Culotte stenting vs. TAP stenting for treatment of de-novo coronary bifurcation lesions with the need for side-branch stenting: the Bifurcations Bad Krozingen (BBK) II angiographic trial.

AIMS: In percutaneous coronary intervention for de-novo coronary bifurcation lesions, the optimal technique for provisional side-branch stenting is still a matter of debate. We tested whether in this setting culotte stenting reduces the incidence of restenosis as compared with T-and-protrusion (TAP) stenting. METHODS AND RESULTS: This trial included 300 patients with a coronary bifurcation lesion requiring a side-branch stent. Patients were randomly assigned to culotte stenting or TAP stenting using drug-eluting stents in a 1:1 fashion. Primary endpoint was maximal per cent diameter stenosis of the bifurcation lesion at 9-month angiographic follow-up. As clinical endpoints we assessed target lesion re-intervention (TLR) and target lesion failure (composite of cardiac death, target vessel myocardial infarction, and TLR).Angiographic follow-up was available in 91% of the patients. After culotte stenting, the maximum per cent diameter stenosis in the treated bifurcation lesion was 21 ± 20% as compared with 27 ± 25% after TAP stenting (P = 0.038). The respective corresponding binary restenosis rates were 6.5 and 17% (P = 0.006). The 1-year incidence of TLR was 6.0% after culotte stenting vs. 12.0% after T-stenting (P = 0.069). Target lesion failure occurred in 6.7% of the culotte group and in 12.0% of the TAP group (P = 0.11). Only one patient of the culotte group incurred a definite stent thrombosis during 1-year follow-up. CONCLUSIONS: Compared with the TAP stenting, culotte stenting was associated with a significantly lower incidence of angiographic restenosis.

Discordant cardiac biomarker levels independently predict outcome in ST-segment elevation myocardial infarction.

AIMS: To investigate the prognostic relevance of elevated Troponin T (cTnT) levels in patients with ST-segment elevation myocardial infarction (STEMI) without significant creatine kinase (CK) elevation on admission. METHODS AND RESULTS: From January 1, 2002 to December 31, 2006 patients with STEMI without significant CK elevation (<2-fold) on admission treated with percutaneous coronary intervention (PCI) were included and stratified according to cTnT plasma levels. Univariate and multivariate regression analyses were used to find independent predictors for mortality. During the 5-year period 514 patients with STEMI and normal CK plasma levels were included. 308 (59.9 %) patients had cTnT levels <0.1 µg/l and 206 (40.1 %) patients had cTnT levels ≥0.1 µg/l. Multivariate logistic regression analysis identified cTnT levels ≥0.1 µg/l and 3-vessel disease as positive, and hemoglobin levels as negative independent predictors for long-term mortality. Discordantly elevated cTnT plasma levels independently predicted higher mortality rates in the first year (HR 3.9, 95 % CI 1.7-9.1, p = 0.002) and during 5 years (HR 2.3, 95 % CI 1.4-3.9, p = 0.002) after PCI for STEMI. CONCLUSIONS: Discordant elevation of cTnT in the presence of normal CK plasma levels on admission is associated with increased mortality in STEMI patients undergoing primary PCI. This may be due to preceding microembolization.

The porcine valve type predicts obstructive thrombosis beyond the first three postoperative months in bioprostheses in the aortic position.

