Search

In the randomized PREPARE-CALC trial, lesion preparation of calcified lesions with upfront rotational atherectomy (RA) prior to drug-eluting stent (DES) implantation resulted in higher acute success as compared to a provisional modified balloon (MB) strategy. We aimed to investigate the impact of calcified lesion complexity on the treatment effect with either MB or RA.Two hundred patients were randomized to lesion preparation with either MB or RA. The study population was stratified according to lesion complexity into at least one type-C lesion or into exclusively non-type-C lesions. Endpoints were strategy success, need for bail-out RA, acute lumen gain, and late lumen loss (LLL) at 9 months.In total, 143 patients were graded as type-C (45% patients were allocated to MB), whereas 57 patients were graded as non-type-C (61% patients were allocated to MB). In patients with at least one type-C lesion, strategy success with RA was higher than with MB (97% vs 72%, p 0.001), but superiority of RA was not observed in patients with non-type-C lesions (100% vs 97%, p = 1.00; pIn patients with calcified non-type-C lesions, the treatment strategy with RA or MB before DES implantation results in comparable success rates, whereas in type-C lesions upfront RA appears to be the superior upfront strategy.

Objectives The purpose of this study was to evaluate clinical and echocardiographic outcome data of the CHOICE (Randomized Comparison of Transcatheter Heart Valves in High Risk Patients with Severe Aortic Stenosis: Medtronic CoreValve Versus Edwards SAPIEN XT) trial at 5 years. Background The CHOICE trial was designed to compare device performance of a balloon-expandable (BE) transcatheter heart valve (THV) versus a self-expanding (SE) THV. Methods The CHOICE trial is an investigator-initiated trial that randomized 241 high-risk patients with severe symptomatic aortic stenosis and an anatomy suitable for treatment with both BE and SE THVs to transfemoral transcatheter aortic valve replacement with either device. The primary endpoint was device success. Patients were followed up to 5 years, with assessment of clinical outcomes, and echocardiographic evaluation of valve function and THV durability. Results After 5 years, there were no statistically significant differences between BE and SE valves in the cumulative incidence of death from any cause (53.4% vs. 47.6%; p = 0.38), death from cardiovascular causes (31.6% vs. 21.5%; p = 0.12), all strokes (17.5% vs. 16.5%; p = 0.73), and repeat hospitalization for heart failure (28.9% vs. 22.5%; p = 0.75). SE patients had larger prosthetic valve area (1.6 ± 0.5 cm2 vs. 1.9 ± 0.5 cm2; p = 0.02) with a lower mean transprosthetic gradient (12.2 ± 8.7 mm Hg vs. 6.9 ± 2.7 mm Hg; p = 0.001) at 5 years. No differences were observed in the rates of paravalvular regurgitation. Clinical valve thrombosis occurred in 7 BE patients (7.3%) and 1 SE patient (0.8%; p = 0.06), and moderate or severe structural valve deterioration in 6 BE patients (6.6%) and no SE patient (0%; p = 0.018). The rate of bioprosthetic valve failure was low and not significantly different between both groups (4.1% vs. 3.4%; p = 0.63). Conclusions Five-year follow-up of patients in the CHOICE trial revealed clinical outcomes after transfemoral transcatheter aortic valve replacement with early-generation BE and SE valves that were not statistically significantly different, with limited statistical power. Forward flow hemodynamics were significantly better with the SE valve. Moderate or severe structural valve deterioration was uncommon but occurred more frequently with the BE valve. (A Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: The CHOICE Trial [CHOICE]; NCT01645202)

Although the activated partial thromboplastin time (aPTT) has historically been the method of choice for anticoagulation monitoring in patients undergoing mechanical circulatory support with intravenous unfractionated heparin, it is being progressively superseded by the anti-factor Xa (anti-Xa) method. A retrospective single-arm, single-centre analysis of 20 patients who underwent total artificial heart implantation entailed simultaneous determinations of aPTT and anti-Xa. Agreement between these parameters was assessed using the Bland–Altman method. Despite a positive correlation between aPTT and anti-Xa, normal target ranges were poorly aligned: from 5th to 30th postoperative day, for anti-Xa values of 0.2 and 0.4 U/ml corresponding aPTT values were 52.1 and 65.2 s, 7.9 and 14.8 lower than predicted values, respectively. This was not associated with thromboembolic sequalae. It was not possible to demonstrate a significant relationship between the predictor variables (postoperative day; white blood cell count; C-reactive protein concentration; alanine transaminase and alkaline phosphatase level; bilirubin; haemoglobin; albumin and total protein concentration) and the agreement between aPTT and anti-Xa levels. In summary, when anti-Xa levels were used to guide anticoagulation therapy, corresponding aPTT levels were low with respect to target range. Methodology applied in this study is generalizable to other forms of mechanical circulatory support., The activated partial thromboplastin time (aPTT) has been the historical method of choice for anticoagulation monitoring in patients undergoing mechanical circulatory support with intravenous unfractionated heparin (IVUFH).

Background: Percutaneous intervention of calcified coronary lesions often requires lesion preparation with either balloon dilatation or atherectomy. We sought to evaluate the impact of lesion preparation strategy on stent expansion following preparation of severely calcified coronary lesions with modified (cutting/scoring) balloons (MB) versus rotational atherectomy (RA) and to evaluate the impact of calcium burden as assessed by optical coherence tomography (OCT) on acute stent performance. Methods: In the PREPARE-CALC trial (Comparison of Strategies to Prepare Severely Calcified Coronary Lesions), 200 patients with severely calcified coronary lesions were randomly assigned to receive either lesion preparation with MB or RA. In 122 patients, OCT was performed before lesion preparation and at the end of the procedure. The principal end point of this OCT sub-analysis was stent expansion as assessed by OCT. The key secondary end points included stent asymmetry and eccentricity. Results: The maximal calcific arc (257.5±96.7° versus 248.7±82.1°, P =0.59), thickness (1.34±0.29 versus 1.32±0.27 mm, P =0.76), and length of calcification (21.1±9.7 versus 24.0±10.9 mm, P =0.12) did not differ between the MB versus RA group. Lesion preparation with MB versus RA lead to comparable stent expansion (73.5±13.3% versus 73.1±12.2%, respectively, P =0.85). The use of RA did not have a significant impact on stent asymmetry or eccentricity compared with the use of MB. Length of calcified plaque appeared to be increased in patients with stent underexpansion, while thickness of calcified plaque was increased in patients with stent asymmetry. Target lesion revascularization at 9 months was 3.3% when MB was used and 1.6% when RA was performed ( P =0.62). Conclusions: In this OCT sub-analysis from the PREPARE-CALC trial, calcified plaque length was increased in patients with stent underexpansion, while its thickness was higher in patients with stent asymmetry, with no impact of the lesion preparation strategy. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02502851.

Objectives To determine whether a permanent pacemaker (PPM) in situ can enhance survival after transcatheter aortic valve implantation (TAVI), in a predominantly inoperable or high risk cohort. Background New conduction disturbances are the most frequent complication of TAVI, often necessitating PPM implantation before hospital discharge. Methods We performed an observational cohort analysis of the UK TAVI registry (2007-2015). Primary and secondary endpoints were 30-day post-discharge all-cause mortality and long-term survival, respectively. Results Of 8,651 procedures, 6,815 complete datasets were analyzed. A PPM at hospital discharge, irrespective of when implantation occurred (PPM 1.68% [22/1309] vs. no PPM 1.47% [81/5506], odds ratio [OR] 1.14, 95% confidence interval [CI] 0.71-1.84; p = .58), or a PPM implanted peri- or post-TAVI only (PPM 1.44% [11/763] vs. no PPM 1.47% [81/5506], OR 0.98 [0.51-1.85]; p = .95) did not significantly reduce the primary endpoint. Patients with a PPM at discharge were older, male, had right bundle branch block at baseline, were more likely to have received a first-generation self-expandable prosthesis and had experienced more peri- and post-procedural complications including bailout valve-in-valve rescue, bleeding and acute kidney injury. A Cox proportional hazards model demonstrated significantly reduced long-term survival in all those with a PPM, irrespective of implantation timing (hazard ratio [HR] 1.14 [1.02-1.26]; p = .019) and those receiving a PPM only at the time of TAVI (HR 1.15 [1.02-1.31]; p = .032). The reasons underlying this observation warrant further investigation. Conclusions A PPM did not confer a survival advantage in the first 30 days after hospital discharge following TAVI.

