Coinfection of Pneumocystis jirovecii and invasive pulmonary aspergillosis in an immunocompromised patient: a diagnostic challenge.

BACKGROUND: Invasive infections caused by Aspergillus fumigatus as well as Pneumocystis pneumonia are serious and often lethal diseases in severely immunocompromised patients. CASE REPORT: We report on a rare case of a pulmonary coinfection of Pneumocystis jirovecii and Aspergillus fumigatus in a 59-year-old female patient with a history of astrocytoma treated with high doses of corticosteroids and a subsequent CD4 lymphocyte count of 30/µl. CONCLUSION: A heightened clinical awareness and a stringent and accurate diagnostic work-up encompassing diagnostic tools to detect even coincident fungal infections is crucial for sufficient and early antifungal treatment in immunocompromised patients with lung infiltrates.

Echocardiographic assessment of mitral regurgitation: discussion of practical and methodologic aspects of severity quantification to improve diagnostic conclusiveness.

The echocardiographic assessment of mitral valve regurgitation (MR) by characterizing specific morphological features and grading its severity is still challenging. Analysis of MR etiology is necessary to clarify the underlying pathological mechanism of the valvular defect. Severity of mitral regurgitation is often quantified based on semi-quantitative parameters. However, incongruent findings and/or interpretations of regurgitation severity are frequently observed. This proposal seeks to offer practical support to overcome these obstacles by offering a standardized workflow, an easy means to identify non-severe mitral regurgitation, and by focusing on the quantitative approach with calculation of the individual regurgitant fraction. This work also indicates main methodological problems of semi-quantitative parameters when evaluating MR severity and offers appropriateness criteria for their use. It addresses the diagnostic importance of left-ventricular wall thickness, left-ventricular and left atrial volumes in relation to disease progression, and disease-related complaints to improve interpretation of echocardiographic findings. Finally, it highlights the conditions influencing the MR dynamics during echocardiographic examination. These considerations allow a reproducible, verifiable, and transparent in-depth echocardiographic evaluation of MR patients ensuring consistent haemodynamic plausibility of echocardiographic results.

Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter.

BACKGROUND: Treatment of coronary in-stent restenosis is hampered by a high incidence of recurrent in-stent restenosis. We assessed the efficacy and safety of a paclitaxel-coated balloon in this setting. METHODS: We enrolled 52 patients with in-stent restenosis in a randomized, double-blind, multicenter trial to compare the effects of a balloon catheter coated with paclitaxel (3 microg per square millimeter of balloon surface area) with those of an uncoated balloon catheter in coronary angioplasty. The primary end point was late luminal loss as seen on angiography. Secondary end points included the rates of restenosis (a binary variable) and major adverse cardiac events. RESULTS: Multivessel disease was present in 80% of patients in both groups. Quantitative coronary angiography revealed no significant differences in baseline measures. At 6 months, angiography showed that the mean (+/-SD) in-segment late luminal loss was 0.74+/-0.86 mm in the uncoated-balloon group versus 0.03+/-0.48 mm in the coated-balloon group (P=0.002). A total of 10 of 23 patients (43%) in the uncoated-balloon group had restenosis, as compared with 1 of 22 patients (5%) in the coated-balloon group (P=0.002). At 12 months, the rate of major adverse cardiac events was 31% in the uncoated-balloon group and 4% in the coated-balloon group (P=0.01). This difference was primarily due to the need for target-lesion revascularization in six patients in the uncoated-balloon group (P=0.02). CONCLUSIONS: Treatment of coronary in-stent restenosis with paclitaxel-coated balloon catheters significantly reduced the incidence of restenosis. These data suggest that the inhibition of restenosis by local drug delivery may not require stent implantation and sustained drug release at the site of injury. (ClinicalTrials.gov number, NCT00106587 [ClinicalTrials.gov].).

Electromechanical coupling in patients with the short QT syndrome: further insights into the mechanoelectrical hypothesis of the U wave.

