Bivalirudin Versus Heparin During PCI in NSTEMI: Individual Patient Data Meta-Analysis of Large Randomized Trials.

BACKGROUND: The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI. METHODS: We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized ≥1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding. RESULTS: A total of 12 155 patients were randomized: 6040 to bivalirudin (52.3% with a post-PCI bivalirudin infusion), and 6115 to heparin (53.2% with planned glycoprotein IIb/IIIa inhibitor use). Thirty-day mortality was not significantly different between bivalirudin and heparin (1.2% versus 1.1%; adjusted odds ratio, 1.24 [95% CI, 0.86-1.79]; P=0.25). Cardiac mortality, reinfarction, and stent thrombosis rates were also not significantly different. Bivalirudin reduced serious bleeding (both access site-related and non-access site-related) compared with heparin (3.3% versus 5.5%; adjusted odds ratio, 0.59; 95% CI, 0.48-0.72; P<0.0001). Outcomes were consistent regardless of use of a post-PCI bivalirudin infusion or routine lycoprotein IIb/IIIa inhibitor use with heparin and during 1-year follow-up. CONCLUSIONS: In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites.

Risk of Major Bleeding With Potent Antiplatelet Agents After an Acute Coronary Event: A Comparison of Ticagrelor and Clopidogrel in 5116 Consecutive Patients in Clinical Practice.

Background Major bleeding after acute coronary syndrome predicts a poor outcome but is challenging to define. The choice of antiplatelet influences bleeding risk. Methods and Results Major bleeding, subsequent myocardial infarction (MI), and all-cause mortality to 1 year were compared in consecutive patients with acute coronary syndrome treated with clopidogrel (n=2491 between 2011 and 2013) and ticagrelor (n=2625 between 2012 and 2015) in 5 English hospitals. Clinical outcomes were identified from national hospital episode statistics. Bleeding and MI events were independently adjudicated by 2 experienced clinicians, blinded to drug, sequence, and year. Bleeding events were categorized using Bleeding Academic Research Consortium 3 to 5 and PLATO (Platelet Inhibition and Patient Outcomes) criteria and MI by the Third Universal Definition. Multivariable regression analysis was used to adjust outcomes for case mix. The median age was 68 years and 34% were women. 39% underwent percutaneous coronary intervention and 13% coronary artery bypass graft surgery. Clinical outcome data were 100% complete for bleeding and 99.7% for MI. No statistically significant difference was seen in crude or adjusted major bleeding for ticagrelor compared with clopidogrel (Bleeding Academic Research Consortium 3-5, hazard ratio [HR], 1.23; 95% CI, 0.90-1.68; P=0.2, PLATO major adjusted HR, 1.30; 95% CI, 0.98-1.74; P=0.07) except in the non-coronary artery bypass graft cohort (n=4464), where bleeding was more frequent with ticagrelor (Bleeding Academic Research Consortium 3-5, adjusted HR, 1.58; 95% CI, 1.09-2.31; P=0.017; and PLATO major HR, 1.67; 95% CI, 1.18-2.37; P=0.004). There was no difference in crude or adjusted subsequent MI (adjusted HR, 1.20; 95% CI, 0.87-1.64; P=0.27). Crude mortality was higher in the clopidogrel group but not after adjustment, using either Cox proportional hazards or propensity matched population (HR, 0.90; 95% CI, 0.76-1.10; P=0.21) as was the case for stroke (HR, 0.82; 95% CI, 0.52-1.32; P=0.42). Conclusions This observational study indicates that the apparent benefit of ticagrelor demonstrated in a clinical trial population may not be observed in the broader population encountered in clinical practice. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02484924.

Twelve-month mortality from the "How Effective are Antithrombotic Therapies in Primary Percutaneous Coronary Intervention (HEAT-PPCI) Trial".

