Simultaneous [18F]fluoride and gadobutrol enhanced coronary positron emission tomography/magnetic resonance imaging for in vivo plaque characterization.

AIMS: 18F-sodium fluoride ([18F]fluoride) and gadobutrol are promising probes for positron emission tomography (PET) and magnetic resonance imaging (MRI) characterizing coronary artery disease (CAD) activity. Unlike [18F]fluoride-PET/computed tomography (CT), the potential of PET/MR using [18F]fluoride and gadobutrol simultaneously, has so far not been evaluated. This study assessed feasibility and diagnostic potential of [18F]fluoride and gadobutrol enhanced dual-probe PET/MR in patients with CAD. METHODS AND RESULTS: Twenty-one patients (age, 66.7 ± 6.7 years) with CAD scheduled for invasive coronary angiography (XCA) underwent simultaneous [18F]fluoride (mean activity/effective dose: 157.2 ± 29.7 MBq/3.77 ± 0.72 mSv) and gadobutrol enhanced PET/MR on an integrated PET/MRI (3 T) scanner. Optical coherence tomography (OCT) was used as reference. Target-to-background ratio (TBR, [18F]fluoride-PET) and contrast-to-noise ratio (CNR) values (MRI, gadobutrol) were calculated for each coronary segment. Previously suggested PET/CT-TBR thresholds for adverse coronary events were evaluated. High-risk plaques, i.e. calcified and non-calcified thin-cap fibroatheromas (TCFAs) were predominantly located in segments with a TBR >1.28 (P = 0.012). Plaques containing a lipid core on OCT, were more frequently detected in segments with a TBR >1.25 (P < 0.001). TBR values significantly correlated with maximum calcification thickness (P = 0.009), while fibrous cap thickness was significantly less in segments with a TBR >1.28 (P = 0.044). Above a TBR threshold of >1.28, CNR values significantly correlated with the presence of calcified TCFAs (P = 0.032). CONCLUSION: Simultaneous [18F]fluoride and gadobutrol dual-probe PET/MRI is feasible in clinical practice and may facilitate the identification of high-risk patients. The combination of coronary MR-derived CNR values post gadobutrol and [18F]fluoride based TBR values may improve identification of high-risk plaque features.

Imaging coronary plaques using 3D motion-compensated [18F]NaF PET/MR.

BACKGROUND: Cardiac PET has recently found novel applications in coronary atherosclerosis imaging using [18F]NaF as a radiotracer, highlighting vulnerable plaques. However, the resulting uptakes are relatively small, and cardiac motion and respiration-induced movement of the heart can impair the reconstructed images due to motion blurring and attenuation correction mismatches. This study aimed to apply an MR-based motion compensation framework to [18F]NaF data yielding high-resolution motion-compensated PET and MR images. METHODS: Free-breathing 3-dimensional Dixon MR data were acquired, retrospectively binned into multiple respiratory and cardiac motion states, and split into fat and water fraction using a model-based reconstruction framework. From the dynamic MR reconstructions, both a non-rigid cardiorespiratory motion model and a motion-resolved attenuation map were generated and applied to the PET data to improve image quality. The approach was tested in 10 patients and focal tracer hotspots were evaluated concerning their target-to-background ratio, contrast-to-background ratio, and their diameter. RESULTS: MR-based motion models were successfully applied to compensate for physiological motion in both PET and MR. Target-to-background ratios of identified plaques improved by 7 ± 7%, contrast-to-background ratios by 26 ± 38%, and the plaque diameter decreased by -22 ± 18%. MR-based dynamic attenuation correction strongly reduced attenuation correction artefacts and was not affected by stent-related signal voids in the underlying MR reconstructions. CONCLUSIONS: The MR-based motion correction framework presented here can improve the target-to-background, contrast-to-background, and width of focal tracer hotspots in the coronary system. The dynamic attenuation correction could effectively mitigate the risk of attenuation correction artefacts in the coronaries at the lung-soft tissue boundary. In combination, this could enable a more reproducible and reliable plaque localisation.

Cannabidivarin for HIV-Associated Neuropathic Pain: A Randomized, Blinded, Controlled Clinical Trial.

