS: Among 2407 patients enrolled, 675 pairs of patients achieving complete or incomplete myocardial revascularization were matched. The primary (21.6% versus 18.2%, hazard ratio' 0.88 [95% CI, 0.66-1.18]; P=0.38) and co-primary composite (29.0% versus 27.1%, hazard ratio' 0.97 [95% CI, 0.76-1.24]; P=0.83) outcome did not differ between patients achieving complete or incomplete myocardial revascularization, respectively. These results were consistent across different prespecified subgroups of patients (< or >75 years of age, Society of Thoracic Surgeons score > or <4%, angina at baseline, diabetes, left ventricular ejection fraction > or <40%, New York Heart Association class I/II or III/IV, renal failure, proximal CAD, multivessel CAD, and left main/proximal anterior descending artery CAD; all P values for interaction >0.10). CONCLUSIONS: The present analysis of the REVASC-TAVI registry showed that, among TAVI patients with significant stable CAD found during the TAVI work-up, completeness of myocardial revascularization achieved either staged or concomitantly with TAVI was similar to a strategy of incomplete revascularization in reducing the risk of all cause death, as well as the risk of death, stroke, myocardial infarction, and rehospitalization for heart failure at 2 years, regardless of the clinical and anatomical situations.

Technical Aspects and Development of Transcatheter Aortic Valve Implantation.

Aortic stenosis is the most common valve disease requiring surgery or percutaneous treatment. Since the first-in-man implantation in 2002 we have witnessed incredible progress in transcatheter aortic valve implantation (TAVI). In this article, we review the technical aspects of TAVI development with a look at the future. Durability, low thrombogenicity, good hydrodynamics, biocompatibility, low catheter profile, and deployment stability are the attributes of an ideal TAVI device. Two main design types exist-balloon-expandable and self-expanding prostheses. Balloon-expandable prostheses use a cobalt-chromium alloy frame providing high radial strength and radiopacity, while the self-expanding prostheses use a nickel-titanium (Nitinol) alloy frame, which expands to its original shape once unsheathed and heated to the body temperature. The valve is sewn onto the frame and consists of the porcine or bovine pericardium, which is specially treated to prevent calcinations and prolong durability. The lower part of the frame can be covered by polyethylene terephthalate fabric or a pericardial skirt, providing better sealing between the frame and aortic annulus. The main future challenges lie in achieving lower rates of paravalvular leaks and new pacemaker implantations following the procedure, lower delivery system profiles, more precise positioning, longer durability, and a good hemodynamic profile. Patient-specific design and the use of autologous tissue might solve these issues.

Enhanced Detection of Cardiac Surgery-Associated Acute Kidney Injury by a Composite Biomarker Panel in Patients with Normal Preoperative Kidney Function.

We have recently shown that minor subclinical creatinine dynamic changes enable the excellent detection of acute kidney injury (AKI) within 6-12 h after cardiac surgery. The aim of the present study was to examine a combination of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC) and creatinine for enhanced AKI detection early after cardiac surgery. Elective patients with normal renal function undergoing cardiac surgery using cardiopulmonary bypass were enrolled. Concentrations of plasma NGAL, serum CysC and serum creatinine were determined after the induction of general anesthesia, at the termination of the cardiopulmonary bypass and 2 h thereafter. Out of 119 enrolled patients, 51 (43%) developed AKI. A model utilizing an NGAL, CysC and creatinine triple biomarker panel including sequential relative changes provides a better prediction of cardiac surgery-associated acute kidney injury than any biomarker alone already 2 h after the termination of the cardiopulmonary bypass. The area under the receiver-operator curve was 0.77, sensitivity 77% and specificity 68%.

Center Valve Preference and Outcomes of Transcatheter Aortic Valve Replacement: Insights From the AMTRAC Registry.

