A comparison of transcatheter aortic valve implantation and surgical aortic valve replacement in 1,141 patients with severe symptomatic aortic stenosis and less than high risk.

OBJECTIVES: To assess outcomes for patients undergoing transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement but with less than high risk. BACKGROUND: While there is abundant data for high risk patients there is insufficient data for reduced risk. METHODS: Patients undergoing TAVI or SAVR between 2007 and 2012 in Karlsruhe were considered. They were assessed by cardiac computed tomography, transoesophageal echocardiogram, and logistic EuroSCORE I (ES) and groups compared using Propensity Score Matching. RESULTS: The mean ES was 10.1±2.8 in the TAVI group (n = 419) and 5.7 ± 3.2 in the SAVR group (n = 722; P < 0.0001). Mean survival probability over 3 years was higher in patients undergoing surgery (P < 0.0001). A total of 432 patients were considered for the matched-pairs analysis based on propensity scores (216 in each group). Major vascular complications (10.6% vs. 0.0%; P < 0.0001), new pacemaker implantation (13.9% vs. 4.6%; P < 0.001) and moderate aortic insufficiency (3.2% vs. 0.5%; P = 0.03) were more frequent in patients undergoing TAVI. Major (20.8% vs. 4.2%; P < 0.0001) and life-threatening (14.5% vs. 2.3%; P < 0.0001) bleeding complications were more frequent in those undergoing surgery. Survival probability over 3 years in the propensity matched cohort was comparable between both groups (P = 0.16). CONCLUSIONS: In this large, single center, real world dataset there was no difference in mortality between patients undergoing TAVI or SAVR during a 3-year follow-up but there was a TAVI related increase in major vascular complications, new pacemaker implantation and aortic insufficiency and a SAVR related increased bleeding risk.

Long-term results of transapical versus transfemoral TAVI in a real world population of 1000 patients with severe symptomatic aortic stenosis.

BACKGROUND: Transapical transcatheter aortic valve implantation is generally perceived to be associated with increased morbidity compared with transfemoral transcatheter aortic valve implantation. We aimed to compare access-related complications and survival using propensity score matching. METHODS AND RESULTS: Prospective, single-center registry of 1000 consecutive patients undergoing transapical and transfemoral transcatheter aortic valve implantation between May 2008 and April 2012. Transapical was performed in 413 patients and transfemoral in 587 patients. Patients with transapical access were less often women and less had pulmonary hypertension. Further they had more peripheral arterial disease, coronary artery disease, carotid stenosis, and recurrent surgery and a higher logistic EuroSCORE I (24.3% ± 16.2% for transapical versus 22.2% ± 16.2% for transfemoral; P < 0.01). After building 2 propensity score-matched groups of 354 patients each with either access route (total 708 patients), baseline characteristics were comparable. In this analysis, there was no significant difference in 30 day mortality (5.9% transapical versus 8.5% transfemoral; P = 0.19), the rate of myocardial infarction (2.5% transapical versus 2.0% transfemoral; P = 0.61), stroke (2.0% transapical versus 2.3% transfemoral; P = 0.79), bleeding complications, pacemaker implantation rates, or moderate aortic insufficiency. Stage 1 renal complications were more common in transapical patients (odds ratio, 2.81; 95% confidence interval, 1.93-4.09), whereas major vascular complications were less common (odds ratio, 0.14; 95% confidence interval, 0.06-0.29). Survival probability over the long term was not statistically different (hazard ratio, 0.89; 95% confidence interval, 0.72-1.10; log-rank Test, P = 0.27). CONCLUSIONS: The data demonstrate that in an experienced multidisciplinary heart team, either access route can be performed with comparable results.

Cumulative radiation exposure and cancer risk of patients with ischemic heart diseases from diagnostic and therapeutic imaging procedures.

