Percutaneous balloon pericardiotomy: efficacy in a series of malignant and nonmalignant cases.

OBJECTIVE: In the case of malignant pericardial effusion and cardiac tamponade, balloon pericardiotomy is an established minimally invasive option to the surgical creation of a subxiphoid pericardial window. Percutaneous balloon pericardiotomy effectively drains recurrent pericardial fluid by creating a pleuro (-abdominal-) pericardial communication. Design. A series of 26 patients with underlying malignant (n = 12) and nonmalignant (n = 14) diseases underwent percutaneous balloon pericardiotomy between 2008 and 2021. All interventions were done through a subxiphoid access under local anesthesia. Results. The mean survival in the malignant and nonmalignant groups was 1.2 versus 48.0 months, respectively (p < .001). There were neither severe periinterventional complications nor in-hospital deaths. In two patients with nonmalignant disease the surgical creation of a pericardial window was necessary during follow-up. The originally described procedure was modified by the removal of all catheters at the end of the intervention. The procedure was safe. It prevented immobility and facilitated an early discharge from the hospital. Conclusion. Our experiences show that percutaneous balloon pericardiotomy is a minimally invasive approach to successfully provide palliation in the group of patients with underlying malignant disease. On the other hand, we have shown that this technique is safe and feasible in the treatment of pericardial effusion based on nonmalignant disease. We think thereby that pericardial balloon pericardiotomy can be considered as a less invasive alternative to surgery in both groups of patients.

Impact of an In-Hospital Endocarditis Team and a State-Wide Endocarditis Network on Perioperative Outcomes.

BACKGROUND: Infective endocarditis (IE) requires multidisciplinary management. We established an endocarditis team within our hospital in 2011 and a state-wide endocarditis network with referring hospitals in 2015. We aimed to investigate their impact on perioperative outcomes. METHODS: We retrospectively analyzed data from patients operated on for IE in our center between 01/2007 and 03/2018. To investigate the impact of the endocarditis network on referral latency and pre-operative complications we divided patients into two eras: before (n = 409) and after (n = 221) 01/2015. To investigate the impact of the endocarditis team on post-operative outcomes we conducted multivariate binary logistic regression analyses for the whole population. Kaplan-Meier estimates of 5-year survival were reported. RESULTS: In the second era, after establishing the endocarditis network, the median time from symptoms to referral was halved (7 days (interquartile range: 2-19) vs. 15 days (interquartile range: 6-35)), and pre-operative endocarditis-related complications were reduced, i.e., stroke (14% vs. 27%, p < 0.001), heart failure (45% vs. 69%, p < 0.001), cardiac abscesses (24% vs. 34%, p = 0.018), and acute requirement of hemodialysis (8% vs. 14%, p = 0.026). In both eras, a lack of recommendations from the endocarditis team was an independent predictor for in-hospital mortality (adjusted odds ratio: 2.12, 95% CI: 1.27-3.53, p = 0.004) and post-operative stroke (adjusted odds ratio: 2.23, 95% CI: 1.12-4.39, p = 0.02), and was associated with worse 5-year survival (59% vs. 40%, log-rank < 0.001). CONCLUSION: The establishment of an endocarditis network led to the earlier referral of patients with fewer pre-operative endocarditis-related complications. Adhering to endocarditis team recommendations was an independent predictor for lower post-operative stroke and in-hospital mortality, and was associated with better 5-year survival.

Giant Aneurysm of the Right Coronary Artery: Multimodality Imaging and Interventional Management.

A large (40-mm) circular structure in the right atrioventricular groove was detected by transthoracic echocardiography and was diagnosed as a giant aneurysm of the right coronary artery. Through invasive mapping by a guide extension catheter, the aneurysm could be excluded by implantation of 3 overlapping stent grafts. (Level of Difficulty: Beginner.).

Cardiac tamponade following aortic root erosion by an Amplatzer PFO-Occluder in a 41-year-old woman: Only a matter of sizing?

