Prognostic markers for the clinical course in the blood of patients with SARS-CoV-2 infection.

BACKGROUND: The presentation of peptides and the subsequent immune response depend on the MHC characteristics and influence the specificity of the immune response. Several studies have found an association between HLA variants and differential COVID-19 outcomes and have shown that HLA genotypes are associated with differential immune responses against SARS-CoV-2, particularly in severely ill patients. Information, whether HLA haplotypes are associated with the severity or length of the disease in moderately diseased individuals is absent. METHODS: Next-generation sequencing-based HLA typing was performed in 303 female and 231 male non-hospitalized North Rhine Westphalian patients infected with SARS-CoV2 during the first and second wave. For HLA-Class I, we obtained results from 528 patients, and for HLA-Class II from 531. In those patients, who became ill between March 2020 and January 2021, the 22 most common HLA-Class I (HLA-A, -B, -C) or HLA-Class II (HLA -DRB1/3/4, -DQA1, -DQB1) haplotypes were determined. The identified HLA haplotypes as well as the presence of a CCR5Δ32 mutation and number of O and A blood group alleles were associated to disease severity and duration of the disease. RESULTS: The influence of the HLA haplotypes on disease severity and duration was more pronounced than the influence of age, sex, or ABO blood group. These associations were sex dependent. The presence of mutated CCR5 resulted in a longer recovery period in males. CONCLUSION: The existence of certain HLA haplotypes is associated with more severe disease.

Acute cardiac side effects after COVID-19 mRNA vaccination: a case series.

BACKGROUND: Vaccination against SARS-CoV-2 has been the main tool to contain the pandemic. The rush development of the 3 vaccines and their expedited approval have led to inoculation of millions of patients around the world, leading to a containment of the disease. Despite continuous viral mutations and the identification of weaker variants, the severity of the infections has been mild, with many patients being either asymptomatic or recovering at home. Currently the focus has shifted from the host of organ damage related to the infection to potential side effects of the vaccine. Myocarditis has been reported as one of the potential side effects from the mRNA vaccine, affecting young healthy individuals. Up to September 30, 2021, 1.243 cases of myocarditis after vaccination with BNT162b2 Comirnaty© were registered in young adults by the Paul-Ehrlich-Institute in Germany alone. The exact pathophysiology and the risk factors for myocarditis following vaccination remain unclear. We present a case series of eight patients with cardiac symptom shortly after SARS-CoV-2 mRNA vaccination (BNT162b6, Biontech, Comirnaty© or mRNA-1237 Moderna, Spikevax©). PATIENTS AND METHODS: Eight patients between 13 and 56 years of age, vaccinated with either BNT162b2 or mRNA-1273 mRNA vaccine between January and August 2021 developed cardiac side effects shortly after either their first or second dose of the vaccine. Clinical data were retrieved from the clinical information system and analyzed. To support diagnosis of myocarditis or pericarditis, cardiac magnetic resonance imaging (MRI) was performed shortly after the onset of symptoms, with further investigations in severe cases. Symptoms were defined as dyspnea, chest pain and cardiac arrhythmia as determined by electrocardiography. RESULTS: Eight patients (5 males and 3 females) developed cardiac symptoms compatible with myocarditis, according to the CDC criteria, shortly after SARS-CoV-2 mRNA vaccination. Three patients (2 males, 1 female) required hospitalization due to severe chest pain and elevated troponin levels. All patients recovered fully within 7 days from the symptom onset. CONCLUSIONS: Our data suggest that cardiac adverse events such as myocarditis or pericarditis shortly after SARS-CoV-2 mRNA vaccination are rare but possible and occur particularly in male patients.

Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19.