HIV remains a major burden to the health care system and neuropathic pain is the most common neurological complication of HIV infection. Because current treatment strategies often lack satisfying pain relief, cannabinoids (CBs) are discussed as a new option. We investigated cannabidivarin (CBDV) as treatment for HIV-associated neuropathic pain. We conducted a randomized, double-blind, placebo-controlled crossover study. Patients underwent two successive treatment phases (4 weeks each) and were treated with CBDV (400 mg/day) or placebo in a randomized order. A 3-week washout phase was designed to eliminate potential carry-over effects. Patients were followed up for 3 weeks after the end of the second treatment phase. The primary end point was pain intensity on an 11-point numeric rating scale, recorded in a diary. Secondary end points were additional pain medication, pain characteristics, and quality of life. We included 32 patients. The mean pain intensity under CBDV was 0.62 points higher compared with placebo (P = 0.16, 95% confidence interval -0.27 to 1.51). CBDV did not influence the amount of additional pain medication, pain characteristics, or quality of life. The incidence of adverse events was similar during both treatments. No suspected unexpected adverse reactions occurred during either treatment. CBDV was safe but failed to reduce neuropathic pain in patients with HIV. This may be explained by a lack of CB receptor activation, as indicated by preclinical experiments. Although a larger patient number might be desirable, we would not expect a change in the conclusions because the present differences are far from statistical significance. Therefore, we would currently not consider CBDV as a clinically meaningful treatment option for neuropathic pain.

Pulmonary Hypertension in Patients With Severe Aortic Stenosis: Prognostic Impact After Transcatheter Aortic Valve Replacement: Pulmonary Hypertension in Patients Undergoing TAVR.

OBJECTIVES: The authors investigated the development of pulmonary hypertension (PH), predictors of PH regression, and its prognostic impact on short, mid-, and long-term outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). BACKGROUND: PH represents a common finding in patients with AS. Although TAVR is frequently associated with regression of PH, the predictors of reversible PH and its prognostic significance remain uncertain. METHODS: In this study, 617 consecutive patients undergoing TAVR between 2009 and 2015 were stratified per baseline tertiles of pulmonary artery systolic pressure (PASP) as follows: normal (PASP <34 mm Hg), mild-to-moderate (PASP ≥34 mm Hg and <46 mm Hg), and severe PASP elevation (PASP ≥46 mm Hg). After TAVR, 520 patients with PH at discharge were stratified according to the presence or absence of PASP reduction. Primary outcome was all-cause mortality at 30 days, 1 year, and long-term follow-up at a maximum of 5.9 years. RESULTS: In patients with both mild-to-moderate and severe PH at baseline, PASP decreased significantly at discharge (ΔPASP 3.0 ± 9.3 mm Hg and 12.0 ± 10.0 mm Hg, respectively) and 1 year (ΔPASP 5.0 ± 9.7 mm Hg and 18.0 ± 14.0 mm Hg, respectively). At a median follow-up of 370 days (interquartile range [IQR]: 84 to 500 days), the risk of all-cause mortality was similar among baseline PASP groups at all time intervals evaluated. After TAVR, a significant regression of PH was observed in 46% of patients. Contrarily, patients with residual PH had a higher risk of all-cause mortality at 30 days (hazard ratio [HR]: 3.49, 95% confidence interval [CI]: 1.74 to 6.99; p < 0.001), 1 year (HR: 3.12, 95% CI: 2.06 to 4.72; p < 0.001), and long-term (HR: 2.47, 95% CI: 1.74 to 3.49; p < 0.001). Left ventricular ejection fraction (LVEF) >40% (odds ratio [OR]: 3.56, 95% CI: 2.24 to 5.65; p < 0.001), baseline PASP ≥46 mm Hg (OR: 3.26, 95% CI: 2.07 to 5.12; p < 0.001), absence of concomitant tricuspid regurgitation (TR) ≥ moderate (OR: 0.53, 95% CI: 0.34 to 0.84; p < 0.001), and logistic EuroSCORE <25% (OR: 1.59, 95% CI: 1.04 to 2.45; p = 0.03) were independent predictors of PASP reduction. CONCLUSIONS: In most patients with PH and AS, TAVR is associated with a significant early and late reduction of PASP. Patients with reversible PH after TAVR are at lower risk of all-cause mortality at early, mid-, and long-term follow-up. Therefore, the presence of PH should not preclude treatment with TAVR.