BACKGROUND: There is ongoing uncertainty regarding the safety and efficacy of unfractionated heparin and bivalirudin when used for systemic anticoagulation in patients undergoing primary percutaneous coronary intervention (PPCI). This paper reports 12-month mortality from the HEAT-PPCI randomised trial. METHODS: In this open-label, randomised controlled trial (RCT) we enrolled consecutive adults with suspected ST-elevation myocardial infarction (STEMI). Patients were randomised to heparin (bolus 70 U/kg) or bivalirudin (bolus 0.75 mg/kg followed by an infusion 1.75 mg/kg/h for the duration of the procedure). We report the pre-specified secondary outcome of all-cause mortality at 12 months. Mortality was classified as cardiovascular or not, blinded to treatment allocation. Deaths in the first 28 days were classified by formal event adjudication and later events classified from death certificates. RESULTS: Mortality status at 12 months was obtained for 1805/1812 = 99.6% of participants. Overall mortality was 160/1812 = 8.9%. There were more deaths in those randomised to bivalirudin (95/902 = 10.5% vs 65/903 = 7.2%; HR 1.48; 95% CI 1.08 to 2.03; p = 0.015). Most deaths were classified as cardiovascular (71/902 = 7.9% in the bivalirudin group and 53/904 = 5.9% in the heparin group). The difference between the rates of cardiovascular deaths in each treatment group did not reach statistical significance: HR 1.35; 95% CI 0.95 to 1.93; p = 0.095. CONCLUSIONS: At 12 months, treatment with bivalirudin, rather than heparin, was associated with a higher rate of all-cause mortality. Cardiovascular mortality was higher with bivalirudin although this difference was not statistically significant.

A comparison of hospital episode statistics and traditional methods to identify outcomes in a randomized trial; a sub-study of HEAT-PPCI.

BACKGROUND: This study aims to compare information from hospital episode statistics (HES) and traditional direct patient contact to identify readmission and clinical events in the follow-up of a randomized controlled trial (RCT). METHODS: The study followed 1812 patients for 28 days using direct contact (DC). In addition, we obtained HES for this period. We examined medical records for all suspected readmissions and determined confirmed events by adjudication. We compared the ability of the individual DC and HES methods to determine readmission and the occurrence of trial-specific events, confirmed at adjudication. RESULTS: In the ascertainment of readmission, compared to DC, HES demonstrated a trend towards better sensitivity (identifying 153/166 = 92.2% versus 144/166 = 86.7%; difference = 5.4%, 95% CI: 0.1-11.5%) and better specificity (1492/1492 = 100% versus 1426/1492 = 95.5%; difference = 4.4%, 95% CI: 4.2-5.6%).An examination of HES coding does not identify rates for specific events that match those from adjudication, with limitations in both sensitivity and specificity. CONCLUSION: HES is effective in the ascertainment of readmission and is a useful tool in follow-up. Information from HES provides a reflection of a patient's course and associated cost, as perceived by the healthcare system. Future studies could modify outcome definitions to reflect episode coding.

Individual Patient Data Pooled Analysis of Randomized Trials of Bivalirudin versus Heparin in Acute Myocardial Infarction: Rationale and Methodology.

BACKGROUND: Individual randomized controlled trials (RCTs) of periprocedural anticoagulation with bivalirudin versus heparin during percutaneous coronary intervention (PCI) have reported conflicting results. Study-level meta-analyses lack granularity to adjust for confounders, explore heterogeneity, or identify subgroups that may particularly benefit or be harmed. OBJECTIVE: To overcome these limitations, we sought to develop an individual patient-data pooled database of RCTs comparing bivalirudin versus heparin. METHODS: We conducted a systematic review to identify RCTs in which ≥1,000 patients with acute myocardial infarction (AMI) undergoing PCI were randomized to bivalirudin versus heparin. RESULTS: From 738 identified studies, 8 RCTs met the prespecified criteria. The principal investigators of each study agreed to provide patient-level data. The data were pooled and checked for accuracy against trial publications, with discrepancies addressed by consulting with the trialists. Consensus-based definitions were created to resolve differing antithrombotic, procedural, and outcome definitions. The project required 3.5 years to complete, and the final database includes 27,409 patients (13,346 randomized to bivalirudin and 14,063 randomized to heparin). CONCLUSION: We have created a large individual patient database of bivalirudin versus heparin RCTs in patients with AMI undergoing PCI. This endeavor may help identify the optimal periprocedural anticoagulation regimen for patient groups with different relative risks of adverse ischemic versus bleeding events, including those with ST-segment and non-ST-segment elevation MI, radial versus femoral access, use of a prolonged bivalirudin infusion or glycoprotein inhibitors, and others. Adherence to standardized techniques and rigorous validation processes should increase confidence in the accuracy and robustness of the results.

Radial versus femoral vascular access in ST-elevation myocardial infarction: Are the results of femoral operators unfairly represented in observational research?

