Preliminary investigation of the clinical value of vascular endothelial growth factor and hypoxia-inducible factor-1alpha in pericardial fluid in diagnosing malignant and tuberculous pericardial effusion.

OBJECTIVES: To investigate the clinical value of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1alpha (HIF-1alpha) in diagnosing malignant and tuberculous pericardial effusion. METHODS: Eighty patients with exudative pericardial effusion undergoing pericardiocentesis and drainage were divided into 2 groups, namely those with malignancy and those with tuberculosis. The levels of HIF-1alpha, VEGF, lactate dehydrogenase (LDH) and adenosine deaminase (ADA) in pericardial fluid and serum were measured. Routine and cytological examination of pericardial fluid, clinical characteristics and some blood parameters were compared between the 2 groups. RESULTS: There were 33 patients with tuberculous pericardial effusion and 47 with malignant pericardial effusion. The levels of VEGF and HIF-1alpha in pericardial fluid in the malignancy group were significantly higher than those in the tuberculosis group (p < 0.01), and there was a moderate positive correlation between the levels of VEGF and HIF-1alpha (r = 0.79, p < 0.01). The sensitivity and specificity of combining VEGF and HIF-1alpha were 90.8 and 88.3%, respectively. The 2 groups showed no differences with regard to gender distribution, occurrence of fever, erythrocyte sedimentation rate or the levels of hemoglobin, LDH, ADA, serum HIF-1alpha and VEGF. CONCLUSIONS: Both VEGF and HIF-1alpha in pericardial fluid have determinative value in the differential diagnosis of malignant and tuberculous pericardial effusion.

Alcohol-induced electrical remodeling: effects of sustained short-term ethanol infusion on ion currents in rabbit atrium.

BACKGROUND: In some patients, above-average alcohol consumption before occurrence of atrial fibrillation (AF) in terms of a "holiday heart syndrome" (HHS) can be determined. There is evidence that long before development of apparent alcohol-induced cardiomyopathy, above-average alcohol consumption generates an arrhythmogenic substrate which abets the onset of AF. Changes of atrial current densities in terms of an electrical remodeling after sustained short-term ethanol infusion in rabbits as a potential part of HHS pathophysiology were examined in this study. METHODS: Rabbits of the ethanol group (EG) received sustained short-term intravenous alcohol infusion for 120 hours (during infusion period, blood alcohol level did not fall below 158 mg/dl), whereas NaCl 0.9% was infused in the placebo group (PG). Using patch clamp technique in whole-cell mode, atrial current densities were measured and compared between both groups. RESULTS: Ethanol infusion did not alter current densities of I(to) [58.7 +/- 5.0 pA/pF (PG, n = 20 cells) vs. 53.9 +/- 5.0 pA/pF (EG, n = 24)], I(sus) [11.3 +/- 1.4 pA/pF (PG, n = 20) vs. 10.2 +/- 1.0 pA/pF (EG, n = 24)], and I(K1) [-1.6 +/- 0.3 pA/pF (PG, n = 17) vs. -2.0 +/- 0.3 pA/pF (EG, n = 22)]. However, alcohol infusion resulted in a remarkable reduction of I(Ca,L) current densities [-28.4 +/- 1.8 pA/pF (PG, n = 20) vs. -15.2 +/- 1.4 pA/pF (EG, n = 22)] and I(Na) [-75.4 +/- 3.6 pA/pF (PG, n = 17) vs. -35.4 +/- 4.4 pA/pF (EG, n = 21)], respectively. CONCLUSION: Sustained short-term ethanol infusion in rabbits alters atrial current densities. HHS might be favored by alcohol-induced atrial electrical remodeling.

Impaired platelet function reduces myocardial infarct size in Galphaq knock-out mice in vivo.

Platelet aggregation and secretion play a crucial role in acute coronary syndromes. In Galpha(q) knock-out mice (Galpha(q)(-/-)) platelet function is eliminated in terms of aggregation and secretion of cytokines. We investigated whether restricted platelet aggregation and secretion reduces myocardial infarct size in vivo. Thirty minute regional myocardial ischemia was followed by 24 h reperfusion (I/R) in vivo. Infarct size was determined by counterstaining. Left ventricular function was measured by ultrasound. Infarct size to area at risk ratio was significantly smaller in Galpha(q)(-/-) mice (5.6+/-1.6%) compared to wild-type (WT) mice (27.2+/-3.0%, p<0.01). Fractional shortening was improved in Galpha(q)(-/-) mice compared to WT (42.2+/-1.4% versus 30.5+/-1.4%, respectively, p<0.01). WT mice, transplanted with Galpha(q)(-/-) bone marrow showed a significant reduction in infarct size compared to control (7.8+/-2.2% versus 18.4+/-2.7%, respectively, p<0.01). Platelets of Galpha(q)(-/-) mice had an impaired aggregation and secretion phenotype. In the in vivo model of ischemia and reperfusion, beyond impaired platelet aggregation, platelet secretion plays an additional role in myocardial infarct extension. Blocking platelet aggregation in combination with secretion might be a promising supplementary therapeutic strategy in acute myocardial infarction.