BACKGROUND: Historically the elderly have been under-represented in non-ST-elevation myocardial infarction (NSTEMI) management trials. AIMS: The aim of this trial was to demonstrate that an intervention-guided strategy is superior to optimal medical therapy (OMT) alone for treating NSTEMI in elderly individuals. METHODS: Patients (≥80 years, chest pain, ischaemic ECG, and elevated troponin) were randomised 1:1 to an intervention-guided strategy plus OMT versus OMT alone. The primary endpoint was a composite of all-cause mortality and non-fatal myocardial reinfarction at 1 year. Ethics approval was obtained by the institutional review board of every recruiting centre. RESULTS: From May 2014 to September 2018, 251 patients (n=125 invasive vs n=126 conservative) were enrolled. Almost 50% of participants were female. The trial was terminated prematurely due to slow recruitment. A Kaplan-Meier estimate of event-free survival revealed no difference in the primary endpoint at 1 year (invasive 18.5% [23/124] vs conservative 22.2% [28/126]; p=0.39). No significant difference persisted after Cox proportional hazards regression analysis (hazard ratio 0.79, 95% confidence interval 0.45-1.35; p=0.39). There was greater freedom from angina at 3 months (p

OBJECTIVES We sought to identify baseline demographics and procedural factors that might independently predict in-hospital stroke following transcatheter aortic valve implantation (TAVI). BACKGROUND Stroke is a recognized, albeit infrequent, complication of TAVI. Established predictors of procedure-related in-hospital stroke; however, remain poorly defined. METHODS We conducted an observational cohort analysis of the multicenter UK TAVI registry. The primary outcome measure was the incidence of in-hospital stroke. RESULTS A total of 8,652 TAVI procedures were performed from 2007 to 2015. There were 205 in-hospital strokes reported by participating centers equivalent to an overall stroke incidence of 2.4%. Univariate analysis showed that the implantation of balloon-expandable valves caused significantly fewer strokes (balloon-expandable 96/4,613 [2.08%] vs. self-expandable 95/3,272 [2.90%]; p = .020). After multivariable analysis, prior cerebrovascular disease (CVD) (odds ratio [OR] 1.51, 95% confidence interval [CI 1.05-2.17]; p = .03), advanced age at time of operation (OR 1.02 [0.10-1.04]; p = .05), bailout coronary stenting (OR 5.94 [2.03-17.39]; p = .008), and earlier year of procedure (OR 0.93 [0.87-1.00]; p = .04) were associated with an increased in-hospital stroke risk. There was a reduced stroke risk in those who had prior cardiac surgery (OR 0.62 [0.41-0.93]; p = .01) and a first-generation balloon-expandable valve implanted (OR 0.72 [0.53-0.97]; p = .03). In-hospital stroke significantly increased 30-day (OR 5.22 [3.49-7.81]; p

The purpose of this study was to evaluate clinical and echocardiographic outcome data of the CHOICE (Randomized Comparison of Transcatheter Heart Valves in High Risk Patients with Severe Aortic Stenosis: Medtronic CoreValve Versus Edwards SAPIEN XT) trial at 5 years.The CHOICE trial was designed to compare device performance of a balloon-expandable (BE) transcatheter heart valve (THV) versus a self-expanding (SE) THV.The CHOICE trial is an investigator-initiated trial that randomized 241 high-risk patients with severe symptomatic aortic stenosis and an anatomy suitable for treatment with both BE and SE THVs to transfemoral transcatheter aortic valve replacement with either device. The primary endpoint was device success. Patients were followed up to 5 years, with assessment of clinical outcomes, and echocardiographic evaluation of valve function and THV durability.After 5 years, there were no statistically significant differences between BE and SE valves in the cumulative incidence of death from any cause (53.4% vs. 47.6%; p = 0.38), death from cardiovascular causes (31.6% vs. 21.5%; p = 0.12), all strokes (17.5% vs. 16.5%; p = 0.73), and repeat hospitalization for heart failure (28.9% vs. 22.5%; p = 0.75). SE patients had larger prosthetic valve area (1.6 ± 0.5 cmFive-year follow-up of patients in the CHOICE trial revealed clinical outcomes after transfemoral transcatheter aortic valve replacement with early-generation BE and SE valves that were not statistically significantly different, with limited statistical power. Forward flow hemodynamics were significantly better with the SE valve. Moderate or severe structural valve deterioration was uncommon but occurred more frequently with the BE valve. (A Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: The CHOICE Trial [CHOICE]; NCT01645202).

Background We investigated changes in estimated glomerular filtration rate (eGFR) after left ventricular assist device (LVAD) implant and the impact on long-term outcomes. Methods A retrospective analysis was conducted for 255 patients with LVADs, divided into 2 groups based on preimplant eGFR ( 60 mL/min/1.73 m2) and into 6 grades (grade 1, >90 mL/min/1.73 m2 normal; grade 2, 60-89 mild dysfunction; grade 3, 45-59 moderate; grade 4, 30-44 moderate to severe; grade 5, 15-29 severe; or grade 6, Results One-month postimplant eGFR of the total cohort increased from a baseline of 75.19 ± 34.35 to 118.97 ± 67.62 mL/min/1.73 m2 (P 60 followed the same pattern as the entire cohort. The preimplant eGFR 60 was 76%, 54%, and 48% and for eGFR Conclusions Patients with a low preimplant eGFR derive benefit from LVAD therapy, with eGFR remaining elevated above preimplant levels. Preimplant renal dysfunction did not impact negatively on long-term morbidity and mortality.

Purpose The Activated Partial Thromboplastin Time (aPTT) has been the historical method of choice for anticoagulation monitoring in patients undergoing mechanical circulatory support with intravenous unfractionated heparin (IVUFH). However, the assay is susceptible to interference effects and is being progressively superseded by the anti-Factor Xa (anti-Xa) method. The study aim was to investigate the agreement between aPTT and anti-Xa measurements in patients receiving post-operative anticoagulation with IVUFH following Syncardia Inc. Total Artificial Heart (TAH) implantation. Methods A retrospective single arm, single centre analysis of 20 patients who underwent TAH implantation from July 2014 to October 2018 entailed simultaneous determinations of aPTT and anti-Xa. Agreement between these parameters was assessed using a novel statistical approach based on the Bland-Altman method. Results In spite of a positive correlation between aPPT and anti-Xa measurements, normal target ranges were poorly aligned: from 5th to 30th post-operative day, for anti-Xa values of 0.2 and 0.4 U/mL corresponding APTT values were 51.1 and 64.3 seconds, respectively. Moreover, white blood cell count was associated with a trend towards lower aPTT levels with respect to anti-Xa. Conversely, bilirubin level was significantly associated with an increase in aPTT levels with respect to anti-Xa values. Conclusion A novel method developed to investigate the agreement between aPTT and anti-Xa in the peri-operative phase of TAH therapy showed comparatively low levels of anticoagulation (with respect to historical target aPTT range) were not associated with thromboembolic sequalae. Methodology developed for this study is generalisable to other forms of mechanical circulatory support.

Balloon dilatation or debulking seems to be essential to allow successful stent implantation in calcified coronary lesions. Compared with standard balloon predilatation, debulking using high-speed rotational atherectomy (RA) is associated with higher initial procedural success albeit with higher in-stent late lumen loss at intermediate-term follow-up. Whether modified (scoring or cutting) balloons (MB) could achieve similar procedural success compared with RA is not known. In addition, whether new-generation drug-eluting stents could counterbalance the excessive neointimal proliferation triggered by RA remains to be determined.We randomly assigned patients with documented myocardial ischemia and severely calcified native coronary lesions undergoing percutaneous coronary intervention to a strategy of lesion preparation using MB or RA followed by drug-eluting stent implantation. Stenting was performed using a third-generation sirolimus-eluting stent with a bioabsorbable polymer. The trial had 2 primary end points: strategy success (defined as successful stent delivery and expansion with attainment of20% in-stent residual stenosis in the presence of TIMI [Thrombolysis in Myocardial Infarction] 3 flow without crossover or stent failure; powered for superiority) and in-stent late lumen loss at 9 months (powered for noninferiority). Two hundred patients were enrolled at 2 centers in Germany (n=100 in each treatment group). The mean age of the study population was 74.9±7.0 years; 76% were men, and 33.5% had diabetes mellitus. Strategy success was significantly more common in the RA group (81% versus 98%; relative risk of failure with an MB- versus RA-based strategy, 9.5; 95% CI, 2.3-39.7; P=0.0001), but mean fluoroscopy time was longer (19.6±13.4 versus 23.9±12.2 minutes; P=0.03). At 9 months, mean in-stent late lumen loss was 0.16±0.39 mm in the MB group and 0.22±0.40 mm in the RA group ( P=0.21, P=0.02 for noninferiority). Target lesion revascularization (7% versus 2%; P=0.17), definite or probable stent thrombosis (0% versus 0%; P=1.00), and target vessel failure (8% versus 6%; P=0.78) were low and not significantly different between the MB and RA groups.Lesion preparation with upfront RA before drug-eluting stent implantation is feasible in nearly all patients with severely calcified coronary lesions, is more commonly successful as a primary strategy compared with MB, and is not associated with excessive late lumen loss. A strategy of provisional MB remains feasible, safe, and effective as long as bailout RA is readily available and may offer the advantages of compatibility with smaller sized catheters and less irradiation. Both strategies are associated with excellent clinical outcome at 9 months.URL: https://www.clinicaltrials.gov . Unique identifier: NCT02502851.