BACKGROUND: COVID-19, the pandemic disease caused by infection with SARS-CoV-2, may take highly variable clinical courses, ranging from symptom-free and pauci-symptomatic to fatal disease. The goal of the current study was to assess the association of COVID-19 clinical courses controlled by patients' adaptive immune responses without progression to severe disease with patients' Human Leukocyte Antigen (HLA) genetics, AB0 blood group antigens, and the presence or absence of near-loss-of-function delta 32 deletion mutant of the C-C chemokine receptor type 5 (CCR5). PATIENT AND METHODS: An exploratory observational study including 157 adult COVID-19 convalescent patients was performed with a median follow-up of 250 days. The impact of different HLA genotypes, AB0 blood group antigens, and the CCR5 mutant CD195 were investigated for their role in the clinical course of COVID-19. In addition, this study addressed levels of severity and morbidity of COVID-19. The association of the immunogenetic background parameters were further related to patients' humoral antiviral immune response patterns by longitudinal observation. RESULTS: Univariate HLA analyses identified putatively protective HLA alleles (HLA class II DRB1*01:01 and HLA class I B*35:01, with a trend for DRB1*03:01). They were associated with reduced durations of disease instead decreased (rather than increased) total anti-S IgG levels. They had a higher virus neutralizing capacity compared to non-carriers. Conversely, analyses also identified HLA alleles (HLA class II DQB1*03:02 und HLA class I B*15:01) not associated with such benefit in the patient cohort of this study. Hierarchical testing by Cox regression analyses confirmed the significance of the protective effect of the HLA alleles identified (when assessed in composite) in terms of disease duration, whereas AB0 blood group antigen heterozygosity was found to be significantly associated with disease severity (rather than duration) in our cohort. A suggestive association of a heterozygous CCR5 delta 32 mutation status with prolonged disease duration was implied by univariate analyses but could not be confirmed by hierarchical multivariate testing. CONCLUSION: The current study shows that the presence of HLA class II DRB1*01:01 and HLA class I B*35:01 is of even stronger association with reduced disease duration in mild and moderate COVID-19 than age or any other potential risk factor assessed. Prospective studies in larger patient populations also including novel SARS-CoV-2 variants will be required to assess the impact of HLA genetics on the capacity of mounting protective vaccination responses in the future.

Delayed skin reaction after mRNA-1273 vaccine against SARS-CoV-2: a rare clinical reaction.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is associated with a wide clinical spectrum of skin manifestations, including urticarial, vesicular, vasculitic and chilblain-like lesions. Recently, delayed skin reactions have been reported in 1% individuals following mRNA vaccination against SARS-CoV-2. The exact pathophysiology and the risk factors still remain unclear. PATIENTS AND METHODS: 6821 employees and patients were vaccinated at our institutions between February and June 2021. Every patient received two doses of the mRNA-1273 vaccine in our hospitals, and reported back in case of any side effects which were collected in our hospital managed database. RESULTS: Eleven of 6821 vaccinated patients (0.16%) developed delayed skin reactions after either the first or second dose of the mRNA-1273 vaccine against SARS-CoV-2. Eight of 11 patients (73%) developed a rash after the first dose, while in 3/11 (27%), the rash occurred after the second dose. More females (9/11) were affected. Four of 11 patients required antihistamines, with two needing additional topical steroids. All the cutaneous manifestations resolved within 14 days. None of the skin reactions after the first dose of the vaccine prevented the administration of the second dose. There were no long-term cutaneous sequelae in any of the affected individuals. CONCLUSION: Our data suggests that skin reactions after the use of mRNA-1273 vaccine against SARS-CoV-2 are possible, but rare. Further studies need to be done to understand the pathophysiology of these lesions.

Informed consent and informed intervention: SARS-CoV-2 vaccinations not just call for disclosure of newly emerging safety data but also for hypothesis generation and testing.

BACKGROUND: COVID-19 infection is a major threat to patients and health care providers around the world. One solution is the vaccination against SARS-CoV-2. METHODS: We performed a comprehensive query of the latest publications on the prevention of viral infections including the recent vaccination program and its side effects. RESULTS: The situation is evolving rapidly and there is no reasonable alternative to population-scale vaccination programs as currently enrolled. CONCLUSION: Therefore, regulatory authorities should consider supplementing their conventional mandate of post-approval pharmacovigilance, which is based on the collection, assessment, and regulatory response to emerging safety findings.

Measures of infection prevention and incidence of SARS-CoV-2 infections in cancer patients undergoing radiotherapy in Germany, Austria and Switzerland.