A 41-year-old woman who had suffered an acute stroke underwent closure of a persistent patent foramen ovale (PFO) two months later. Eleven months after PFO closure the patient was hospitalized with signs of cardiogenic shock due to cardiac tamponade. Imaging studies showed a correct position of the left occluder disc, whereas the right atrial disc was in direct contact with the aortic root. At day 6, the patient underwent surgery via a minimally invasive route under cardiopulmonary bypass. The left atrial disc of the occluder was in a correct position. A too big right atrial disc together with a sharp angle misalignment toward the right atrial wall led to an erosion of the right atrial wall and of the wall of the aortic root. The occluder was explanted and the PFO closed by direct suture. Given the increasing number of procedures performed, serious and potentially life-threatening complications - even if rare - deserve special attention. Even though device oversizing was the most likely factor causing the erosion, other factors may play a role, as the patient used whole-body vibration starting three months before the incident. This could explain why the event happened as late as 11 months after the initial PFO closure. .

Left atrial appendage closure in patients with chronic kidney disease: results from the German multicentre LAARGE registry.

OBJECTIVES: Chronic kidney disease (CKD) is associated with an increased complication rate after cardiac interventions. Although CKD has a high prevalence among atrial fibrillation patients, the impact of CKD on periprocedural complications and the outcome after an interventional left atrial appendage closure (LAAC) is unclear. The present study, therefore, aimed to investigate whether CKD influences the procedure's effectiveness and safety. METHODS: LAARGE is a prospective, non-randomised registry. LAAC was conducted with different standard commercial devices, and the follow-up period was one year. CKD was defined by an eGFR < 60 mL/min/1.73 m2, and subgroups were further analysed (i.e. eGFR < 15, 15-29, and 30-59 mL/min/1.73 m2, respectively). RESULTS: Two hundred ninety-nine of 623 patients (48.0%) revealed a CKD. The prevalence of cardiovascular comorbidity, CHA2DS2-VASc score (4.9 vs. 4.2), and HAS-BLED score (4.3 vs. 3.5) was significantly higher in CKD patients (each p < 0.001). Implantation success was similarly high across all GFR groups (97.9%). Periprocedural MACCE (0.7 vs. 0.3%), and other major complications (4.7 vs. 3.7%) were comparably infrequent. Survival free of stroke was significantly lower among CKD patients within 1 year (82.0 vs. 93.0%; p < 0.001; consistent after adjustment for confounding factors), without significant accentuation in advanced CKD (i.e. eGFR < 30 mL/min/1.73 m2; p > 0.05 vs. eGFR 30-59 mL/min/1.73 m2). Non-fatal strokes were absolutely infrequent during follow-up (0 vs. 1.1%). Severe non-fatal bleedings were observed only among CKD patients (1.4 vs. 0%; p = 0.021). CONCLUSIONS: Despite an increased cardiovascular risk profile of CKD patients, device implantation was safe, and LAAC was associated with effective stroke prevention across all CKD stages.

Comparison in Patients < 75 Years of Age - Versus - Those > 75 Years on One-year-Events With Atrial Fibrillation and Left Atrial Appendage Occluder (From the Prospective Multicenter German LAARGE Registry).

Left atrial appendage closure (LAAC) is an alternative to oral anticoagulation therapy in patients with non-valvular atrial fibrillation for the prevention of embolic stroke and systemic embolism. Although elderly patients (>75 years) have both higher ischemic and bleeding risk as compared with younger patients, they benefit from optimal anticoagulation. The subanalysis aimed to assess the indications, the safety, efficacy, and 1-year outcomes of interventional LAAC in elderly patients (≥ 75 years) compared with younger (< 75 years) patients in clinical practice. We analyzed data from the prospective Left-Atrium-Appendage Occluder Registry Germany. A total of 638 patients were included in the registry, 402 (63%) were aged ≥ 75 years. Compared with younger subjects, patients aged ≥75 were more likely to have higher CHA2DS2-VASC and HAS-BLED scores. Procedural success rate was high und similar in both groups (97.6%). Periprocedural adverse events were not statistically significant in groups (11.9% in <75 years vs 12.9% in ≥75 years; p = 0.80). At 1 year follow-up, all-cause mortality was higher in patients aged ≥75 compared withwith younger group (13.0% vs 7.8 %,p = 0.04), mainly due to non-cardiovascular causes (10.6% vs 6.0%). No significant differences in major bleeding, stroke, systemic embolism were observed. In conclusion, LAAC is feasible and safe in patients with AF at high stroke risk and with contraindications for OAC and should be considered as candidates for LAA closure. Elderly patients often present these characteristics and could benefit from this novel therapy.