Background: Balloon dilatation or debulking seems to be essential to allow successful stent implantation in calcified coronary lesions. Compared with standard balloon predilatation, debulking using high-speed rotational atherectomy (RA) is associated with higher initial procedural success albeit with higher in-stent late lumen loss at intermediate-term follow-up. Whether modified (scoring or cutting) balloons (MB) could achieve similar procedural success compared with RA is not known. In addition, whether new-generation drug-eluting stents could counterbalance the excessive neointimal proliferation triggered by RA remains to be determined. Methods and Results: We randomly assigned patients with documented myocardial ischemia and severely calcified native coronary lesions undergoing percutaneous coronary intervention to a strategy of lesion preparation using MB or RA followed by drug-eluting stent implantation. Stenting was performed using a third-generation sirolimus-eluting stent with a bioabsorbable polymer. The trial had 2 primary end points: strategy success (defined as successful stent delivery and expansion with attainment of P =0.0001), but mean fluoroscopy time was longer (19.6±13.4 versus 23.9±12.2 minutes; P =0.03). At 9 months, mean in-stent late lumen loss was 0.16±0.39 mm in the MB group and 0.22±0.40 mm in the RA group ( P =0.21, P =0.02 for noninferiority). Target lesion revascularization (7% versus 2%; P =0.17), definite or probable stent thrombosis (0% versus 0%; P =1.00), and target vessel failure (8% versus 6%; P =0.78) were low and not significantly different between the MB and RA groups. Conclusions: Lesion preparation with upfront RA before drug-eluting stent implantation is feasible in nearly all patients with severely calcified coronary lesions, is more commonly successful as a primary strategy compared with MB, and is not associated with excessive late lumen loss. A strategy of provisional MB remains feasible, safe, and effective as long as bailout RA is readily available and may offer the advantages of compatibility with smaller sized catheters and less irradiation. Both strategies are associated with excellent clinical outcome at 9 months. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02502851.

Background: Cardiogenic shock remains the most serious complication of patients hospitalized with acute myocardial infarction (AMI). Early revascularization is the cornerstone of invasive therapy, while mechanical support with intra-aortic balloon pump (IABP) is debatable. From our institutional shock registry we sought to determine predictors of in-hospital mortality—including the aspect of IABP timing—and to develop a clinical risk score for shock patients with AMI. Methods: From January 2005 till December 2010, 102 patients with cardiogenic shock due to AMI treated with primary percutaneous coronary intervention (PCI) and IABP were analyzed. Univariate and multivariate logistic regression analyses were used to identify independent predictors of in-hospital mortality. Logistic regression analysis and receiver-operating curves were used to generate a mortality risk score. Results: The mean age of the cohort was 70.1 ± 11.0 years and 70 % were men. One third of patients had a non-ST segment elevation myocardial infarction and 30 % had to be resuscitated before coronary intervention. Mean left ventricular ejection fraction was 25 %. After admission, 23 % of patients developed an acute renal failure and 10 % needed renal dialysis during hospital stay. In 52 % of patients IABP therapy was initiated after primary PCI, while the remaining patients had an IABP-assisted primary PCI. All-cause in-hospital mortality was 40.2 %. Using multivariate analysis, age (odds ratio [OR] 1.08, p = 0.006), resuscitation before PCI (OR 3.46, p = 0.045), vasopressor use (OR 7.88, p = 0.003), acute renal failure (OR 11.18, p = 0.001), and IABP implantation after PCI (OR 4.36, p = 0.011) were independently associated with in-hospital mortality. Based on these predictors, a mortality-risk score was calculated as follows: 1.5 × IABP timing before PCI + 0.1 × age + resuscitation before PCI + 2 × vasopressor use + 2.5 × acute renal failure. Using a cut-off value of 10.4, this score had a specificity of 83 % and a sensitivity of 82 % for prediction of in-hospital death. Conclusions: We identified age, vasopressor use, resuscitation before PCI, acute renal failure and IABP implantation after PCI as independent predictors of in-hospital mortality in patients with cardiogenic shock due to AMI. The timing of IABP insertion was the only modifiable factor predicting in-hospital mortality in our cohort. Consequently, balloon pumping should be started before PCI to improve outcome of cardiogenic shock patients.

BACKGROUND The use of a balloon-expandable transcatheter heart valve previously resulted in a greater rate of\ud device success compared with a self-expandable transcatheter heart valve.\ud OBJECTIVES The aim of this study was to evaluate clinical and echocardiographic outcome data at longer term\ud follow-up.\ud METHODS The investigator-initiated trial randomized 241 high-risk patients with symptomatic severe aortic stenosis\ud and anatomy suitable for treatment with both balloon- and self-expandable transcatheter heart valves to transfemoral\ud transcatheter aortic valve replacement with either device. Patients were followed-up for 1 year, with assessment of\ud clinical outcomes and echocardiographic evaluation of valve function.\ud RESULTS At 1 year, the rates of death of any cause (17.4% vs. 12.8%; relative risk [RR]: 1.35; 95% confidence interval\ud [CI]: 0.73 to 2.50; p ¼ 0.37) and of cardiovascular causes (12.4% vs. 9.4%; RR: 1.32; 95% CI: 0.63 to 2.75; p ¼ 0.54) were\ud not statistically significantly different in the balloon- and self-expandable groups, respectively. The frequencies of all\ud strokes (9.1% vs. 3.4%; RR: 2.66; 95% CI: 0.87 to 8.12; p ¼ 0.11) and repeat hospitalization for heart failure (7.4% vs.\ud 12.8%; RR: 0.58; 95% CI: 0.26 to 1.27; p ¼ 0.19) did not statistically significantly differ between the 2 groups. Elevated\ud transvalvular gradients during follow-up were observed in 4 patients in the balloon-expandable group (3.4% vs. 0%;\ud p ¼ 0.12); all were resolved with anticoagulant therapy, suggesting a thrombotic etiology. More than mild paravalvular\ud regurgitation was more frequent in the self-expandable group (1.1% vs. 12.1%; p ¼ 0.005).\ud CONCLUSIONS Despite the higher device success rate with the balloon-expandable valve, 1-year follow-up of patients\ud in CHOICE (Randomized Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis:\ud Medtronic CoreValve Versus Edwards SAPIEN XT Trial), with limited statistical power, revealed clinical outcomes after\ud transfemoral transcatheter aortic valve replacement with both balloon- and self-expandable prostheses that were not\ud statistically significantly different. (A Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic\ud Stenosis: The CHOICE Trial; NCT01645202) (J Am Coll Cardiol 2015;66:791–800) © 2015 by the American College of\ud Cardiology Foundation.