Segmental pulmonary vein ablation: success rates with and without exclusion of areas adjacent to the esophagus.

BACKGROUND: Catheter ablation has become the first line of therapy in patients with symptomatic recurrent, drug-refractory atrial fibrillation (AF). The occurrence of an atrioesophageal fistula is a rare but serious complication after AF-ablation procedures. This risk is even present during segmental pulmonary vein (PV) ablation procedures because the esophagus does frequently have a very close anatomical relationship to the right or left PV ostia. The aim of the present study was to analyze whether the exclusion of areas adjacent to the esophagus does have a significant effect on the success rates after segmental pulmonary vein ablation procedures. METHODS: Forty-three consecutive patients with symptomatic paroxysmal AF were enrolled in this study. In all patients, a segmental PV ablation procedure was performed. The procedures were facilitated by a 3D real-time visualization of the circumferential mapping catheter placed in the pulmonary veins using the NavX system (St. Jude Medical, St. Paul, MN, USA; open irrigated tip ablation catheter; 43 degrees C; 30 W). In 21 patients, a complete ostial PV isolation was attempted regardless of the anatomical relationship between the ablation sites and the esophagus (group A). In the remaining 22 patients, the esophagus was marked by a stomach tube and areas adjacent to the esophagus were excluded from the ablation procedure (group B). After discharge, patients were scheduled for repeated visits at the arrhythmia clinic at 1, 3, and 6 months after the ablation procedure. RESULTS: The segmental pulmonary vein ablation procedure could be performed as planned in all patients. In group A, all pulmonary veins could be isolated successfully in 14 out of 21 patients (67%). A mean number of 3.7 pulmonary veins (SD +/- 0.5 PVs) were isolated per patient. The main reasons for an incomplete PV isolation were: small diameter of the PVs, side branches close to the ostium, or poorly accessible PV ostia. In group B, all PVs could be isolated successfully in only 12 out of 22 patients (55%; P = 0.54). A mean number of 3.2 PVs (SD +/- 0.9 PVs) were isolated per patient (P = 0.05). This was mostly due to a close anatomical relationship to the esophagus. The ablation strategy had to be modified in 16/22 patients in group B because of a close anatomical relationship between the left (n = 10) or right (n = 6) PV ostia and the esophagus. After 3 months, the percentage of patients free from an AF recurrence was not significantly different between the two groups (90% vs 95%; P = 0.61). After 6 months, there was no significant difference between the success rates either (81% vs 82%; P = 1.0). There were no major complications in both groups. CONCLUSIONS: The exclusion of areas adjacent to the esophagus results in a moderately higher percentage of incompletely isolated PVs. However, it does not have a significant effect on the AF recurrence rate during short-term and mid-term follow-up.

Thrombolysis is an appropriate treatment in lead-associated infective endocarditis with giant vegetations located on the right atrial lead.

CD endocarditis is a potentially lethal complication after implantation of permanent pacemakers or implantable cardioverter-defibrillators. Complete extraction of the hardware along with antibiotic treatment is the standard therapy. However, there is no standard procedure in the treatment of lead-associated infective endocarditis with large thrombotic vegetations. The authors present the case of a 60-year-old patient with a large vegetation located on the right atrial lead. Due to a high surgical and thrombembolic risk, especially of acute massive pulmonary embolism, the patient received recombinant tissue plasminogen activator to dissolve the thrombus under echocardiographic monitoring. The thrombotic masses were substantially reduced after thrombolysis. Therefore, standard transvenous extraction of the leads could be performed and high risk cardiac re-operation could be avoided.

Catheter ablation of persistent atrial fibrillation: anatomically based circumferential pulmonary vein ablation in combination with a potential-guided segmental approach to achieve complete pulmonary vein isolation.