BACKGROUND: Data on outcomes of transcatheter aortic valve replacement (TAVR) using balloon-expandable valves (BEVs) or self-expandable valves (SEVs) as well as the impact of center valve preference on these outcomes are limited. OBJECTIVES: The aim of this study was to compare outcomes of TAVR procedures using third-generation BEVs and SEVs stratified by center valve preference. METHODS: In a multicenter registry (n = 17), 13 centers exhibited valve preference (66.6%-90% of volume) and were included. Outcomes were compared between BEVs and SEVs stratified by center valve preference. RESULTS: In total, 7,528 TAVR procedures (3,854 with SEVs and 3,674 with BEVs) were included. The mean age was 81 years, and the mean Society of Thoracic Surgeons score was 5.2. Baseline characteristics were similar between BEVs and SEVs. Need for pacemaker implantation was higher with SEVs at BEV- and SEV-dominant centers (17.8% vs 9.3% [P < 0.001] and 12.7% vs 10.0% [P = 0.036], respectively; HR: 1.51; P for interaction = 0.021), risk for cerebrovascular accident was higher with SEVs at BEV-dominant but not SEV-dominant centers (3.6% vs 1.1% [P < 0.001] and 2.2% vs 1.4% [P = 0.162]; HR: 2.08; P for interaction < 0.01). Aortic regurgitation greater than mild was more frequent with SEVs at BEV-dominant centers and similar with BEVs regardless of center dominance (5.2% vs 2.8% [P < 0.001] and 3.4% vs 3.7% [P = 0.504], respectively). Two-year mortality was higher with SEVs at BEV-dominant centers but not at SEV-dominant centers (21.9% vs 16.9% [P = 0.021] and 16.8% vs 16.5% [P = 0.642], respectively; HR: 1.20; P for interaction = 0.032). CONCLUSIONS: Periprocedural outcomes, aortic regurgitation greater than mild, and 2-year mortality are worse when TAVR is performed using SEVs at BEV-dominant centers. Outcomes are similar regardless of valve type at SEV-dominant centers. The present results stress the need to account for this factor when comparing BEV and SEV outcomes. (The Aortic+Mitral Transcatheter [AMTRAC] Valve Registry; NCT04031274).

The impact of mild therapeutic hypothermia on platelet reactivity in comatose survivors of cardiac arrest with acute myocardial infarction treated with ticagrelor.

BACKGROUND: The aim of the study was to assess the antiplatelet effect of ticagrelor in patients with myocardial infarction (MI) after out-of-hospital cardiac arrest (OHCA) treated with percutaneous coronary intervention (PCI) and mild therapeutic hypothermia (MTH) vs. MI patients without OHCA treated with PCI. METHODS: The study was designed and performed as a phase IV, single-center, investigator-initiated, prospective, observational study assessing the early pharmacodynamic effect (within first 24 h) of a ticagrelor loading dose (180 mg) in both groups of patients (MTH group vs. MI group). For assessment of ticagrelor pharmacodynamics Multiple Electrode Aggregometry (MEA) was applied. RESULTS: Compared with the MTH group, platelet inhibition was persistently stronger in the MI group over the entire observation period (up to 24 h), with the highest difference at 4 hours after loading with ticagrelor (25.8 ± 26.4 vs. 75.8 ± 40.9 U, p = 0.002). As a consequence, there was a higher prevalence of high platelet reactivity in the MTH group, with the most explicit difference at 6 hours after the loading dose of ticagrelor (78% vs. 7%, p < 0.001). CONCLUSIONS: In comparison with patients treated with primary PCI for uncomplicated MI, the antiplatelet effect of ticagrelor in patients with MI complicated with OHCA, undergoing MTH and primary PCI, is attenuated and delayed.

Clinical outcomes of transcatheter aortic valve implantation in patients younger than 70 years rejected for surgery: the AMTRAC registry.

