Coronary steal: how many thieves are out there?

The colorful term "coronary steal" arose in 1967 to parallel "subclavian steal" coined in an anonymous 1961 editorial. In both instances, the word "steal" described flow reversal in the setting of an interconnected but abnormal vascular network-in one case a left subclavian stenosis proximal to the origin of the vertebral artery and in the other case a coronary fistula. Over time, the term has morphed to include a larger set of pathophysiology without explicit flow reversal but rather with a decrease in stress flow due to other mechanisms. This review aims to shed light on this phenomenon from a clinical and a pathophysiological perspective, detailing the anatomical and physiological conditions that allow so-called steal to appear and offering treatment options for six distinct scenarios.

Ventricular pacing burden in patients with left bundle branch block after transcatheter aortic valve replacement therapy.

INTRODUCTION: Electrophysiological testing has been proposed in the latest European Society of Cardiology (ESC) guidelines for cardiac pacing to identify left bundle branch block (LBBB) patients with infrahisian conduction delay (IHCD) after transcatheter aortic valve replacement (TAVR). While in general IHCD is defined by a His-ventricular (HV) interval of >55 ms, a cut-off of ≥70 ms to trigger pacemaker (PM) implantation has been proposed in the latest ESC guidelines. The ventricular pacing (VP) burden during follow-up in such patients is largely unknown. As such, we aimed to assess the VP burden during follow-up of patients receiving PM therapy for LBBB after TAVR based on an HV interval > 55 ms and ≥70 ms. METHODS: All patients with new-onset or pre-existing LBBB after undergoing TAVR at a tertiary referral center underwent EP testing the day after TAVR. In patients with a prolonged HV interval (>55 ms), PM implantation was performed by a trained electrophysiologist in a standardized fashion. All devices were programmed to avoid unnecessary VP by specific algorithms (e.g., AAI-DDD). RESULTS: 701 patients underwent TAVR at the University Hospital of Basel. One hundred seventy-seven patients presented with new-onset or pre-existing LBBB the day following TAVR and underwent EP testing. An HV interval > 55 ms was found in 58 patients (33%) and an HV interval ≥ 70 ms in 21 patients (12%). 51 patients (mean age 84 ± 6.2 years, 45% women) agreed to receive a PM, out of which 20 (39%) patients had an HV Interval over 70 ms. Atrial fibrillation was present in 53% of the patients. A dual chamber PM was implanted in 39 (77%), and a single chamber PC in 12 (23%) patients, respectively. Median follow-up was 21 months. The median VP burden overall was 3%. The median VP burden was not significantly different between patients with an HV ≥ 70 ms (6.5 [0.8-52]) and those with an HV between 55 and 69 ms (2 [0-17], p = .23). 31% of patients demonstrated a VP burden < 1%, 27% 1%-5% and 41% > 5%. The median HV intervals in patients with VP burdens < 1%, 1%-5% and >5% were 66 (IQR 62-70) ms, 66 (IQR 63-74) ms and 68 (IQR 60-72) ms, respectively, p = .52. When only assessing patients with an HV interval 55-69 ms, 36% demonstrated a VP burden of <1%, 29% of 1%-5% and 35% of >5%. In patients with an HV Interval ≥ 70 ms, 25% demonstrated a VP burden < 1%, 25% of 1%-5% and 50% of >5% %, p = .64 (Figure). CONCLUSION: In patients with LBBB after TAVR and IHCD defined by an HV interval > 55 ms, VP burden is relevant in a non-negligible amount of patients during follow-up. Further studies are warranted to define the optimal cut-off value for the HV interval or to develop risk models incorporating HV measurements and other risk factors to trigger PM implantation in patients with LBBB after TAVR.

Unrecoverable stent deformation in the left main: Crush it or remove it?

Serial ostial and distal left main lesions continue to be one of the most difficult tasks for the interventional cardiologist, with many potential complications occurring. We present such a high-risk percutaneous coronary intervention where immediate stent explantation was deemed necessary because the metal deformation and high radial strength of the particular stent platform would prevent an acceptable procedural result if it had been crushed to the vessel wall. The aim of this paper was to discuss left main stent deformation, debate the risks and benefits of stent explantation and finally test in-vitro our theory on "insufficient" crush with stents with high radial strength and compare it with conventional stents. Bench-testing supports our ad-hoc explantation decision showing stent underexpansion, recoil, and malapposition, obtaining an inadequate minimal stent area.