PURPOSE: COVID-19 infection has manifested as a major threat to both patients and healthcare providers around the world. Radiation oncology institutions (ROI) deliver a major component of cancer treatment, with protocols that might span over several weeks, with the result of increasing susceptibility to COVID-19 infection and presenting with a more severe clinical course when compared with the general population. The aim of this manuscript is to investigate the impact of ROI protocols and performance on daily practice in the high-risk cancer patients during this pandemic. METHODS: We addressed the incidence of positive COVID-19 cases in both patients and health care workers (HCW), in addition to the protective measures adopted in ROIs in Germany, Austria and Switzerland using a specific questionnaire. RESULTS: The results of the questionnaire showed that a noteworthy number of ROIs were able to complete treatment in SARS-CoV­2 positive cancer patients, with only a short interruption. The ROIs reported a significant decrease in patient volume that was not impacted by the circumambient disease incidence, the type of ROI or the occurrence of positive cases. Of the ROIs 16.5% also reported infected HCWs. About half of the ROIs (50.5%) adopted a screening program for patients whereas only 23.3% also screened their HCWs. The range of protective measures included the creation of working groups, instituting home office work and protection with face masks. Regarding the therapeutic options offered, curative procedures were performed with either unchanged or moderately decreased schedules, whereas palliative or benign radiotherapy procedures were more often shortened. Most ROIs postponed or cancelled radiation treatment for benign indications (88.1%). The occurrence of SARS-CoV­2 infections did not affect the treatment options for curative procedures. Non-university-based ROIs seemed to be more willing to change their treatment options for curative and palliative cases than university-based ROIs. CONCLUSION: Most ROIs reported a deep impact of SARS-CoV­2 infections on their work routine. Modification and prioritization of treatment regimens and the application of protective measures preserved a well-functioning radiation oncology service and patient care.

Face masks: benefits and risks during the COVID-19 crisis.

BACKGROUND: The German government has made it mandatory to wear respiratory masks covering mouth and nose (MNC) as an effective strategy to fight SARS-CoV-2 infections. In many countries, this directive has been extended on shopping malls or public transportation. The aim of this paper is to critically analyze the statutory regulation to wear protective masks during the COVID-19 crisis from a medical standpoint. METHODS: We performed an extensive query of the most recent publications addressing the prevention of viral infections including the use of face masks in the community as a method to prevent the spread of the infection. We addressed the issues of practicability, professional use, and acceptability based on the community and the environment where the user resided. RESULTS: Upon our critical review of the available literature, we found only weak evidence for wearing a face mask as an efficient hygienic tool to prevent the spread of a viral infection. However, the use of MNC seems to be linked to relevant protection during close contact scenarios by limiting pathogen-containing aerosol and liquid droplet dissemination. Importantly, we found evidence for significant respiratory compromise in patients with severe obstructive pulmonary disease, secondary to the development of hypercapnia. This could also happen in patients with lung infections, with or without SARS-CoV-2. CONCLUSION: Epidemiologists currently emphasize that wearing MNC will effectively interrupt airborne infections in the community. The government and the politicians have followed these recommendations and used them to both advise and, in some cases, mandate the general population to wear MNC in public locations. Overall, the results seem to suggest that there are some clinically relevant scenarios where the use of MNC necessitates more defined recommendations. Our critical evaluation of the literature both highlights the protective effects of certain types of face masks in defined risk groups, and emphasizes their potential risks.

The history and value of face masks.

In the human population, social contacts are a key for transmission of bacteria and viruses. The use of face masks seems to be critical to prevent the transmission of SARS-CoV-2 for the period, in which therapeutic interventions are lacking. In this review, we describe the history of masks from the middle age to modern times.

Paroxysmal and persistent atrial fibrillation ablation outcomes with the pulmonary vein ablation catheter GOLD duty-cycled phased radiofrequency ablation catheter: quality of life and 12-month efficacy results from the GOLD Atrial Fibrillation Registry.