BACKGROUND: The mean age of transcatheter aortic valve implantation (TAVI) patients is steadily decreasing. AIMS: The aim of the study was to describe the characteristics, the indications for and the outcomes of TAVI in patients <70 years old. METHODS: All patients undergoing TAVI (n=8,626) from the 18 participating centres between January 2007 and June 2020 were stratified by age (70). For patients <70, the indications for TAVI were extracted from Heart Team discussions and the baseline characteristics and mortality were compared between the two groups. RESULTS: Overall, 640 (7.4%) patients were <70 (9.1% during 2018-2020, p<0.001); the mean age was 65.0±2.3 years. The younger patients were more often male, with bicuspid valves or needing valve-in-valve procedures. They had a higher prevalence of lung disease and diabetes. In 80.7% of cases, the Heart Team estimated an increased surgical risk and TAVI was selected, reflected by an STS score >4% in 20.4%. Five-year mortality was similar (29.4 vs 29.8%, HR 0.95, p=0.432) in the <70 and >70 groups. In the <70 group, mortality was higher for those referred for TAVI due to an increased surgical risk compared to those referred for other reasons (31.6 vs 24.5%, HR 1.23, p=0.021). Mortality was similar regardless of the STS stratum in patients judged by the Heart Team to be at increased surgical risk (32.6 vs 30.4%, HR 0.98, p=0.715). CONCLUSIONS: Use of TAVI in patients <70 is becoming more frequent. The main reason for choosing TAVI is due to an increased surgical risk not adequately represented by the STS score. The outcomes for these patients are similar to those for older TAVI patients. Dedicated trials of TAVI/SAVR in younger patients are needed to guide decisions concerning expansion of TAVI indications. ((ClinicalTrials.gov: NCT04031274).

Left Ventricular Pseudoaneurysm: Unexpected Finding in a Patient Who Presented With Bacterial Endophthalmitis.

A large left ventricular pseudoaneurysm was discovered in a patient who presented with bacterial endophthalmitis 1 year after medically treated Staphylococcus aureus mitral valve endocarditis. After medical therapy, the patient underwent cardiac surgery uneventfully. We present a rare finding of a pseudoaneurysm complicated with a very late ocular septic event. (Level of Difficulty: Advanced.).

Effect of Transcatheter Aortic Valve Replacement on Concomitant Mitral Regurgitation and Its Impact on Mortality.

OBJECTIVES: The purpose of this study was to examine the impact of residual mitral regurgitation (MR) on mortality in patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: MR is common in patients undergoing TAVR. Data on optimal management of patients with significant MR after TAVR are limited. METHODS: The registry consisted of 16 TAVR centers (n = 7,303). Outcomes of patients with ≥ moderate versus lesser grade MR after TAVR were compared. RESULTS: In 1,983 (27.2%) patients, baseline MR grade was ≥ moderate. MR regressed in 874 (44.1%) patients and persisted in 1,109 (55.9%) after TAVR. Four-year mortality was higher for those with MR persistence, but not for those with MR regression after TAVR, compared with nonsignificant baseline MR (43.8% vs. 35.1% vs. 32.4%; hazard ratio [HR]: 1.38; p = 0.008; HR: 1.02; p = 0.383, respectively). New York Heart Association functional class III to IV after TAVR was more common in those with MR persistence vs. regression (14.4% vs. 3.9%; p < 0.001). In a propensity score-matched cohort (91 patients' pairs), with significant residual MR after TAVR who did or did not undergo staged mitral intervention, staged intervention was associated with a better functional class through 1 year of follow-up (82.4% vs. 33.3% New York Heart Association functional class I or II; p < 0.001), and a numerically lower 4-year mortality, which was not statistically significant (64.6% vs. 37.5%; HR: 1.66; p = 0.097). CONCLUSIONS: Risk stratification based on improvement in MR and symptoms after TAVR can identify patients at increased mortality risk after TAVR. These patients may benefit from a staged transcatheter mitral intervention, but this requires further proof from future studies. (Transcatheter Treatment for Combined Aortic and Mitral Valve Disease. The Aortic+Mitral TRAnsCatheter [AMTRAC] Valve Registry [AMTRAC]; NCT04031274).

Percutaneous mechanical thrombectomy in patients with high-risk pulmonary embolism and contraindications for thrombolytic therapy.