OBJECTIVES: To present a detailed analysis of the cumulative radiation exposure and cancer risk of patients with ischemic heart diseases (IHD) from diagnostic and therapeutic imaging. METHODS: For 1219 IHD patients, personal and examination data were retrieved from the information systems of a university hospital. For each patient, cumulative organ doses and the corresponding effective dose (E) resulting from all imaging procedures performed within 3 months before and 12 months after the date of the diagnosis were calculated. The cumulative lifetime attributable risk (LAR) of the patients to be diseased by radiation-related cancer was estimated using sex-, age-, and organ-specific risk models. RESULTS: Among the 3870 procedures performed in the IHD patients, the most frequent were radiographic examinations (52.4%) followed by coronary catheter angiographies and percutaneous cardiac interventions (41.3%), CT scans (3.9%), and perfusion SPECT (2.3%). 87% of patient exposure resulted from heart catheter procedures. E and LAR were significantly higher in males than females (average, 13.3 vs. 10.3 mSv and 0.09 vs. 0.07%, respectively). Contrary to the effective dose, the cancer risk decreased markedly for both sexes with increasing age. CONCLUSIONS: Although IHD patients were partially exposed to considerable amounts of radiation, estimated LARs were small as compared to their baseline risk to develop cancer in the remaining life.

Detection of myocardial ischemia by automated, motion-corrected, color-encoded perfusion maps compared with visual analysis of adenosine stress cardiovascular magnetic resonance imaging at 3 T: a pilot study.

PURPOSE: The purpose of this study was to compare automated, motion-corrected, color-encoded (AMC) perfusion maps with qualitative visual analysis of adenosine stress cardiovascular magnetic resonance imaging for detection of flow-limiting stenoses. MATERIALS AND METHODS: Myocardial perfusion measurements applying the standard adenosine stress imaging protocol and a saturation-recovery temporal generalized autocalibrating partially parallel acquisition (t-GRAPPA) turbo fast low angle shot (Turbo FLASH) magnetic resonance imaging sequence were performed in 25 patients using a 3.0-T MAGNETOM Skyra (Siemens Healthcare Sector, Erlangen, Germany). Perfusion studies were analyzed using AMC perfusion maps and qualitative visual analysis. Angiographically detected coronary artery (CA) stenoses greater than 75% or 50% or more with a myocardial perfusion reserve index less than 1.5 were considered as hemodynamically relevant. Diagnostic performance and time requirement for both methods were compared. Interobserver and intraobserver reliability were also assessed. RESULTS: A total of 29 CA stenoses were included in the analysis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detection of ischemia on a per-patient basis were comparable using the AMC perfusion maps compared to visual analysis. On a per-CA territory basis, the attribution of an ischemia to the respective vessel was facilitated using the AMC perfusion maps. Interobserver and intraobserver reliability were better for the AMC perfusion maps (concordance correlation coefficient, 0.94 and 0.93, respectively) compared to visual analysis (concordance correlation coefficient, 0.73 and 0.79, respectively). In addition, in comparison to visual analysis, the AMC perfusion maps were able to significantly reduce analysis time from 7.7 (3.1) to 3.2 (1.9) minutes (P < 0.0001). CONCLUSIONS: The AMC perfusion maps yielded a diagnostic performance on a per-patient and on a per-CA territory basis comparable with the visual analysis. Furthermore, this approach demonstrated higher interobserver and intraobserver reliability as well as a better time efficiency when compared to visual analysis.

The relationship between the severity of coronary artery disease and epicardial adipose tissue depends on the left ventricular function.

BACKGROUND: Epicardial adipose tissue (EAT) is an active metabolic and endocrine organ. Previous studies focusing mainly on patients with preserved left ventricular function (LVF) could show a correlation between increased amounts of EAT and the extent and activity of coronary artery disease (CAD). However, to date, there are no data available about the relationship between EAT and the severity of CAD with respect to the whole spectrum of LVF impairment. Therefore, we evaluated this relationship in patients with CAD. METHODS: 250 patients with CAD and 50 healthy controls underwent CMR examination to assess EAT. The severity of CAD was defined using the angiographic Gensini score (GSS). RESULTS: The GSS ranged from 2-364. Linear regression analysis revealed a significant correlation between EAT and GSS (r = 0.177, p = 0.01). Patients with mild (GSS≤10) and moderate CAD (GSS>10-≤40) showed comparable EAT to healthy controls. However, in patients with severe CAD (GSS>40) EAT was significantly reduced (p<0.0001) compared to healthy controls. Interestingly, patients with the same GSS revealed different EAT depending on the left ventricular function (LVF). Patients with preserved LVF (LVF≥50%) showed more EAT mass compared to those with reduced LVF (LVF<50%) regardless of the GSS. In patients with preserved LVF and mild CAD, EAT was comparable to healthy controls (61.8±19.4 g vs. 62.9±14.4 g, p = 0.8). In patients with moderate CAD, EAT rose significantly to 83.1±24.9 g (p = 0.01) and started to decline to 66.4±23.6 g in patients with severe CAD (p = 0.03). Contrary, in CAD patients with reduced LVF, EAT was already significantly reduced in patients with mild CAD as compared to healthy controls (p = 0.001) and showed a stepwise decline with increasing CAD severity. CONCLUSION: The relationship between EAT and the severity of CAD depends on LVF. These findings emphasize the multifactorial interaction between EAT and the severity of CAD.