BACKGROUND: Obstructive thrombosis of bioprosthetic valves is considered rare but may have dramatic consequences for the individual patient including repeat valve replacement, thrombolysis, or long-term anticoagulation. Whether the risk of obstructive thrombosis is dependent on the type of bioprosthesis (porcine versus bovine pericardial) is uncertain. METHODS AND RESULTS: Between 2007 and 2012 a total of 1751 patients received a single stented bioprosthesis in the aortic valve position, 749 (43%) were porcine and 1002 (57%) bovine. During a mean follow-up of 3.4±1.9years, obstructive thrombosis (identified by an increase in mean pressure gradient≥20mm Hg or a decrease in velocity ratio≥0.05 and confirmed by either ECG-gated computer tomography, a return to baseline of stenosis parameters under treatment with a vitamin K antagonist, or histology in case of reoperation) was diagnosed in 17 patients with a porcine (2.3%) and none with a bovine valve (p<0.001). The cumulative probability of developing an obstructive thrombosis was significantly higher in patients with a porcine valve (p<0.001 log-rank test). Adjusting for differences in baseline variables and stratification by the estimated propensity score showed that strata with a high probability of receiving a bovine valve had the highest number of obstructive thrombosis in porcine valves. These findings were further confirmed in a Poisson model and a competing risk model including all-cause mortality. Treatment of obstructive thrombosis with a vitamin K antagonist was safe and effective in 15/17 patients. CONCLUSION: The porcine valve type is an independent predictor of obstructive thrombosis in bioprostheses in the aortic position.

Pulmonary capillary wedge pressure during exercise and long-term mortality in patients with suspected heart failure with preserved ejection fraction.

AIMS: In patients with suspected heart failure with preserved ejection fraction (HFpEF), invasive exercise testing may be considered when measurements at rest are inconclusive. However, the prognostic impact of invasive exercise testing is uncertain, so far. METHODS AND RESULTS: We retrospectively analysed mortality in 355 patients [mean age 61.2 ± 11.3 years, 235 (66.2%) women] with unexplained dyspnoea and suspected HFpEF. During an invasive haemodynamic stress test pulmonary capillary wedge pressure (PCWP) at rest and the PCWP response to exercise, expressed as the ratio of PCWP at peak exercise to workload normalized to body weight [PCWL (mmHg/W/kg)], were recorded. Both PCWP at rest and PCWL were significant and independent predictors of long-term mortality. Adding PCWL to PCWP at rest improved reclassification of patients into survivors or non-survivors with a net reclassification improvement (NRI) of 0.56 (95% CI: 0.29-0.83; P < 0.001). Ten-year mortality was 6.6% in subjects with low PCWP at rest (≤ 12 mmHg) and low PCWL (≤ 25.5 mmHg/W/kg); 28.2% in patients with low PCWP and high PCWL and 35.2% in those with high PCWP and high PCWL. Compared with patients with low PCWP and low PCWL, the adjusted hazard ratio for mortality was 2.37 (95% CI: 1.09-5.17; P = 0.029) for the low-PCWP/high-PCWL group and 4.75 (95% CI: 1.90-11.84; P < 0.001) for patients with high PCWP/high PCWL. CONCLUSION: In patients with suspected HFpEF, invasive exercise testing substantially improves prediction of long-term mortality. An excessive rise of PCWP during exercise despite normal PCWP at rest is associated with increased mortality and may be considered as early HFpEF.

Indexing aortic valve area by body surface area increases the prevalence of severe aortic stenosis.

BACKGROUND: To account for differences in body size in patients with aortic stenosis, aortic valve area (AVA) is divided by body surface area (BSA) to calculate indexed AVA (AVAindex). Cut-off values for severe stenosis are <1.0 cm2 for AVA and <0.6 cm2/m2 for AVAindex. OBJECTIVE: To investigate the influence of indexation on the prevalence of severe aortic stenosis and on the predictive accuracy regarding clinical outcome. METHODS: Echocardiographic and anthropometric data from a retrospective cohort of 2843 patients with aortic stenosis (jet velocity >2.5 m/s) and from 1525 patients prospectively followed in the simvastatin and ezetimibe in aortic stenosis (SEAS) trial were analysed. RESULTS: The prevalence of severe stenosis increased with the AVAindex criterion compared to AVA from 71% to 80% in the retrospective cohort, and from 29% to 44% in SEAS (both p<0.001). Overall, the predictive accuracy for aortic valve events was virtually identical for AVA and AVAindex in the SEAS population (mean follow-up of 46 months; area under the receiver operating characteristic curve: 0.67 (95% CI 0.64 to 0.70) vs. 0.68 (CI 0.65 to 0.71) (NS). However, 213 patients additionally categorised as severe by AVAindex experienced significantly less valve related events than those fulfilling only the AVA criterion (p<0.001). CONCLUSIONS: Indexing AVA by BSA (AVAindex) significantly increases the prevalence of patients with criteria for severe stenosis by including patients with a milder degree of the disease without improving the predictive accuracy for aortic valve related events.