The impact of chronic total occlusions in patients undergoing transcatheter aortic valve replacement: A systematic review and meta-analysis.

Coronary artery disease (CAD) is frequently encountered in patients evaluated for transcatheter aortic valve replacement (TAVR) due to severe aortic stenosis. The prognostic relevance of chronic total occlusions (CTOs) in this setting is poorly understood. We conducted a search of MEDLINE and EMBASE to identify studies evaluating patients who underwent TAVR and evaluated outcomes depending on the presence of coronary CTOs. Pooled analysis was performed to estimate the rate and risk ratio for mortality. Four studies involving 25,432 patients fulfilled the inclusion criteria. The follow up ranged from in-hospital outcomes to 8-years follow-up. Coronary artery disease was present in 67.8% to 75.5% of patients in 3 studies which reported this variable. The prevalence of CTOs varied between 2% and 12.6% in this cohort. The presence of CTOs was associated with increase in length of stay (8.1 ± 8.2 vs. 5.9 ± 6.5, p < 0.01), cardiogenic shock (5.1% vs. 1.7%, p < 0.01), acute myocardial infarction (5.8% vs. 2.8%, p = 0.02) and acute kidney injury (18.6% vs. 13.9%, p = 0.048). The pooled 1-year death rate revealed 41 deaths in 165 patients in the CTO group and 396 deaths in 1663 patients with no CTO ((24.8%) vs. (23.8%)). The meta-analysis of death with CTO versus no CTO showed a nonsignificant trend toward increased mortality with CTOs (risk ratio 1.11 95% CI 0.90-1.40, I2 = 0%). Our analysis suggests that concomitant CTO lesions in patients undergoing TAVR are common, and its presence was associated with increased in-hospital complications. However, CTO presence by itself was not associated with increased long-term mortality, only a nonsignificant trend toward an increased risk of death in patients with CTO was found. Further studies are warranted to assess the prognostic relevance of CTO lesion in TAVR patients.

Anatomical predictors for suture-based closure of the patent foramen ovale: A multicenter experience.

BACKGROUND: NobleStitch EL is a novel suture-based technique used for patent foramen ovale (PFO) closure and an alternative to traditional double-disc devices without the need for antithrombotic therapy. However, successful closure rates are still unknown, and certain anatomies may be unfavorable for successful closure. AIMS: We assessed the efficacy of the NobleStitch EL and sought to identify patient-related anatomical features associated with successful suture-based closure. METHODS: We included 55 patients who underwent PFO closure with the NobleStitch EL in The Netherlands and Switzerland. Successful closure was defined as residual right-to-left shunt grade ≤1 with Valsalva maneuver at a cardiac ultrasound. Predefined possible anatomical determinants for effective closure included PFO length, atrial septal aneurysm, PFO entry- and exit diameter. RESULTS: Successful closure was achieved in 33 patients (60%). The PFO length was shorter in patients with successful closure compared to unsuccessful closure with a median length of 9.6 mm (IQR 8.0-15.0) versus 13.3 mm (IQR 11.4-18.6) on preprocedural ultrasound (p = 0.041) and 9.9 mm (IQR 8.0-13.1) versus 12.5 mm (IQR 9.7-15.4) on angiography (p = 0.049). Additionally, the PFO exit diameter and PFO volume were smaller in patients with successful closure than unsuccessful closure, with a mean diameter of 7.0 ± 3.1 mm versus 9.5 ± 3.8 mm (p = 0.015) and a median volume of 381 mm3 (IQR 286-894) versus 985 mm3 (IQR 572-1550) (p = 0.016). CONCLUSION: In our study cohort, the successful PFO closure rate using NobleStitch EL was relatively low (60%). With this alternative procedure, patients with a small PFO driven by a short PFO tunnel length and small exit diameter seem to be eligible for successful suture-based closure.

Crystalline sirolimus-coated balloon (cSCB) angioplasty in an all-comers, patient population with stable and unstable coronary artery disease including chronic total occlusions: rationale, methodology and design of the SCORE trial.