BACKGROUND: Catheter ablation has become the first line of therapy in patients with symptomatic, recurrent, drug-refractory atrial fibrillation. However, catheter ablation of persistent atrial fibrillation is still a challenge. Various rather complex ablation strategies exist and their results are not very favorable. Therefore, the aim of our study was to evaluate a well-defined reasonable approach to catheter ablation of persistent atrial fibrillation. The strategy consisted of a circumferential pulmonary vein ablation in combination with a potential-guided segmental approach to achieve complete pulmonary vein isolation and a linear lesion at the roof of the left atrium. METHODS: A total of 43 patients (30 men, 13 women; mean age 55 years (SD ± 9 years)) with symptomatic persistent atrial fibrillation were enrolled in this study. All patients underwent catheter ablation of persistent atrial fibrillation using the above-mentioned approach (with the CARTO or the NAVX system). Additionally, catheter ablation of the mitral isthmus and the right atrial isthmus was performed in selected cases. In all patients, cardiac MRI or multi-detector spiral computed tomography was performed prior to the ablation procedure and a surface rendered model of the left atrium was created. After discharge, patients were scheduled for repeated visits at the arrhythmia clinic at 1, 3, 6, 9, and 12 months after the ablation procedure. RESULTS: The ablation procedure could be performed as planned in all 43 patients. Nine patients had to undergo a repeat ablation procedure, so that a total of 52 procedures were evaluated. An additional linear lesion was created at the mitral isthmus in three patients (7%) during the initial procedure and in one patient (2.3%) during the second procedure. Catheter ablation of the right atrial isthmus was performed in 11 patients (25.6%) during the first procedure and in four additional patients during the redo procedure (9.3%). Twenty-four out of 43 patients (55.8%) experienced an arrhythmia recurrence within the first 3 months after ablation requiring an electrical cardioversion. At 1-year follow-up, analysis of a 7-day Holter monitoring revealed no evidence for an arrhythmia recurrence in 26 of 43 patients (60.5%). In nine of 43 patients (20.9%), only short episodes of paroxysmal atrial fibrillation were documented. In eight patients (18.6%), a recurrence of persistent atrial fibrillation (>48 h) was revealed by the long-term recordings. A duration of persistent atrial fibrillation >3 months was the most powerful predictor for arrhythmia recurrences at 1-year follow-up. A subgroup analysis revealed a markedly higher rate of stable sinus rhythm at 1-year follow-up in patients with a short duration of atrial fibrillation (≤ 3 months) compared to patients with a longer duration of AF (>3 months) prior to the procedure (72.0% versus 44.4%). There were no major complications. CONCLUSIONS: Catheter ablation of persistent atrial fibrillation can be performed safely and effectively using this ablation strategy (especially in patients with short-lasting persistent atrial fibrillation (≤ 3 months)).

Restrictive cardiomyopathy in inherited ATTR amyloidosis (TTR-Ser23Asn) in a patient of German-Italian extraction.

Amyloidosis occurs when certain soluble proteins are transformed into amyloid fibrils in the extracellular space. Most common are the light-chain amyloidoses; less common is the AA-amyloidosis, which follows chronic inflammatory diseases, and the amyloidoses of transthyretin (TTR) origin. We report on a women of Italian-German origin with the mutation TTR (Ser23Asn). Whole body scintigraphy using TC99m-DPD showed end stage hereditary amyloidosis caused by ATTR with predominant tracer retention in the myocardium. Myocardial biopsies revealed the presence of amyloid by Congo red staining. Further immunohistochemical analysis showed ATTR amyloidosis. DNA sequencing revealed a point mutation of the transthyretin gene leading to a single amino acid substitution. The only effective treatment in patients with manifest cardiac ATTR amyloidosis is combined heart and liver transplantation. Our patient was placed on a list for this procedure, but unfortunately she died during the standby procedure due to urosepsis.

Catheter ablation of atrial fibrillation using the Navx-/Ensite-system and a CT-/MRI-guided approach.