Enhanced efficiency of a novel porous tip irrigated RF ablation catheter for pulmonary vein isolation.

INTRODUCTION: Irrigated tip radiofrequency (RF) catheter ablation is the most frequently used technology for pulmonary vein isolation (PVI). The purpose of this study was to compare the efficiency and the safety of 2 different open irrigated tip RF ablation catheters. METHODS AND RESULTS: A total of 160 patients with symptomatic AF (29% persistent, 68% male, 61 ± 10 years) were randomized to circumferential PVI using 2 different irrigated tip catheters: (1) the novel Thermocool SF(®) with a porous tip (56 holes) or (2) the Thermocool(®) catheter with 6 irrigation holes at the distal tip in both power- and temperature-controlled modes. PVI procedural time and RF duration were significantly shorter with SF(®) versus Thermocool(®) catheter: 104.5 versus 114 minutes (P = 0.023) and 35.4 minutes versus 39.9 minutes (P < 0.001), respectively. Similarly, the total fluoroscopy time and dose were shorter with SF(®) versus. Thermocool(®) catheter: 21 minutes versus 24 minutes (P = 0.02) and 1014.5 µGy*m(2) versus 1377 µGy*m(2) (P < 0.0001), respectively. Irrigation volume was lower with SF(®): 600 mL versus 1100 mL, (P < 0.0001) and the rates of complications were not significantly different (0.6% vs 0.49%, P = 0.66). At 20.5 ± 7.5 months follow-up, there were no significant differences with regard to arrhythmia freedom between SF(®) (59.2%) and TC® groups (59.3%), (P = 0.61). CONCLUSIONS: Using the novel irrigated tip SF catheter, PVI is achieved within a shorter ablation and procedural durations. The underlying mechanisms and potential differences in RF lesion size remain to be elucidated.

Role of euroSCORE II in predicting long-term outcome after percutaneous catheter intervention for coronary triple vessel disease or left main stenosis.

OBJECTIVES: The SYNTAX score (Ssc) assessing the complexity of coronary anatomy predicts survival after percutaneous coronary intervention (PCI). We tested the hypothesis that the newly developed euroSCORE II (eSC2) can improve the prediction of outcome after complex PCI by the Ssc. METHODS AND RESULTS: Our study comprised 1262 consecutive patients with triple vessel disease or left main stenosis, who were contacted 3 years after elective PCI with drug-eluting stents. We calculated eSC2, Ssc, logistic euroSCORE, and ACEF score. Prediction of 3-year all-cause mortality by these scores was assessed by Cox proportional hazard models. Models were compared by the Hosmer-Lemeshow test for calibration (HL), the C-statistics (AUC) for discrimination and by net reclassification indices (NRI). eSC2 and Ssc were significant predictors of 3-year mortality (unadjusted hazard ratios [95%-confidence limits], 1.050 [1.033-1.067], 1.180 [1.146-1.215], respectively, P<0.001). The predictive value of eSC2 was improved by logarithmic transformation. Adding eSC2 to the model with Ssc improved calibration (HL 7.4 vs. 11.1) and discrimination (increase in AUC [95%-confidence limits] 0.12 [0.07 to 0.17]) and yielded a significant NRI of 0.38 (95%-confidence limits 0.28 to 0.47). The absolute difference in 3-year mortality between strata of Ssc (≤22, >22-32, >32) was smaller with eSC2<1% (1.4%, 3.4%, 9.7%, respectively), than with eSC2>1.6% (11.2%, 20.2%, 30.6%, respectively). The predictive ability of eSC2 was similar to that of the other clinical scores. CONCLUSIONS: eSC2 predicts 3-year mortality after complex PCI and modifies the impact of angiographic complexity on outcome.