Coronary Artery Fistula Unmasking the Absence of Left Pulmonary Artery in an Adult.

Coronary artery fistulae are an incidental finding in patients undergoing coronary angiography or computed tomography (CT) coronary angiography. A 60-year-old man with known coronary artery disease presented with dyspnea. Coronary angiography revealed a large fistula arising from the circumflex artery (CX) without a clear intrathoracic target vessel or chamber in the heart. CT angiography revealed the agenesis of the left pulmonary artery. The fistula arising from the CX ensured left lung tissue supply. Unilateral absence of a pulmonary artery is an extremely rare condition. In this case, the identification of a fistula from the heart triggered the correct diagnosis.

PCI and CABG for Treating Stable Coronary Artery Disease: JACC Review Topic of the Week.

Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are considered revascularization procedures, but only CABG can prolong life in stable coronary artery disease. Thus, PCI and CABG mechanisms may differ. Viability and/or ischemia detection to guide revascularization have been unable to accurately predict treatment effects of CABG or PCI, questioning a revascularization mechanism for improving survival. By contrast, preventing myocardial infarction may save lives. However, the majority of infarcts are generated by non-flow-limiting stenoses, but PCI is solely focused on treating flow-limiting lesions. Thus, PCI cannot be expected to significantly limit new infarcts, but CABG may do so through providing flow distal to vessel occlusions. All comparisons of CABG to PCI or medical therapy that demonstrate survival effects with CABG also demonstrate infarct reduction. Thus, CABG may differ from PCI by providing "surgical collateralization," prolonging life by preventing myocardial infarctions. The evidence is reviewed here.

Coronary computed tomography angiography for heart team decision-making in multivessel coronary artery disease.

Aims: Coronary computed tomography angiography (CTA) has emerged as a non-invasive diagnostic method for patients with suspected coronary artery disease, but its usefulness in patients with complex coronary artery disease remains to be investigated. The present study sought to determine the agreement between separate heart teams on treatment decision-making based on either coronary CTA or conventional angiography. Methods and results: Separate heart teams composed of an interventional cardiologist, a cardiac surgeon, and a radiologist were randomized to assess the coronary artery disease with either coronary CTA or conventional angiography in patients with de novo left main or three-vessel coronary artery disease. Each heart team, blinded for the other imaging modality, quantified the anatomical complexity using the SYNTAX score and integrated clinical information using the SYNTAX Score II to provide a treatment recommendations based on mortality prediction at 4 years: coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or equipoise between CABG and PCI. The primary endpoint was the agreement between heart teams on the revascularization strategy. The secondary endpoint was the impact of fractional flow reserve derived from coronary CTA (FFRCT) on treatment decision and procedural planning. Overall, 223 patients were included. A treatment recommendation of CABG was made in 28% of the cases with coronary CTA and in 26% with conventional angiography. The agreement concerning treatment decision between coronary CTA and conventional angiography was high (Cohen's kappa 0.82, 95% confidence interval 0.74-0.91). The heart teams agreed on the coronary segments to be revascularized in 80% of the cases. FFRCT was available for 869/1108 lesions (196/223 patients). Fractional flow reserve derived from coronary CTA changed the treatment decision in 7% of the patients. Conclusion: In patients with left main or three-vessel coronary artery disease, a heart team treatment decision-making based on coronary CTA showed high agreement with the decision derived from conventional coronary angiography suggesting the potential feasibility of a treatment decision-making and planning based solely on this non-invasive imaging modality and clinical information. Trial registration number: NCT02813473.