AIMS: The GOLD AF Registry has been designed to prospectively assess the population, indications, and outcomes using second-generation phased radiofrequency (RF) ablation (pulmonary vein ablation catheter GOLD) in a global examination of standard-of-care use for the treatment of paroxysmal and persistent atrial fibrillation (AF). METHODS AND RESULTS: GOLD AF (NCT02433613) is a prospective, observational, multi-centre registry designed to characterize efficacy and safety of phased RF ablation in patients with AF. The primary endpoint was freedom from AF recurrence at 12-month follow-up after a 90-day blanking period. Ancillary objectives include safety, procedural efficiency, and quality of life (QoL). The QoL assessment using the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and the European Heart Rhythm Association (EHRA) Score of AF-related symptoms was collected at baseline and 12 months. In total, 1054 patients were included in this analysis (age 60.6, 67.6% male, 26.5% PersAF). Kaplan-Meier estimate of freedom from AF recurrence was 77.7% at 12 months. Peri-procedural device or procedure-related complications were observed in 26 (2.5%) patients, with a low stroke rate of 0.3%. One-year post-ablation, the EHRA AF Symptom score decreased in 68% of patients. The AFEQT score improvement was observed in 88.4% and 90.4% of patients who completed the questionnaire in-person or interviewed by phone at 12 month follow-up, respectively. CONCLUSION: Phased RF ablation for the treatment of paroxysmal and persistent AF demonstrated a 77.7% freedom from AF recurrence at 12 months in addition to a significant reduction in arrhythmia symptoms and clinically meaningful improved QoL. Low peri-procedural complication rate of <3% was reported.

Diagnostic performance of magnetic resonance first pass perfusion imaging is equally potent in female compared to male patients with coronary artery disease.

BACKGROUND: Noninvasive diagnosis of coronary artery disease (CAD) in women is crucial because of a lower prevalence of CAD in premenopausal women, different cardiac risk profile and pattern of CAD, lower exercise tolerance and more atypical symptoms compared to men. Therefore, we tested the diagnostic power of cardiac magnetic resonance first pass perfusion imaging (CMR-FPPI) for the diagnosis of significant coronary stenoses in females versus males. METHODS AND RESULTS: 256 consecutive patients, 77 females and 179 males with atypical or typical chest pain and intermediate risk of CAD were studied by coronary angiography and CMR-FPPI (1.5T Intera CV). A three-slice, short-axis perfusion scan with a saturation prepulse was performed during infusion of adenosine and at rest followed by late enhancement imaging for myocardial scar. Gadolinium-DTPA was administered at 0.1 mmol/kg body weight. Perfusion images were visually analysed, coronary stenoses by quantitative coronary angiography. Sensitivity, specificity and accuracy of CMR-FPPI for detection of a significant coronary artery stenosis (> or = 50% luminal narrowing) in the entire group were 91.3, 81.7 and 88.6%, the corresponding values for females were 90.9, 90.6 and 90.8% and for males 91.4, 74.4 and 87.7%, and in the subgroup of females with suspected primary CAD 83.3, 96.0 and 93.6%, and for suspected progression 92.1, 71.4 and 88.9%. CONCLUSION: Diagnostic accuracy of CMR-FPPI is very high in women with intermediate risk of CAD and comparable or in part superior to results in males. With the advantage of the absence of radiation exposure and high spatial and temporal resolution, CMR-FPPI has the potential to become the preferred imaging test to select women for coronary angiography.

Assessment of myocardial perfusion for detection of coronary artery stenoses by steady-state, free-precession magnetic resonance first-pass imaging.

OBJECTIVE: To evaluate the diagnostic impact of magnetic resonance imaging (MRI) first-pass perfusion using steady-state, free-precession (SSFP) sequences with parallel imaging (SENSE) for detection of coronary stenoses. DESIGN: Prospective observational study. SETTING: University hospital, cardiac MRI and catheterisation laboratories. PATIENTS AND METHODS: 228 patients were examined with coronary angiography and MRI (1.5 T Intera CV). A three-slice, short-axis SSFP perfusion scan with a saturation prepulse was performed during infusion of adenosine and at rest followed by myocardial scar (late enhancement) imaging. Gadolinium-DTPA was given at 0.1 mmol/kg body weight. Perfusion images were visually assessed. Analysis for myocardial hypoperfusion was done according to patient group and according to vessel. RESULTS: Sensitivity, specificity and accuracy of MRI first-pass perfusion for detection of a coronary artery stenosis (>50% luminal narrowing) in the total patient group were 93.0%, 85.7%, 91.2% and for a significant lesion (>70% luminal narrowing) 96.1%, 72.0%, 88.2%, respectively. Based on 536 coronary artery territories without myocardial scar, the sensitivity of MRI perfusion analysis for detection of a significant lesion was for the left anterior descending artery 91.4%, for the circumflex artery 81.6% and for the right coronary artery 65.1% (p<0.001). CONCLUSIONS: MRI first-pass perfusion analysis using an SSFP sequence with three myocardial slices was a highly accurate diagnostic method for detection of coronary artery stenoses. This MRI technique can be included in daily practice and has the potential to guide the indication for invasive coronary angiography.