Transcriptome analysis in patients with progressive coronary artery disease: identification of differential gene expression in peripheral blood.

Inflammation as a systemic process plays a central role in atherosclerotic plaque progression (PP). Here we investigated other systemic correlates of PP by global gene expression profiling (GEP) in peripheral blood. From a database of 45,727 coronary angiograms, we identified two patient groups with good risk factor control, but different clinical evolution: First, 16 patients had significant PP leading to repeated coronary interventions, and second, 16 patients had angiographically documented stable courses. GEP revealed 93 differentially expressed genes, of which 23 have unknown function. Among the remaining 70 genes, 10 were associated with progenitor and pluripotent cells, but only three genes with atherosclerosis. We developed a risk prediction gene signature by a multivariable statistical model integrating comprehensive laboratory and clinical patient data. This signature identified PP with high sensitivity and specificity for new patients, as estimated by resampling techniques. GEP results were validated by qPCR for ANK2 and GSTT1.

Usefulness of phenprocoumon for the treatment of obstructing thrombus in bioprostheses in the aortic valve position.

Bioprosthetic valve replacement is the treatment of choice in older patients with symptomatic severe aortic valve disease. Thrombosis of bioprosthetic valves has been considered a rare complication; however, in the presence of valvular obstruction, therapeutic consequences for the individual patient may be dramatic including repeat valve replacement or thrombolysis. We therefore evaluated oral anticoagulation with phenprocoumon as an alternative treatment for obstructive thrombosis of bioprosthetic valves. Six of 470 patients who had received a single stented bioprosthetic aortic valve from January 2007 through December 2008 at our hospital presented with obstructive bioprosthetic valve thrombosis within 14 months postoperatively. All 6 patients (1% of study population) had received a porcine valve (p = 0.1 vs pericardial), were hemodynamically stable, were in sinus rhythm, and were taking acetylsalicylic acid 100 mg/day. Echocardiography showed an increase in mean pressure gradient early postoperatively from 23.3 ± 4 to 57.0 ± 10 mm Hg (p <0.001). Five patients were started on phenprocoumon and followed for 114 ± 54 days, when mean pressure gradient had returned to 23.5 ± 6 mm Hg. No adverse events were observed during that period. One patient presenting with dyspnea and fever underwent emergency repeat valve replacement for suspected endocarditis, with histology showing long-term thrombosis of the explanted valve. In conclusion, oral anticoagulation with phenprocoumon represents a safe and effective treatment in clinically stable patients with obstructive thrombosis of bioprosthetic aortic valves, thus obviating repeat valve surgery or thrombolysis.

Inconsistent grading of aortic valve stenosis by current guidelines: haemodynamic studies in patients with apparently normal left ventricular function.