Objectives The aim of this study was to determine whether drug-eluting stents (DES) are superior to bare-metal stents (BMS) in octogenarian patients with angina. Background Patients ≥80 years of age frequently have complex coronary disease warranting DES but have a higher risk of bleeding from prolonged dual antiplatelet therapy. Methods This multicenter randomized trial was conducted in 22 centers in the United Kingdom and Spain. Patients ≥80 years of age underwent stent placement for angina. The primary endpoint was a 1-year composite of death, myocardial infarction, cerebrovascular accident, target vessel revascularization, or major hemorrhage. Results In total, 800 patients (83.5 ± 3.2 years of age) were randomized to BMS (n = 401) or DES (n = 399) for treatment of stable angina (32%) or acute coronary syndrome (68%). Procedural success did not differ between groups (97.7% for BMS vs. 95.4% for DES; p = 0.07). Thirty-eight percent of patients had ≥2-vessel percutaneous coronary intervention, and 66% underwent complete revascularization. Patients who received BMS had shorter stent implants (24.0 ± 13.4 mm vs. 26.6 ± 14.3 mm; p = 0.01). Rates of dual antiplatelet therapy at 1 year were 32.2% for patients in the BMS group and 94.0% for patients in the DES group. The primary endpoint occurred in 18.7% of patients in the BMS group versus 14.3% of patients in the DES group (p = 0.09). There was no difference in death (7.2% vs. 8.5%; p = 0.50), major hemorrhage (1.7% vs. 2.3%; p = 0.61), or cerebrovascular accident (1.2% vs. 1.5%; p = 0.77). Myocardial infarction (8.7% vs. 4.3%; p = 0.01) and target vessel revascularization (7.0% vs. 2.0%; p = 0.001) occurred more often in patients in the BMS group. Conclusions BMS and DES offer good clinical outcomes in this age group. DES were associated with a lower incidence of myocardial infarction and target vessel revascularization without increased incidence of major hemorrhage. (Xience or Vision Stent–Management of Angina in the Elderly [XIMA]; ISRCTN92243650 )

Background Estimates of atrial fibrillation (AF) burden (AFB) derived from intermittent rhythm monitoring (IRM) are increasingly being used as an outcome measure after therapeutic interventions; however, their accuracy has never been validated. The aim of this study was to compare IRM-derived AFB estimates to the true AFB as measured by implantable continuous monitoring (CM) devices. Methods Rhythm histories from 647 patients (mean AFB: 12 ± 22%; 687 patient·years) with CM devices were analyzed. IRM of various frequencies and durations were simulated and the obtained IRM-derived AF burdens were compared to the true AFB measured by CM. Results The relative error of the IRM burden estimates was dependent on the IRM length (P 80% of the true AFB. The relative error decreased with higher true AF burdens, lower AF densities, and higher IRM frequency or duration (P 20%, P < 0.001) and resulted in a substantial measurement error. Conclusion IRM-derived AFB estimates are unreliable estimators of the true AFB. Particularly for paroxysmal AF patients, IRM-derived AFB estimates should not be used to evaluate outcomes after AF interventions.

Introduction Duration of dual antiplatelet therapy (DAPT) following drug eluting stent (DES) implantation remains poorly defined. Endothelialisation of biodegradable polymer biolimus-eluting stents occurs early, and 6 months DAPT may be adequate. Aims We evaluated long term outcome in patients treated with biolimus-eluting stents who were treated with 6 months DAPT. Endpoints included cardiac death and non-fatal stent thrombosis occurring 6 to 12 months after stent implantation. Methods 692 patients (77.2% male), aged 65.6±12.5years received biolimus-eluting DES (March 2008 –November 2011). Vital status was tracked through the Medical Research Information Service. Episodes of non-fatal stent thrombosis, (Academic Research Consortium definition) between months 6 and 12 were tracked via systematic database searches (5 PCI centres). Results Presentations included acute coronary syndrome (47.2%) and stable coronary disease (52.8%). Vessels treated included left main stem (6.8%), left anterior descending (37.4%), circumflex (19.1%), right coronary artery (34.5%) and saphenous vein graft (2.1%) respectively. High-risk subsets included diabetes (15.6%); AHA type C lesions (35.1%) and chronic total occlusions (12.8%). During median follow-up of 700 days (0 to 1392) there were 42 deaths (6.1%); 4.2% at 0–6months, 1.0% at 6–12months and 0.9% at >12months. Of the 7 deaths between 6 and 12months, one death was adjudicated as possible stent thrombosis. There were no cases of non-fatal known stent thrombosis. All cause mortality accrued with smooth decremental incidence. Statistical examination showed no evidence of event clustering between 6 and 12 months. Conclusions After implantation of biodegradable polymer biolimus-eluting coronary stents, 6 months DAPT appears to be adequate, safe and effective.

Rotational atherectomy (RA) is widely used for treating calcified coronary lesions. Clinical data however remain limited.We assessed outcome and survival among patients undergoing percutaneous coronary intervention (PCI) with or without RA in the UK between September 2007 and March 2011.Data from 221,669 percutaneous coronary intervention (PCI) procedures were analysed; 2152 patients (0.97%) underwent RA (RA+); the remainder underwent conventional PCI (RA-). RA+ patients were older (71.7±9.6 vs. 64.1±12.8 year; p0.001), and had a higher incidence of diabetes (26.4% vs. 18.0%; p0.001), hypertension, (61.9% vs. 49.4%; p0.001), peripheral vascular disease (9.9% vs. 4.2%, p0.001), cerebrovascular disease (5.5% vs. 3.4%, p0.001), renal impairment (3.4% vs. 1.5%, p0.001) and poor left ventricular function (11.4% vs. 4.3%,p0.001). Procedural success was lower among RA+ patients (90.3% vs 94.6%; p0.001) and procedural complications were more frequent (9.7% vs 5.4%; p0.001). After 2.4±1.2 years follow-up, unadjusted Cox proportional hazard modeling demonstrated poorer survival for RA+ patients (HR 2.21, 95%CI 1.97-2.49; p0.0001). This disadvantage remained after adjustment for adverse variables (HR 1.26, 95%CI 1.11-1.44; p=0.0004) and following propensity analysis. There was evidence however of improved survival for RA+ patients with left main stem disease (HR 0.52, 95%CI 0.35-0.75, p0.0001), and peripheral vascular disease (HR 0.65, 95%CI 0.43-0.98, p0.0005).Rotational atherectomy was undertaken in patients with higher pre-procedural risk. Medium term survival was worse among patients undergoing rotational atherectomy, and this survival disadvantage remained after correction for available adverse factors. Rotational atherectomy however remains clinically useful for patients with calcified coronary lesions.

Background: The Ross operation provides the advantage of growth potential of the pulmonary autograft in the aortic position. However, development of autograft dilatation and regurgitation may occur. We sought to assess the progression of autograft diameters and aortic regurgitation (AR) with regard to patient age at the time of the Ross operation. Methods: Autograft echo dimensions from 48 children Results: The mean z values of all patients showed a significant increase with follow-up time at the sinus (0.5 ± 0.1/year, P < .001) and the sinotubular junction (0.7 ± 0.2/year, P < .001) but not at the annulus (0.1 ± 0.1/year, P = .59). There was no significant difference in the z values of sinus and the sinotubular junction between younger and older children at implantation and with time. The initial annulus z value was significantly larger in younger children ( P < .0001), whereas the annual increase was significantly higher in older children ( P = .021). Age at operation has no impact on the initial AR grade ( P = .60). The AR tends to increase more quickly in older patients ( P = .040). Sinus and sinotubular junction dilate with time, regardless of patient age. Conclusions: Young children show larger initial annulus sizes than older children. However, annulus diameters tend to normalize in young children, whereas they increase in older children. Autograft regurgitation develops slowly, but significantly, and predominantly in older children. Stabilizing measures to prevent autograft root dilatation are warranted in adolescents, but they are not required in young children.

Aims Cardiac troponins are measured in acute coronary syndrome (ACS) and other conditions. The authors investigate the prognostic significance of cardiac troponin T (TnT) test and comorbid medical conditions. Methods Consecutive patients admitted to the Aintree University Hospital, Liverpool, between 2 January 2004 and 29 February 2004 who had TnT measurement were included. Patients were separated into normal ( Results Of 1021 patients, 313 had raised TnT (195 ACS, 118 non-ACS) and 708 normal TnT (80 ACS, 628 non-ACS). Age (HR 1.06; 95% CI 1.05 to 1.07), congestive cardiac failure (HR 1.37; 95% CI 1.11 to 1.69), cerebrovascular disease (HR 1.37; 95% CI 1.10 to 1.71), chronic obstructive airway disease (HR 1.44; 95% CI 1.19 to 1.75), liver disease (HR 4.16; 95% CI 2.37 to 7.31), renal disease (HR 1.83; 95% CI 1.27 to 2.64), tumour (HR 1.39; 95% CI 1.07 to 1.79), lymphoma (HR 4.81; 95% CI 2.07 to 11.16), metastatic cancer (HR 3.55; 95% CI 2.32 to 5.45) and a higher Charlson's comorbidity score (HR 1.20, 95% CI 1.13 to 1.26) were adverse predictors. Both raised TnT with ACS (HR 1.92, 95% CI 1.54 to 2.39) and raised TnT with non-ACS (HR 2.37, 95% CI 1.87 to 3.00) were associated with worse survival. Raised TnT with non-ACS had a worse survival than raised TnT with ACS (p=0.001). Conclusion Hospitalised patients with raised TnT levels from any cause predicted a higher mortality than normal TnT, with worst survival in those without an obvious ACS.

