Diaphragmatic myoclonus owing to electrode dislocation of implantable cardioverter defibrillator.

Myoclonus is a sudden and brief involuntary muscle contraction presenting with jerk-like movements that can occasionally involve the trunk muscles or the diaphragm as in the case of spinal myoclonus1. We here present an unusual case with unilateral diaphragmatic myoclonus owing to electrode dislocation of an implantable cardioverter defibrillator.

Heart Rate Variability and Arrhythmic Burden in Pulmonary Hypertension.

A growing body of evidence indicates that sudden cardiac death constitutes a major cause of mortality in pulmonary hypertension (PH). As validated method to evaluate cardiac autonomic system dysfunction, alterations in heart rate variability (HRV) are predictive of arrhythmic events, particularly in left ventricular disease. Here, we sought to determine the clinical value of HRV assessment in PH. Sixty-four patients were allocated to different PH-subgroups in this prospectively conducted trial: 25 patients with pulmonary arterial hypertension (PAH), 11 patients with chronic thromboembolic PH (CTEPH), and 28 patients with COPD-induced PH. All patients underwent 24-h Holter electrocardiogram for HRV assessment by time- and frequency-domain analysis. Arrhythmic burden was evaluated by manual analysis and complementary automatic measurement of premature atrial and ventricular contractions. The results were compared to 31 healthy controls. The PAH patients offered a significantly higher mean heart rate (78.6 ± 10.4 bpm vs. 70.1 ± 10.3 bpm, p = 0.04), a higher burden of premature ventricular contractions (p < 0.01), and decreases in HRV (SDNN: p < 0.01; SDANN: p < 0.01; very low frequency: p < 0.01; low frequency/high frequency ratio: p < 0.01; total power: p = 0.02). In CTEPH patients, only the amount of premature ventricular contractions differed from controls (p < 0.01), whereas in COPD both premature atrial contraction count and frequency-domain-based HRV manifested significant differences. In conclusion, PAH appears to be primarily affected by HRV alterations and ventricular arrhythmic burden, indicating a high risk for malignant arrhythmic events.

Influence of intimal Chlamydophila pneumoniae persistence on cardiovascular complications after coronary intervention.

PURPOSE: Chlamydophila pneumoniae has been implicated in atherosclerosis/restenosis; however, clear evidence is missing. Therefore, the aim of our study was to examine the influence of intimal infection and systemic inflammation on cardiovascular complications after coronary intervention. METHODS: 45 atheroma specimens from patients with symptomatic coronary artery disease who underwent directional endatherectomy with stent implantation were analyzed by immunohistochemistry to detect chlamydial (c) and human (h) heat shock protein (HSP) 60. The antibodies used against cHSP60 and hHSP60 were characterized by specificity and lack of cross immunoreactivity. In addition, serum Ig antibodies against Chlamydophila pneumoniae and against mycobacterial (m) HSP65 as well as serum CRP levels were measured. At follow-up of 6 months, quantitative coronary angiography was performed and major adverse cardiac events (MACE) were assessed. RESULTS: Atheroma specimens of all 10 patients with MACE were positive for cHSP60 with overall higher cHSP60 tissue expressions (1.1 ± 0.4 %) and serum CRP levels (2.18 ± 0.85 mg/dl) compared to the remaining 35 patients without MACE (7 of 35 specimens positive for cHSP60, mean cHSP60 expression: 0.4 ± 0.1 %, CRP levels: 0.67 ± 0.16 mg/dl, p < 0.05). Colocalization of both HSP60 homologues was more frequent in the MACE group. Anti-mHSP65 serum titers were significantly higher in MACE (1:510) versus non-MACE patients (1:335) and correlated positively with plaque expressions of cHSP60 and hHSP60 (r = 0.54, p < 0.05; r = 0.46, p < 0.05; resp.). CONCLUSIONS: Intimal presence of cHSP60, systemic CRP and antibodies against mHSP65 are predictors for occurrence of MACE after coronary intervention.

Influence of obstructive sleep apnea on heart rate turbulence.