BACKGROUND: A decade ago, the iopromide-paclitaxel coated balloon (iPCB) was added to the cardiologist's toolbox to initially treat in-stent restenosis followed by the treatment of de novo coronary lesions. In the meantime, DES technologies have been substantially improved to address in-stent restenosis and thrombosis, and shortened anti-platelet therapy. Recently, sirolimus-coated balloon catheters (SCB) have emerged to provide an alternative drug to combat restenosis. METHODS: The objective of this study is to determine the safety and efficacy of a novel crystalline sirolimus-coated balloon (cSCB) technology in an unselective, international, large-scale patient population. Percutaneous coronary interventions of native stenosis, in-stent stenosis, and chronic total occlusions with the SCB in patients with stable coronary artery disease or acute coronary syndrome were included. The primary outcome variable is the target lesion failure (TLF) rate at 12 months, defined as the composite rate of target vessel myocardial infarction (TV-MI), cardiac death or ischemia-driven target lesion revascularization (TLR). The secondary outcome variables include TLF at 24 months, ischemia driven TLR at 12 and 24 months and all-cause death, cardiac death at 12 and 24 months. DISCUSSION: Since there is a wealth of patient-based all-comers data for iPCB available for this study, a propensity-score matched analysis is planned to compare cSCB and iPCB for the treatment of de novo and different types of ISR. In addition, pre-specified analyses in challenging lesion subsets such as chronic total occlusions will provide evidence whether the two balloon coating technologies differ in their clinical benefit for the patient. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04470934.

Arrhythmias after COVID-19 Vaccination: Have We Left All Stones Unturned?

SARS-CoV-2 vaccination offered the opportunity to emerge from the pandemic and, thereby, worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe, but side effects are being reported more frequently as more and more people around the world become treated. Myopericarditis is the major, but not the only cardiovascular complication of this vaccine; hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post-mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database, we found that heart rhythm disorders after COVID vaccination are not uncommon and deserve more clinical and scientific attention. Since the COVID vaccine is the only vaccination related to this side effect, questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit ratio is clearly in favor of vaccination, heart rhythm disorders are not a negligible issue, and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we reviewed the potential molecular pathways for the COVID vaccine to impact cardiac electrophysiology and cause heart rhythm disorders.

Distal versus conventional radial access for coronary angiography and intervention: Design and rationale of DISCO RADIAL study.

BACKGROUND: Transradial access (TRA) has become the default access method for coronary diagnostic and interventional procedures. As compared to transfemoral access, TRA has been shown to be safer, cost-effective and more patient-friendly. Radial artery occlusion (RAO) represents the most frequent complication of TRA, and precludes future coronary procedures through the radial artery, the use of the radial artery as a conduit for coronary artery bypass grafting or as arteriovenous fistula for patients on hemodialysis. Recently, distal radial access (DRA) has emerged as a promising alternative to TRA, yielding potential for minimizing the risk of RAO. However, an international multicenter randomized comparison between DRA, and conventional TRA with respect to the rate of RAO is still lacking. TRIAL DESIGN: DISCO RADIAL is a prospective, multicenter, open-label, randomized, controlled, superiority trial. A total of 1300 eligible patients will be randomly allocated to undergo coronary angiography and/or percutaneous coronary intervention (PCI) through DRA or TRA using the 6 Fr Glidesheath Slender sheath introducer. Extended experience with both TRA and DRA is required for operators' eligibility and optimal evidence-based best practice to reduce RAO systematically implemented by protocol. The primary endpoint is the incidence of forearm RAO assessed by vascular ultrasound at discharge. Several important secondary endpoints will also be assessed, including access-site cross-over, hemostasis time, and access-site related complications. SUMMARY: The DISCO RADIAL trial will provide the first large-scale multicenter randomized evidence comparing DRA to TRA in patients scheduled for coronary angiography or PCI with respect to the incidence of RAO at discharge.

Association of lipoprotein(a) with intrinsic and on-clopidogrel platelet reactivity.