BACKGROUND: Patients with a short QT syndrome (SQTS) are at risk of sudden cardiac death (SCD). It is not known whether abbreviation of cardiac repolarization alters mechanical function in SQTS. Controversies persist regarding whether the U wave is a purely electrical or mechanoelectrical phenomenon. OBJECTIVE: The present study uses echocardiographic measurements to discriminate between the hypotheses for the origin of the U wave. METHODS: Diagnostic work-up including echocardiography and electrocardiogram was performed in 5 SQTS patients (39 +/- 19 years old) from 2 unrelated families with a history of SCD and 5 age-matched and gender-matched control subjects. RESULTS: QT intervals were 268 +/- 18 ms (QTc 285 +/- 28 ms) in SQTS versus 386 +/- 20 ms (QTc 420 +/- 22 ms) in control subjects (P < .005). In SQTS patients, the end of the T wave preceded aortic valve closure by 111 +/- 30 ms versus -12 +/- 11 ms in control subjects (P < .005). The interval from aortic valve closure to the beginning of the U wave was 8 +/- 4 ms in patients and 15 +/- 11 ms in control subjects (P = .25). Thus, the inscription of the U wave in SQTS patients coincided with aortic valve closure and isovolumic relaxation, supporting the hypothesis that the U wave is related to mechanical stretch. CONCLUSION: Our data show for the first time a significant dissociation between the ventricular repolarization and the end of mechanical systole in SQTS patients. Coincidence of the U wave with termination of mechanical systole provides support for the mechanoelectrical hypothesis for the origin of the U wave.

Local paclitaxel delivery after coronary stenting in an experimental animal model.

The goal of this study was to test the safety and efficacy of local paclitaxel delivery via a newly designed application catheter in an experimental animal study. Drug-eluting stents reduce restenosis in comparison to bare-metal stents. The drug-eluting polymer, however, may exert potential thrombogenic and inflammatory effects. A catheter-based local paclitaxel delivery offers further advantages, particularly a homogenous drug transfer into the vessel wall and a pharmacotherapy of the stent edges. In 30 pigs, both bare-metal stent (3.0 x 13 mm) implantation and balloon angioplasty were performed. Ten pigs received subsequent local delivery of paclitaxel-solution via a newly designed catheter (Genie, ACROSTAK corp., Switzerland), 10 animals served as a sham group and received vehicle (0.9% NaCl solution) and 10 animals were used as a control group. All animals were treated with aspirin and clopidogrel to prevent stent thrombosis. After final angiography the vessels were excised 42 days after intervention and prepared for histological and histomorphometric analysis. All coronary arteries showed complete endothelialization 42 days following treatment. Paclitaxel treatment led to a marked reduction of neointimal proliferation either post stent implantation (neointimal area: 1.04 +/- 0.10 mm(2) vs. 2.37 +/- 0.23 mm(2), p < 0.001) or post balloon dilatation (neontimal area: 0.35 +/- 0.14 mm(2), vs. 0.68 +/- 0.24 mm(2), p < 0.01). There were no significant angiographic or histomorphometric differences between the control and the sham group. In both paclitaxel groups neither angiographic edge phenomena nor a significant histomorphometric inflammatory response were found in the treated vessel segments. In conclusion, the local application of paclitaxel via the Genie catheter is safe and effective to significantly reduce the proliferative response post-stent implantation or balloon dilatation in an experimental animal model.

Catecholaminergic polymorphic ventricular tachycardia and midventricular Takotsubo cardiomyopathy: a novel association?

Takotsubo cardiomyopathy (TTC) is a recently recognized clinical syndrome characterized by transient ventricular dysfunction in the absence of obstructive coronary artery disease. TTC primarily affects postmenopausal women; TTC in children and adolescents is only rarely reported. Furthermore, simultaneous occurrence of Takotsubo cardiomyopathy and primary electrical diseases has been previously reported in only four recent cases of female patients with congenital long QT syndrome. Here, we report the novel association of catecholaminergic polymorphic ventricular tachycardias and a midventricular type of TTC observed in a young female patient.