Predictors of future arrhythmic events in patients with unexplained syncope.

AIMS: The purpose of this study was to examine the usefulness of implantable loop recorders (ILRs) for symptom-rhythm correlation and to identify predictors of future arrhythmic events. PATIENTS AND METHODS: In our dual-centre study, we analysed ILR data of 189 patients (mean age 67.4 ± 15.2 years, 114 male) with unexplained syncope (single syncope 21 patients, recurrent 168 patients, traumatic injury 43 patients). Patients had severe comorbidities such as hypertension (n = 127), coronary artery disease (n = 31), diabetes mellitus (n = 33) and chronic renal insufficiency (n = 18). The median ILR usage was 29 months (M), with a range between 1 and 46 M. RESULTS: Forty-nine (26%) patients experienced syncope during the study, with a median of 8 M to first recurrence of syncope. In 43 patients, pacemaker implantation was performed because of sinus node disease (n = 29), high-degree AV-block (n = 6) or atrial fibrillation with slow ventricular rate (n = 8). In five patients, an ICD was implanted because of documented ventricular tachycardia (n = 4) or left ventricular ejection fraction <35% (n = 1). One patient received ablation of the cavotricuspid isthmus because of documented atrial flutter. Concerning the clinical course, in five patients explantation of the ILR was necessary due to pocket infection. Three patients died due to non-cardiac causes. Logistic regression analysis revealed that older patients had a significantly higher risk for future arrhythmic events (OR 1.3, p = .039). CONCLUSIONS: ILR monitoring is effective in indicating causes of unexplained syncope by providing symptom-rhythm associations. Only age was a predictor of future arrhythmic events. The mortality in patients with unexplained syncope was very low.

Photodynamic antimicrobial effect of safranine O on an ex vivo periodontal biofilm.

BACKGROUND AND OBJECTIVE: The increasing resistance of oral pathogens against antibiotic measures urgently requires new therapeutic strategies. In this context, antimicrobial photodynamic therapy (aPDT) may play a crucial part in the future. The aim of the present study was to compare the antibacterial efficiency of aPDT using the photosensitizer safranine O with that of chlorhexidine (0.2% CHX) on an ex vivo biofilm. METHODS: First the antibacterial activity of both measures against planktonic cultures of Streptococcus gordonii ATCC 33399, Streptococcus mutans ATCC 25175, Fusobacterium nucleatum ATCC 10953, Aggregatibacter actinomycetemcomitans ATCC 33384 and Porphyromonas gingivalis ATCC 33277 was observed. Then a patient specific ex vivo biofilm was established from plaque and saliva samples of patients (n = 19) with chronic periodontitis. The antibacterial effects of aPDT and of 0.2% CHX were determined on the ex vivo biofilms cultivated for 24 and 72 hours. After cultivation of the treated samples on blood agar (2 days) the results were quantified by counting the colony forming units (cfu/ml). RESULTS: Photodynamic treatment with safranine O showed a distinct antibacterial effect on F. nucleatum and P. gingivalis. Whereas S. gordonii was suppressed completely by aPDT, treatment with 0.2% CHX caused only a partial reduction. In the ex vivo biofilm model (24-hour biofilm), aPDT caused a significantly higher bacterial killing than treatment with 0.2% CHX. Compared to the untreated control, there was no significant difference on the 72-hour biofilm for both methods. CONCLUSIONS: The results show that oral-pathogenic species in planktonic solution can be suppressed significantly by aPDT with safranine O. Especially for bacteria in a 24-hour ex vivo biofilm, this method is more effective than treatment with 0.2% CHX. Both antibacterial treatments did not show any significant effect on the biofilm cultivated for 72 hours.

Low level myocardial parvovirus B19 persistence is a frequent finding in patients with heart disease but unrelated to ongoing myocardial injury.