Feasibility and Diagnostic Value of Cardiovascular Magnetic Resonance Imaging After Acute Ischemic Stroke of Undetermined Origin.

BACKGROUND AND PURPOSE: Etiology of acute ischemic stroke remains undetermined (cryptogenic) in about 25% of patients after state-of-the-art diagnostic work-up. METHODS: One-hundred and three patients with magnetic resonance imaging (MRI)-proven acute ischemic stroke of undetermined origin were prospectively enrolled and underwent 3-T cardiac MRI and magnetic resonance angiography of the aortic arch in addition to state-of-the-art diagnostic work-up, including transesophageal echocardiography (TEE). We analyzed the feasibility, diagnostic accuracy, and added value of cardiovascular MRI (cvMRI) compared with TEE for detecting sources of stroke. RESULTS: Overall, 102 (99.0%) ischemic stroke patients (median 63 years [interquartile range, 53-72], 24% female, median NIHSS (National Institutes of Health Stroke Scale) score on admission 2 [interquartile range, 1-4]) underwent cvMRI and TEE in hospital; 89 (86.4%) patients completed the cvMRI examination. In 93 cryptogenic stroke patients, a high-risk embolic source was found in 9 (8.7%) patients by cvMRI and in 11 (11.8%) patients by echocardiography, respectively. cvMRI and echocardiography findings were consistent in 80 (86.0%) patients, resulting in a degree of agreement of κ=0.24. In 82 patients with cryptogenic stroke according to routine work-up, including TEE, cvMRI identified stroke etiology in additional 5 (6.1%) patients. Late gadolinium enhancement consistent with previous myocardial infarction was found in 13 (14.6%) out of 89 stroke patients completing cvMRI. Only 2 of these 13 patients had known coronary artery disease. CONCLUSIONS: Our study demonstrated that cvMRI was feasible in the vast majority of included patients with acute ischemic stroke. The diagnostic information of cvMRI seems to be complementary to TEE but is not replacing echocardiography after acute ischemic stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01917955.

Restrictive cardiomyopathy : Delayed occurrence after radiotherapy of breast cancer.

A 74-year-old female patient was referred to our department in 2015 with dyspnea, cough and dysphagia. She had been diagnosed with adenocarcinoma of the right breast in 1986 and underwent mastectomy. When she presented with a local recurrence in 1988, she was receiving high-voltage radiation therapy. Transthoracic echocardiography and magnetic resonance imaging revealed tricuspid regurgitation grade III and unclear right heart failure with a massively dilated right atrium. Coronary heart disease could be ruled out. In summary, the patient's findings represented right ventricular myocardial restriction which we attributed to irradiation of the right anterior chest 17 years previously.

Long-term prognostic value of restitution slope in patients with ischemic and dilated cardiomyopathies.

BACKGROUND: An action potential duration (APD) restitution curve with a steep slope ≥1 has been associated with increased susceptibility for malignant ventricular arrhythmias. We aimed to evaluate the "restitution hypothesis" and tested ventricular APD restitution slope as well as effective refractory period (ERP)/APD ratio for long-term prognostic value in patients with ischemic (ICM) or dilated cardiomyopathy (DCM). METHODOLOGY/PRINCIPAL FINDINGS: Monophasic action potentials were recorded in patients with ICM (n = 32) and DCM (n = 42) undergoing routine programmed ventricular stimulation (PVS). Left ventricular ejection fraction was 32±7% and 28±9%, respectively. APD and ERP were measured at baseline stimulation (S(1)) and upon introduction of one to three extrastimuli (S(2)-S(4)). ERP/APD ratios and the APD restitution curve were calculated and the maximum restitution slope was determined. After a mean follow-up of 6.1±3.0 years, the combined end-point of mortality and and/or implantable cardioverter-defibrillator shock was not predicted by restitution slope or ERP/APD ratios. Comparing S(2) vs. S(3) vs. S(4) extrastimuli for restitution slope (1.5±0.6 vs. 1.4±0.4 vs. 1.3±0.5; p = NS), additional extrastimuli did not lead to a steepening restitution slope. ERP/APD ratio decreased with additional extrastimuli (0.98±0.09 [S(1)] vs. 0.97±0.10 [S(2)] vs. 0.93±0.11 [S(3)]; p = 0.03 S(1) vs. S(3)). Positive PVS was strongly predictive of outcome (p = 0.006). CONCLUSIONS/SIGNIFICANCE: Neither ventricular APD restitution slope nor ERP/APD ratios predict outcome in patients with ICM or DCM.