Lipoprotein(a) [Lp(a)] is an independent, genetically determined, and causal risk factor for cardiovascular disease. Laboratory data have suggested an interaction of Lp(a) with platelet function, potentially caused by its interaction with platelet receptors. So far, the potential association of Lp(a) with platelet activation and reactivity has not been proven in larger clinical cohorts. This study analyzed intrinsic platelet reactivity before loading with clopidogrel 600 mg and on-treatment platelet reactivity tested 24 h following loading in patients undergoing elective coronary angiography. Platelet reactivity was tested by optical aggregometry following stimulation with collagen or adenosine diphosphate as well as by flow cytometry. Lp(a) levels were directly measured in all patients from fresh samples. The present analysis included 1912 patients. Lp(a) levels ranged between 0 and 332 mg/dl. There was a significant association of rising levels of Lp(a) with a higher prevalence of a history of ischemic heart disease (p < 0.001) and more extensive coronary artery disease (p = 0.001). Results for intrinsic (p = 0.80) and on-clopidogrel platelet reactivity (p = 0.81) did not differ between quartiles of Lp(a) levels. Flow cytometry analyses of expression of different platelet surface proteins (CD41, CD62P or PAC-1) confirmed these findings. Correlation analyses of levels of Lp(a) with any of the tested platelet activation markers did not show any correlation. The present data do not support the hypothesis of an interaction of Lp(a) with platelet reactivity.

Long-term efficacy and safety of drug-coated balloons versus drug-eluting stents for small coronary artery disease (BASKET-SMALL 2): 3-year follow-up of a randomised, non-inferiority trial.

BACKGROUND: In the treatment of de-novo coronary small vessel disease, drug-coated balloons (DCBs) are non-inferior to drug-eluting stents (DESs) regarding clinical outcome up to 12 months, but data beyond 1 year is sparse. We aimed to test the long-term efficacy and safety of DCBs regarding clinical endpoints in an all-comer population undergoing percutaneous coronary intervention. METHODS: In this prespecified long-term follow-up of a multicentre, randomised, open-label, non-inferiority trial, patients from 14 clinical sites in Germany, Switzerland, and Austria with de-novo lesions in coronary vessels <3 mm and an indication for percutaneous coronary intervention were randomly assigned 1:1 to DCB or second-generation DES and followed over 3 years for major adverse cardiac events (ie, cardiac death, non-fatal myocardial infarction, and target-vessel revascularisation [TVR]), all-cause death, probable or definite stent thrombosis, and major bleeding (Bleeding Academic Research Consortium bleeding type 3-5). Analyses were performed on the full analysis set according to the modified intention-to-treat principle. Dual antiplatelet therapy was recommended for 1 month after DCB and 6 months after DES with stable symptoms, but 12 months with acute coronary syndromes. The study is registered with ClinicalTrials.gov, NCT01574534 and is ongoing. FINDINGS: Between April 10, 2012, and Feb 1, 2017, of 883 patients assessed, 758 (86%) patients were randomly assigned to the DCB group (n=382) or the DES group (n=376). The Kaplan-Meier estimate of the rate of major adverse cardiac events was 15% in both the DCB and DES groups (hazard ratio [HR] 0·99, 95% CI 0·68-1·45; p=0·95). The two groups were also very similar concerning the single components of adverse cardiac events: cardiac death (Kaplan-Meier estimate 5% vs 4%, HR 1·29, 95% CI 0·63-2·66; p=0·49), non-fatal myocardial infarction (both Kaplan-Meier estimate 6%, HR 0·82, 95% CI 0·45-1·51; p=0·52), and TVR (both Kaplan-Meier estimate 9%, HR 0·95, 95% CI 0·58-1·56; p=0·83). Rates of all-cause death were very similar in DCB versus DES patients (both Kaplan-Meier estimate 8%, HR 1·05, 95% CI 0·62-1·77; p=0·87). Rates of probable or definite stent thrombosis (Kaplan-Meier estimate 1% vs 2%; HR 0·33, 95% CI 0·07-1·64; p=0·18) and major bleeding (Kaplan-Meier estimate 2% vs 4%, HR 0·43, 95% CI 0·17-1·13; p=0·088) were numerically lower in DCB versus DES, however without reaching significance. INTERPRETATION: There is maintained efficacy and safety of DCB versus DES in the treatment of de-novo coronary small vessel disease up to 3 years. FUNDING: Swiss National Science Foundation, Basel Cardiovascular Research Foundation, and B Braun Medical.

Usefulness of updated logistic clinical SYNTAX score based on MI-SYNTAX score in patients with ST-elevation myocardial infarction.