While myocardial parvovirus B19 (B19V), aside from enteroviruses (EV) and adenoviruses (ADV), has recently been found often in patients with myocarditis and idiopathic dilated cardiomyopathy (IDC), the pathogenetic significance of B19V genomes in those patients has not yet been sufficiently elucidated. In the present study, left ventricular endomyocardial biopsies from 24 patients with left ventricular ejection fraction (LVEF) below 55% due to IDC, and tissue from the right atrial appendage of 10 control patients undergoing bypass surgery with normal LVEF (>55%) were investigated for B19V, ADV, and EV genomes by specific nested polymerase chain reaction (PCR), by real time PCR or by reverse-transcription PCR, respectively. The myocardial tissue samples from the 10 controls were analyzed each in three different virological laboratories for B19V. In the IDC group, the frequency of the myocardial virus genomes found in 54% (13/24) of the patients was as follows: B19V: 50% (12/24), EV: 8% (2/24), including one patient with B19V and EV, and ADV: 0% (0/24). For comparison, the prevalence of B19V genomes was between 30% and 60% in the control group as detected in three different laboratories, but all these control subjects were EV- and ADV-negative. The number of B19V gene copies, however, was very low and similar both in the IDC and control group. In the majority of patients myocardial B19V persistence was associated with a low virus load irrespective of the underlying heart disease so that it may be of no importance in the pathogenesis of IDC.

Detection of viral genome in the myocardium: lack of prognostic and functional relevance in patients with acute dilated cardiomyopathy.

BACKGROUND: The presence of viral genome in the myocardium of patients with dilated cardiomyopathy (DCM) has been suggested as causative for the underlying cardiac disease. Nevertheless, the results of present studies are conflicting regarding the natural course of heart diseases associated with detection of viral genome. This study was undertaken to determine if the detection of viral genome in the myocardium of patients with DCM is of functional and prognostic relevance under modern treatment strategies of heart insufficiency. METHODS: In 197 patients with DCM, left ventricular endomyocardial biopsies were performed. Analysis for genome of adenovirus, enterovirus (EV), and parvovirus B19 as well as enteroviral replication and immunohistology was performed. RESULTS: The increase in ejection fraction (EF) was 14.5 +/- 12.4% in the EV-positive group compared with 11.1 +/- 14.2 in the EV-negative group (P = not significant [NS]) after a mean follow-up (FU) of 19.5 and 17.6 months. The increase in EF in the virus-positive group (positive for EV, adenovirus, or parvovirus B19) was 15.3 +/- 13.3% compared with 12.3 +/- 11.9% in the virus-negative group (P = NS) after a mean FU of 17.6 and 11.5 months. There was no significant difference in the change of EF between the EV-positive and virus-negative groups. Detection of enteroviral RNA replication (detection of EV minus-strand RNA) did not result in a deterioration of left ventricular function compared with the virus-negative group (P = NS) after mean FU of 11.2 and 12.0 months. The transplantation-free survival of the patients was not influenced by detection of viral genome. CONCLUSIONS: Our results favor the view that the presence of viral genome in the myocardium of patients with DCM is of no functional and prognostic relevance.

Genetic and phenotypic analysis of dilated cardiomyopathy with conduction system disease: demand for strategies in the management of presymptomatic lamin A/C mutant carriers.

BACKGROUND: One-third of cases of dilated cardiomyopathy (DCM) is of familial aetiology. Several genes have been reported to cause the autosomal dominant form of DCM. AIMS: To analyze the lamin A/C gene (LMNA) in 31 unrelated patients with DCM and conduction system disease (CSD). METHODS: Patients and family members underwent physical examination, ECG/Holter-ECG, echocardiography, and selective coronary angiography. Genetic analysis of all coding exons of LMNA was performed using PCR and sequencing. RESULTS: Three different LMNA mutations (Arg377His, c.1397delA, c.424_425ins21nt) were identified in three families with autosomal dominant disease comprised of 39 individuals. 21 individuals were mutation carriers, of whom 12 were symptomatic. We observed a progressive and age-dependent form of DCM with CSD and arrhythmias. First, the patients developed a moderate left ventricular dilatation without symptoms. Later, systolic function declined progressively and the patients became symptomatic resulting in a high mortality due to sudden death and heart failure. CONCLUSIONS: Genetic screening leads to the identification of symptomatic and asymptomatic mutant carriers. The latter at a young age should be regarded as "presymptomatic" because of the age-dependent disease manifestation. New guidelines are required for the management of these individuals.