BACKGROUND: Patients with obstructive sleep apnea (OSA) are at increased risk for cardiovascular disease. Increased sympathetic drive is considered as one of the underlying mechanisms. Both heart rate turbulence (HRT) and heart rate variability (HRV) are parameters to describe autonomic regulation. We investigated the influence of sleep-disordered breathing (SDB) on HRT and HRV in patients with OSA. METHODS: Sixty-five patients underwent overnight polysomnography for clinically suspected SDB and simultaneous Holter monitoring (11 p.m.-6 a.m.). Patients with diabetes mellitus, a history of cardiac disease, left ventricular dysfunction, periodic breathing pattern, and those on beta-blockers or theophylline were excluded. According to the apnea-hypopnea index (AHI), the patients were assigned to group A (AHI <20, n = 31) or group B (AHI > or =20, n = 34). HRV (time domain, frequency domain) and HRT (onset, slope) were then related to the severity of SDB. RESULTS: Nighttime turbulence slope (TS) correlated inversely with the AHI (r = -0.45, p = 0.01) and was significantly lower in group B (8.9 +/- 1.6 ms/R-R interval) compared with that in group A (19.8 +/- 4.0 ms/R-R interval, P = 0.01). This relationship remained stable after adjusting TS for the number of ventricular premature contractions. No significant differences in turbulence onset or parameters of nighttime HRV were observed. CONCLUSIONS: Alterations in nighttime HRT correlate with the severity of SDB, indicating abnormalities in cardiac autonomic activity in moderate-to-severe OSA even in the absence of overt cardiac disease. These changes may be associated with the subsequent development of cardiovascular disease.

[Interventional catheter closure of persistent foramen ovale (PFO) in a patient with paradoxical embolism and Brugada's syndrome]. / Katheterinterventioneller PFO-Verschluss bei einem Patienten mit paradoxer Embolie und Brugada-Syndrom.

HISTORY AND ADMISSION FINDINGS: A 41-year-man was admitted because of acute bluish-grey skin discoloration in cold sensation in the right hand. His brother had suffered sudden cardiac death, aged 42 years. INVESTIGATIONS: Angiography demonstrated embolic occlusion of the digital artery of the right thumb. Transesophageal echocardiography showed a persistent foramen ovale (PFO) with an aneurysm of the atrial septum (ASA) with marked right-to-left shunt of contrast medium during a Valsalva maneuvre as well as two smaller septal fenestrations. There was no evidence of any other source of embolism. The resting electrocardiogram showed an incomplete right bundle branch block with ST elevations in V (1)-V (3), changes like those described in Brugada's syndrome. TREATMENT AND COURSE: Paradoxical embolism having been demonstrated, the PFO with ASA were closed with a percutaneously introduced Helex septum occluder. Later an implantable cardioverter-defibrillator (ICD) was introduced. CONCLUSIONS: A PFO, particularly if associated with an atrial aneurysm, is an important site of paradoxical embolism. In symptomatic patients percutaneous transcatheter septal occlusion should be considered preceding any ICD insertion thought necessary for concurrent Brugada's syndrome.

Transcatheter PFO closure with a prominent Eustachian valve.

We report the successful PFO closure in a 57-year old woman with complex atrial anatomy. To avoid the risk of interfering with the occluder device due to a prominent Eustachian valve, a Helex Septal Occluder was implanted. Differential therapeutic considerations and specific device characteristics are outlined.

[Prevalence of intimal pathogen burden in acute coronary syndromes]. / Prävalenz von intimalem Pathogen burden bei akutem Koronarsyndrom.

Increasing evidence supports a link between serological evidence of prior exposure to infectious pathogens, pathogen burden, and the risk for future myocardial infarction and death in patients with coronary artery disease. Based on this concept, we evaluated the intimal presence of four pathogens in human coronary atheroma, clinically associated with acute coronary syndromes (ACS) and stable angina (SA), and the effect of pathogen burden on the expression of human heatshock protein 60 (hHSP60), a key protein in (auto-)immune pathogenesis of atherosclerosis. Coronary atherectomy specimens retrieved from 53 primary target lesions of patients with ACS (n=33) or SA (n=20) were assessed immunohistochemically for the presence of Chlamydia pneumoniae (C. pn.), Helicobacter pylori (H.p.), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV), and for the expression of hHSP60. Chlamydia pneumoniae was present in 74%, Helicobacter pylori in 32%, CMV in 13% and EBV in 42%. Exclusively C.pn. revealed a prevalence in ACS (91%) vs SA (45%; p<0.001). Immunohistochemical analysis revealed 6 lesions without, 21 lesions with 1, 17 lesions with 2, 6 lesions with 3 and 3 lesions with 4 infectious agents. As an important finding, the mean value in ACS lesions was significantly increased compared to those in SA (1.9 vs 1.1; p<0.01). ACS-subgroup analysis revealed the highest mean value in patients with pain at rest within the last two days (Braunwald class III). In addition, expression of hHSP60 was significantly higher in ACS (8.7%) compared to SA (1.3%; p<0.001). Pathogen burden correlated highly significant (p<0.01) with the expression of hHSP60 (r=0.44).Our data demonstrate the impact of intimal pathogen burden in plaque instability, and suggest the presence of (auto-)immunoreactions against upregulated hHSP60 as an important pathomechanism that may contribute to acute coronary syndromes.