OBJECTIVES: To compare the predictive performances of the prewiring, postwiring MI-SYNTAX scores, prewiring, and postwiring Updated Logistic Clinical SYNTAX score (LCSS) for 2-year all-cause mortality post percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients. BACKGROUND: In patients with STEMI and undergoing primary PCI, coronary stenosis(es) distal to the culprit lesion is often observed after the restoration of coronary flow. To address comprehensively the complex coronary anatomy in these patients, prewiring and postwiring MI-SYNTAX scores have been reported in the literature. Furthermore, to enable individualized risk estimation for long-term all-cause mortality, the Updated LCSS has been developed by combining the anatomical SYNTAX score and clinical factors. METHODS: In the randomized GLOBAL LEADERS trial, anatomical SYNTAX score analysis was performed by an independent angiographic corelab for the first 4,000 consecutive patients as a prespecified analysis; of these, 545 presented with STEMI. The efficacy of the mortality predictions of the four scores at 2 years were evaluated based on their discrimination and calibration abilities. RESULTS: Complete data was available in 512 patients (93.9%). When the patients were stratified into two groups based on the median of the scores, the prewiring and postwiring Updated LCSSs demonstrated that the high-score groups were associated with higher rates of 2-year all-cause mortality compared to the low-score groups (6.6 vs. 1.2%; log-rank p = .001 and 6.6 vs. 1.2%; log-rank p = .001, respectively). There were no statistically significant differences for predicting the mortality between the prewiring (area under the curve [AUC] 0.625), postwiring MI-SYNTAX score (AUC 0.614), prewiring (AUC 0.755), and postwiring Updated LCSS (AUC 0.757). In the integrated discrimination improvement (IDI), the prewiring MI-SYNTAX score had a better discrimination for the mortality than the postwiring MI-SYNTAX score (IDI -0.0082; p = .029). The four scores had acceptable calibration abilities for 2-year all-cause mortality. CONCLUSIONS: The prewiring Updated LCSS predicts long-term all-cause mortality with clearly useful discrimination and acceptable calibration. Since the postwiring MI-SYNTAX score does not improve mortality prediction, the prewiring MI-SYNTAX score may be preferred for the 2-year mortality prediction using the Updated LCSS.

Thin Strut CoCr Biodegradable Polymer Biolimus A9-Eluting Stents versus Thicker Strut Stainless Steel Biodegradable Polymer Biolimus A9-Eluting Stents: Two-Year Clinical Outcomes.

BACKGROUND: While thinner struts are associated with improved clinical outcomes in bare-metal stents (BMS), reducing strut thickness may affect drug delivery from drug-eluting stents (DES) and there are limited data comparing otherwise similar thin and thick strut DES. We assessed 2-year outcomes of patients treated with a thin strut (84-88um) cobalt-chromium, biodegradable polymer, Biolimus A9-eluting stent (CoCr-BP-BES) and compared these to patients treated with a stainless steel, biodegradable polymer, Biolimus A9-eluting stent (SS-BP-BES). METHODS: In total, 1257 patients were studied: 400 patients from 12 centres receiving ≥1 CoCr-BP-BES in the prospective Biomatrix Alpha registry underwent prespecified comparison with 857 patients who received ≥1 Biomatrix Flex SS-BP-BES in the LEADERS study (historical control). The primary outcome was major adverse cardiac events (MACE)-cardiac death, myocardial infarction (MI), or clinically driven target vessel revascularization (cd-TVR). Propensity analysis was used to adjust for differences in baseline variables and a landmark analysis at day-3 to account for differences in periprocedural MI definitions. RESULTS: MACE at 2 years occurred in 6.65% CoCr-BP-BES versus 13.23% SS-BP-BES groups (unadjusted HR 0.48 [0.31-0.73]; P=0.0005). Following propensity analysis, 2-year adjusted MACE rates were 7.4% versus 13.3% (HR 0.53 [0.35-0.79]; P=0.004). Definite or probable stent thrombosis, adjudicated using identical criteria in both studies, occurred less frequently with CoCr-BP-BES (1.12% vs. 3.22%; adjusted HR 0.32 [0.11-0.9]; P=0.034). In day-3 landmark analysis, the difference in 2-year MACE was no longer significant but there was a lower patient-orientated composite endpoint (11.7% vs. 18.4%; HR 0.6 [0.43-0.83]; P=0.006) and a trend to lower target vessel failure (5.8% vs. 9.1%; HR 0.63 [0.4-1.00]; P=0.078). CONCLUSION: At 2-year follow-up, propensity-adjusted analysis showed the thin strut (84-88um) Biomatrix Alpha CoCr-BP-BES was associated with improved clinical outcomes compared with the thicker strut (114-120um) Biomatrix Flex SS-BP-BES.