BACKGROUND: On echocardiography approximately one-third of patients with severe aortic valve stenosis based on aortic valve area (AVA<1.0 cm(2)) demonstrate a non-severe mean pressure gradient (DeltaPm; < or =40 mm Hg) despite apparently normal left ventricular function. It has been suggested that inconsistent echocardiographic grading may be due to 'paradoxical' low stroke volume. However, the correct echocardiographic assessment of stroke volume hinges on the often problematic measurement of the left ventricular outflow tract (LVOT) diameter. OBJECTIVE: To investigate whether inconsistent grading and reduced stroke volume persist when the quantification of aortic valve stenosis is based on cardiac catheterisation which is independent of LVOT measurements. METHODS AND RESULTS: 333 consecutive patients underwent cardiac catheterisation within 30 days after their index echocardiography showing an AVA < or =2 cm(2) and shortening fraction > or =30%. On invasive testing 85 patients (26%) demonstrated inconsistent (AVA<1 cm(2) and DeltaPm< or =40 mm Hg) and 153 (46%) consistent grading (AVA<1 cm(2) and DeltaPm>40 mm Hg) with the remainder (28%) presenting with a calculated AVA> or =1 cm(2). Inconsistently graded patients were older (71 vs 67 years, p<0.006) with no differences in sex or body surface area between groups. Stroke volume and stroke volume index were significantly lower in inconsistently graded patients (63+/-14 vs 73+/-18 ml and 35+/-7 vs 39+/-7 ml/m(2), respectively, both p<0.001). However, 41/85 (48%) of inconsistently graded patients had a normal stroke volume index >35 ml/m(2). CONCLUSION: In the framework of current guidelines inconsistent grading of aortic valve stenosis is common, extends to cardiac catheterisation and is only partially explained by low stroke volume despite apparently normal left ventricular systolic function.

Long-term outcome of percutaneous catheter intervention for de novo coronary bifurcation lesions with drug-eluting stents or bare-metal stents.

BACKGROUND: The purpose of this study was to assess the long-term risks and benefits of drug-eluting stents (DESs) compared with bare-metal stents (BMSs) for treatment of coronary bifurcation lesions. METHODS: Our registry comprised 1,038 patients treated for coronary bifurcation lesion according to the provisional T-stenting strategy who were followed up for 3 years. RESULTS: Target lesion revascularization rates were 24.3% for BMSs (n = 337), 15.6% for sirolimus-eluting stents (SESs, n = 422), and 17.3% for paclitaxel-eluting stents (PESs, n = 279) (P = .003 BMSs vs DESs, P = .54 SESs vs PESs). The respective incidences were 11.4%, 9.5%, and 14.8% (P = .65, P = .13) for death and myocardial infarction and 9.9%, 6.5%, and 10.6% (P = .72, P = .19) for death. Propensity score adjusted hazard ratios (95% CI) for DESs versus BMSs were 0.49 (0.35-0.68, P < .001) for target lesion revascularization, 0.94 (0.64-1.40, P = .078) for death and myocardial infarction, and 0.85 (0.55-1.32, P = .47) for death. We did not find any significant differences between SESs and PESs, except for an increased risk of death after PESs compared with SESs (but not BMSs) in the subgroup receiving a side-branch stent (adjusted hazard ratio 2.45, 95% CI 1.05-5.73, P = .035). CONCLUSIONS: Compared with BMSs, both PESs and SESs substantially reduced the long-term need for repeated revascularization but did not increase the risk of death and myocardial infarction.

Randomized trial on routine vs. provisional T-stenting in the treatment of de novo coronary bifurcation lesions.

AIMS: We investigated whether routine T-stenting reduces restenosis of the side branch as compared with provisional T-stenting in patients with de novo coronary bifurcation lesions. METHODS AND RESULTS: Our randomized study assigned 101 patients with a coronary bifurcation lesion to routine T-stenting with sirolimus-eluting stents (SES) in both branches and 101 patients to provisional T-stenting with SES placement in the main branch followed by kissing-balloon angioplasty and provisional SES placement in the side branch only for inadequate results. Primary endpoint was per cent diameter stenosis of the side branch at 9 month angiographic follow-up. Angiographic follow-up in 192 (95%) patients revealed a per cent stenosis of the side branch of 23.0 +/- 20.2% after provisional T-stenting (19% with side-branch stent) and of 27.7 +/- 24.8% (P = 0.15) after routine T-stenting (98.2% with side-branch stent). The corresponding binary restenosis rates were 9.4 and 12.5% (P = 0.32), prompting re-intervention in 5.0 and 7.9% (P = 0.39), respectively. In the main branch, binary restenosis rates were 7.3% after provisional and 3.1% after routine T-stenting (P = 0.17). The overall 1 year incidence of target lesion re-intervention was 10.9% after provisional and 8.9% after routine T-stenting (P = 0.64). CONCLUSIONS: Routine T-stenting with SES did not improve the angiographic outcome of percutaneous coronary intervention of coronary bifurcation lesions as compared with stenting of the main branch followed by kissing-balloon angioplasty and provisional side-branch stenting.