Background High-risk pulmonary embolism is associated with a high early mortality rate. We report our experience with percutaneous mechanical thrombectomy in patients with high-risk pulmonary embolism and contraindications for thrombolytic therapy. Patients and methods This was a retrospective analysis of consecutive patients with high-risk pulmonary embolism and contraindications to thrombolytic therapy. They were treated with percutaneous mechanical thrombectomy which included thrombectomy and additional thrombus aspiration when needed. Clinical parameters and survival to discharge were measured. Results From November 2005 to September 2015 we treated 25 patients with a mean age of 62.6 ± 12.7 years, 64% were men. Mean simplified Pulmonary Embolism Severity Index was 2.9. Mean maximum lactate levels were 7.8 ± 6.6 mmol/L, vasopressors were used in 77%, and 59% needed mechanical ventilation. Mechanical treatment included thrombus fragmentation complemented with aspiration (56%) and aspiration using Aspirex®S catheter (44%). Local (5 patients; 20%) and systemic (3 patients; 12%) thrombolytics were used as a salvage therapy. We observed nonsignificant improvements in systemic blood pressure (100 ± 41 mm Hg vs 119 ± 34; p = 0.100) and heart frequency (99 ± 35 min-1 vs 87 ± 31 min-1; p = 0.326) before and after treatment, respectively. Peak systolic tricuspid pressure gradient was significantly lower after treatment (57 ± 14 mm Hg vs 31 ± 3 mm Hg; p = 0.018). Overall the procedure was technically successful in 20 patients (80%) and 17 patients (68%) survived to hospital discharge. Conclusions In patients with high-risk pulmonary embolism who cannot receive thrombolytic therapy, percutaneous mechanical thrombectomy is a promising alternative to reduce pulmonary artery pressure.

Valve-in-valve transcatheter aortic valve implantation with fracturing of a failed small surgical aortic bioprosthesis: a case report.

BACKGROUND: Failure of a small surgical aortic bioprosthesis represents a challenging clinical scenario with valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) often resulting in patient-prosthesis mismatch. Bioprosthetic valve fracture (BVF) performed as a part of the ViV TAVI has recently emerged as an alternative approach with certain types of surgical bioprostheses. CASE SUMMARY: An 81-year-old woman with a history of three surgical aortic valve procedures presented with heart failure. Aortic bioprosthesis degeneration with severe stenosis and moderate regurgitation was found. The patient was deemed a high-risk surgical candidate and the heart team decided that ViV TAVI was the preferred treatment option. Due to the very small 19 mm stented surgical aortic bioprosthesis Mitroflow 19 mm (Sorin Group, Italy) we decided to perform BVF as a part of ViV TAVI to prevent patient-prosthesis mismatch. Since this was the first BVF procedure in our centre, an ex vivo BVF of the same kind of bioprosthetic valve was performed first. Subsequently, successful BVF with implantation of Evolut R 23 mm (Medtronic, USA) self-expandable transcatheter valve was performed. Excellent haemodynamic result was achieved and no periprocedural complications were present. The patient had an immediate major improvement in clinical status and remains asymptomatic after 6 months. DISCUSSION: Bioprosthetic valve fracture together with ViV TAVI is a safe and effective emerging technique for treatment of small surgical aortic bioprosthesis failure. Bioprosthetic valve fracture allows marked oversizing of implanted self-expandable transcatheter aortic valves, leading to excellent haemodynamic and clinical results. An ex vivo BVF can serve as an important preparatory step when introducing the new method.

Impact of mild therapeutic hypothermia on bioavailability of ticagrelor in patients with acute myocardial infarction after out-of-hospital cardiac arrest.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) frequently occurs in the early phase of acute myocardial infarction (MI). Survivors require percutaneous coronary intervention (PCI) with concomitant dual antiplatelet therapy. Target temperature management, including mild therapeutic hypothermia (MTH), should be applied in comatose patients after resuscitation. However, an increased risk of stent thrombosis in patients undergoing hypothermia is observed. The aim of this study was to assess the impact of MTH on pharmacokinetics of ticagrelor in cardiac arrest survivors with MI treated with MTH and PCI. METHODS: In a prospective, observational, single-center study pharmacokinetics of ticagrelor were evaluated in 41 MI patients, including 11 patients after OHCA undergoing MTH (MTH group) and 30 MI patients without OHCA and MTH (no-MTH group). Blood samples were drawn before administration of a 180 mg ticagrelor loading dose, and 30 min, 1, 2, 4, 6, 12, and 24 h after the loading dose. RESULTS: In patients treated with MTH total exposure to ticagrelor during the first 12 h after the loading dose and maximal plasma concentration of ticagrelor were significantly lower than in the no-MTH group (AUC(0-12): 3403 ± 2879 vs. 8746 ± 5596 ng·h/mL, difference: 61%, p = 0.01; Cmax: 475 ± 353 vs. 1568 ± 784 ng/mL, p = 0.0002). Time to achieve maximal ticagrelor plasma concentration was also delayed in the MTH group (tmax for ticagrelor: 12 [6-24] vs. 4 [2-12] h, p = 0.01). CONCLUSIONS: Bioavailability of ticagrelor was substantially decreased and delayed in MI patients treated with MTH after OHCA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02611934.