Simple Techniques for Antegrade Guiding Catheter Engagement after Retrograde CTO Crossing.

Interventional treatment of chronic total occlusions (CTOs) is nowadays counting on a wide span of procedural possibilities, and retrograde approaches are becoming more and more frequent as they warrant high success rates at the cost of a slightly higher incidence of donor vessel damage. Retrograde lesion crossing needs to be followed by procedural conversion to an antegrade approach to dilate and stent the lesion, and new techniques are being proposed to address this issue and achieve a safer recanalization of the vessel. In this context, we propose novel and simple techniques to antegrade guiding catheter engagement by the retrograde wire, enhancing the chances for procedural success.

Drug-coated balloons for small coronary artery disease (BASKET-SMALL 2): an open-label randomised non-inferiority trial.

BACKGROUND: Drug-coated balloons (DCB) are a novel therapeutic strategy for small native coronary artery disease. However, their safety and efficacy is poorly defined in comparison with drug-eluting stents (DES). METHODS: BASKET-SMALL 2 was a multicentre, open-label, randomised non-inferiority trial. 758 patients with de-novo lesions (<3 mm in diameter) in coronary vessels and an indication for percutaneous coronary intervention were randomly allocated (1:1) to receive angioplasty with DCB versus implantation of a second-generation DES after successful predilatation via an interactive internet-based response system. Dual antiplatelet therapy was given according to current guidelines. The primary objective was to show non-inferiority of DCB versus DES regarding major adverse cardiac events (MACE; ie, cardiac death, non-fatal myocardial infarction, and target-vessel revascularisation) after 12 months. The non-inferiority margin was an absolute difference of 4% in MACE. This trial is registered with ClinicalTrials.gov, number NCT01574534. FINDINGS: Between April 10, 2012, and February 1, 2017, 382 patients were randomly assigned to the DCB group and 376 to DES group. Non-inferiority of DCB versus DES was shown because the 95% CI of the absolute difference in MACE in the per-protocol population was below the predefined margin (-3·83 to 3·93%, p=0·0217). After 12 months, the proportions of MACE were similar in both groups of the full-analysis population (MACE was 7·5% for the DCB group vs 7·3% for the DES group; hazard ratio [HR] 0·97 [95% CI 0·58-1·64], p=0·9180). There were five (1·3%) cardiac-related deaths in the DES group and 12 (3·1%) in the DCB group (full analysis population). Probable or definite stent thrombosis (three [0·8%] in the DCB group vs four [1·1%] in the DES group; HR 0·73 [0·16-3·26]) and major bleeding (four [1·1%] in the DCB group vs nine [2·4%] in the DES group; HR 0·45 [0·14-1·46]) were the most common adverse events. INTERPRETATION: In small native coronary artery disease, DCB was non-inferior to DES regarding MACE up to 12 months, with similar event rates for both treatment groups. FUNDING: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Basel Cardiovascular Research Foundation, and B Braun Medical AG.

N-Terminal Pro-B-Type Natriuretic Peptide-Guided Therapy in Chronic Heart Failure Reduces Repeated Hospitalizations-Results From TIME-CHF.