Incidence of pulmonary embolism in an emergency department cohort evaluated with a simple symptom-based diagnostic algorithm.

BACKGROUND: Although complex scores were recommended for diagnosis of pulmonary embolism (PE), acceptance in clinical practice is limited. In our Emergency Department a symptom-based algorithm for patients with suspected PE including computed tomographic pulmonary angiography (CTPA) and D-dimer testing was implemented. PATIENTS AND METHODS: The cases of 492 patients presenting with either chest pain, dyspnea or syncope for whom this algorithm was applied, were retrospectively analyzed with respect to the incidence of PE, D-dimer and high-sensitive troponin levels. RESULTS: Our algorithm detected PE in 59 out of 492 patients. D-Dimer levels were significantly higher in the PE group than in the patients without PE (p<0.0001). High-sensitive troponin was significantly increased in patients with central PE compared to other patients (p<0.01). CONCLUSION: Our data demonstrate the utility and practicability of our symptom-based algorithm in combination with D-dimer testing and the use of CTPA in patients with suspected PE.

Cardiac computed tomographic angiography in patients with acute chest pain and moderately-increased troponin.

AIM: The aim of the study was to investigate patients with undefined chest pain and moderately increased troponin based on the results of cardiac computed tomographic (CT) angiography (CCTA). PATIENTS AND METHODS: We analysed the cases of 43 patients with acute chest pain and moderately increased troponin in whom CCTA was performed. Patients with suspected stenosis on CCTA underwent percutaneous coronary angiography (PCA). RESULTS: CCTA ruled-out significant coronary stenosis in 32 patients. Eleven patients had suspected significant coronary stenosis on CCTA. Ten patients underwent PCA, which verified significant coronary lesions in nine. Out of these, four patients were treated by percutaneous coronary intervention (PCI). One patient had to undergo coronary artery bypass grafting. A triple-rule-out CT protocol was performed in 18 patients, demonstrating pulmonary embolism in three and pericardial effusion of unknown origin in two. CONCLUSION: CCTA accurately identifies or rules out patients with undefined chest pain and moderately elevated troponin, which require PCA and allows detection of other significant clinical findings.

Benefit of combining quantitative cardiac CT parameters with troponin I for predicting right ventricular dysfunction and adverse clinical events in patients with acute pulmonary embolism.

OBJECTIVE: To prospectively evaluate the diagnostic accuracy of quantitative cardiac CT parameters alone and in combination with troponin I for the assessment of right ventricular dysfunction (RVD) and adverse clinical events in patients with acute pulmonary embolism (PE). MATERIALS AND RESULTS: This prospective study had institutional review board approval and was HIPAA compliant. In total 83 patients with confirmed PE underwent echocardiography and troponin I serum level measurements within 24 h. Three established cardiac CT measurements for the assessment of RVD were obtained (RV/LVaxial, RV/LV4-CH, and RV/LVvolume). CT measurements and troponin I serum levels were correlated with RVD found on echocardiography and adverse clinical events according to Management Strategies and Prognosis in Pulmonary Embolism Trial-3 (MAPPET-3 criteria. 31 of 83 patients with PE had RVD on echocardiography and 39 of 83 patients had adverse clinical events. A RV/LVvolume ratio>1.43 showed the highest area under the curve (AUC) (0.65) for the prediction of adverse clinical events when compared to RV/LVaxial, RV/LV4Ch and troponin I. The AUC for the detection of RVD of RV/LVaxial, RV/LV4Ch, RV/LVvolume, and troponin I were 0.86, 0.86, 0.92, and 0.69, respectively. Combination of RV/LVaxial, RV/LV4Ch, RV/LVvolume with troponin I increased the AUC to 0.87, 0.87 and 0.93, respectively. CONCLUSION: A combination of cardiac CT parameters and troponin I measurements improves the diagnostic accuracy for detecting RVD and predicting adverse clinical events if compared to either test alone.