[Chlamydial and human heat shock protein 60 homologues in acute coronary syndromes. (Auto-)immune reactions as a link between infection and atherosclerosis]. / Chlamydiales und humanes Hitzeschockprotein 60 bei akutem Koronarsyndrom. Antikörpervermittelte (Auto-)Immunreaktionen als Link zwischen Infektion und Arteriosklerose.

Recent studies provide evidence that infectious agents play a causal role in the pathogenesis of atherosclerosis. In this respect, a chronic persistent Chlamydia pneumoniae infection, indicated by the presence of chlamydial heat shock protein 60 (cHSP 60), is of central interest. Both cHSP60 and endogenous human (h) HSP60 are upregulated under stress conditions in intimal cells and serve as a target for cross-reactive cytotoxic HSP-serum-antibodies. Therefore, the present study evaluates the expressions of both HSP60 homologues in advanced human coronary lesions and a correlation between intimal tissuebound protein and serum antibodies (Ab) to HSP65. Coronary atherectomy specimens retrieved from 114 primary target lesions of patients with acute coronary syndrome (ACS; n=46) or stable angina (SA; n=68) were assessed immunohistochemically for the presence of cHSP60 and hHSP60. Chronic persistency of Chlamydia pneumoniae was additionally examined by transmission electron microscopy. Blood samples from30 patients were tested for anti-Chlamydia pneumoniae-IgG/IgA- and anti-HSP65-Ab titers and for serum CRP levels. Coronary plaques revealed immunoreactive cHSP60 in 47% and hHSP60 in 57% of the lesions colocalized within macrophages/foam cells. Chlamydia in foam cells most often presented ultrastructural patterns that pointed to the persistency of the pathogen. Intact, non-atherosclerotic vessels showed no signals. Mean expressions were 3.1% for cHSP60 and 3.3% for hHSP60. As a central finding, the expression of both HSP homologues was significantly (each p<0.001) higher in ACS lesions compared to SA lesions (cHSP60: 6.2 vs 1.0%, and hHSP60: 7.2 vs 0.7%). Moreover, we found positive correlations between both determinants in ACS and SA lesions (r=0.41, r=0.37; p<0.01). Most interestingly, cHSP60 revealed no relationship with anti-Chlamydia pneumoniae-IgG/IgA titers, whereas expression of cHSP60 as well as that of hHSP60 correlated with anti-HSP65-Ab titers (r=0.50, p<0.01, and r=0.42, p<0.05, respectively).cHSP60 and hHSP60 colocalize within coronary primary atheroma, most prevalent in lesions associated with ACS. For the first time, our data demonstrate a significant correlation between the intimal expression of these HSP60 homologues and serum HSP65 antibodies, thereby suggesting that humoral immune reactions to bacterial and human HSPs may play an important role in coronary atherosclerosis and plaque instability.

[C-reactive protein in coronary plaques -- prevalence with acute coronary syndrome]. / C-reaktives Protein in koronarem Plaquegewebe -- Prävalenz bei akutem Koronarsyndrom.