BACKGROUND: Although heart failure (HF) patients are known to experience repeated hospitalizations, most studies evaluated only time to first event. N-Terminal B-type natriuretic peptide (NT-proBNP)-guided therapy has not convincingly been shown to improve HF-specific outcomes, and effects on recurrent all-cause hospitalization are uncertain. Therefore, we investigated the effect of NT-proBNP-guided therapy on recurrent events in HF with the use of a time-between-events approach in a hypothesis-generating analysis. METHODS AND RESULTS: The Trial of Intensified Versus Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized 499 HF patients, aged ≥60 years, left ventricular ejection fraction ≤45%, New York Heart Association functional class ≥I,I to NT-proBNP-guided versus symptom-guided therapy for 18 months, with further follow-up for 5.5 years. The effect of NT-proBNP-guided therapy on recurrent HF-related and all-cause hospitalizations and/or all-cause death was explored. One hundred four patients (49 NT-proBNP-guided, 55 symptom-guided) experienced 1 and 275 patients (133 NT-proBNP-guided, 142 symptom-guided) experienced ≥2 all-cause hospitalization events. Regarding HF hospitalization, 132 patients (57 NT-proBNP-guided, 75 symptom-guided) experienced 1 and 122 patients (57 NT-proBNP-guided, 65 symptom-guided) experienced ≥2 events. NT-proBNP-guided therapy was significant in preventing 2nd all-cause hospitalizations (hazard ratio [HR] 0.83; P = .01), in contrast to nonsignificant results in preventing 1st all-cause hospitalization events (HR 0.91; P = .35). This was not the case regarding HF hospitalization events (HR 0.85 [P = .14] vs HR 0.73 [P = .01]) The beneficial effect of NT-proBNP-guided therapy was seen only in patients aged <75 years, and not in those aged ≥75 years (interaction terms with P = .01 and P = .03 for all-cause hospitalization and HF hospitalization events, respectively). CONCLUSION: NT-proBNP-guided therapy reduces the risk of recurrent events in patients <75 years of age. This included all-cause hospitalization by mainly reducing later events, adding knowledge to the neutral effect on this end point when shown using time-to-first-event analysis only. CLINICAL TRIAL REGISTRATION: isrctn.org, identifier: ISRCTN43596477.

Acute and long-term effect of percutaneous coronary intervention on serially-measured oxidative, inflammatory, and coagulation biomarkers in patients with stable angina.

To derive insights into the temporal changes in oxidative, inflammatory and coagulation biomarkers in patients with stable angina undergoing percutaneous coronary intervention (PCI). PCI is associated with a variety of biochemical and mechanical stresses to the vessel wall. Oxidized phospholipids are present on plasminogen (OxPL-PLG) and potentiate fibrinolysis in vitro. We recently showed that OxPL-PLG increase following acute myocardial infarction, suggesting that they are involved in atherothrombosis. Plasma samples were collected before, immediately after, 6 and 24 h, 3 and 7 days, and 1, 3, and 6 months after PCI in 125 patients with stable angina undergoing uncomplicated PCI. Plasminogen levels, OxPL-PLG, and an array of 16 oxidative, inflammatory and coagulation biomarkers were measured with established assays. OxPL-PLG and plasminogen declined significantly immediately post-PCI, rebounded to baseline, peaked at 3 days and slowly returned to baseline by 6 months (p < 0.0001 by ANOVA). The temporal trends to maximal peak in biomarkers were as follows: immediately post PCI: OxPL-apoB and lipoprotein (a); Day 1-the inflammatory biomarker IL-6; Day 3-CRP and coagulation biomarkers OxPL-PLG, plasminogen and tissue plasminogen activity; Day 3 to 7-plasminogen activator inhibitor activity, and complement factor H binding to malondialdehyde-LDL and MDA-LDL IgG; Day 7-30 MDA-LDL IgM, CuOxLDL IgM, and ApoB-IC IgM and IgG; >30 days uPA activity, uPA antigen, CuOxLDL IgG and peptide mimotope to MDA-LDL. Most of the biomarkers trended to baseline by 6 months. PCI results in a specific, temporal sequence of changes in plasma biomarkers. These observations provide insights into the effects of iatrogenic barotrauma and plaque disruption during PCI and suggest avenues of investigation to explain complications of PCI and development of targeted therapies to enhance procedural success.

Circulating levels of plasminogen and oxidized phospholipids bound to plasminogen distinguish between atherothrombotic and non-atherothrombotic myocardial infarction.