Immunopathogenesis of dilated cardiomyopathy. Evidence for the role of TH2-type CD4+T lymphocytes and association with myocardial HLA-DR expression.

BACKGROUND: An immunological pathogenesis underlying dilated cardiomyopathy and myocarditis has been suggested on the basis of the subtype of lymphocyte infiltrates and the degree of HLA expression in cardiac tissue. In the present study, we investigated the relation between the peripheral CD4+T-cell subset and the degree of HLA expression in the heart. METHODS: Fifty-four patients with heart insufficiency included in the study were biopsied after coronary heart disease had been excluded. Immunohistological staining of the left ventricular tissue were performed employing anti-CD3, -CD4, -CD8, -CD14, and HLA-DR monoclonal antibodies. Intracellular expression of IL-2, IL-4, IL-5, IFN-gamma, and TNF-alpha in peripheral CD4+T lymphocytes was determined using flow cytometry. The severity of heart insufficiency was determined by measurement of brain natriuretic peptide (BNP) and the NYHA class. On the basis of HLA expression in the heart, the patients were divided into three groups: Group I (mild-to-none), Group II (moderate), and Group III (strong-to-very strong). RESULTS: Of the 54 patients included in this study, 33 (61%) patients were diagnosed as having idiopathic dilated cardiomyopathy and 10 (18.5%) borderline or healing myocarditis according to the Dallas criteria. Both patient groups were found in all three HLA-DR groups. There was no difference in BNP level or NYHA class between the three groups. However, a significant difference in the proportion of CD4+T lymphocytes producing IL-2 (39.2 versus 21.8%), IFN-gamma (19.5 versus 7.8%), and TNF-alpha (35.8 versus 16.1%) between Groups I and III could be detected, whereas the distribution of IL-4 and IL-5 producing CD4+T lymphocytes was similar. The myocardium of Group III patients exhibited a significant higher number of CD3+T cells (11.4 versus 4.3 per mm2) and CD4+T cells (4.7 versus 0.8 per mm2) compared to Group I patients, while no difference existed with respect to CD8+T cells. CONCLUSION: High myocardial expression of the HLA-DR antigen is associated with an increase of peripheral-blood CD4+T lymphocytes expressing cytokines of the TH2 subset. The degree of HLA-DR expression is not associated with the degree of heart insufficiency or underlying diagnosis, but correlates with an increase of activated T cells in the myocardium. The data suggest that CD4+T lymphocytes infiltrating cardiac tissue may play a pathogenic role in dilated cardiomyopathy.

Outcome after cardiac arrest: predictive values and limitations of the neuroproteins neuron-specific enolase and protein S-100 and the Glasgow Coma Scale.

BACKGROUND AND PURPOSE: Patients resuscitated from cardiac arrest are at risk of subsequent death or poor neurological outcome up to a persistent vegetative state. We investigated the prognostic value of several epidemiological and clinical markers and two neuroproteins, neuron-specific enolase (NSE) and S-100 protein (S-100), in 97 patients undergoing cardiopulmonary resuscitation (CPR) after non-traumatic cardiac arrest between 1998 and 2002. RESULTS: 52.6% of the patients died, 28.8% survived with severe, moderate or without neurological disorders, and 18.6% remained in a persistent vegetative state. Unconsciousness>48 h after CPR predicted a 60.6-fold (95% CI 14.3287-257.205, p=0.001) and a Glasgow Coma Scale (GCS)<6 points after 72 h a 11.2-fold (CI 95%, 3.55-36.44, p<0.001) risk of poor neurological outcome. Serum levels>or=65 ng/ml for NSE and >or=1.5 microg/l for S-100 increased the risk of death and persistent vegetative state 16.8 (95% CI 2.146-131.520)- and 12.6 (95% CI 1.1093-99.210)-fold, respectively. By combination of the GCS with elevated serum concentrations of both neuroproteins above the cut off levels on third day after CPR a poor neurological outcome was predicted with a specificity of 100%. CONCLUSION: The combination of GCS with the serum levels of both neuroproteins at 72 h after CPR permit a more reliable prediction of outcome in post arrest coma than the single markers alone, independent of the application of anaesthetic agents.

