Impact of the Right Ventricular Lead Position on Clinical End Points in CRT Recipients--A Subanalysis of the Multicenter Randomized SPICE Trial.

BACKGROUND: The impact of right ventricular (RV) lead location on clinical end points in patients undergoing cardiac resynchronization therapy (CRT) is unclear. We evaluated the impact of different RV lead locations on clinical outcome in CRT patients enrolled in the Septal Positioning of ventricular implantable cardioverter-defibrillator (ICD) Electrodes (SPICE) trial, which randomized recipients of implantable cardioverter defibrillators to apical versus midseptal RV lead positioning. METHODS: Ninety-eight CRT recipients were included in the multicenter SPICE trial and followed for 12 months: Fifty-three patients were randomized to receive an apical (A) and 45 to receive a midseptal (S) lead position. We compared echocardiographical and electrocardiographical parameters and outcome. RESULTS: Echocardiographic response with respect to improvement of left ventricular ejection fraction (A: +15.8 ± 14.6%, S: +9.7 ± 12.6%, P = 0.156) and reduction of left ventricular end-diastolic diameter (A: -4.2 ± 10.7 mm, S: -7.5 ± 10.7 mm, P = 0.141) was comparable in apical and midseptal groups. Paced QRS width neither differed at prehospital discharge (A: 129 ± 21 ms, S: 135 ± 21 ms, P = 0.133) nor at 12-month follow-up (A: 131 ± 23 ms, S: 134 ± 28 ms, P = 0.620). No differences were found with respect to the risk of ventricular tachyarrhythmia or ICD therapy. Septal RV lead position, however, was associated with a significant longer time to a first heart failure event (P = 0.040) and a longer survival time (P = 0.019). CONCLUSIONS: In CRT recipients, midseptal RV lead position was not superior with respect to improvement of echocardiographic parameters or paced QRS width. It did not predispose to ventricular arrhythmias or ICD therapy. The finding that midseptal lead position was associated with a longer time to first heart failure event and a longer survival time deserves further investigation.

Use, efficacy and safety of prasugrel in patients with ST segment elevation myocardial infarction scheduled for primary percutaneous coronary intervention in clinical practice. Results of the prospective ATACS-registry.

BACKGROUND: Prasugrel compared to clopidogrel has been shown to improve outcome in patients with ST elevation myocardial infarction (STEMI) in the TRITON-TIMI 38 trial. Little is known about the use, efficacy and safety of prasugrel in patients with STEMI in clinical practice. METHODS: We conducted a prospective registry including patients with STEMI scheduled for primary percutaneous coronary intervention (PCI). Between October 2009 and February 2013 a total of 3291 patients with STEMI receiving a loading dose of either clopidogrel or prasugrel were included in this analysis. RESULTS: Prasugrel was predominantly used in patients <75 years, body weight >60 kg and those without prior stroke. In-hospital mortality was numerically lower in the prasugrel group (1.7% vs. 4.4%), as well as non-fatal reinfarction (0.2% vs. 0.5%), non-fatal stroke (0.1% vs. 0.3%) and major cardiac and cerebrovascular events (MACCE) (2.1% vs. 5.2%), while there was no difference in major bleeding complications (0.8% vs. 0.9%). In the multivariate analysis the MACCE-rate tended to be lower in prasugrel treated patients (odds ratio 0.71, 95% confidence intervals 0.42-1.08) but bleeding-rates tended to be higher. CONCLUSIONS: In this real life experience in patients with STEMI scheduled for primary PCI, prasugrel was almost exclusively used in the label-recommended patient population and tended to be more effective but associated with more bleedings compared to clopidogrel. These results support the findings in the STEMI population in the randomized TRITON-TIMI 38 study.

A stepwise electrocardiographic algorithm for differentiation of mid-septal vs. apical right ventricular lead positioning: the SPICE ECG substudy.