Oxidized phospholipids (OxPL) are abundant in atherosclerotic plaques. They are also bound to circulating plasminogen after myocardial infarction (MI), and their binding to plasminogen may accentuate fibrinolysis. We sought to assess whether circulating levels of plasminogen and OxPL bound to plasminogen (OxPL-PLG) increase following acute MI and whether this increase differs between atherothrombotic (Type 1) and non-atherothrombotic (Type 2) MI. We measured circulating levels of plasminogen and OxPL-PLG at 0, 6, 24, 48 h, and >3 months (stable state) following acute MI and following an angiogram for stable coronary artery disease (CAD). Forty-nine subjects met the criteria for acute MI, of whom 34 had clearly defined atherothrombotic (n = 22) or non-atherothrombotic (n = 12) MI; 15 patients met the criteria for stable CAD. Mean baseline levels of plasminogen and OxPL-PLG were lower in the acute MI group than in the stable CAD group (9.75 vs 20.2, p < 0.0001 for plasminogen and 165.5 vs 275.1, p = 0.0002 for OxPL-PLG) and did not change over time or between time points, including the 3-month follow-up. Mean baseline levels of plasminogen and OxPL-PLG were also lower in atherothrombotic (Type 1) than in non-atherothrombotic (Type 2) MI subjects (8.65 vs 12.1, p < 0.03 for plasminogen and 164.5 vs 245.7, p = 0.02 for OxPL-PLG), and this relationship did not change over time or between time points. Plasminogen and OxPL-PLG were lower in patients presenting with an acute MI than in those with stable CAD and also in those with atherothrombotic MI (Type 1) vs. those with non-atherothrombotic MI (Type 2). These findings persisted at a median follow-up of 3 months post-MI. The association of plasminogen and OxPL-PLG with acute MI, particularly atherothrombotic MI (Type 1), could reflect a reduced fibrinolytic capacity, associated with an increased risk of atherothrombotic events differentiating stable CAD from unstable CAD and atherothrombotic MI (Type 1) from non-atherothrombotic MI (Type 2). Additional study with a larger sample size is warranted.

[Blood pressure limits--the lower, the better?]. / Blutdruckgrenzwerte - je tiefer, desto besser?

Arterial hypertension is a widespread risk factor for cardiovascular disease. The benefit of a consistent drug therapy is proportionally associated with the degree of blood pressure reduction. By extrapolating the data, the assumption arose "the lower the better" and was widely accepted. However, several studies found an increase in morbidity and mortality with an excessive reduction of blood pressure (J-curve). This seems to affect mainly cardiac risk, and only at lower blood pressures<60 mmHg also the cerebral risk. An important factor here is the diastolic blood pressure. Others found a linear correlation. Overall, a j-shaped connection remains controversial and is not considered equally for all organ systems. At the same time cardiovascular risk seems not to increase with additional reduction in blood pressure of <140 mm Hg to <120 mmHg. This has led to the latest guidelines of all societies recommending higher target values. Reasons for higher targets in drug therapy of arterial hypertension, are increased adverse drug reactions or increased healthcare costs with few additional benefit. The current recommendations of the ESH/ESC, AHA/ACC/ASH and the JNC 8 set a higher target value for some subgroups, but remain inconsistent among themselves.

Percutaneous retrieval of a twisted guide catheter using a longer second radial sheath.

Coronary angiography and percutaneous coronary intervention (PCI) over the radial approach are becoming more frequent and are recommended by the European Association of Percutaneous Cardiovascular Interventions and European Society of Cardiology. The radial approach leads to less bleeding and improved survival in ST-segment elevation myocardial infarction. Pronounced guide catheter manipulation in cases with tortuous access routes and requirement of extra backup during complex PCI may structurally damage the guide shaft and facilitate twisting and bending. We present three cases where a twisted coronary catheter became stuck in the radial artery and describe a minimally invasive retrieval technique using a second introducer sheath of same French (F) size and greater length.

Lipoprotein(a), platelet function and cardiovascular disease.

Lipoprotein(a) (Lp(a)) is associated with atherothrombosis through several mechanisms, including putative antifibrinolytic properties. However, genetic association studies have not demonstrated an association between high plasma levels of Lp(a) and the risk of venous thromboembolism, and studies in patients with highly elevated Lp(a) levels have shown that Lp(a) lowering does not modify the clotting properties of plasma ex vivo. Lp(a) can interact with several platelet receptors, providing biological plausibility for a pro-aggregatory effect. Observational clinical studies suggest that elevated plasma Lp(a) concentrations are associated with worse long-term outcomes in patients undergoing revascularization. Furthermore, in these patients, those with elevated plasma Lp(a) levels derive more benefit from prolonged dual antiplatelet therapy than those with normal Lp(a) levels. The ASPREE trial in healthy older individuals treated with aspirin showed a reduction in ischaemic events in those who had a single-nucleotide polymorphism in LPA that is associated with elevated Lp(a) levels in plasma, without an increase in bleeding events. In this Review, we re-examine the role of Lp(a) in the regulation of platelet function and suggest areas of research to define further the clinical relevance to cardiovascular disease of the observed associations between Lp(a) and platelet function.