Incidence and severity of coronary artery disease in patients with atrial fibrillation undergoing first-time coronary angiography.

BACKGROUND: In standard reference sources, the incidence of coronary artery disease (CAD) in patients with atrial fibrillation (AF) ranged between 24 and 46.5%. Since then, the incidence of cardiovascular risk factors (CRF) has increased and modern treatment strategies ("pill in the pocket") are only applicable to patients without structural heart disease. The aim of this study was to investigate the incidence and severity of CAD in patients with AF. METHODS: From January 2005 until December 2009, we included 261 consecutive patients admitted to hospital with paroxysmal, persistent or permanent AF in this prospective study. All patients underwent coronary angiography and the Framingham risk score (FRS) was calculated. Patients with previously diagnosed or previously excluded CAD were excluded. RESULTS: The overall incidence of CAD in patients presenting with AF was 34%; in patients >70 years, the incidence of CAD was 41%. The incidence of patients undergoing a percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) was 21%. Patients with CAD were older (73±8 years vs 68±10 years, p = 0.001), had significantly more frequent hypercholesterolemia (60% vs 30%, p<0.001), were more frequent smokers (26% vs 13%, p = 0.017) and suffered from angina more often (37% vs 2%, p<0.001). There was a significant linear trend among the FRS categories in percentage and the prevalence of CAD and PCI/CABG (p<0.0001). CONCLUSIONS: The overall incidence of CAD in patients presenting with AF was relatively high at 34%; the incidence of PCI/CABG was 21%. Based upon increasing CRF in the western world, we recommend a careful investigation respecting the FRS to either definitely exclude or establish an early diagnosis of CAD--which could contribute to an early and safe therapeutic strategy considering type Ic antiarrhythmics and oral anticoagulation.

Effect of atorvastatin on cellular adhesion molecules on leukocytes in patients with normocholesterolemic coronary artery disease.

BACKGROUND: Expression of cellular adhesion molecules on leukocytes plays a key role in coronary artery disease (CAD). The aim of the present study was to assess whether atorvastatin therapy has an impact on the expression of cellular adhesion molecules on leukocytes in patients with normocholesterolemic CAD. PATIENTS AND METHODS: In 54 patients with CAD and atorvastatin treatment and 54 CAD patients without atorvastatin therapy, expression of CD40L, CD11a, CD11b, CD54, CD62L and CD41 on leukocytes was measured using flow cytometry. All patients were normocholesterolemic. RESULTS: Atorvastatin treatment led to a significantly lower expression of CD40L, CD11b and CD54 on monocytes (p<0.05) and neutrophils (p<0.05). Expression of CD11a was significantly lower on monocytes (p<0.05) in atorvastatin-treated patients. CONCLUSION: The present results indicate that atorvastatin apparently improves chronic inflammation and may have a beneficial effect on hemostasis by reducing the expression of cellular adhesion molecules on leukocytes.

Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction.

BACKGROUND: The aim of this study was to investigate the clinical outcome 2 years after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Using a double-blind, placebo-controlled, multicenter trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone marrow-derived progenitor cells (BMC) or placebo medium into the infarct artery 3 to 7 days after successful infarct reperfusion therapy. At 2 years, the cumulative end point of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (hazard ratio, 0.58; 95% CI, 0.36 to 0.94; P=0.025). Likewise, the combined end point death and recurrence of myocardial infarction and rehospitalization for heart failure, reflecting progression toward heart failure, was significantly reduced in the BMC group (hazard ratio, 0.26; 95% CI, 0.085 to 0.77; P=0.015). Intracoronary administration of BMC remained a significant predictor of a favorable clinical outcome by Cox regression analysis when adjusted for classical predictors of poor outcome after AMI. There was no evidence of increased restenosis or atherosclerotic disease progression after BMC therapy nor any evidence of increased ventricular arrhythmias or neoplasms. In addition, regional left ventricular contractility of infarcted segments, as assessed by MRI in a subgroup of patients at 2-year follow-up, was significantly higher in the BMC group compared with the placebo group (P<0.001). CONCLUSIONS: Intracoronary administration of BMC is associated with a significant reduction of the occurrence of major adverse cardiovascular events maintained for 2 years after AMI. Moreover, functional improvements after BMC therapy may persist for at least 2 years. Larger studies focusing on clinical event rates are warranted to confirm the effects of BMC administration on mortality and progression of heart failure in patients with AMIs. Clinical Trial Registration- clinicaltrials.gov. Identifier: NCT00279175.

Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial.

AIMS: To investigate the clinical outcome after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Using a double-blind, placebo-controlled multicentre trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone-marrow-derived progenitor cells (BMCs) or placebo medium into the infarct artery 3-7 days after successful infarct reperfusion therapy. At 12 months, the pre-specified cumulative endpoint of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (P=0.009). Likewise, the combined endpoint death, recurrence of myocardial infarction, and rehospitalization for heart failure was significantly (P=0.006) reduced in patients receiving intracoronary BMC administration. Intracoronary administration of BMC remained a significant predictor of a favourable clinical outcome by Cox regression analysis, adjusting for classical predictors of poor outcome after AMI. CONCLUSION: Intracoronary administration of BMCs is associated with a significant reduction of the occurrence of major adverse cardiovascular events after AMI. Large-scale studies are warranted to confirm the effects of BMC administration on mortality and morbidity in patients with AMIs.

Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction.

BACKGROUND: Pilot trials suggest that the intracoronary administration of autologous progenitor cells may improve left ventricular function after acute myocardial infarction. METHODS: In a multicenter trial, we randomly assigned 204 patients with acute myocardial infarction to receive an intracoronary infusion of progenitor cells derived from bone marrow (BMC) or placebo medium into the infarct artery 3 to 7 days after successful reperfusion therapy. RESULTS: At 4 months, the absolute improvement in the global left ventricular ejection fraction (LVEF) was significantly greater in the BMC group than in the placebo group (mean [+/-SD] increase, 5.5+/-7.3% vs. 3.0+/-6.5%; P=0.01). Patients with a baseline LVEF at or below the median value of 48.9% derived the most benefit (absolute improvement in LVEF, 5.0%; 95% confidence interval, 2.0 to 8.1). At 1 year, intracoronary infusion of BMC was associated with a reduction in the prespecified combined clinical end point of death, recurrence of myocardial infarction, and any revascularization procedure (P=0.01). CONCLUSIONS: Intracoronary administration of BMC is associated with improved recovery of left ventricular contractile function in patients with acute myocardial infarction. Large-scale studies are warranted to examine the potential effects of progenitor-cell administration on morbidity and mortality.

Coagulation activation and expression of CD40 ligand on platelets upon in vitro lipopolysaccharide-challenge in patients with unstable angina.

BACKGROUND: Elevated markers of inflammation and coagulation are found in patients with coronary heart disease. A role of inflammatory stimulation on coagulation time and expression of CD40 ligand on platelets in acute coronary syndromes has not been described yet. METHODS AND RESULTS: Whole blood samples of 9 patients with coronary heart disease and stable angina, 10 patients with unstable angina, 7 patients with acute myocardial infarction and 7 patients without coronary heart disease were incubated with lipopolysaccharide (LPS). Coagulation time was measured in arterial and coronary blood with the ReoRox(R), a viscometric whole blood coagulometer. CD40L and CD62P expression on platelets and platelet-monocyte aggregates were measured by flow cytometry. Without LPS, patients with unstable angina showed a significantly decreased coagulation time in arterial and coronary blood compared to patients without coronary heart disease. After incubation with LPS, in patients with unstable angina, a significantly decreased coagulation time in coronary blood was observed compared to patients with stable angina or patients without coronary heart disease. CD40L expression on platelets in patients with unstable angina was significantly higher in arterial and coronary blood compared to patients with stable angina. No significant differences between the patient groups were observed concerning CD62P expression on platelets, tissue factor binding on monocytes, platelet-monocyte aggregates and plasma levels of platelet factor 4. CONCLUSIONS: Patients with unstable angina show an enhanced coagulation activation and an upregulation of CD40L on platelets. This may be of importance in the understanding of coronary plaque rupture and formation of coronary thrombosis.