Doubling the clopidogrel dose in patients with reduced responsiveness to the standard dose is associated with a limited effectiveness as evaluated by impedance aggregometry.

BACKGROUND: Different methods are available for quantifying platelet function inhibition. Measuring vasodilator-stimulated phosphoprotein (VASP) phosphorylation is currently the most specific method for assessing the clopidogrel effect. The aim of our study was to compare different tests in view of a clinically applicable bedside test. Further, we examined whether doubling the clopidogrel dose to 150mg/d in clopidogrel low-responder would lead to a reduction in platelet reactivity. METHODS AND RESULTS: ADP-, ADP Hs-, and TRAP-induced platelet aggregation were measured by impedance aggregometry in 100 patients with CAD and 18 healthy controls. Moreover, platelet aggregation was assessed by flow cytometrical detection of VASP-phosphorylation and surface P-selectin in a subgroup of 34 patients and in healthy controls. Another 10 patients with CAD, identified as low-responder, were treated with a clopidogrel dose of 150mg/d. Thereafter, ADP-induced platelet aggregation was assessed by impedance aggregometry. Significant correlations were observed between ADP-induced platelet aggregation assessed by VASP-phosphorylation and by impedance aggregometry. Doubling the dose of clopidogrel to 150mg/d was associated with a reduction of ADP-induced platelet aggregation in only 60% of the patients. CONCLUSIONS: Impedance aggregometry is a valuable bedside test to assess platelet function inhibition. Doubling the clopidogrel dose is not effective to reduce high on-treatment platelet reactivity in almost half of these patients, pointing to the need of a more powerful platelet inhibitor.

High frequency of Tropheryma whipplei in culture-negative endocarditis.

"Classical" Whipple's disease (cWD) is caused by Tropheryma whipplei and is characterized by arthropathy, weight loss, and diarrhea. T. whipplei infectious endocarditis (TWIE) is rarely reported, either in the context of cWD or as isolated TWIE without signs of systemic infection. The frequency of TWIE is unknown, and systematic studies are lacking. Here, we performed an observational cohort study on the incidence of T. whipplei infection in explanted heart valves in two German university centers. Cardiac valves from 1,135 patients were analyzed for bacterial infection using conventional culture techniques, PCR amplification of the bacterial 16S rRNA gene, and subsequent sequencing. T. whipplei-positive heart valves were confirmed by specific PCR, fluorescence in situ hybridization, immunohistochemistry, histological examination, and culture for T. whipplei. Bacterial endocarditis was diagnosed in 255 patients, with streptococci, staphylococci, and enterococci being the main pathogens. T. whipplei was the fourth most frequent pathogen, found in 16 (6.3%) cases, and clearly outnumbered Bartonella quintana, Coxiella burnetii, and members of the HACEK group (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae). In this cohort, T. whipplei was the most commonly found pathogen associated with culture-negative infective endocarditis.

T-wave alternans testing in pacemaker patients: comparison of pacing modes and long-term prognostic relevance.

BACKGROUND: T-wave alternans (TWA) is a useful method for identifying patients who are at risk for sudden cardiac death. We aimed to determine the effects of different pacing modes on test results and long-term prognostic relevance of TWA in patients following a dual-chamber (DDD) pacemaker implantation. METHODS: Sixty-three patients (mean age 68 ± 13 years) with structural heart disease and recently implanted DDD pacemakers were enrolled. Left ventricular (LV) function was normal or moderately impaired (mean LV ejection fraction 61 ± 13%). All patients underwent sequential TWA testing using atrial and ventricular pacing. RESULTS: During atrial pacing requiring physiologic conduction to the ventricles, 21% of TWA tests were positive, 43% negative, and 36% indeterminate. When using right ventricular (RV) pacing in the same patients, 19% of tests were positive, 40% negative, and 41% indeterminate. When positive and indeterminate tests were grouped as nonnegative, the concordance between atrial and ventricular pacing was 62% (κ= 0.22). After a mean follow-up of 5.9 ± 1.9 years, 18 (29%) patients had died. Improved survival was predicted by a negative TWA test using atrial pacing (P = 0.028), but not with ventricular pacing (P = 0.722). CONCLUSIONS: In patients with dual-chamber pacemakers, there is a low concordance of TWA test results between atrial pacing with intrinsic conduction to the ventricles and apical RV pacing via pacemaker electrode. However, TWA during atrial pacing clearly exerts long-term prognostic relevance in a patient group with preserved LV function and structural heart disease.