AIMS: Right ventricular (RV) septum is a non-apical site targeted during lead implantation. Electrocardiographic (ECG) recognition of mid-septal lead location is challenging. The aim of the study is to determine ECG correlates of RV mid-septal pacing. METHODS AND RESULTS: The present study is a pre-specified analysis of a prospective, multicenter study, which randomized recipients of an implantable cardioverter defibrillator to an apical vs. mid-septal RV lead positioning. Following implantation, a 12-lead ECG was recorded during intrinsic rhythm and RV pacing. In total, 227 patients, 121 in the apical group (76.9% males, 67.1 ± 11.3 years) and 106 in the mid-septal group (82.1% males, age 64.7 ± 12.7 years) were included. Apically as compared with septally paced patients had significantly longer paced QRS duration (177.0 ± 25.0 vs. 170.4 ± 21.7, respectively, P = 0.03) and significantly more leftward paced QRS axis (-71.6 ± 33.3° vs. 9.4 ± 86.5°, respectively, P < 0.001). A significantly higher proportion of patients in the mid-septal as compared with the apical group displayed predominantly positive QRS in lead V6 (62.3 vs. 4.1%, P < 0.001), predominantly positive QRS in any of the inferior leads (53.8 vs. 4.1%, P < 0.001), and a QR pattern in lead aVL (53.3 vs. 3.3%, P < 0.001). These ECG correlates were incorporated in a stepwise algorithm with total sensitivity of 87% and specificity of 90% for the identification of a mid-septal lead location. CONCLUSION: A mid-septal lead location may be identified using a simple stepwise algorithm, based on the presence of positive QRS in lead V6, positive QRS in any of the inferior leads, and a QR pattern in lead aVL.

Electrocardiographic identification of prior myocardial infarction during right ventricular pacing--effect of septal versus apical pacing.

BACKGROUND: Electrocardiographic (ECG) identification of prior myocardial infarction (MI) during right ventricular (RV) pacing is of clinical importance. Proposed ECG criteria have been evaluated only during apical pacing. We evaluated the effect of pacing site on the predictive performance of ECG signs of prior MI. METHODS: The present study is a secondary analysis of a prospective, multicenter study which randomized recipients of an implantable cardioverter defibrillator to an apical versus septal RV lead positioning. ECGs of patients with or without prior MI were analyzed for the presence of the following criteria: Cabrera sign, Chapman sign, QR pattern in leads I, aVL, V5 or V6, QR in inferior leads and notching in the descending slope of the QRS complex in inferior leads. RESULTS: The MI group included 89 patients (55.1% apically paced), while 99 patients had no prior MI (50.5% apically paced). In the total population, the Cabrera sign presented the highest specificity (97%) and diagnostic accuracy (62.2%), with a sensitivity of 23.6%. The Cabrera sign was the only significant predictor of a prior MI [OR=9.9, (95%CI:2.8-34.5), p<0.001], among all ECG markers. Pacing site did not significantly influence the sensitivity and specificity of the Cabrera sign for detection of prior MI. CONCLUSIONS: In our study, the Cabrera sign was the only ECG marker that predicted the presence of prior MI during ventricular paced rhythm. Septal RV lead positioning did not affect the predictive performance of the Cabrera sign.

Safety of mid-septal electrode placement in implantable cardioverter defibrillator recipients--results of the SPICE (Septal Positioning of ventricular ICD Electrodes) study.

BACKGROUND: Detrimental effects of right ventricular (RV) apical pacing have directed the interest toward alternative pacing sites such as the RV mid-septum. As safety data are scarce for implantable cardioverter defibrillator (ICD) recipients the study aims to evaluate ICD lead performance in the mid-septal position. METHODS AND RESULTS: A total of 299 ICD recipients (79% male, aged 65.2 ± 12.1 years, 83% primary prevention of sudden cardiac death) were randomized to receive the RV ICD electrode either in a mid-septal (n=145) or apical (n=154) location. Event-free survival was evaluated at 3 (primary endpoint) and 12 months (secondary endpoint). Events included a composite of lead revision, suboptimal right ventricular electrode performance (including defibrillation thresholds (DFT)>25 J) or lead position not in accordance with randomized location. Event-free survival at 3 (12) months was observed in 80.6% (72.3%) of patients randomized to a mid-septal and in 82.2% (72.1%) of patients randomized to an apical lead position, p=0.726 (p=0.969). Pre-defined margins for non-inferiority were not reached at 3 or 12 months. High DFT was found in 7 patients (5.0%) of the mid-septal and in 3 (2.2%) patients of the apical group (p=0.209). CONCLUSION: In ICD recipients electrode positioning to the RV mid-septum or the RV apex results in slightly different rates concerning the survival free of lead revision, suboptimal right ventricular electrode performance or non-randomized lead position. Non-inferiority of the mid-septal lead location cannot be concluded. This should be taken into consideration when a mid-septal lead position is pursued. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00745745.