BACKGROUND: Recent randomized controlled trials comparing femoral and radial access in primary percutaneous coronary intervention (PPCI) have shown conflicting results regarding the incidence of major adverse cardiovascular events (MACE) and major bleeding. METHODS: Using data from the HEAT-PPCI trial, we compared the primary efficacy (all-cause mortality, stroke, new myocardial infarction or unplanned repeat revascularization) and safety (major bleeding BARC 3-5) outcomes at 28 days, by final access site used (radial or femoral) and by default operator type. We then assessed outcomes in femoral cases performed by both operator types. RESULTS: Radial access (RA) was associated with fewer MACE (91/1472 = 6.2% vs. 36/332 = 10.8% P = .003) and major bleeding events (38/1472 = 2.6% vs 22/332 = 6.6% P = .001) when compared to femoral access (FA). When analyzing outcomes by default operator type, there was a similar incidence of MACE (111/1575 = 7% vs 16/229 = 7% P = .97) and major bleeding events (49/1575 = 3.1% vs 11/229 = 4.8% P = .18). In cases where FA was performed by default radial operators, there was a higher rate of MACE (22/122 = 18% vs 14/210 = 6.7% P = .003) and major bleeding events (11/122 = 9% vs 11/210 = 5.2% P < .001), potentially explained by a higher risk profile in these cases. CONCLUSION: Default femoral operators achieved comparable outcomes when compared to default radial operators. The less favorable outcomes observed in FA cases may result from its selective use by radial operators in high risk cases.

Comparison of the antiplatelet and antithrombotic effects of bivalirudin versus unfractionated heparin: A platelet substudy of the HEAT PPCI trial.

In randomised trials, bivalirudin has been associated with higher rates of acute stent thrombosis (AST) compared to unfractionated heparin (UFH), without mechanistic explanation. Furthermore, data are discrepant regards the antiplatelet effects of bivalirudin. This prespecified study, part of a larger HEAT-PPCI Platelet Substudy, aimed to compare the antiplatelet and antithrombotic effects of bivalirudin and UFH using short thrombelastography (s-TEG), an ex vivo whole blood platelet function assay. In HEAT-PPCI, patients were randomised to receive UFH or bivalirudin before angiography. Assay with s-TEG was performed in 184 patients (10.2%) at end of procedure (EOP) and repeated at 24 h. In addition to adenosine diphosphate- (ADP) and arachidonic acid- (AA) mediated platelet aggregation, thrombin-mediated clotting (TMC) was assessed using kaolin with and without heparinase. There were no significant differences between UFH and bivalirudin in ADP- and AA-mediated platelet aggregation at EOP or 24 h. Whilst UFH obliterated TMC at EOP, bivalirudin prolonged R time (19.7 min [15.9-25.4] vs. 8.4 min [7.5-10]; P < 0.0001), K time (2.4 min [1.9-3.4] vs. 2.2 min [1.8-2.7]; P = 0.007) and significantly increased maximum clot strength (MA 62.7 mm [58.7-67.4] vs. 58.6 [55-63]; P = 0.0005), compared to control. In conclusion, there were no significant differences in the antiplatelet effects of UFH and bivalirudin. However, whilst UFH obliterated TMC, bivalirudin prolonged clot initiation but potentiated maximum clot strength. As AST is likely multifactorial in aetiology, in patients treated with bivalirudin, increased clot strength may contribute to this hazard in some individuals and this observation warrants further investigation.

Comparison of the effects of P2Y12 receptor antagonists on platelet function and clinical outcomes in patients undergoing Primary PCI: A substudy of the HEAT-PPCI trial.