Prehospital versus periprocedural abciximab in ST-elevation myocardial infarction treated by percutaneous coronary intervention.

OBJECTIVE: To investigate the potential benefit of an earliest possible out-of-hospital start of abciximab (ReoPro) therapy in ST-elevation myocardial infarction (STEMI; Lilly, Bad Homburg, Germany) and planned primary percutaneous intervention compared with periprocedural abciximab treatment on reperfusion and clinical outcome. METHODS: Randomization of one hundred and one patients with STEMI to prehospital or periprocedural abciximab treatment. Evaluation of thrombolysis in myocardial infarction (TIMI) flow, ST-segment resolution, myocardial blush grade, and maximal creatine kinase release before and after as well as clinical follow-up until 6 months after the index event. RESULTS: Prehospital abciximab (group 1) was initiated a median of 101 min (37-165 min) earlier compared with periprocedural treatment (group 2). Initial TIMI 3 flow (24 vs. 15%, P=NS), ST-segment resolution before percutaneous coronary intervention (PCI) (<30%: 33 vs. 46%, P=NS; >70%: 38 vs. 33%, P=NS), post-PCI myocardial blush grade 2 and 3 (72 vs. 75%, P=NS), maximal cardiac enzyme release (creatinine kinase MB median 77 U/l; range 33-137 vs. 74 U/l; range 39-143 U/l, P=NS), and 6 months follow-up (recurrent myocardial infarction or repeat coronary intervention, and PCI, need for coronary bypass surgery) did not differ significantly between both treatment groups. CONCLUSION: Prehospital intravenous administration of abciximab, although safe and feasible in a trained surrounding, does not add angiographic or clinical benefit to patients with STEMI.

Complication rate of right ventricular endomyocardial biopsy via the femoral approach: a retrospective and prospective study analyzing 3048 diagnostic procedures over an 11-year period.

BACKGROUND: An unequivocal diagnosis of myocarditis and cardiac virus persistence is based on histological, immunohistological, and molecular biological analyses of endomyocardial biopsies (EMBs). Biopsy-based diagnosis of myocarditis has become increasingly important because recent studies have demonstrated the beneficial effects of biopsy-based causal treatment strategies (immunosuppressive or antiviral). Because the risks of major complications caused by EMB procedures have not yet been well defined, we evaluated the incidence of major and minor complications of right ventricular EMB procedures in this retrospective and prospective single-center study. METHODS AND RESULTS: With the use of a modified Cordis bioptome, 1919 patients underwent 2505 EMB procedures retrospectively over a 9-year period (January 1995 to December 2003), and 496 patients underwent 543 EMB procedures prospectively between January 2004 and December 2005. A total of 2415 patients had 3048 EMB procedures via the right femoral vein approach under biplane fluoroscopic control to evaluate unexplained left ventricular dysfunction (retrospective left ventricular ejection fraction, 49.8+/-18.8%; prospective, 48.8+/-19.7%) after exclusion of secondary causes. During each EMB procedure, an average of 8.2+/-0.8 EMBs were obtained retrospectively and 10.1+/-0.6 specimens prospectively for a total of 26 025 specimens. No patient died or required emergency cardiac surgery. Other major complications like cardiac tamponade requiring pericardiocentesis or complete atrioventricular block requiring permanent pacing were very rare: 0.12% in the retrospective study and 0% in the prospective study. Minor complications such as pericardial effusion, conduction abnormalities, or arrhythmias occurred in 0.20% of the EMB procedures in the retrospective study and 5.5% in the prospective study. CONCLUSIONS: The EMB procedure via the femoral vein approach under fluoroscopic guidance has a very low complication rate when performed by experienced operators.