Mechanism and extent of myocardial injury associated with out-of-hospital cardiac arrest.

AIM: We investigated the mechanism and extent of myocardial injury associated with out-of-hospital cardiac arrest (OHCA). METHODS: 159 consecutive patients undergoing immediate coronary angiography after OHCA were included and divided into groups with acute culprit lesion (A), stable obstructive coronary disease (B) and non-obstructive or absent coronary disease (C). Post-resuscitation electrocardiogram (ECG) and serial measurements of high sensitivity cardiac troponin I (cTnI) were compared. RESULTS: ST-elevation myocardial infarction (STEMI) was documented in 65% in group A, 26% in group B, and 11% in group C (p < 0.001). cTnI, which was 0.88 ng/mL, 0.44 ng/mL and 0.19 ng/mL in groups A, B and C on admission (p < 0.001), increased to a maximum of 63.96 ng/mL, 10.00 ng/mL and 2.35 ng/mL, respectively (p < 0.001). Within the group A, cTnI was significantly larger in patients with acute occlusion than in patients with spontaneous reperfusion at initial angiography. Within groups B and C, peak cTnI correlated with duration of resuscitation, number of defibrillations and cumulative adrenaline (epinephrine) dose. If admission cTnI exceeded 0.46 ng/mL and STEMI was present in ECG, sensitivity for detection of acute culprit lesion was 88% and specificity 54%. CONCLUSIONS: Significant myocardial injury associated with OHCA occurs in the presence of acute culprit lesion while extent of myocardial injury in stable or absent coronary disease is significantly smaller and correlates with the duration and intensity of cardiac resuscitation. Admission cTnI, although combined with post-resuscitation ECG, have insufficient accuracy to securely predict presence of acute culprit lesion.

Emergency percutaneous implantation of veno-arterial extracorporeal membrane oxygenation in the catheterisation laboratory.

AIMS: Our aim was to describe our protocol for emergency percutaneous implantation of femoral veno-arterial extracorporeal membrane oxygenation (VA ECMO) in the catheterisation laboratory and to compare its effectiveness and safety with implantation in the intensive care unit and the operating room. METHODS AND RESULTS: Our retrospective observational study enrolled 56 consecutive patients undergoing VA ECMO implantation in the catheterisation laboratory (n=23), the intensive care unit (n=8) and the operating room (n=25). Among patients undergoing catheterisation laboratory implantation, 11 patients had profound cardiogenic shock but preserved arterial pulsations, and 12 patients had refractory cardiac arrest undergoing automated mechanical chest compression. Using our fluoroscopy-guided protocol, arterial and venous cannulas were successfully implanted and the desired ECMO flow obtained in each patient. There was no vessel perforation/dissection. Moderate/severe GUSTO or BARC 3 and 5 bleeding occurred in 13%. Ipsilateral limb ischaemia occurred in one of eight patients (13%) with upfront perfusion sheath implantation, and in two of three patients (75%) in whom this strategy was not used (p=0.15). There was no infection at the site of cannula implantation. Complications related to implantation in the catheterisation laboratory were comparable to surgical implantation in the operating room and percutaneous implantation in the intensive care unit using ultrasound guidance. CONCLUSIONS: Fluoroscopy-guided emergency implantation of femoral VA ECMO by an interventional cardiologist in the catheterisation laboratory is effective and safe for both patients in cardiogenic shock and those in refractory cardiac arrest.