AIMS: The HEAT-PPCI trial compared bivalirudin and unfractionated heparin in patients undergoing primary percutaneous coronary intervention (PPCI). The aim of this study was to report pre-specified, secondary analyses comparing the effects of P2Y12 inhibiting agents on platelet reactivity and clinical events. METHODS AND RESULTS: All patients received preprocedural oral antiplatelet therapy. During the early stages of the trial, the P2Y12 inhibitor of choice was prasugrel with some use of clopidogrel. Later, routine therapy switched to ticagrelor. For cases performed during working hours, multiple electrode aggregometry (MEA) was used to assess ADP-induced platelet aggregation at the end of the index procedure. The effect of P2Y12 inhibitors on the primary efficacy (major adverse cardiac events [MACE]) and safety (major bleeding) outcomes was assessed in all patients. Multiple logistic regression was used to adjust for differences in baseline characteristics. With MEA data from 469 patients, prasugrel therapy resulted in significantly greater suppression of ADP-induced platelet aggregation at 40 U (23, 78) (median; interquartile range [IQR]) when compared against ticagrelor 75 U (41, 100.75); p<0.001 or clopidogrel 79 U (56, 96); p<0.001. In the entire study population (N=1,803), prasugrel therapy was associated with significantly fewer MACE (26/497; 5.2%) in comparison to ticagrelor (83/1,123; 7.4%) or clopidogrel (18/183; 9.8%); odds ratio (OR) 0.64, confidence interval (CI): 0.41-0.99, p=0.045. For major bleeding, there were no significant differences among the three groups - clopidogrel (3/183; 1.6%), prasugrel (13/497; 2.6%) and ticagrelor (43/1,123; 3.8%); OR 0.73, CI: 0.39-1.35, p=0.31. Patients treated with clopidogrel had more high-risk features and clopidogrel use was more common as an alternative to prasugrel. After adjustment, there were no significant differences in the rates of MACE (OR 0.70, CI: 0.41-1.21, p=0.20) or major bleeding (OR 0.80, CI: 0.41-1.60, p=0.53). CONCLUSIONS: In HEAT-PPCI, patients who received prasugrel (rather than clopidogrel or ticagrelor) had significantly greater suppression of ADP-induced platelet aggregation at the end of the procedure. After adjustment for differences in baseline characteristics, there were no significant differences in ischaemic or bleeding outcomes among the antiplatelet therapies.

Computed tomography angiography planning identifies the target vessel for optimum infarct location and improves clinical outcome in alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

AIMS: Alcohol septal ablation (ASA) is an established treatment option in hypertrophic obstructive cardiomyopathy (HOCM). ASA is ineffective in some: inaccurate infarct and inability to identify a vessel contribute. We aimed to improve accuracy of infarct using CT angiography guidance and provide a more predictable and satisfactory outcome. METHODS AND RESULTS: Twenty-one successive patients with symptomatic LVOT obstruction refractory to medication underwent CT angiography planning to guide ASA. CT was performed using a dual-source CT system. Alcohol was delivered to the artery identified from CT: in 17/21 this was a sub-branch of a septal artery, in 2/21 the septal vessel was identified from the circumflex artery. Peak gradient improved from 98 (IQR 89.50-111.50) mmHg to 14 (IQR 8.50-22) mmHg (p=0.003). Systolic anterior motion (SAM) improved in 18/20 patients. NYHA class improved by ≥1 in 18/20. Peak VO2 improved from 79.19% of predicted value (±14.01) to 91.62% (±12.02) predicted (p<0.0001). Success at the first procedure is greater with CT guidance, 17/20 vs. 50/75 with traditional methods (pre-CT guidance) (p=0.02); 9/20 had six-month CMR with target septum infarct in all. ASA-related RBBB reduced from 62% to 13% (p=0.0004). CONCLUSIONS: CT angiography planning improves localisation of infarct and procedural success at the first attempt in ASA when compared to traditional methods. Follow-up to six months suggests a symptomatic, functional and haemodynamic improvement.

Describing Activity in Primary Percutaneous Coronary Intervention: An Exploration of Denominators. From the HEAT Trial - A Systematic Evaluation of PPCI Activations in Liverpool, Explaining Denominators (HEAT-SEALED).

BACKGROUND: The provision of primary percutaneous coronary intervention (PPCI) in the emergency management of ST-elevation myocardial infarction (STEMI) is expensive and resource intensive. Accurate data collection is essential not only for outcomes analysis but also to characterize activity and performance for regions, centers, and operators. Inconsistency in the use of denominators currently creates problems in data interpretation. OBJECTIVE: To establish a system of denominator groupings, seeking to better describe the range of clinical activity resulting from an unselected series of PPCI activations. METHODS: The HEAT-SEALED pathway designates a key denominator group (n1-n9) to each phase of PPCI activity and identifies a final "destination category" for each patient leaving the pathway. HEAT-PPCI (How Effective are Antithrombotic Therapies in Primary Percutaneous Coronary Intervention) is a true "all-comers" trial and provides an ideal platform to collect data for prospective validation of the pathway. We report data from all PPCI activation events for the HEAT-PPCI trial. RESULTS: Our findings demonstrate important differences between the sizes of key PPCI denominator groups and hence the potential for variation in reported outcomes depending on the denominator category selected. The main figures are: all activations (n1 = 2490); all suspected MI cases (n4 = 1940; 77.91%); patients in whom angiography was performed (n5 = 1904; 76.46%); cases in which diagnosis was confirmed with a probable culprit lesion (n6 = 1657; 66.54%), and cases with complete PCI success (n9 = 1441; 57.87%). CONCLUSION: The HEAT-SEALED pathway offers a practical and comprehensive solution to the problem of describing denominators in STEMI and PPCI. Routine application would facilitate a more consistent and precise description of activity and outcome.