Myocardial perfusion reserve in cardiovascular magnetic resonance: Correlation to coronary microvascular dysfunction.

The present study examined the association of myocardial perfusion reserve index (MPRI) in cardiovascular magnetic resonance (CMR) with coronary microvascular dysfunction (CMD) and serum levels of markers of inflammation or endothelial activation. Twelve patients with typical angina pectoris without coronary artery disease were enrolled in this study, and CMR perfusion was analyzed using a steady-state-free-precession sequence with 3 short axis slices per heartbeat during first pass of 0.025 mmol Gadolinium-DTPA/kg body weight. The upslope of myocardial signal intensity curves was used to calculate MPRI. CMD was assessed by intracoronary Doppler flow measurement and biplane angiography. Both MPRI and CMD were assessed during endothelium-independent stimulation with intravenous adenosine and during endothelium-dependent stimulation with intracoronary infusion of acetylcholine. Serum values of soluble CD40 ligand (sCD40L), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), and C-reactive protein (CRP) were measured. Impaired MPRI correlated significantly with a decrease in coronary blood flow reserve after both endothelium-dependent (p = 0.033) and endothelium-independent (p = 0.022) stimulation. Serum levels above the median of all normal ranged biomarkers sCD40L, TNF-alpha, IL-6, sICAM-1 and CRP were associated with an impaired MPRI for stimulation with adenosine as well as acetylcholine. In multivariable analyses, sCD40L (p < 0.001) and TNF-alpha (p = 0.011) were significantly associated with a decrease in MPRI on adenosine, as were TNF-alpha (p = 0.016) and sICAM-1 (p = 0.022) for a decrease in MPRI on acetylcholine. MPRI on adenosine significantly correlated with MPRI on acetylcholine (p < 0.001). Therefore, the present study demonstrates safety and feasibility of an intracoronary infusion of acetylcholine during CMR perfusion analysis, thus allowing direct assessment of endothelial dependent vasomotor function at the myocardial level by CMR. Furthermore, we show that an impaired myocardial perfusion reserved in CMR is associated with established biomarkers of early atherosclerosis and significantly correlated with CMD. CMR combined with adenosine could be proposed as a non-invasive tool to evaluate CMD.

Cardiac magnetic resonance imaging and transesophageal echocardiography in patients with transcatheter closure of patent foramen ovale.

OBJECTIVES: We studied the value of cardiac magnetic resonance imaging (CMRI) before and after closure of patent foramen ovale (PFO) in patients with cryptogenic ischemic events. BACKGROUND: Cardiac magnetic resonance imaging is a powerful noninvasive tool for detailed assessment of cardiac anatomy and function. The relevance of CMRI compared with transesophageal echocardiography (TEE) in patients undergoing transcatheter PFO closure has not been evaluated so far. METHODS: Contrast-enhanced CMRI and TEE were performed in 75 patients before and after PFO closure. Twelve months after PFO closure, both imaging techniques were repeated in 61 patients with contrast application. To determine provokable atrial right-to-left shunting in CMRI, we applied a contrast-enhanced perfusion imaging technique. Detection of atrial septal aneurysm (ASA) was achieved by means of a high-resolution cine imaging technique. RESULTS: Before PFO closure, ASA was seen with CMRI in 28 of 75 cases (37.3%), compared with 47 of 75 (62.7%) cases using TEE. There were a total of 211 CMRI studies with a corresponding TEE performed in 75 patients. No shunt was present in 107 of 211 studies with both techniques. Contrast-enhanced right-to-left shunting was detected by CMRI in 48 of 72 (66.6%) cases with moderate or severe shunts seen with TEE, but only in 6 of 32 (18.8%) studies with mild shunts with TEE. Anomalous venous returns were excluded in all patients. In two patients, coronary anomalies were seen. CONCLUSIONS: The present CMRI technique is inferior to TEE in detection of contrast-enhanced right-to-left shunting and identification of ASA.

Myocardial biopsy findings and gadolinium enhanced cardiovascular magnetic resonance in dilated cardiomyopathy.