Platelet reactivity in comatose survivors of cardiac arrest undergoing percutaneous coronary intervention and hypothermia.

AIMS: To investigate the effects of clopidogrel and eptifibatide on platelet reactivity in patients resuscitated from cardiac arrest undergoing percutaneous coronary intervention (PCI) and hypothermia. METHODS AND RESULTS: VerifyNow® and Multiplate® aggregometry were used before, and 4, 12, 22 and 48 hours after 600 mg clopidogrel treatment in 28 post-cardiac arrest hypothermic patients and in 14 normothermic patients with acute coronary syndrome. Basal platelet reactivity after stimulation with iso-thrombin receptor-activating peptide (TRAP) and PAR4-activating peptide (BASE) was significantly lower in the post-cardiac arrest group and persisted up to 48 hours. The antiplatelet effect of clopidogrel measured by VerifyNow and expressed as % inhibition was significantly lower in the post-cardiac arrest group. It was close to zero with an increase to only around 10% after 48 hours. Post-cardiac arrest patients receiving eptifibatide showed profound platelet inhibition measured by both VerifyNow IIb/IIIa and Multiplate TRAP tests for at least 22 hours after administration. CONCLUSIONS: Post-resuscitation syndrome with ongoing hypothermia is associated with decreased platelet reactivity. Clopidogrel loading does not significantly affect platelet function during the first 48 hours. This is in contrast with eptifibatide which produces profound platelet inhibition, and may be used to bridge insufficient inhibition by clopidogrel.

Oestrogen receptor dinucleotide (TA) polymorphism affects total and LDL cholesterol but does not predict premature myocardial infarction in Caucasian men.

OBJECTIVE: The aim of this association study was to test the hypothesis whether the oestrogen receptor gene dinucleotide (TA) polymorphism is a risk factor for premature myocardial infarction in Caucasian men. Moreover, we investigated an association between oestrogen receptor gene dinucleotide (TA) polymorphism and serum lipid levels. METHODS AND RESULTS: One hundred and thirty men with premature myocardial infarction were compared with healthy men. Cases and controls did not demonstrate a statistically significant difference in distribution of the oestrogen receptor dinucleotide (TA) gene polymorphism alleles. Neither did we demonstrate the length of the dinucleotide (TA) repeats of the oestrogen gene to be associated with premature myocardial infarction in Caucasian men. Subjects with larger alleles (both alleles of > or =19 repeats) differed from subjects with other genotypes in serum total and LDL cholesterol, but not in HDL cholesterol and triglycerides. CONCLUSIONS: Despite an association between the oestrogen receptor gene dinucleotide (TA) polymorphism in the regulatory region of the alpha oestrogen receptor gene and serum total and LDL cholesterol, our study suggests that the oestrogen polymorphism is not associated with premature myocardial infarction in Caucasian men.

The -429 T/C and -374 T/A gene polymorphisms of the receptor of advanced glycation end products gene (RAGE) are not risk factors for coronary artery disease in Slovene population with type 2 diabetes.

Receptor for advanced glycation end products (RAGE) plays a role in atherosclerosis in diabetics. There are two functional polymorphisms in the promoter of the RAGE gene (-429T/C and -374T/A). The aim of this study was to look for a relationship between the -429T/C and the -374T/A gene polymorphisms of the RAGE gene and the development of coronary artery disease (CAD) in the Slovene population with type 2 diabetes of duration longer than 10 years. One hundred and sixty-eight subjects with diabetes and CAD were compared to 241 diabetic subjects without CAD. The -429T/C and the -374T/A RAGE genotype distributions in patients with CAD (-429T/C: CC: 3%, TC: 31%, TT: 66.0%; -374T/A:AA: 7.7%, TA: 48.2%, TT: 44.1%) were not significantly different from those in patients without CAD (-429 T/C: CC: 1.7%, TC: 26.1%, TT: 72.2%; -374T/A: AA: 11.2%, TA: 43.2%, TT: 45.6%). Our study failed to demonstrate an association between either the -429T/C or the -374T/A gene polymorphism of the RAGE gene and CAD in the Slovene population with type 2 diabetes of duration longer than 10 years.