Radiofrequency ablation of the interventricular septum to treat outflow tract gradients in hypertrophic obstructive cardiomyopathy: a novel use of CARTOSound® technology to guide ablation.

AIMS: Septal reduction is needed for hypertrophic obstructive cardiomyopathy (HOCM) patients with severe left ventricular outflow tract (LVOT) gradients and symptoms despite medication. Myectomy cannot be performed in all. Alcohol septal ablation cannot be performed in 5-15% due to technical difficulties. A method of delivering percutaneous tissue damage to the septum that is not reliant on coronary anatomy is desirable. To directly ablate the interventricular septum at the mitral valve (MV) systolic anterior motion (SAM)-septal contact point using radiofrequency (RF) energy guided by CARTOSound. METHODS AND RESULTS: Five patients underwent RF ablation (RFA); we describe follow-up at 6 months in four patients. Intracardiac echocardiography (ICE) images are merged with CARTO to create a shell of the cardiac chambers. The SAM-septal contact area is marked from ICE images and mapped on to the CARTO shell; this becomes the target for RF delivery. Conduction tissue is mapped and avoided where possible. Twenty-eight to 42 min of RF energy was delivered to the target area using retrograde aortic access and SmartTouch catheters. Resting LVOT gradient improved from 64.2 (±50.6) to 12.3 (±2.5) mmHg. Valsalva/exercise-induced gradient reduced from 93.5 (±30.9) to 23.3 (±8.3) mmHg. Three patients improved New York Heart Association status from III to II, one patient improved from class III to I. Exercise time on bicycle ergometer increased from 612 to 730 s. Cardiac magnetic resonance shows late gadolinium enhancement up to 8 mm depth at LV target myocardium. One patient died following a significant retroperitoneal haemorrhage. CONCLUSION: Radiofrequency ablation using CARTOSound(®) guidance is accurate and effective in treating LVOT gradients in HOCM in this preliminary group of patients.

Intra-cardiac echocardiography in alcohol septal ablation: a prospective comparative study against trans-thoracic echocardiography.

Alcohol septal ablation (ASA) in hypertrophic obstructive cardiomyopathy reduces left ventricular outflow tract gradients. A third of patients do not respond; inaccurate localisation of the iatrogenic infarct can be responsible. Transthoracic echocardiography (TTE) using myocardial contrast can be difficult in the laboratory environment. Intra-cardiac echocardiography (ICE) provides high-quality images. We aimed to assess ICE against TTE in ASA. The ability of ICE and TTE to assess three key domains (mitral valve (MV) anatomy and systolic anterior motion, visualisation of target septum, adjacent structures) was evaluated in 20 consecutive patients undergoing ASA. Two independent experts scored paired TTE and ICE images off line for each domain in both groups. The ability to see myocardial contrast following septal arterial injection was also assessed by the cardiologist performing ASA. In patients undergoing ASA, ICE was superior in viewing MV anatomy (P=0.02). TTE was superior in assessing adjacent structures (P=0.002). There was no difference in assessing target septum. Myocardial contrast: ICE did not clearly identify the area of contrast in 17/19 patients due to dense acoustic shadowing (8/19) and inadequate opacification of the myocardium (6/19). ICE only clearly localised contrast in 2/19 cases. ICE does not visualise myocardial contrast well and therefore cannot be used to guide ASA. TTE was substantially better at viewing myocardial contrast. There was no significant difference between ICE and TTE in the overall ability to comment on cardiac anatomy relevant to ASA.

Intervention in HCM: patient selection, procedural approach and emerging techniques in alcohol septal ablation.