BACKGROUND: In some patients suffering from dilated cardiomyopathy (DCM) magnetic resonance imaging (MRI) shows late gadolinium enhancement with variable distribution. Myocardial biopsies in DCM reveal a chronic myocardial inflammatory process in almost 50% and myocardial persistence of adenoviral or enteroviral genome in about 15% of the patients. AIMS: We prospectively investigated whether the pattern of late gadolinium enhancement correlates with myocardial biopsy findings. METHODS AND RESULTS: 42 patients with DCM and 42 control subjects underwent contrast MRI. In the DCM group, endomyocardial biopsies were performed and evaluated for inflammation and viral genome. None of the control subjects showed late gadolinium enhancement whereas in 29 DCM patients (69%) gadolinium enhancement was detectable (p<0.001). 21 of the DCM patients (50%) showed midwall septal enhancement, 7 patients (17%) showed a patchy distribution of hyperenhancement and 1 patient (2%) showed enhancement typical for ischemic heart disease. In myocardial biopsy analysis, 2 patients (5%) showed persistence of viral genome, 18 patients (43%) showed inflammation and in 22 patients (52%) neither virus nor inflammation was detected. The pattern of late gadolinium enhancement and myocardial biopsy findings were not significantly correlated (p = 0.854). CONCLUSION: MRI as a non-invasive technique cannot replace myocardial biopsy for the differential diagnosis of DCM.

Sequelae of acute myocardial infarction regarding cardiac structure and function and their prognostic significance as assessed by magnetic resonance imaging.

AIMS: Because of its high spatial resolution and tissue contrast, magnetic resonance imaging (MRI) was used to assess cardiac structure and function in a large population of patients with acute myocardial infarction (AMI). METHODS AND RESULTS: One hundred and ten patients were studied by MRI 6.1 +/- 2.2 days after AMI. Infarct size (IS), persistent microvascular obstruction (PMO), left and right ventricular (LV/RV) volumes, and functions were measured. The same MRI measurements were repeated in 89 patients after a mean follow-up period of 225 +/- 92 days. IS was 11.9 +/- 7.3% of total LV muscle mass. PMO was detected in 51/110 (46.4%) patients and comprised 15.6 +/- 8.5% of IS and 2.8 +/- 2.3% of LV muscle mass. Papillary muscle infarct was seen in 26%, RV infarction in 16%, pericarditis in 40%, and pericardial effusion in 66% of the patients. During follow-up, there were 16 major adverse cardiac events (MACE) including seven deaths. IS, PMO, and amount of transmural infarction were predictive for LV adverse remodelling defined as > 20% increase in LV end-diastolic volume. Multivariable analysis revealed LV end-diastolic volume, LV ejection fraction, and PMO as significant predictors for the occurrence of MACE. CONCLUSION: MRI is a highly sensitive and reliable tool to detect morphologic and functional sequelae of AMI providing baseline MRI parameters with relevant predictive power for LV adverse remodelling and occurrence of MACE.

Optimal acquisition parameters for contrast enhanced magnetic resonance imaging after chronic myocardial infarction.

The aim of this study was to simplify the imaging of myocardial infarction based on theoretical aspects and patient variables and to define the optimal time for image acquisition. Thirteen patients with chronic myocardial infarction underwent magnetic resonance imaging. After injection of 0.2 mmol/kg body weight Gd-DTPA an inversion recovery turbo gradient echo sequence with different prepulse delays was applied every 3 to 5 minutes within an interval of 3 to 30 minutes. As parameters of investigation, the area of signal enhancement and the contrast between enhanced and nonenhanced myocardium were used. There was no influence of prepulse delay or time after contrast injection on the enhanced area. The contrast between enhanced and normal myocardium showed a peak at 6 minutes post Gd-DTPA injection and remained high. The contrast between blood and enhanced myocardium was best at 6 and 25 minutes with best intra- and interobserver variability. In conclusion, if a suitable contrast was achieved, the area of enhancement is independent of prepulse delay or imaging time. In most patients the highest contrast between blood, enhanced and normal myocardium is achieved 6 minutes and 25 minutes after contrast injection.

Salvage treatment with amphotericin B in progressive human alveolar echinococcosis.