Long-term follow-up after treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter.

OBJECTIVES: This study presents long-term clinical follow-up, including binary restenosis rate and major adverse cardiovascular events, of the PACCOCATH-ISR (Treatment of In-Stent Restenosis by Paclitaxel Coated PTCA Balloons) I and II trial. BACKGROUND: The PACCOCATH-ISR trial was a first-in-human study with a drug-coated balloon catheter and the first study for the treatment of coronary ISR with a drug-coated balloon. So, far no long-term follow-up data have been presented. METHODS: This study enrolled 108 patients in a randomized, double-blinded multicenter trial on the efficacy and safety of a paclitaxel-coated balloon (3 µg/mm(2) balloon surface; PACCOCATH [Bayer AG, Germany]) compared with an uncoated balloon. The main inclusion criteria were a diameter stenosis of ≥ 70% and <30-mm length with a vessel diameter of 2.5 to 3.5 mm. The primary endpoint was angiographic late lumen loss in-segment after 6 months. Combined antiplatelet therapy was continued only for 1 month followed by treatment with aspirin alone. RESULTS: During a follow-up of 5.4 ± 1.2 years, the clinical event rate was significantly reduced in patients treated with the drug-coated balloon (major adverse cardiovascular events: 59.3% vs. 27.8%, p = 0.009), which was mainly driven by the reduction of target lesion revascularization from 38.9% to 9.3% (p = 0.004). CONCLUSIONS: Treatment of coronary ISR with paclitaxel-coated balloon catheters is safe and persistently reduces repeat revascularization during long-term follow-up. The initial results were sustained over the 5-year period. (Treatment of In-Stent Restenosis by Paclitaxel Coated PTCA Balloons [PACCOCATH ISR I]; NCT00106587. Treatment of In-Stent Restenosis by Paclitaxel Coated PTCA Balloons [PACCOCATH ISR II]; NCT00409981).

Midregional pro-atrial natriuretic peptide: a novel marker of myocardial fibrosis in patients with hypertrophic cardiomyopathy.

We aimed to determine the diagnostic performance of biomarkers in predicting myocardial fibrosis assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) in patients with hypertrophic cardiomyopathy (HCM). LGE CMR was performed in 40 consecutive patients with HCM. Left and right ventricular parameters, as well as the extent of LGE were determined and correlated to the plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), carboxy-terminal pro-vasopressin (CT-proAVP), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8). Myocardial fibrosis was assumed positive, if CMR indicated LGE. LGE was present in 26 of 40 patients with HCM (65%) with variable extent (mean: 14%, range: 1.3-42%). The extent of LGE was positively associated with MR-proANP (r = 0.4; P = 0.01). No correlations were found between LGE and MR-proADM (r = 0.1; P = 0.5), CT-proET-1 (r = 0.07; P = 0.66), CT-proAVP (r = 0.16; P = 0.3), MMP-9 (r = 0.01; P = 0.9), TIMP-1 (r = 0.02; P = 0.85), and IL-8 (r = 0.02; P = 0.89). After adjustment for confounding factors, MR-proANP was the only independent predictor associated with the presence of LGE (P = 0.007) in multivariate analysis. The area under the ROC curve (AUC) indicated good predictive performance (AUC = 0.882) of MR-proANP with respect to LGE. The odds ratio was 1.268 (95% confidence interval 1.066-1.508). The sensitivity of MR-proANP at a cut-off value of 207 pmol/L was 69%, the specificity 94%, the positive predictive value 90% and the negative predictive value 80%. The results imply that MR-proANP serves as a novel marker of myocardial fibrosis assessed by LGE CMR in patients with HCM.

Challenging pacemaker implantation in a patient with acquired dextrocardia after pneumonectomy, skoliosis and complete heart block.