Isolated dextrocardia with situs solitus (dextroversion).

Dextrocardia refers to the position of the heart in the right side of the chest. It is a rare clinical phenomenon with a reported incidence of 1 in 5,000-30,000. Although there is a variation in terminology and classification with regard to dextrocardia, the condition of right-sided heart with situs solitus is most commonly referred to as dextroversion. The authors report the case of dextroversion in a patient who presented in their hospital for evaluation of chest pain on exertion. Cardiac catheterization produced unfamiliar angiographic images, but there was no severe technical problem during coronary angiography. Apart from dextroversion, no further cardiac or noncardiac anomaly was found.

Left atrial intramural hematoma after percutaneous coronary intervention.

We described a complication during percutaneous coronary intervention. A bleeding into the left atrial wall occurred after stenting of the right coronary artery. Echocardiography revealed the diagnosis of a left atrial intramural hematoma. Conservative treatment was performed. After 4 weeks the hematoma resolved completely. Left atrial intramural hematoma as a complication after percutaneous coronary intervention has not been reported in the literature yet.

Positron emission tomography-measured abnormal responses of myocardial blood flow to sympathetic stimulation are associated with the risk of developing cardiovascular events.

OBJECTIVES: We sought to assess prospectively whether patients with normal coronary angiograms but with impaired myocardial blood flow (MBF) increases to cold pressor testing (CPT) are at increased risk for cardiovascular events. BACKGROUND: Invasive angiographic assessments of coronary vasomotor function have demonstrated an impairment of endothelium-related coronary flow increases to independently predict future cardiovascular events. It is unknown whether noninvasive positron emission tomography (PET)-measured MBF alterations to sympathetic stimulation with CPT are associated with the risk of developing cardiovascular events. METHODS: A total of 72 patients (44 men, 28 women, age 58 +/- 8 years) referred for diagnostic cardiac catheterization were studied. Myocardial blood flow was measured in absolute units with (13)N-ammonia using PET, at baseline and during CPT in each patient. Cardiovascular events (cardiovascular death, acute coronary syndrome, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, ischemic stroke, or peripheral revascularization) were assessed as clinical outcome parameters over a mean follow-up period of 66 +/- 8 months. Patients were assigned to three groups: group 1, patients with >/=40% increase in MBF (%DeltaMBF), n = 22; group 2, patients with >0 and <40% increases in MBF, n = 32; and group 3, patients with decreases in MBF (

Chronic inflammation and impaired coronary vasoreactivity in patients with coronary risk factors.

BACKGROUND: The goal of this study was to examine a possible association between systemic microinflammation, as reflected by C-reactive protein (CRP) serum levels, and coronary vasomotion in patients with coronary risk factors but with angiographically normal coronary arteries. METHODS AND RESULTS: Coronary vasomotor function was studied in response to cold pressor testing (CPT) in 71 patients with normal angiograms. In all patients, CPT-induced changes in epicardial luminal area (LA; mm2) were assessed with quantitative angiography. Within 20 days, myocardial blood flow (MBF) responses to CPT were measured (mL x g(-1) x min(-1)) noninvasively with 13N-ammonia and PET imaging. The CPT-induced mean changes in LA and in MBF in patients with elevated CRP (> or =0.5 mg/dL) were significantly impaired compared with patients presenting with CRP levels within normal range (<0.5 mg/dL) (DeltaLA, -1.09+/-0.86 versus 0.45+/-0.63 mm2; DeltaMBF, 0.06+/-0.18 versus 0.44+/-0.31 mL x g(-1) x min(-1); P<0.0001, respectively). Coronary LA changes and MBF responses to CPT were inversely correlated with CRP serum levels (r=-0.84 and r=-0.63; P<0.0001). Lastly, regression analysis revealed a significant correlation between the changes in LA and MBF during CPT for patients with elevated CRP levels and those for patients with normal CRP levels (r=0.56 and r=0.66; P<0.001). CONCLUSIONS: These findings suggest a direct association between systemic microinflammation and altered coronary vasomotor function of both the epicardial conductance and the arteriolar resistance vessels.