Preformed donor HLA-specific antibodies are a known indicator for poor patient survival after cardiac transplantation. The role of de novo donor-specific antibodies (DSA) formed after cardiac transplantation is less clear. Here we have retrospectively analyzed 243 cardiac transplant recipients, measuring HLA antibody production every year after transplantation up to 13 years post-transplant. Production of de novo DSA was analyzed in patients who had been negative for DSA prior to their transplant. DSA including transient antibodies were associated with poor patient survival (p = 0.0018, HR = 3.198). However, de novo and persistent DSA was strongly associated with poor patient survival (p = 0.0001 HR = 4.351). Although complement fixing persistent DSA correlated with poor patient survival, this was not increased compared to noncomplement fixing persistent DSA. Multivariable analysis indicated de novo persistent DSA to be an independent predictor of poor patient survival along with HLA-DR mismatch and donor age. Only increasing donor age was found to be an independent risk factor for earlier development of CAV. In conclusion, patients who are transplanted in the absence of pre-existing DSA make de novo DSA after transplantation which are associated with poor survival. Early and regular monitoring of post-transplant DSA is required to identify patients at risk of allograft failure.

OBJECTIVES: The Ross operation in the setting of a bicuspid aortic valve (BAV) remains controversial. Using data from the German Ross Registry, we sought to investigate the effect of the presence of a BAV on autograft function and diameters over time after the Ross operation compared with the presence of a tricuspid aortic valve (TAV). METHODS: A total of 1277 patients (mean age 42.2 + or - 15.3 years) with intra-operatively documented aortic valve morphology during the Ross operation were analysed in the present study (sub-coronary technique, n=648, root replacement technique, n=629 patients). A BAV was present in 70.9% of patients. Clinical and echocardiographic follow-up was performed preoperatively and at pre-specified intervals (mean follow-up 5.7 + or - 3.8 years, 6806 patient-years). Hierarchical multilevel modelling techniques were used for the statistical analysis of serial measurements and comparisons among groups. RESULTS: Initial neo-aortic regurgitation was lower in the BAV group (0.52 vs 0.62 aortic insufficiency (AI) grades, p=0.008), whereas the annual increase of it did not differ among groups. In both surgical techniques, no significant development of neo-aortic regurgitation (

Background. The Ross operation may be the ideal aortic valve replacement in pediatric patients. However, reoperations for replacement of the homograft in the pulmonary position are inevitable. This study determined influencing factors for the development of homograft stenosis and regurgitation in pediatric Ross patients. Methods. Follow-up echocardiograms of 116 children (86 boys) undergoing Ross operations at a mean age, 9.3 +/- 4.9 years were analyzed using hierarchic multilevel modeling. Mean duration of the echocardiographic follow- up was 5.3 +/- 4.2 years (609 patient-years, 398 examinations). Results. Median homograft diameter z value was 0.3 (range -2.2 to +7.3). Mean homograft pressure gradient at implantation was 5.0 mm Hg with a significant increase of 4.2 mm Hg/y (p < 0.001) within the first 2 years and a steady state thereafter. Older donor age was significantly associated with lower mean pressure gradient at implantation (p = 0.037). Larger z value had no significant influence on the annual increase of pressure gradient (p = 0.87). Mean grade of regurgitation at implantation was 0.9, without significant annual increase (0.02 grade/y, (p = = 0.32). Older recipient (p = 0.005) and donor age (p < 0.0001) were significantly associated with lower mean regurgitation at implantation. Larger z value was associated with a higher annual increase of regurgitation (p = 0.014). Conclusions. Relevant midterm homograft regurgitation is rare in children after the Ross operation. However, a significant annual increase occurs in the pressure gradient that cannot be influenced by larger graft size. Homograft oversizing may lead to a higher annual increase of regurgitation. (Ann Thorac Surg 2009; 88: 609-15) (C) 2009 by The Society of Thoracic Surgeons

Minimisation is a method often used in clinical trials to balance the treatment groups with respect to some prognostic factors. In the case of two treatments, the predictability of this method is calculated for different numbers of factors, different numbers of levels of each factor and for different proportions of the population at each level. It is shown that if we know nothing about the previous patients except the last treatment allocation, the next treatment can be correctly guessed more than 60% of the time if no biased coin is used. If the two previous assignments are known to have been the same, the next treatment can be guessed correctly around 80% of the time. Therefore, it is suggested that a biased coin should always be used with minimisation. Different choices of biased coin are investigated in terms of the reduction in predictability and the increase in imbalance that they produce. An alternative design to minimisation which makes use of optimum design theory is also investigated, by means of simulation, and does not appear to have any clear advantages over minimisation with a biased coin.

Objective To examine the effects of comorbidity and hospital care on mortality in patients with elevated cardiac troponin T. Design Observational study. Setting A large university hospital with on-site diagnostic cardiac catheter laboratory. Patients All hospitalised patients with elevated cardiac troponin T level (⩾0.01 μg/l) over an 8-week period. Main outcome measures 6-month all-cause mortality. Results Among 313 patients with elevated cardiac troponin T, 195 had acute coronary syndrome and 118 had other conditions. Multivariate analysis showed that among patients with acute coronary syndrome, increasing comorbidity score (odds ratio (OR) 1.23 per point increase, 95% confidence interval (CI) 1.00 to 1.51; p = 0.048), age (OR 1.08 per year, 95% CI 1.04 to 1.13; p Conclusions Comorbidity was associated with a higher 6-month mortality in patients having acute coronary syndrome, and lesser use of effective medicines among hospital survivors. Cardiologist care was associated with better 6-month survival in patients with acute coronary syndrome, but not in those without acute coronary syndrome.

Aims The HORIZONS trial reported a survival advantage for bivalirudin over heparin-with-glycoprotein inhibitors (GPIs) in primary PCI for ST elevation myocardial infarction. This drove an international shift in clinical practice. Subsequent studies have produced divergent findings on mortality benefits with bivalirudin. We investigated this issue in a larger population than studied in any of these trials, using the United Kingdom national PCI registry. Methods and results 61 136 primary PCI procedures were performed between January 2008 and January 2012. Demographic and procedural data were obtained from the registry. Mortality information was obtained through the UK Office of National Statistics. Multivariable logistic regression and propensity analysis modelling were utilized to study the association of different anti-thrombotic strategies with outcomes. Unadjusted data demonstrated near-identical survival curves for bivalirudin and heparin-plus-GPI groups. Significantly higher early and late mortality was found in patients treated with heparin alone ( P < 0.0001) but this group had a markedly higher baseline risk. After propensity matching, the bivalirudin vs. heparin-plus-GPI groups still demonstrated very similar adjusted mortality (odds ratio 1.00 at 30 days, and 0.96 at 1 year). Patients treated with heparin alone continued to show higher mortality after adjustment, although effect size was considerably diminished (odds ratio vs. other groups 1.17–1.24 at 30 days). Conclusions Analysis of recent UK data showed no significant difference in short- or medium-term mortality between ST elevation myocardial infarction patients treated with bivalirudin vs. heparin-plus-GPI at primary PCI.

Endoaneurysmorrhaphy (EAR) has become an important therapeutic option in the treatment of patients with left ventricular (LV) aneurysm and congestive heart failure. Today, more and more patients are referred for EAR with a dilated akinetic LV rather than a classic dyskinetic LV aneurysm. Little is known about the contribution of the extent of akinesis to perioperative mortality. We reviewed the data of 147 patients with anterior left ventricular aneurysms undergoing EAR. Seventy percent of the patients were male; mean age was 62 9 years. Demographic, hemodynamic, angiographic and surgical variables were analyzed using univariate statistic tests in order to determine risk factors for in-hospital mortality. Eighty-two percent of the LV aneurysms had at least some dyskinesia, but 70% were mainly akinetic. 133 patients had additional bypass surgery, one had additional mitral valve replacement. In-hospital mortality was 4.1% (n=6). Risk factors for in-hospital mortality were the total extent of akinetic myocardium (p=0.027) in the 30degrees RAO view and the duration of cardiopulmonary bypass (CPB, p=0.0068) which was itself dependent on the IV ejection fraction (p=0.001), the number of stenosed coronary arteries (p = 0.004), and the extent of akinesis (p = 0.023). The extent of dyskinesia was not associated with either perioperative mortality (p=0.36) or CPB duration. EAR can be performed with acceptable perioperative results. Because akinesis increases in many patients with time, and because the duration of ECC was dependent on variables reflecting the severity of the underlying heart disease, our findings underscore the importance of optimal timing for the surgical intervention.