Hypertrophic cardiomyopathy (HCM) is a highly heterogeneous disease with varied patterns of hypertrophy. Basal septal hypertrophy and systolic anterior motion (SAM) of the mitral valve (MV) are the key pathophysiological components to left ventricular outflow tract (LVOT) obstruction in HCM. LVOT is associated with higher morbidity and mortality in patients with HCM. Percutaneous septal reduction therapy with alcohol septal ablation (ASA) can lead to a significant improvement in left ventricle haemodynamics, patient symptoms and perhaps prognosis. ASA delivers pure alcohol to an area of myocardium via septal coronary arteries; this creates damage to tissue akin to a myocardial infarction. The basal septal myocardium involved in SAM-septal contact is the target for this iatrogenic infarct. Appropriate patient selection and accurate delivery of alcohol are critical to safe and effective ASA. Securing the correct diagnosis and ensuring suitable cardiac anatomy are essential before considering ASA. Pre-procedural planning and intra-procedural imaging guidance are important to delivering precise damage to the desired area. The procedure is performed worldwide and is generally safe; the need for a pacemaker is the most prominent complication. It is successful in the majority of patients but room for improvement exists. New techniques have been proposed to perform percutaneous septal reduction. We present a review of the relevant pathophysiology, current methods and a summary of available evidence for ASA. We also provide a glimpse into emerging techniques to deliver percutaneous septal reduction therapy.

Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: Safe and Apparently Efficacious But Does Reporting of Aggregate Outcomes Hide Less-Favorable Results, Experienced by a Substantial Proportion of Patients?

AIMS: To describe individual and aggregate outcomes for patients undergoing alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy (HOCM). METHODS: Retrospective case series reviewing all patients undergoing ASA at a United Kingdom tertiary referral center from 2000-2012. Aggregate and individual outcomes are described in terms of symptomatic and hemodynamic response. RESULTS: Eighty-eight patients were reviewed. Alcohol was delivered in 84, with clinical status data available in 82 and hemodynamic data available in 74. All patients had resting or exercise stress left ventricular outflow tract (LVOT) gradient >50 mm Hg. Mean age was 60.3 ± 14.3 years. Follow-up period was 4.2 ± 3.3 years. Twenty-four patients (27%) required ≥2 procedures. Complete heart block was observed in 17%. New York Heart Association (NYHA) class pre ASA was 2.80 ± 0.46, improving to 1.92 ± 0.84 post ASA (P<.001). Fifty-eight out of 82 patients (71%) had improved NYHA class. Resting peak gradient was 99.80 ± 45.86 mm Hg. Post-ASA peak gradient fell to 23.77 ± 41.87 mm Hg (P<.001). Sixty-one out of 74 patients (82%) had successful treatment of LVOT gradient. A successful outcome in both symptomatic and gradient treatment was seen in 66% of patients. No patient who received alcohol suffered sudden cardiac death. Fifteen patients had implantable cardioverter defibrillator implantation; no appropriate therapy was delivered. CONCLUSIONS: ASA is safe, with few major complications. Aggregate outcomes are good, but can hide individual failure. There is a need to refine case selection, procedure planning, and performance to secure more uniform favorable outcomes.

Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial.

BACKGROUND: Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure. METHODS: In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age [<75 years vs ≥75 years] and presence of cardiogenic shock [yes vs no]) to heparin (70 U/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3-5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov, number NCT01519518. FINDINGS: Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients [13%] in the bivalirudin group and 140 patients [15%] in the heparin group). The primary efficacy outcome occurred in 79 (8·7%) of 905 patients in the bivalirudin group and 52 (5·7%) of 907 patients in the heparin group (absolute risk difference 3·0%; relative risk [RR] 1·52, 95% CI 1·09-2·13, p=0·01). The primary safety outcome occurred in 32 (3·5%) of 905 patients in the bivalirudin group and 28 (3·1%) of 907 patients in the heparin group (0·4%; 1·15, 0·70-1·89, p=0·59). INTERPRETATION: Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially. FUNDING: Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).

Improvement in refractory heart failure by nephrectomy for renal tumour.

Hypoalbuminaemia and anaemia are conditions known to aggravate congestive cardiac failure (CCF). Renal cell carcinoma is often associated with hypoalbuminaemia and anaemia. The authors report an interesting case of a patient with severe refractory CCF who incidentally was found to have a massive renal cell tumour. Clinically, his heart failure was being aggravated by hypoalbuminaemia and anaemia. Despite aggressive diuretic therapy and multiple blood and albumin transfusions, there was no clinical improvement. He subsequently underwent nephrectomy of the renal tumour, with subsequent dramatic clinical improvement in his heart failure. His symptoms resolved completely and he did not require any further diuretic therapy.