Most patients with alveolar echinococcosis are diagnosed at a late stage when the disease has advanced to unresectable hepatic lesions. These patients require lifelong therapy with benzimidazoles, the only medical treatment currently available. To date, no treatment option remains for patients with benzimidazole intolerance or treatment failure. Amphotericin B was recently shown to exert antiparasitic activity in vitro. Here, we report the efficacy of amphotericin B in human alveolar echinococcosis. In three patients with extensive disease and without further treatment options, disease progression had been documented over several months. They were treated with amphotericin B intravenously at a dose of 0.5 mg/kg of body weight three times per week. Follow-up parameters were physical examination, laboratory parameters, and imaging techniques. Amphotericin B treatment effectively halted parasite growth in all three patients. The antiparasitic effect was most evident by spontaneous closure of cutaneous fistulae in two patients and by constant size of parasitic lesions during treatment, as assessed radiologically. Metabolic activity in parasitic areas was visualized by positron emission tomography and significantly decreased during treatment. However, progressive affection of the heart in one patient could not be stopped. All patients currently continue on amphotericin B and have been treated for 25, 17, and 14 months, respectively. We introduce amphotericin B as salvage treatment for alveolar echinococcosis patients with intolerance or resistance to benzimidazoles, as it effectively suppresses parasite growth. Amphotericin B is not parasitocidal; therefore long-term treatment has to be anticipated.

Intracoronary beta-irradiation with a rhenium-188-filled balloon catheter: a randomized trial in patients with de novo and restenotic lesions.

BACKGROUND: Restenosis requiring reintervention is the main limitation of coronary angioplasty. Intracoronary irradiation reduces neointimal proliferation. We studied the efficacy of a self-centering liquid rhenium-188-filled balloon catheter for coronary beta-brachytherapy. METHODS AND RESULTS: After successful coronary angioplasty with or without stenting, 225 patients (71% de novo lesions) were randomly assigned to receive 22.5 Gy intravascular beta-irradiation in 0.5-mm tissue depth (n=113) or to receive no additional intervention (n=112). Clinical and procedural data did not differ between the groups except a higher rate of stenting in the control group (63%) compared with the rhenium-188 group (45%, P<0.02). After 6 months of follow-up, late loss was significantly lower in the irradiated group compared with the control group, both of the target lesion (0.11+/-0.54 versus 0.69+/-0.81 mm, P<0.0001) and of the total segment (0.22+/-0.67 versus 0.70+/-0.82 mm, P<0.0001). This was also evident in the subgroup of patients with de novo lesions and independent from stenting. Binary restenosis rates were significantly lower at the target lesion (6.3% versus 27.5%, P<0.0001) and of the total segment (12.6% versus 28.6%, P<0.007) after rhenium-188 brachytherapy compared with the control group. Target vessel revascularization rate was significantly lower in the rhenium-188 (6.3%) compared with the control group (19.8%, P=0.006). CONCLUSIONS: Intracoronary beta-brachytherapy with a rhenium-188 liquid-filled balloon is safe and efficiently reduces restenosis and revascularization rates after coronary angioplasty.

Reduction of major adverse cardiac events with intracoronary compared with intravenous bolus application of abciximab in patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty.

BACKGROUND: In patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty, abciximab reduces major adverse cardiac events (MACE). Clinical trials have studied intravenous administration only. Intracoronary bolus application of abciximab causes very high local drug concentrations and may be more effective. We studied whether intracoronary bolus administration of abciximab is associated with a reduced MACE rate compared with the standard intravenous bolus application. METHODS AND RESULTS: We stratified 403 consecutive patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty according to the type of application of abciximab. A 20-mg bolus of abciximab was given intravenously in 109 patients and intracoronarily in 294 patients. There were no differences between the groups with regard to diabetes mellitus, cardiogenic shock, successful intervention, or preprocedural and postprocedural TIMI flow. At 30 days, the incidence of MACE (death, myocardial infarction, urgent revascularization) was significantly lower in the patients with intracoronary compared with intravenous administration of abciximab (10.2% versus 20.2%; P<0.008), which was independent from stenting in multivariate analysis. The effect was most pronounced in patients with preprocedural TIMI 0/1 flow (MACE: intracoronary 11.8% versus intravenous 27.5%, P<0.002; n=273). CONCLUSIONS: In patients with acute myocardial infarction or unstable angina undergoing emergency coronary angioplasty, intracoronary bolus application of abciximab is associated with a reduction of MACE compared with the standard intravenous bolus application of abciximab. Prospective, randomized trials are warranted to further assess intracoronary application of abciximab.