Side branch occlusion after coronary stent implantation in patients presenting with ST-elevation myocardial infarction: clinical impact and angiographic predictors.

BACKGROUND: The aim of this study was to assess the incidence and clinical outcome of the occlusion of major (> 1 mm) side branches following coronary stenting in patients undergoing percutaneous coronary intervention for acute ST-elevation myocardial infarction (STEMI). METHODS: Among 276 consecutive patients presenting with STEMI, we found 80 patients (29%) with 101 stent-covered side branches. Clinical data and quantitative angiographic analysis were evaluated. Angiographic follow-up was available in 56 (70%) patients, and clinical follow-up could be completed in all patients. RESULTS: Acute side branch occlusion after stent implantation (SBO) was observed in 10 (12.5%) patients involving 11 (10.9%) side branches. Predictors for SBO were: (1) reference side branch diameter at baseline < or = 1.4 mm; (2) ostial side branch stenosis > 50%; and (3) minimal side branch diameter at baseline < or = 0.6 mm. During hospitalization, in the SBO group, 2 patients died in cardiogenic shock and 1 underwent bypass surgery; no events were causally related to SBO. During long-term follow-up, 1 patient with SBO developed repeat MI as opposed to 7 patients in the non-SBO group who developed major adverse cardiac events (1 death, 6 repeat revascularizations). CONCLUSIONS: The presence of a side branch originating from the target lesion in patients undergoing coronary stenting for acute STEMI is a frequent observation (29%) and is associated with a low incidence of side branch occlusion. Major predictors for SBO are the side branch size and the presence of an ostial side branch stenosis.

[Chlamydia pneumoniae--a new risk factor for calcific aortic stenosis?]. / Chlamydia pneumoniae--ein neuer Risikofaktor bei kalzifizierender Aortenklappenstenose?

BACKGROUND: Nonrheumatic, calcific aortic stenosis is the main heart valve disease and the main cause of heart valve replacement in the elderly. Recent studies suggest that it is based on a chronic inflammatory process. The pathogenetic mechanisms, however, are unclear. METHODS: A MEDLINE search was conducted for the phrases "chlamydia pneumoniae" and "aortic valve", and all articles published between 1966 and May 2004 were evaluated. Data presented as letter or congress abstract was also included. RESULTS: Clinical and histopathologic studies demonstrate an association of calcific aortic stenosis and cardiovascular risk factors similar to atherosclerosis. As for atherosclerosis, infection with Chlamydia (C.) pneumoniae is also discussed as a further potential risk factor for calcific aortic stenosis. Previous seroepidemiologic and pathologic studies using various detection methods yielded heterogeneous results. CONCLUSION: Thus, data suggesting a pathogenetic association of C. pneumoniae and calcific aortic stenosis should be interpreted cautiously.

Utilization of eptifibatide for treatment of severe dissections as a bail-out procedure.

BACKGROUND: It has been shown in several large trials that the inhibition of glycoprotein (GP) IIb/IIIa receptors of platelets can reduce the rate of ischemic complications following percutaneous transluminal coronary angioplasty (PTCA). We sought to determine the efficacy of eptifibatide in patients with severe dissections or threatened vessel closure after PTCA in small coronary arteries (< 2.5 mm). METHODS: Eptifibatide was used in 51 patients after conventional balloon angioplasty complicated by severe dissections with or without threatened vessel occlusion. Eptifibatide was administered as a double-bolus of 180 microg/kg bodyweight, followed by a continuous infusion at a dosage of 2.0 microg/kg min over a time period of 20 h. In this situation, the implantation of a coronary stent was avoided if a prompt antegrade flow of contrast dye could be maintained. RESULTS: Using the GP IIb/IIIa antagonist eptifibatide, it was possible to increase or to maintain antegrade blood flow in 28 (55%) patients. In 45% of the patient population, however, repeat PTCA was needed, and in four patients (7.8%) an intracoronary stent had to be implanted. During hospitalization three (6%) patients underwent target lesion revascularization (two Re-PTCAs, one coronary bypass graft operation). There were no myocardial infarctions and there was no intrahospital death. The cumulative event rate including acute and long term events was 25%. CONCLUSIONS: The findings of our study indicate that eptifibatide is able to prevent vessel occlusion after PTCA complicated by severe dissections with or without threatened vessel occlusion associated with a low-in-hospital complication rate.