BACKGROUND: Catheter ablation has become the first line of therapy in patients with symptomatic, recurrent, drug refractory atrial fibrillation. However, catheter ablation of atrial fibrillation is still a challenge. This is partially due to the high degree of variability with regard to the individual anatomy. Nevertheless, 3D imaging systems (CT, MRI) provide detailed information about the individual left atrial and pulmonary vein morphology. A 3D CT or MRI reconstruction of the left atrium can be displayed in the Navx-/Ensite-system in a synchronised way during the ablation procedure, thereby facilitating the intervention. This study summarizes our preliminary experience with different strategies of AF ablation using the Navx-/Ensite-system and a CT-/MRI-guided approach. METHODS: In a total of 41 patients, cardiac MRI (n = 7) or multi-detector spiral computed tomography (n = 34) was performed prior to an ablation procedure. Catheter ablation was performed for paroxysmal atrial fibrillation in 31 patients and for persistent atrial fibrillation in 10 patients. A 3D MRI or high resolution spiral CT data acquisition was performed and a surface rendered model of the LA was created. This model was displayed in the Navx-/Ensite-system throughout the ablation procedure. RESULTS: Catheter ablation was performed using the Navx-system (n = 38) or the Ensite-system (n = 3). Three strategies were used depending on the type of atrial fibrillation: segmental isolation of the pulmonary veins (facilitated by a 3D real-time visualization of the ablation catheter and a circumferential mapping catheter; group A: 20 patients), linear lesions (group C: 3 patients) and a combined approach (group B; 18 patients). The CT-/MRI-models provided an excellent overview over the pulmonary veins and the left atrial appendage. They revealed a high degree of variability with regard to the individual anatomy (e.g. dimensions of the left atrial appendage, pulmonary vein ostia). The CT scans provided a more detailed reconstruction of the left atrial anatomy than the MRI scans (especially in patients who were in atrial fibrillation at the time of the data acquisition). In some patients, the CT-/MRI-models revealed a very small diameter of some pulmonary veins or side branches close to the ostium (e.g. right inferior pulmonary vein). Therefore, no attempt was made to achieve complete pulmonary vein isolation in some patients. In group A, 16/20 (80%) patients had no arrhythmia recurrence [mean follow-up 359 days (SD +/- 317 days)]. Twelve out of eighteen (67%) patients in group B [mean follow-up 452 days (SD +/- 311 days)] and 2/3 (67%) patients in group C did not experience an arrhythmia recurrence [mean follow-up 1,000 days (SD +/- 34 days)]. There were no major complications. CONCLUSIONS: The information derived from 3D CT- or MRI-reconstructions facilitates AF ablations performed with the Navx-/Ensite-mapping system and enhances the safety of these procedures. Furthermore, the availability of an additional impedance-based 3D real-time visualization of the ablation catheter and the circular mapping catheter placed in the pulmonary veins represents a major advantage of the Navx system.

Inhibition of the renin-angiotensin system: effects on tachycardia-induced early electrical remodelling in rabbit atrium.

INTRODUCTION: Tachycardia-induced atrial remodelling (as an equivalent to atrial fibrillation) can be influenced by the renin-angiotensin system. Effects of a seven-day enalapril pre-treatment (EPT, 0.16 mg/kg body weight subcutaneously every 24 h) on ionic currents underlying tachycardia-induced early electrical remodelling after 24 h rapid atrial pacing (RAP, 600 beats/min) in rabbit atrium were studied. MATERIALS AND METHODS: Animals were divided into four groups (n=4 each): control; paced only; enalapril only; and enalapril and paced, respectively. Using patch-clamp technique in whole-cell mode, current densities were measured in isolated atrial myocytes. RESULTS: EPT nearly doubled L-type calcium current (ICa,L, -7.7+/-0.6 pA/pF [control] vs. f -12.3+/-1.2 pA/pF [enalapril only]). RAP reduced ICa,L to -3.6+/-0.7 pA/pF (paced only). Also after EPT, RAP led to a significant downregulation of ICa,L by 39% (-7.5+/-1.3 pA/pF [paced and enalapril]). RAP decreased transient outward potassium current (Ito, -45%, 51.5+/-3.9 pA/pF [control] vs. 28.5+/-4.5 pA/pF [paced only]). EPT did not alter Ito (44.2+/-8.1 pA/pF [enalapril only]). However, RAP did not affect Ito in enalapril-treated animals and averaged 50.4+/-9.8 pA/pF (paced and enalapril). CONCLUSIONS: In summary, EPT has several effects on ion channels in rabbit atrium: 1) EPT increases ICa,L current density, but cannot prevent its downregulation due to RAP; 2) EPT has no influence on Ito current density, but can prevent its downregulation due to RAP. Although changes of single ion channels must be interpreted in context of the complex atrial electrophysiology as a whole, our results provide a possible explanation of the in vivo observation that angiotensin-converting enzyme inhibition is mainly beneficial on the early electrical remodelling due to the atrial fibrillation-equivalent RAP.