Inconsistencies of echocardiographic criteria for the grading of aortic valve stenosis.

AIM: The present study tests the consistency of echocardiographic criteria for the grading of aortic valve stenosis. METHODS AND RESULTS: Current guidelines/recommendations define severe stenosis as an aortic valve area (AVA) <1 cm2 (or <0.6 cm2 adjusted for body surface area), mean pressure gradient (DeltaPm) >40 mmHg, or peak flow velocity (Vmax) >4 m/s. We tested the consistency of the three criteria for the grading of aortic valve stenosis in 3483 echocardiography studies performed in 2427 patients with normal left ventricular (LV) systolic function and a calculated AVA of < or =2 cm2. We calculated curve fits for the relationship between AVA and DeltaPm using the Gorlin equation and between AVA and Vmax based on the continuity equation for our study population. An AVA of 1.0 cm2 correlated to a DeltaPm of 21 mmHg and a Vmax of 3.3 m/s. Conversely, a DeltaPm of 40 mmHg corresponds to an AVA of 0.75 cm2 and a Vmax of 4.0 m/s to an AVA of 0.82 cm2. Consequently, severe stenosis was diagnosed in 69% of patients based on AVA, 45% on Vmax, and 40% on DeltaPm. Stroke volume was lower in inconsistently graded patients (65 +/- 11 mL vs. consistently graded: 70 +/- 14 mL, P < 0.001). CONCLUSION: The criteria for the grading of aortic stenosis are inconsistent in patients with normal systolic LV function. On the basis of AVA, a higher proportion of patients is classified as having severe aortic valve stenosis compared with mean pressure gradient and peak flow velocity. Discrepant grading in these patients may be partly due to reduced stroke volume.

Randomized evaluation of the effects of filter-based distal protection on myocardial perfusion and infarct size after primary percutaneous catheter intervention in myocardial infarction with and without ST-segment elevation.

BACKGROUND: In acute myocardial infarction, distal embolization of debris during primary percutaneous catheter intervention may curtail microvascular reperfusion of the infarct region. Our randomized trial investigated whether distal protection with a filter device can improve microvascular perfusion and reduce infarct size after primary percutaneous catheter intervention. METHODS AND RESULTS: We enrolled 200 patients who had angina within 48 hours after onset of pain plus at least 1 of 3 additional criteria: ST-segment elevation, elevated myocardial marker proteins, and angiographic evidence of thrombotic occlusion. Among the patients included (83% men; mean age, 62+/-12 years), 100 were randomly assigned to the filter-wire group and 100 to the control group. The primary end point was the maximal adenosine-induced Doppler flow velocity in the recanalized infarct artery; the secondary end point was infarct size estimated by the volume of delayed enhancement on nuclear MRI. ST-segment elevation myocardial infarction was present in 68.5% of the patients; the median time from onset of pain was 6.9 hours. In the filter-wire group, maximal adenosine-induced flow velocity was 34+/-17 compared with 36+/-20 cm/s in the control group (P=0.46). Infarct sizes, assessed in 82 patients in the filter-wire group and 78 patients in the control group, were 11.8+/-9.3% of the left ventricular mass in the filter-wire group and 10.4+/-9.4% in the control group (P=0.33). Thirty-day mortality was 2% in filter-wire group and 3% in the control group. CONCLUSIONS: The filter wire as an adjunct to primary percutaneous catheter intervention in myocardial infarction with and without ST-segment elevation did not improve reperfusion or reduce infarct size.