Myocardial viability in patients with ischemic cardiomyopathy-evaluation by 3-D integration of myocardial scintigraphic data--and coronary angiographic data.

PURPOSE: To determine the prevalence of viable myocardium in patients with ischemic cardiomyopathy and, to evaluate the value of three-dimensional (3-D) fusion imaging of myocardial scintigraphic and angiographic data to assign coronary artery lesions to the corresponding viable and nonviable myocardial territory. PROCEDURES: In 105 patients, the combination of perfusion and metabolic imaging with (201)thallium ((201)TI) single-photon emission computed tomography (SPECT) and 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET) determined viability in dysfunctional myocardium. In addition, the value of 3-D scintigraphic fusion imaging was assessed in these patients. RESULTS: Based on the presence of viable dysfunctional myocardium, 54% of patients with ischemic cardiomyopathy may be considered for coronary revascularization. In 31 of 105 patients, the 3-D fusion imaging was estimated to be helpful in the diagnostic and interpretative process. CONCLUSION: In patients with end-stage coronary artery disease scintigraphic imaging is most important in the decision-making process. Three-dimensional fusion imaging may add important information in approximately 30% of these patients.

Coronary vasoregulation in patients with various risk factors in response to cold pressor testing: contrasting myocardial blood flow responses to short- and long-term vitamin C administration.

OBJECTIVES: We sought to determine whether abnormal myocardial blood flow (MBF) responses to the cold pressor test (CPT) in patients with various risk factors may involve different mechanisms that could lead to varying responses of short- and long-term administration of antioxidants. BACKGROUND: There is a growing body of evidence that increased vascular production of reactive oxygen species markedly reduces the bioavailability of endothelium-derived nitric oxide, leading to impaired vasodilator function. It is unknown whether increased oxidative stress is the prevalent mechanism underlying endothelial dysfunction in patients with different coronary risk factors. METHODS: Fifty patients with normal coronary angiograms were studied. The MBF responses to CPT was determined by means of positron emission tomography before and after intravenous infusion of 3 g vitamin C or saline (placebo), as well as after 3 months and 2 years of 2 g vitamin C or placebo supplementation daily. RESULTS: In hypertensive patients, the change in MBF (DeltaMBF) was not modified significantly by short-term vitamin C administration challenges (0.20 +/- 0.20 ml/g/min; p = NS) but was significantly increased after three months and two years of treatment with vitamin C versus baseline (0.58 +/- 0.27 and 0.63 +/- 0.17 vs. 0.14 +/- 0.18 ml/g/min; both p < or = 0.001). In smokers, DeltaMBF in response to CPT was significantly increased after short-term vitamin C infusion and long-term vitamin C treatment (0.52 +/- 0.10, 0.54 +/- 0.13, 0.50 +/- 0.07 vs. -0.08 +/- 0.10 ml/g/min; all p < or = 0.001). In hypercholesterolemic patients, no improvement in DeltaMBF during CPT was observed after short- and long-term vitamin C treatment (0.05 +/- 0.14, 0.08 +/- 0.18, 0.02 +/- 0.19 vs. 0.08 +/- 0.16 ml/g/min; p = NS). The CPT-induced DeltaMBF in hypertensive patients and smokers after follow-up was significant as compared with placebo and control subjects (p < or = 0.001). CONCLUSIONS: The present study revealed marked heterogeneous responses in MBF changes to short- and long-term vitamin C treatment in patients with various risk factors, which highlights the quite complex nature underlying abnormal coronary vasomotion.

Prognostic value of abnormal vasoreactivity of epicardial coronary arteries to sympathetic stimulation in patients with normal coronary angiograms.