Utilization of telemedicine by heart disease patients following hospitalization.

NYHA class III and IV chronic heart failure has been established as a potential indication for telemedical care and monitoring already. We conducted a prospective study to assess the utilization of telemedical services by cardiac patients in order to identify further indications. A total of 540 patients (mean age 59 years) with various heart diseases participated for at least 30 days in a home-based telemedicine service programme. The two primary outcome measures were the rates of symptom-driven telephone calls (A) and ECG transmissions (B) per patient-year. The total follow-up was 68,649 days, with a median of 93 days. Symptomatic patients placed 713 calls and transmitted 221 ECGs. Poisson regression analysis with subset selection yielded four significant (P < 0.05) independent positive predictors of the use of the telemedicine service: (1) recent repeat (at least one previous) percutaneous coronary intervention (A, P = 0.010; B, P = 0.001); (2) recent cardioversion for atrial fibrillation or flutter (A, P < 0.0001; B, P < 0.0001); (3) ejection fraction (A, P = 0.012; B, P > 0.05); and (4) reciprocal of age (A, P < 0.0001; B, P > 0.05). These data suggest that telemedicine may benefit patients following repeat percutaneous coronary intervention or cardioversion for atrial fibrillation. Since patients availed themselves of telemedicine service less with deteriorating ejection fraction and increasing age, individuals with chronic heart failure will need dedicated programmes, especially when they are older.

Impact of telemedical care and monitoring on morbidity in mild to moderate chronic heart failure.

OBJECTIVE: We investigated in a pilot study whether telemedicine is beneficial in mild to moderate chronic heart failure. METHODS: A total of 128 patients with an ejection fraction < or =60% and NYHA class II or III chronic heart failure were evaluated. Thirty-two patients were enrolled prospectively in a staged telemedical service program. Ninety-six controls were matched 3:1 to each telemedicine patient. RESULTS: Median follow-up was 307 days (range 104-459). All-cause hospitalization duration [317 vs. 693 days/100 patient years; relative risk (RR) 0.46; 95% confidence interval (CI) 0.37-0.58; p < 0.0001) and rate (38 vs. 77/100 patient years; RR 0.49; 95% CI 0.25-0.95; p = 0.034) as well as cardiac hospitalization duration (49 vs. 379 days/100 patient years; RR 0.13; 95% CI 0.08-0.23; p < 0.0001] were significantly lower, cardiac hospitalization rate (11 vs. 35/100 patient years; RR 0.31; 95% CI 0.11-1.02; p = 0.058) tended to be lower in the telemedicine compared with the control group. CONCLUSION: These preliminary data suggest that telemedical care and monitoring may reduce morbidity in patients with NYHA class II and III chronic heart failure.

Correlation of epicardial and systemic flow-mediated vasodilation in patients with atypical angina but no evidence of atherosclerotic disease.

BACKGROUND: Atypical angina represents a diagnostic challenge and can be observed in the absence of significant coronary atherosclerosis. Endothelial dysfunction is a relevant marker of prognosis, considering cardiovascular events. The aim of the present study was to compare flow-mediated vasodilation (FMD) in systemic peripheral and epicardial coronary arteries. If noninvasive measurements of FMD in systemic arteries correlated with invasive measurements of coronary FMD, this may facilitate diagnostic approaches and determination of prognosis in patients with atypical angina in the future. Patients with atherosclerosis were excluded, because structural changes of coronary vessels may impair adequate comparison. METHODS: Endothelial function (ENF) of epicardial and systemic arteries was examined in 61 consecutive patients with atypical angina in whom significant atherosclerosis was excluded by coronary angiography. ENF of the epicardial arteries was examined during heart catheterization, measuring diameter changes of the proximal left anterior descending coronary artery (LAD) in response to reactive hyperemia, induced by locally administered adenosine via infusion catheter to the mid-segment of the LAD (coronary FMD [FMDc]). ENF of the radial artery was examined with high-resolution ultrasound, measuring peripheral FMD (FMDp) in response to reactive hyperemia induced by distal cuff occlusion. Endothelium-independent vasoreactivity to glycerol trinitrate was assessed. RESULTS: In patients with atypical angina in the absence of atherosclerosis, there was a significant correlation in ENF between coronary and systemic arteries (r=0.437; P=0.001). The underlying disease was myocardial inflammation (Inf) in 48 patients, in whom the mean (+/- SD) ENF of epicardial (FMDc-Inf 3.40+/-5.55%) and systemic (FMDp-Inf 3.69+/-2.93%) arteries was significantly impaired (P<0.001), compared with 13 control (Co) patients who had normal myocardial biopsies (FMDc-Co 14.51+/-8.62%; FMDp-Co 7.69+/-3.42%). FMD of coronary (r=-0.353; P=0.005) and systemic (r=-0.542; P<0.001) arteries correlated significantly with myocardial inflammation and endothelial activation. CONCLUSIONS: There was a significant correlation in FMD between coronary and systemic arteries in patients with atypical angina but without significant atherosclerosis. Inflammatory processes are associated with endothelial dysfunction of both vascular regions.