Objective Although atrial fibrillation (AF) recurrence is unpredictable in terms of onset and duration, current intermittent rhythm monitoring (IRM) diagnostic modalities are short-termed and discontinuous. The aim of the present study was to investigate the necessary IRM frequency required to reliably detect recurrence of various AF recurrence patterns. Methods The rhythm histories of 647 patients (mean AF burden: 12±22% of monitored time; 687 patient-years) with implantable continuous monitoring devices were reconstructed and analyzed. With the use of computationally intensive simulation, we evaluated the necessary IRM frequency to reliably detect AF recurrence of various AF phenotypes using IRM of various durations. Results The IRM frequency required for reliable AF detection depends on the amount and temporal aggregation of the AF recurrence (p95% sensitivity) of AF recurrence required higher IRM frequencies (>12 24-hour; >6 7-day; >4 14-day; >3 30-day IRM per year; p

Background. Transplant-associated coronary artery disease (TxCAD) is the most serious long-term complication after cardiac transplantation. Anti-endothelial antibodies are associated with disease, and one of the major endothelial antigens recognized in the sera of patients has been shown to be the protein filament vimentin. In this study, we investigated whether antivimentin antibodies are associated with TxCAD and whether their presence can be used to identify patients at high risk of developing angiographically detectable TxCAD. Methods. Up to 5 years after transplantation, 880 sequential sera (7.07+/-1.8 samples/patient) were collected retrospectively from 109 patients; the majority were collected in the first 2 years. Sera were assessed for antivimentin antibodies using ELISA. TxCAD was assessed by annual angiography. Results. Mean titres of antivimentin antibodies, calculated up to 1, 2, and 5 years, were significantly higher in patients who developed TxCAD than those who remained disease free (P 120) produced a test with 63% sensitivity and 76% specificity. Inclusion of persistent rejection or high 1-year mean titre (greater than or equal to 270) as a risk, factor produced a test with 66% sensitivity and 82% specificity. Multivariate analysis of time to occurrence of transplant vasculopathy showed that mean titre at 1 or 2 years was an independent predictor of time until disease in the presence of all other variables. Conclusions. Antivimentin antibodies are an independent predictor of TxCAD and can be used to identify some of the patients who are at high risk. of developing this complication.

OBJECTIVE: To examine the clinical characteristics and 30-day fatality rate among patients with electrocardiograms (ECGs) ineligible for fibrinolysis in a consecutive series in four general hospitals in the UK. METHODS: We studied 2439 consecutive patients who were identified from regular ward visits, surveillance of results from hospital laboratories, and hospital discharge coding. RESULTS: Thirty percent (732) of patients did not have ECGs eligible for fibrinolysis therapy, while indications were uncertain in 55 (2%). Within the ineligible group, patients presenting with ST depression (n = 294) had a higher 30-day fatality rate than those with ST elevation or left bundle branch block (26% versus 17%; P < 0.001); they represented 40% of the group ineligible for fibrinolysis therapy, or 12% of the total cohort. Thirty-day fatality rates in patients presenting with pathological Q waves and no diagnostic ST segment changes (n = 130), those with T wave changes but no other abnormality (n = 168) and those with a normal ECG (n = 128) were 10%, 5% and 3%, respectively. Despite their high fatality rate, fewer patients with ST depression were admitted to coronary care units than those with ECGs eligible for fibrinolysis therapy (61% versus 85%; P < 0.001) and 23% did not receive heparin. The coronary anatomy in a subset of patients with ST depression showed two- or three-vessel disease in 79% and left main stenosis in 9%. The rates of coronary revascularisation were low in all groups (< 10%). CONCLUSION: Patients with ECGs ineligible for fibrinolysis therapy are a disparate group, with a high rate of fatality occurring in patients who present with ST depression. The high prevalence of multiple vessel coronary disease in patients with ST depression suggests that a more active management strategy is required.

Estimates of atrial fibrillation (AF) burden (AFB) derived from intermittent rhythm monitoring (IRM) are increasingly being used as an outcome measure after therapeutic interventions; however, their accuracy has never been validated. The aim of this study was to compare IRM-derived AFB estimates to the true AFB as measured by implantable continuous monitoring (CM) devices.Rhythm histories from 647 patients (mean AFB: 12 ± 22%; 687 patient·years) with CM devices were analyzed. IRM of various frequencies and durations were simulated and the obtained IRM-derived AF burdens were compared to the true AFB measured by CM.The relative error of the IRM burden estimates was dependent on the IRM length (P0.001), frequency of IRM (P0.001), the true AFB (P0.001), and its temporal aggregation (AF density, P0.001). In paroxysmal AF patients, the relative error even with aggressive IRM strategies was80% of the true AFB. The relative error decreased with higher true AF burdens, lower AF densities, and higher IRM frequency or duration (P0.001). However, even in patients with high AF burdens and/or low AF densities, IRM estimates of AFB significantly deviated from the true AFB (relative error20%, P0.001) and resulted in a substantial measurement error.IRM-derived AFB estimates are unreliable estimators of the true AFB. Particularly for paroxysmal AF patients, IRM-derived AFB estimates should not be used to evaluate outcomes after AF interventions.

OBJECTIVE: To confirm the validity of a previously described method for assessment of infarct artery patency involving serial measurements of creatine kinase activity by use of troponin T concentration as an independent plasma marker. DESIGN: Streptokinase (1.5 x 10(6) units) was given intravenously to 60 patients within 6 h of onset of prolonged chest pain and ST segment elevation, and blood was taken for measurement of troponin T concentration at baseline and at 1, 2, 3, 4, 8, 12, 16, 20, and 24 h after starting treatment. Coronary arteriography was performed at 2.6 (SD 0.3) h. Plasma troponin T concentration was assessed by two methods: (1) as the absolute rise between 0 and 3 h; and (2) as the proportion of the total rise (from baseline to peak) over the same period. Accuracy for prediction of infarct artery patency, assessed by receiver operating characteristic curves, was compared for both methods of assessment using troponin T and was in turn compared with previously reported results on the same patients using serial measurements of creatine kinase activity. RESULTS: Sufficient values for prediction of patency using troponin T were available in 53 patients. A rise in troponin T between 0 and 3 h to > or = 9% of peak concentration predicted angiographic patency with sensitivity of 94% and specificity of 100%. By contrast, at the optimum cutoff for absolute rate of rise (0.5 micrograms/l/h) sensitivity was only 66% and specificity 86%. Comparable figures for creatine kinase were 92% and 91% (> or = 20% of peak by 3 h) and 62% and 78% (150 IU/l/h). Receiver operating curves confirmed better predictive accuracy for proportions over absolute rates of rise for both markers (P < 0.01). CONCLUSIONS: For accurate diagnosis of infarct artery patency using plasma markers it is necessary to express the rate of rise as a proportion of the peak level. Analysed in this way, both creatine kinase and troponin T are suitable for use in randomised trials of new thrombolytic or adjuvant drugs.

Background— Intermittent rhythm monitoring (IRM) to detect atrial fibrillation (AF) recurrence is employed to evaluate the success of therapeutic interventions. In a large population of patients with continuous monitoring (CM), we investigated the sensitivity of various frequencies and durations of IRM strategies on the detection of AF recurrence, the dynamics behind AF recurrence detection, and we describe measures to evaluate temporal AF recurrence. Methods and Results— Rhythm histories of 647 patients (mean AF burden, 0.12±0.22; median, 0.014; 687 patient-years) with implantable CM devices were reconstructed and analyzed. With the use of computationally intensive simulation, the sensitivity of IRM of various frequencies and durations on the identification of AF recurrence was evaluated. Prolonged-duration IRM was superior to shorter IRM ( P P P Conclusions— IRM follow-up is significantly inferior to CM. IRM strategies will not identify AF recurrence in a great proportion of patients at risk. Temporal AF characteristics play a significant role in AF recurrence detection with the use of IRM. For the scientific, evidence-based evaluation of AF treatments, CM should be strongly recommended. Prospective studies are required to evaluate whether CM to guide clinical management can also improve patient outcomes. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00806689.