Role of adenosine monophosphate deaminase-1 gene polymorphism in patients with congestive heart failure (influence on tumor necrosis factor-alpha level and outcome).

The Cytosin-->thymidin transition at codon 12 of the adenosine monophosphate deaminase-1 (AMPD1) gene results in a complete loss of its catalytic activity. The increased conversion of adenosine monophosphate to adenosine, which in turn attenuates the expression of tumor necrosis factor-alpha (TNF-alpha) expression, has been suggested as a putative mechanism for prolonged survival in patients with congestive heart failure (CHF) carrying the mutant AMPD1 allele. Therefore, the impact of this polymorphism on circulatory TNF-alpha concentrations and outcome in patients with CHF should be studied. The AMPD1 genotype of each patient with CHF (n = 90; idiopathic dilated cardiomyopathy n = 53; coronary artery disease n = 20; other n = 17) was determined by direct sequencing. Serum TNF-alpha concentrations were measured by enzyme-linked immunosorbent assay. We found 66 patients (75.6%) to be homozygous for the wild-type allele (AMPD1 +/+), and 20 patients (22.2%) were heterozygous and 2 were homozygous (2.2%) for the mutant AMPD1 allele (AMPD1 +/- or -/-). TNF-alpha serum concentrations were 4.2 +/- 2.0 pg/ml for the AMPD1 +/+ genotype and 5.3 +/- 2.9 pg/ml for the AMPD1 +/- and -/- genotypes (p = 0.045). A downregulation of TNF-alpha in patients carrying the mutant allele could therefore be not detected. However, Kaplan-Meier analysis demonstrated a significantly prolonged survival without heart transplantation or revival from sudden death in the AMPD1 +/- & -/- group (p = 0.020). Multivariate analysis identified the AMPD1 wild-type genotype as an independent risk factor (odds ratio 9.34, 95% confidence interval 1.78 to 48.96). The mutant AMPD1 allele, in the context of CHF, is associated with a prognostic benefit. The underlying mechanism of TNF-alpha is unrelated.

Characterization of coxsackievirus B3-caused apoptosis under in vitro conditions.

Among several mechanisms of pathogenesis of the frequent and sometimes serious infections with coxsackievirus B3 (CVB3), one detail is apoptosis. Recently, a new apoptotic mechanism involving the specific interaction between the capsid protein VP2 of the highly virulent variant CVB3H3 and the proapoptotic host protein Siva was identified. The relevance of this observation for virus pathogenicity was shown in a BALB/c mouse model using CVB3H3 and the interaction-deficient mutant virus CVB3H310A1. In this study these results were verified and extended under in vitro conditions. The different apoptotic capability of CVB3H3 versus CVB3H310A1 was demonstrated by apoptotic nuclear condensation, DNA fragmentation, expression of Siva mRNA, and caspase-3 activation. The virus-specific differences were caused by the VP2 capsid proteins, which was shown by overexpression of the single VP2H3 and VP2H310A1 protein. Furthermore, the involvement of apoptosis in virus progeny production and the associated appearance of the cytopathic effect was demonstrated by application of the pan-caspase inhibitor Z-VAD-FMK. These in vitro results indicate that the induction of apoptosis during CVB3H3 infection is based on the interaction between the capsid protein VP2 and the proapoptotic protein Siva, independently from the complex situation in vivo.