Pacemaker implantation after pneumonectomy is rare and there have been no previously reported cases of acquired dextrocardia after implantation. The authors report the case of a pacemaker implantation in a patient with complete heart block, impaired left ventricular function, sclerosis of heart valves and radiation induced vasculopathy resulting in ostial stenosis of the right coronary artery 30 years after radiochemotherapy in childhood. Acquired dextrocardia after right pneumonectomy for mucoepidermoid carcinoma made implantation a challenge due to and poor fluoroscopic visualization of the heart and increased radio-opacity of the right chest when compared to congenital dextrocardia.

Bioimpedance analysis parameters and epicardial adipose tissue assessed by cardiac magnetic resonance imaging in patients with heart failure.

There is increasing evidence that body composition should be considered as a systemic marker of disease severity in congestive heart failure (CHF). Prior studies established bioelectrical impedance analysis (BIA) as an objective indicator of body composition. Epicardial adipose tissue (EAT) quantified by cardiac magnetic resonance (CMR) is the visceral fat around the heart secreting various bioactive molecules. Our purpose was to investigate the association between BIA parameters and EAT assessed by CMR in patients with CHF. BIA and CMR analysis were performed in 41 patients with CHF and in 16 healthy controls. Patients with CHF showed a decreased indexed EAT (22 ± 5 vs. 34 ± 4 g/m(2), P < 0.001) and phase angle (PA) (5.5° vs. 6.4°, P < 0.02) compared to healthy controls. Linear regression analysis showed a significant correlation of CMR indexed EAT with left ventricular ejection fraction (LV-EF) (r = 0.56, P < 0.001), PA (r = 0.31, P = 0.01), total body muscle mass (TBMM) (r = 0.41, P = 0.001), fat-free mass (FFM) (r = 0.30, P = 0.02), and intracellular water (ICW) (0.47, P = 0.0003). Multivariable analysis demonstrated that LV-EF was the only independent determinant of indexed EAT (P < 0.0001). Receiver operating characteristic curve analysis indicated good predictive performance of PA and EAT (area under the curve (AUC) = 0.86 and 0.82, respectively) with respect to cardiac death. After a follow-up period of 5 years, 8/41 (19.5%) patients suffered from cardiac death. Only indexed EAT <22 g/m(2) revealed a statistically significant higher risk of cardiac death (P = 0.02). EAT assessed by CMR correlated with the BIA-derived PA in patients with CHF. EAT and BIA-derived PA might serve as additional prognostic indicators for survival in these patients. However, further clinical studies are needed to elucidate the prognostic relevance of these new findings.

Two year follow-up after treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter.

BACKGROUND: We are presenting an extension of a previously published trial on the efficacy and safety of a paclitaxel-coated balloon in coronary ISR in a larger patient population and after a complete follow-up of 2 years. METHODS: Hundred eight patients were enrolled in two separately randomized, double-blind multicenter trials on efficacy and safety using an identical protocol. Patients were treated by the paclitaxel-coated (3 microg/mm(2) balloon surface; Paccocath) or an uncoated balloon. The main inclusion criteria were a diameter stenosis of >or=70% and <30 mm length with a vessel diameter of 2.5-3.5 mm. The primary endpoint was angiographic late lumen loss in-segment. Secondary endpoints included binary restenosis rate and major adverse cardiovascular events (MACE). RESULTS: Quantitative coronary angiography revealed no differences in baseline parameters. After six months in-segment late lumen loss was 0.81 +/- 0.79 mm in the uncoated balloon group vs. 0.11 +/- 0.45 mm (P < 0.001) in the drug-coated balloon group resulting in a binary restenosis rate of 25/49 vs. 3/47 (P < 0.001). Until 12 months post procedure 20 patients in the uncoated balloon group compared to two patients in the coated balloon group required target lesion revascularization (P = 0.001). Between 12 and 24 only two MACE were recorded, a stroke in the uncoated and a target lesion revascularization in the coated balloon group. CONCLUSION: Treatment of coronary ISR with paclitaxel-coated balloon catheters persistently reduces repeat restenosis up to 2 years. (ClinicalTrials.gov Identifier: NCT00106587, NCT00409981).