Inflammatory mechanisms are central in human atherosclerosis. Although C-reactive protein (CRP) as a serum marker is highly predictive for cardiovascular events, the intimal expression of CRP in clinically relevant coronary lesions is unknown, in particular in acute coronary syndromes (ACS). Shown by reduced CRP serum values, statins have antiinflammatory and plaque-stabilizing effects. In the present study, the presence of CRP in coronary atheromas with ACS versus stable angina (SA) as well as its possible modification by chronic statin medication was assessed. Coronary atherectomy probes from 90 primary stenoses were immunohistochemically analyzed with regard to the presence and the localization of CRP. Intimal results of patients with ACS (n=36), categorized according to the Braunwald classification, were compared with those of patients with SA (n=54). In 40 of 90 lesions (44%), immunoreaction specific for CRP was observed demonstrating a mean CRP expression of 1.7%. CRP was focally localized in a maximum of 69% of all plaque cells, the most in macrophages/foam cells, infrequently in smooth muscle cells. CRP-positive plaques showed more thrombus than plaques without CRP (63% vs 41%). Intact non-atherosclerotic control tissue revealed no signaling. As a central finding, intimal presence and expression were higher (each p<0.001) with ACS (69% and 3.1%, respectively) compared to SA (28% and 0.8%, respective). Subgroup analysis of target lesions associated with ACS according to the clinical Braunwald classification showed an increase of intimal CRP with classes I-III. In the presence of statin medication, intimal CRP was significantly lower than that without statin therapy (29 and 1.3%, vs 61 and 2.6%, respectively; p<0.01), in particular in the subgroup of ACS patients. Intimal CRP is frequently found in coronary primary stenoses, very often with macrophages/foam cells, and shows a highly significant prevalence with ACS. In this subgroup of patients, statin therapy is associated with significantly reduced intimal CRP. Our in situ findings as shown might explain the well-known serum constellations with statin therapy.

[Association between progression of untreated coronary lesions and in-stent restenosis]. / Assoziation zwischen Progression unbehandelter Koronarstenosen und In-Stent-Restenosierung.

BACKGROUND AND OBJECTIVES: Progression of coronary artery disease is only incompletely understood regarding de-novo stenoses as well as in-stent restenoses (ISR) indicative of accelerated atherosclerosis. The objective of the present angiographic study was to prove an association between target lesion ISR and progression of primarily untreated coronary lesions. PATIENTS AND METHODS: A total of 179 high-grade native coronary stenoses (mean diameter stenosis 68+/-16 %) of 131 patients were treated by stent implantation. Additional 101 lesions remained untreated because of their moderate to intermediate diameter stenoses (>30 %). Quantitative coronary angiographic analysis was performed 6+/-2 months later to evaluate ISR (diameter stenosis > 50 %), coronary progression (>20 % increase in diameter stenosis) and regression (>20 % decrease), respectively. Angiographic, procedural and clinical characteristics were assessed for a possible association with ISR and/or coronary progression and regression, respectively. RESULTS: ISR was seen in 70 of 179 (39 %) stented target lesions. Presence of diabetes mellitus (p = 0.04) and cumulative duration of inflations (p = 0.01) as procedural determinant were predictive for ISR. Significant progression was found in ten of 101 (10 %) primarily untreated lesions. Progression of previously normal segments or regression were not seen. Progression of native plaques was associated with ISR presence in nine cases and with ISR absence in only one case (p = 0.01). Of note, smoking (p = 0.02) turned out to be predictive for plaque progression, whereas medication and procedural/angiographic parameters were not. CONCLUSIONS: The findings of the present pilot study demonstrate target lesion ISR associated with progression of other primarily untreated lesions and thereby suggest that both atherosclerosis types share common systemic pathogenetic mechanisms. With presence of ISR, coronary angiography should also include primarily untreated arteries, especially in case of preexisting plaques.

Insights into vascular pathology after intracoronary brachytherapy.

Post-angioplasty restenosis is a major limitation of interventional cardiology. A large body of evidence reveals that expression of myofibroblast activity promoters moves progressively from the neoadventitia to the neointima. Brachytherapy inhibits vascular cell activity (proliferation, migration), mitigates recruitment of intimal cells, and shows a favorable prophylactic effect on late vascular remodeling by preventing adventitial constriction at the injured site. These effects of brachytherapy are dose related. Clinical and experimental data demonstrate that restenosis is determined by the balance between arterial remodeling and intimal hyperplasia. Apparently, brachytherapy-induced positive remodeling plays the principal role in increasing the luminal diameter after PTCA and, in case of a lower dose or dose fall-off, to cause detrimental edge effects. With regard to clinical course, healing defects, endothelial dysfunction and stent-vessel wall malapposition are apparently important and possibly underestimated features of vascular pathology, since they may contribute to late thrombosis and delayed intimal hyperplasia in long-term course after intracoronary brachytherapy.

[Decreased platelet aggregation during angiotensin-converting enzyme inhibitor therapy. Results of a pilot study]. / Verminderte Plättchenaggregation bei ACE-Hemmertherapie. Ergebnisse einer Pilotstudie.