Treatment with ezetimibe plus low-dose atorvastatin compared with higher-dose atorvastatin alone: is sufficient cholesterol-lowering enough to inhibit platelets?

OBJECTIVES: We sought to test the platelet inhibitory and anti-inflammatory effects of a higher statin dosage compared with combined treatment with ezetimibe plus a low statin dose. BACKGROUND: Reducing the level of low-density lipoprotein cholesterol (LDL-C) with statins induces important pleiotropic effects such as platelet inhibition. An insufficient LDL-C reduction often is treated with ezetimibe, an intestinal cholesterol absorption inhibitor, in combination with a low statin dose. It is not known whether this combination therapy has the same pleiotropic effects as a statin monotherapy. METHODS: Fifty-six patients with coronary artery disease were assigned randomly to receive either 40 mg/day of atorvastatin or 10 mg/day of ezetimibe plus 10 mg/day of atorvastatin for 4 weeks. The levels of LDL-C, platelet activation markers after stimulation, platelet aggregation, and plasma chemokine levels (i.e., regulated on activation normally T-cell expressed and secreted [RANTES]) were measured before and after changing lipid-lowering medication. RESULTS: Platelet activation markers (P-selectin) after stimulation (adenosine diphosphate) were reduced by 40 mg/day of atorvastatin (-5.2 +/- 1.6 arbitrary units) but not by ezetimibe plus low-dose atorvastatin (2.1 +/- 1.8 arbitrary units; p < 0.005) despite a similar reduction of LDL-C (atorvastatin -1.01 +/- 0.18 mmol/l vs. ezetimibe plus atorvastatin -1.36 +/- 0.22 mmol/l, p = NS). Thrombin receptor-activating peptide-induced platelet aggregation as well as plasma RANTES levels were reduced by 40 mg/day of atorvastatin but not by ezetimibe plus low-dose atorvastatin. CONCLUSIONS: Platelet reactivity and a proinflammatory chemokine were reduced more by the higher atorvastatin dose than by ezetimibe plus low-dose atorvastatin. In patients with coronary artery disease, it might be important to combine ezetimibe with higher statin dosages to benefit from cholesterol-independent pleiotropic effects.

Cardiac arrest and ventricular tachycardia in Japanese-type apical hypertrophic cardiomyopathy.

Apical hypertrophic cardiomyopathy (HCM) is a specific variant of HCM. This disease has been first described in Japan where the prevalence is much higher than in the western world. The prognosis of apical HCM with regard to sudden cardiac death is believed to be better than that of common HCM. We present, however, two male caucasian patients with apical HCM and malignant arrhythmias. Both patients had marked apical hypertrophy on echocardiography, 'giant' negative T-waves on the ECG and spade-like configuration of the left ventricle on angiography. The first patient had been successfully recussitated from cardiac arrest at the age of 52 years. The second patient had a syncope at the age of 42 years and had non-sustained ventricular tachycardia. In both cases, a cardioverter-defibrillator was implanted and treatment with verapamil was initiated. These observations suggest that the risk of sudden cardiac death might be increased not only in common HCM, but also in Japanese-type apical HCM.

Pseudo current density maps of electrophysiological heart, nerve or brain function and their physical basis.

BACKGROUND: In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular. METHODS: The physical basis of these intuitive maps is clarified by means of analytically solvable problems. RESULTS: Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method. CONCLUSION: Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.