Midregional pro-atrial natriuretic peptide is a useful indicator for the detection of impaired left ventricular function in patients with coronary artery disease.

AIMS: We compared the diagnostic performance of N-terminal pro-brain natriuretic peptide (NT-proBNP) with a newly developed assay for the midregional part of pro-atrial natriuretic peptide (MR-proANP) concerning the detection of impaired left ventricular ejection function (LVEF) among patients with coronary artery disease (CAD). METHODS AND RESULTS: Plasma levels of MR-proANP and NT-proBNP were determined in 102 consecutive patients with a history of ST-elevation myocardial infarction. Plasma levels of both markers were measured during a mean follow-up period of 687 days after acute myocardial infarction. Univariate analyses revealed inverse correlations between MR-proANP levels and LVEF (r=-0.39; p<0.001), NT-proBNP levels and LVEF (r=-0.39; p<0.001) and a positive correlation between MR-proANP and NT-proBNP (r=0.75; p<0.001). After adjustment for traditional risk factors, MR-proANP was the strongest predictor for LVEF (p=0.001) in multivariate analysis, being even superior to NT-proBNP. The area under the ROC curve (AUC) indicated moderate performance (AUC=0.73; p<0.01) of MR-proANP regarding the detection of a reduced LVEF<50%. The AUC of NT-proBNP for detection of impaired LVEF<50% was 0.68 (p=0.019). The negative predictive values of both markers were 86% for MR-proANP at a cut-off >135 pmol/L and NT-proBNP at a cut-off >560 pmol/L. At these cut-offs, the specificity of MR-proANP was 90%, and the specificity of NT-proBNP was 84%. CONCLUSIONS: MR-proANP is a useful indicator for the exclusion of a preserved left ventricular function in patients with coronary artery disease. The study demonstrates that the diagnostic performance of MR-proANP is comparable to the "gold standard" NT-proBNP.

Volumetric assessment of epicardial adipose tissue with cardiovascular magnetic resonance imaging.

OBJECTIVE: Previous studies determined the amount of epicardial fat by measuring the right ventricular epicardial fat thickness. However, it is not proven whether this one-dimensional method correlates well with the absolute amount of epicardial fat. In this prospective study, a new cardiovascular magnetic resonance imaging (CMR) method using the three-dimensional summation of slices method was introduced to assess the total amount of epicardial fat. RESEARCH METHODS AND PROCEDURES: CMR was performed in 43 patients with congestive heart failure and in 28 healthy controls. The absolute amount of epicardial fat was assessed volumetrically in consecutive short-axis views by means of the modified Simpson's rule. Additionally, the right ventricular epicardial fat thickness was measured in two different imaging planes: long-axis view (EFT-4CV) and consecutive short-axis views (EFT-SAX). RESULTS: Using the volumetric approach, patients with congestive heart failure had less epicardial fat mass than controls (51 g vs. 65 g, p=0.01). This finding was supported by EFT-SAX (2.9 mm vs. 4.3 mm, p<0.0001) but not by EFT-4CV (3.5 mm vs. 3.8 mm, p=not significant). Epicardial fat mass correlated moderately with EFT-SAX in both groups (r=0.466, p=0.012 in controls and r=0.590, p<0.0001 in patients) and with EFT-4CV in controls (r=0.387, p=0.042). There were no significant differences between EFT-4CV and EFT-SAX in controls (4.3 mm vs. 3.8 mm, p=0.240). However, in the heart failure group, EFT-4CV was significantly higher compared with EFT-SAX (3.5 mm vs. 2.9 mm, p=0.003). Interobserver variability and reproducibility were superior for the volumetric approach compared with thickness measurements. DISCUSSION: Quantitative assessment of epicardial fat mass using the CMR-based volumetric approach is feasible and yields superior reproducibility compared with conventional methods.