In this paper, we have compared mutant frequency data at the hprt locus in circulating T-lymphocytes from four large datasets obtained in the UK (Sussex), the USA (Vermont), France (Paris) and The Netherlands (Leiden). In total, data from > 500 non-exposed individuals ranging in age from newborns (cord blood samples) to > 80 years old have been included in the analysis. Based on raw data provided by the four laboratories, a model is presented for the analysis of mutant frequency estimations for population monitoring. For three of the laboratories, a considerable body of data was provided on replicate estimates of mutant frequency from single blood samples, as well as estimates from repeat blood samples obtained over a period of time from many of the individual subjects. This enabled us to analyse the sources of variation in the estimation of mutant frequency. Although some variation was apparent in the results from the four laboratories, overall the data were in general agreement. Thus, in all laboratories, cellular cloning efficiency of T-cells was generally high (> 30%), although in each laboratory considerable variation between experiments and subjects was seen. Mutant frequency per clonable T-cell was in general found to be inversely related to cloning efficiency. With the exception of a few outliers (which are to be expected), mutant frequencies at this locus were in the same range in each dataset; no effect of subject gender was found, but an overall clear age effect was apparent. When log mutant frequency was analysed vs log (age + 0.5) a consistent trend from birth to old age was seen. In contrast, the effect of the smoking habit did differ between the laboratories, there being an association of smoking with a significant increase in mutant frequency in the Sussex and Leiden datasets, but not in those from the Vermont or Paris datasets. Possible reasons for this are discussed. One of the objectives of population monitoring is an ability to detect the effect of accidental or environmental exposure to mutagens and carcinogens among exposed persons. The large body of data from non-exposed subjects we have analysed in this paper has enabled us to estimate the size of an effect that could be detected, and the number of individuals required to detect a significant effect, taking known sources of variation into account.(ABSTRACT TRUNCATED AT 400 WORDS)

A retrospective study of 139 glioma patients was conducted in an effort to audit management. Factors affecting survival were studied using a Cox Proportional Hazard Model. These factors included age, sex, location, grade, type of surgery, use of radiotherapy, presenting symptoms, Karnofsky score on admission and Karnofsky score 3 months following surgery. Lower grade, high Karnofsky score on admission, radiotherapy and frontal location were associated with better survival. There was statistically insignificant evidence that the other factors had an influence on survival. Patients presenting with a poor neurological score were treated with burrhole biopsy alone. Only 10% of these patients survived more than 6 months. On the other hand, 26% of patients who had craniotomy on the basis of reasonable clinical status lived less than 6 months. Sixty-six per cent of patients in this craniotomy group were aged 60 years or over, and 66% of those aged over 60 had a Karnofsky score of less than 70. We conclude that careful judgement is required before subjecting patients aged over 60, especially those with a low Karnofsky score, to radical therapy.

Background— The purpose of the study is to report major cardiac and cerebrovascular events after the Ross procedure in the large adult and pediatric population of the German-Dutch Ross registry. These data could provide an additional basis for discussions among physicians and a source of information for patients. Methods and Results— One thousand six hundred twenty patients (1420 adults; 1211 male; mean age, 39.2±16.2 years) underwent a Ross procedure between 1988 and 2008. Follow-up was performed on an annual basis (median, 6.2 years; 10 747 patient-years). Early and late mortality were 1.2% (n=19) and 3.6% (n=58; 0.54%/patient-year), respectively. Ninety-three patients underwent 99 reinterventions on the autograft (0.92%/patient-year); 78 reinterventions in 63 patients on the pulmonary conduit were performed (0.73%/patient-year). Freedom from autograft or pulmonary conduit reoperation was 98.2%, 95.1%, and 89% at 1, 5, and 10 years, respectively. Preoperative aortic regurgitation and the root replacement technique without surgical autograft reinforcement were associated with a greater hazard for autograft reoperation. Major internal or external bleeding occurred in 17 (0.15%/patient-year), and a total of 38 patients had composite end point of thrombosis, embolism, or bleeding (0.35%/patient-year). Late endocarditis with medical (n=16) or surgical treatment (n=29) was observed in 38 patients (0.38%/patient-year). Freedom from any valve-related event was 94.9% at 1 year, 90.7% at 5 years, and 82.5% at 10 years. Conclusions— Although longer follow-up of patients who undergo Ross operation is needed, the present series confirms that the autograft procedure is a valid option to treat aortic valve disease in selected patients. The nonreinforced full root technique and preoperative aortic regurgitation are predictors for autograft failure and warrant further consideration. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00708409.

Objective: Serum cardiac troponins can be elevated in acute coronary syndromes (ACS) and other non-ACS conditions. We investigated the usefulness of a prediction score model comprising clinical variables to distinguish patients with ACS from other non-ACS conditions. Methods: Two independent, non-randomized observational cohorts (groups 1 and 2) were examined, comprising consecutive patients who were admitted to a university teaching hospital and found to have a raised serum troponin T level (>=0.01 [mu]g/l). The international definition was used to confirm acute myocardial infarction. Multivariate logistic regression identified clinical variables in the first cohort, which were used to construct a score model for distinguishing between ACS and non-ACS, and this score was re-evaluated in the second cohort. Results: Of the 313 patients in group 1, a score model was formulated using logarithm troponin T, ischaemic chest pain, ST depression and atrial fibrillation or flutter. Using a score of more than or equal to 1.5, sensitivity and specificity for predicting non-ACS were 0.81 and 0.84. The area under the curve was 0.900 (95% confidence interval 0.867-0.934). Sensitivity and specificity for predicting non-ACS among the 341 patients in group 2 using the same model and a score of more than or equal to 1.5 were 0.76 and 0.89, respectively, and the area under the curve was 0.918 (confidence interval 0.887-0.945). Conclusion: A prediction score model using simple clinical variables has been validated, and this can help clinicians in distinguishing patients with ACS from other non-ACS conditions.

In a cellular radio system a limited number of channels are available and neighbouring cells may not be allocated the same channel simultaneously because of the possibility of interference. Under heavy traffic, therefore, the average rate of losing calls may be reduced if certain calls are rejected as a matter of policy because of the potential inference they may cause. A fixed channel assignment policy is one in which each cell is allocated a fixed set of channels, this set typically being made smaller for cells likely to cause most interference. Sufficient conditions are found for the optimality of fixed channel assignment policies for a variety of layouts, and optimal and ‘good' policies are found in a number of other cases.

Background— Autograft reinforcement interventions (R) during the Ross procedure are intended to preserve autograft function and improve durability. The aim of this study is to evaluate this hypothesis. Methods and Results— 1335 adult patients (mean age:43.5±12.0 years) underwent a Ross procedure (subcoronary, SC, n=637; root replacement, Root, n=698). 592 patients received R of the annulus, sinotubular junction, or both. Regular clinical and echocardiographic follow-up was performed (mean:6.09±3.97, range:0.01 to 19.2 years). Longitudinal assessment of autograft function with time was performed using multilevel modeling techniques. The Root without R (Root−R) group was associated with a 6× increased reoperation rate compared to Root with R (Root+R), SC with R (SC+R), and without R (SC-R; 12.9% versus 2.3% versus 2.5%.versus 2.6%, respectively; P Conclusions— For the time period of the study surgical autograft stabilization techniques preserve autograft function and result in significantly lower reoperation rates. The nonreinforced Root was associated with significant adverse outcome. Therefore, surgical stabilization of the autograft is advisable to preserve long-term autograft function, especially in the Root Ross procedure.

Background. Preexisting IgG antibodies to donor human leukocyte antigens (HLA) are a risk factor for rapid allograft rejection. However, non-HLA antibodies, of the IgM class, also called autoreactive antibodies, are not believed to affect graft survival. The aim of this study was to determine the incidence and clinical relevance of pretransplant lymphocytotoxic non-HLA IgM antibodies on long-term cardiac allograft survival. Methods. A retrospective study of 616 adult recipients of cardiac allografts, transplanted at this center between 1991 and 2003, has been performed. Antibodies in pretransplant sera were initially defined using complement-dependent cytotoxicity assays, and subsequently analyzed for HLA specificities using solid phase assays. Results. HLA antibodies were present in 69 of 616 heart recipients (58 IgG, 11 IgM); in 22 of these, the antibodies were donor-specific. Non-HLA IgM antibodies were detected in 59 of 616 recipients who did not have HLA-specific antibodies; these patients had a 1, 2, 5, and 10 year survival of 55.9%, 54.2%, 49.9%, and 43.3% compared with 75.8%, 73.7%, 66.6%, and 52.8% for those without antibodies (P=0.0085 log-rank test). Multivariate analysis demonstrated pretransplant non-HLA IgM antibodies to be an independent risk factor for mortality (P=0.0001). Myocardial histology of postmortem heart and cardiac biopsies suggested an association with ischemic damage and "primary" allograft failure. Conclusions. We propose the hypothesis that the presence of cytotoxic IgM antibodies to non-HLAs before heart transplantation maybe a risk factor for early allograft failure.