BACKGROUND AND OBJECTIVE: Plaque rupture and subsequent thrombosis are key events in the complication and progression of atherosclerotic disease. Recently, the HOPE study showed a significant decrease in cardiovascular complications with the angiotensin converting enzyme (ACE) inhibitor (ramipril). To assess the therapeutic potential of this drug class, the present study evaluates the coagulative activity in cardiovascular patients with ACE inhibitors and compares these data with those of untreated patients and with those of patients taking aspirin, resp. METHODS: Blood samples from 204 patients with coronary heart disease and/or arterial hypertension were analyzed by whole-blood lumi-aggregometry. Platelet aggregation was determined by the increase in impedance across paired electrodes in response to the stimulatory agents collagen and ADP, respectively. The data were correlated with the presence or absence of ACE inhibitor and/or aspirin medication. Analogously, the coagulative potential of beta-blockers, calcium antagonists, CSE-inhibitors and nitrates were studied. RESULTS: As the central finding, study participants treated with ACE inhibitors showed a decreased platelet aggregation compared to untreated control patients, indicated by a significantly reduced increase in impedance. Platelet aggregation induced by collagen decreased by 18% (p = 0.025), that induced by ADP by 39% (p = 0.039). With aspirin medication, the collagen-induced decrease amounted to 20% (p = 0.020); no significant effect was seen by ADP stimulation. With combined intake of ACE inhibitors and aspirin, collagen-induced platelet aggregation was found markedly reduced. Platelet aggregation decreased by 26% (p = 0.003). Beta-blockers, calcium antagonists, CSE inhibitors and nitrates did not reveal a significant influence on platelet aggregation. CONCLUSIONS: ACE inhibition decreases platelet aggregation, as detected and quantified by ex vivo whole-blood aggregometry. Beyond known effects of this drug class, in particular on endothelium and fibrinolysis, antithrombotic effects may explain the positive influence on major clinical cardiovascular events.

[Persistence of Chlamydia pneumoniae in coronary plaque tissue. A contribution to infection and immune hypothesis in unstable angina pectoris]. / Persistenz von Chlamydia pneumoniae in koronarem Plaquegewebe. Ein Beitrag zur Infektions- und Immunhypothese bei instabiler Angina pectoris.

BACKGROUND AND OBJECTIVE: There is an increasing number of pointers towards a causative connection between Chlamydia pneumoniae and atherosclerosis. But the pathogenetic mechanism and intimal structures that are involved remain unclear. Starting with the hypothesis of a chronic infection, as demonstrated by the presence of the chlamydial stress (heat-shock) protein 60 (HSP 60), the presence and localization of these bacterial products in coronary atheromas was investigated. PATIENTS AND METHODS: Coronary atheroma tissue from primary stenoses in 42 patients (36 men, 6 women, mean age 60.2 +/- 7.3 years) was studied immunohistochemically in the course of a retrospective analysis for chlamydial HSP 60. The findings in clinically acute coronary syndrome (Braunwald's classification) present in 27 patients were compared with those in 15 patients with acute angina and evaluated in relation to expression and site of predilection. RESULTS: An immune reaction to chlamydial HSP 60 was demonstrated in 27 of 42 atheromas (64%). Intact, non-atherosclerotic vessels, such as the mammary artery and sphenous vein, showed no such signals. Chlamydial HSP 60 was localized in maximally 23% of all plaque cells, mostly in macrophages/foam cells, more rarely in smooth muscle cells. Chlamydia in foam cells most often revealed ultrastructural patterns that pointed to the persistence of the pathogen. Sites of predilection of chlamydial HSP were predominantly foam cell areas and cell-poor regions, more rarely inflammatory infiltrates and areas of rupture. When comparing both types of lesion, signals for chlamydial HSP 60 were present in 21 of the 27 atheromas (78%) with unstable angina or acute myocardial infarction, but in only 6 of the 15 atheromas (40%) with stable angina. Within the group with the acute coronary syndrome, the prevalence of chronic chlamydial infection was independent of a previous myocardial infarction. CONCLUSIONS: Chlamydial HSP 60 can often be demonstrated in primary coronary stenosis of symptomatic patients. It is most frequently found in macrophages/foam cells and is highly prevalent in the acute coronary syndrome. In-situ findings suggest a pathogenetically relevant role of chronic persistent infection of Chlamydia pneumoniae in unstable coronary plaques.