OBJECTIVE: We aimed to evaluate prospectively whether patients with normal coronary angiogram but abnormal epicardial vasoreactivity to cold pressor test (CPT) are at increased risk for cardiovascular events. METHODS AND RESULTS: Vasoreactivity in response to CPT and dilation of epicardial arteries to intracoronary application of nitroglycerin were assessed quantitatively (percent change of luminal area, DeltaLA%) in 130 patients with normal coronary angiograms. Cardiovascular events (cardiovascular death, acute coronary syndrome, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary bypass grafting, ischemic stroke, or peripheral revascularization) were assessed as clinical outcome parameters over a mean follow-up period of 45+/-9 months. Based on their vascular responses to CPT, patients were assigned into the following 3 groups: group 1, patients with normal vasodilator response (DeltaLA >0%; n=37); group 2, patients with moderate vasoconstrictor response (DeltaLA between 0% and -15%; n=42); and group 3, patients with severe vasoconstrictor response (DeltaLA < or =-15%; n=51). Although patients from groups 2 and 3 had significantly increased vasoconstrictor response to CPT (group 2, DeltaLA -6+/-3% and group 3, DeltaLA -24+/-6% versus group 1, DeltaLA 11+/-9%; P< or =0.0001), they showed normal endothelial-independent epicardial vasodilation to intracoronary application of nitroglycerin similar to patients from group 1 (DeltaLA 39+/-16% and 34+/-14% versus 41+/-14%; P=NS, respectively). During follow-up, none of the patients from group 1 developed cardiac events. However, 7 cardiovascular events occurred in group 2 and 30 occurred in group 3 in 4 and 22 patients, respectively (P< or =0.0001, univariate by log-rank test). After adjustment for known risk factors for coronary artery disease, impaired epicardial coronary vasoreactivity to CPT remained significantly associated with the risk of developing cardiovascular events (P=0.040, multivariate by Cox regression model). CONCLUSIONS: In patients with normal coronary angiogram, abnormal vasoreactivity of epicardial coronary arteries in response to sympathetic stimulation is associated with the risk of developing cardiovascular events.

[Effect of vitamin C on platelet aggregation in smokers and nonsmokers]. / Wirkung von Vitamin C auf die Thrombozytenaggregation bei Rauchern und Nichtrauchern.

BACKGROUND: Epidemiologic studies suggest a protective effect of regular intake of vitamin C and vitamin E as antioxidant in the manifestation of coronary heart disease. Cigarette smoke contains a large amount of radicals and reactive oxygen-derived substances enhancing aggregation of platelets. We investigated the effect of vitamin C as an important antioxidant in human plasma on the aggregation of human platelets in smokers and nonsmokers. TEST PERSONS AND METHOD: Overall 40 persons (mean age: 28 +/- 9 years) were randomized. The groups of chronic smokers (21 +/- 9 "packyears") and nonsmokers consisted of 20 persons, respectively. In each group ten persons were treated with intravenous infusion of 3 g vitamin C or 100 ml 0.9% saline solution (placebo). The maximal aggregation was measured with an aggregometer after 0, 3, 6, and 24 hours with collagen concentrations of 0.5 microgram/ml and 1.0 microgram/ml, respectively. RESULTS: In smokers with vitamin C application the group comparison by Wilcoxon's rank test demonstrated a significant decrease of platelet aggregation after 6 hours for both collagen concentrations (0.5 microgram/ml and 1.0 microgram/ml) compared to the placebo group (p < or = 0.05), whereas nonsmokers with vitamin C application revealed a significant decrease of platelet aggregation after 3 and 6 hours for both collagen concentrations (0.5 microgram/ml and 1.0 microgram/ml) compared to the placebo group (p < or = 0.03). The comparison between smokers and nonsmokers regarding the effect of vitamin C on platelet aggregation for both collagen concentrations demonstrated no significant difference (3 hours: p = 0.84 and p = 0.97; 6 hours: p = 0.81 and p = 0.59; and 24 hours p = 0.57 and p = 0.06, not significant, respectively). CONCLUSION: These findings suggest that vitamin C exerts an unknown inhibitory effect on collagen-induced platelets aggregation. These observations may represent a further protective effect of vitamin C in the development of coronary heart disease.