Background. For children who require aortic valve replacement, the Ross operation provides a unique advantage of growth potential of the pulmonary autograft in the aortic position. This study assessed the progression of autograft root diameters and its effect on aortic regurgitation (AR). Methods. Neoaortic echo dimensions from 48 children (< 16 years) undergoing Ross operation who had follow-up echocardiograms before age 20 were analyzed (mean follow-up, 5.1 +/- 3.3 years). Results. The mean age at the time of the Ross operation was 10.0 +/- 4.3 years. Mean z values of the neoaortic annulus (1.5 +/- 0.4), sinus (2.5 +/- 0.4), and sinotubular junction (2.6 +/- 0.9) when the autograft was implanted were significantly larger compared with normal values (p < 0.001, all). The mean z values significantly increased with follow-up at the level of the sinus (0.5 +/- 0.1/year, p < 0.001) and the sinotubular junction (0.7 +/- 0.2, p < 0.001), but not at the level of the annulus (0.1 +/- 0.1, p = 0.59). AR increased with follow- up time (0.07 +/- 0.02 grade/year, p < 0.001). AR increased with sinotubular junction diameter (p = 0.028), but there was not significant evidence of an association with annulus diameter (p = 0.25) or sinus diameter (p = 0.40). Conclusions. Children undergoing Ross operation have larger neoaortic root dimensions than healthy children. Growth of the annulus matches somatic growth. The diameters of the sinus and the sinotubular junction increase significantly relative to somatic growth. The latter may explain the development of AR. (Ann Thorac Surg 2009; 88: 594-600) c 2009 by The Society of Thoracic Surgeons

Objective Early results after aortic valve-sparing root reconstruction are excellent. Longer-term follow-up, especially with regard to aortic valve function, is required for further judgment of these techniques. Methods Between July of 1993 and September of 2006, 108 consecutive patients (mean age 53.0 ± 15.8 years) underwent the Yacoub operation (group Y) and 83 patients underwent the David operation (group D). Innovative multilevel hierarchic modeling methods were used to analyze aortic regurgitation over time. Results In general, aortic regurgitation increased with time in both groups. Factors associated with the development of a significant increase in aortic regurgitation were Marfan syndrome, concomitant cusp intervention, and preoperative aortic anulus dimension. In Marfan syndrome, the initial aortic regurgitation was higher in group Y versus group D (0.56 aortic regurgitation vs 0.29 aortic regurgitation, P = .049), whereas the mean annual progression rate of aortic regurgitation was marginally higher in group Y (0.132 aortic regurgitation vs 0.075 aortic regurgitation, P = .1). Concomitant cusp intervention was associated with a significant aortic regurgitation increase in both groups (P < .0001). There was a trend that smaller preoperative aortic annulus diameters in group D and larger diameters in group Y were associated with increased aortic regurgitation over time. Conclusion In regard to aortic regurgitation grade over time, patients with Marfan syndrome and a large preoperative aortic annulus diameter were better treated with the reimplantation technique, whereas those with a smaller diameter were better treated with the remodeling technique. Concomitant free-edge plication of prolapsing cusps was disadvantageous in both groups. Considering these factors may serve to improve the aortic valve longevity after valve-sparing aortic root surgery.

Background— Autograft regurgitation and root dilatation after the Ross procedure is of major concern. We reviewed data from the German Ross Registry to document the development of autograft regurgitation and root dilatation with time and also to compare 2 different techniques of autograft implantation. Methods and Results— Between 1990 and 2006 1014 patients (786 men, 228 women; mean age 41.2±15.3 years) underwent the Ross procedure using 2 different implantation techniques (subcoronary, n =521; root replacement, n =493). Clinical and serial echocardiographic follow up was performed preoperatively and thereafter annually (mean follow up 4.41±3.11 years, median 3.93 years, range 0 to 16.04 years; 5012 patient-years). For statistical analysis of serial echocardiograms, a hierarchical multilevel modeling technique was applied. Eight early and 28 late deaths were observed. Pulmonary autograft reoperations were required in 35 patients. Initial autograft regurgitation grade was 0.49 (root replacement 0.73, subcoronary 0.38) with an annual increase of grade 0.034 (root replacement 0.0259, subcoronary 0.0231). Annulus and sinus dimensions did not exhibit an essential increase over time in both techniques, whereas sinotubular junction diameter increased essentially by 0.5 mm per year in patients with root replacement. Patients with the subcoronary implantation technique showed nearly unchanged dimensions. Bicuspid aortic valve morphology did not have any consistent impact on root dimensions with time irrespective of the performed surgical technique. Conclusions— The present Ross series from the German Ross Registry showed favorable clinical and hemodynamic results. Development of autograft regurgitation for both techniques was small and the annual progression thereof is currently not substantial. Use of the subcoronary technique and aortic root interventions with stabilizing measures in root replacement patients seem to prevent autograft regurgitation and dilatation of the aortic root within the timeframe studied.

Background— The autograft procedure, an option in aortic valve replacement, has undergone technical evolution. A considerable debate about the most favorable surgical technique in the Ross operation is still ongoing. Originally described as a subcoronary implant, the full root replacement technique is now the most commonly used technique to perform the Ross principle. Methods and Results— Between June of 1994 and June of 2005, the original subcoronary autograft technique was performed in 347 patients. Preoperative, perioperative, and follow-up data were collected and analyzed. Mean patient age at implantation was 44±13 years (range 14 to 71 years; 273 male, 74 female). Bicuspid valve morphology was present in 67%. The underlying valve disease was aortic regurgitation in 111 patients, stenosis in 46 patients, combined lesion in 188 patients, and active endocarditis in 22 patients (in 2 patients without stenosis or regurgitation). Concomitant procedures were performed in 130 patients. Clinical and echocardiographic follow-up visits were obtained annually (mean follow up 3.9±2.7 years, 1324 patient-years; completeness of follow-up 99.4%). The in-hospital mortality rate was 0.6% (n =2), and the late mortality was 1.7% (n=6), with 5 noncardiac deaths (4 cancer, 1 multiorgan failure after noncardiac surgery) and 1 cardiac death (sudden death). At last follow-up, 94% of the surviving patients were in New York Heart Association class I. Ross procedure–related valvular reoperations were necessary in 9 patients: Three received autograft explants, 5 received homograft explants, and 1 received a combined auto- and homograft explant. At last follow-up visit, autograft/homograft regurgitation grade II was present in 5/10 patients and grade III in 4/0. Maximum/mean pressure gradients were 7.4±6.2/3.7±2.1 mm Hg across the autograft and 15.3±9.4/7.6±5.0 mm Hg across the right ventricular outflow tract, respectively. Aortic root dilatation was not observed. Freedom from any valve-related intervention was 95% at 8 years (95% confidence interval 91% to 99%). Conclusion— Midterm follow-up of autograft procedures according to the original Ross subcoronary approach proves excellent clinical and hemodynamic results, with no considerable reoperation rates. Revival of the original subcoronary Ross operation should be taken into account when considering the best way to install the Ross principle.

Cardiac allograft vasculopathy (CAV) is a major cause of death more than 1 year after heart transplantation. We evaluated the role and possible predictive value of different etiological factors on development of CAV as diagnosed by quantitative coronary angiography (QCA). A total of 121 patients were studied with baseline QCA and 117 had a follow-up study at 1 year to assess the relationship of mean lumen diameter loss (MLDL) in main coronary arteries to immunological and non-immunological factors potentially affecting long-term survival. Out of them, 103 patients were males (85%), 114 (94%) patients were Caucasians and mean age was 48.5 +/- 10 years. Univariate analysis showed that MLDL at 1 year was inversely related to echocardiographic fractional shortening (FS) measured within the first week after transplantation (p = 0.0098) and to intracranial hemorrhage as cause of donor death (p = 0.04) and was directly related to male donors (p = 0.0008), domino transplants (p = 0.037) and donor negative cytomegalovirus (CMV) status (p = 0.022). Multivariate analysis showed that initial FS (p = 0.006) and donor intracranial hemorrhage as a cause of death (p = 0.042) were inversely related to MLDL whereas donor male sex (p = 0.003) and prednisolone treatment throughout the first year (p = 0.012) were directly related. Thus, left ventricular systolic dysfunction early after heart transplantation was associated with subsequent development of CAV.