The anticipatory proportion (AP), the ratio between perseverative and anticipatory speech errors, is reduced in patients with brain injury. However, it is unknown whether the AP is also reduced in ...elderly speakers with cognitive impairment.
20 elderly speakers with a Mini Mental State Examination (MMSE) score of 25-27 and 20 elderly speakers with an MMSE score of 28-30 were assessed using a tongue-twister-based speech test, the Regensburg Word Fluency Test (RWT) and an object naming test.
The AP in the group of speakers with an MMSE score of 25-27 was significantly lower. Accordingly, the AP and scores in the RWT and the object naming test were higher in persons with an MMSE score of 28-30.
Language alterations in mild cognitive dysfunction are detectable with the AP. Further longitudinal studies are needed to evaluate the predictive value of the AP.
Background:
The long‐QT syndromes (LQTS) are inherited electrical cardiomyopathies characterized by prolonged ventricular repolarization and ventricular arrhythmias. Several genetic reports have ...associated defects in LQTS‐causing genes with atrial fibrillation (AF). We therefore studied whether atrial arrhythmias occur in patients with LQTS under daily‐life conditions.
Methods:
We systematically assessed atrial arrhythmias in LQTS patients and matched controls using implanted defibrillators or pacemakers as monitors of atrial rhythm in a nested case‐control study. Twenty‐one LQTS patients (3 male; 39 ± 18 years old; 18 on β blocker, ICD therapy duration 6.3 ± 2.7 years; 4 LQT1, 6 LQT2, 2 LQT3) were matched to 21 control subjects (13 male; 50 ± 19 years old; 3 on β blocker; pacemaker therapy duration 8.5 ± 5.5 years; 19 higher‐degree AV block, 2 others). LQTS patients were identified by a systematic search of the LQTS patient databases in Münster and Munich.
Results:
One‐third (7 of 21) of the LQTS patients developed self‐terminating atrial arrhythmias (atrial cycle lengths <250 ms). Only one control patient developed a single episode of postoperative AF (P < 0.05 vs LQTS).
Conclusions:
LQTS patients at high risk for ventricular arrhythmias may develop short‐lasting atrial arrhythmias under daily‐life conditions, suggesting that prolonged atrial repolarization may contribute to the initiation of AF.
Dilated cardiomyopathy is a frequent cause of heart failure and is associated with high mortality. Progressive remodeling of the myocardium leads to increased dimensions of heart chambers. The role ...of intracellular proteolysis in the progressive remodeling that underlies dilated cardiomyopathy has not received much attention yet. Here, we report that the lysosomal cysteine peptidase cathepsin L (CTSL) is critical for cardiac morphology and function. One-year-old CTSL-deficient mice show significant ventricular and atrial enlargement that is associated with a comparatively small increase in relative heart weight. Interstitial fibrosis and pleomorphic nuclei were found in the myocardium of the knockout mice. By electron microscopy, CTSL-deficient cardiomyocytes contained multiple large and apparently fused lysosomes characterized by storage of electron-dense heterogeneous material. Accordingly, the assessment of left ventricular function by echocardiography revealed severely impaired myocardial contraction in the CTSL-deficient mice. In addition, echocardiographic and electrocardiographic findings to some degree point to left ventricular hypertrophy that most likely represents an adaptive response to cardiac impairment. The histomorphological and functional alterations of CTSL-deficient hearts result in valve insufficiencies. Furthermore, abnormal heart rhythms, like supraventricular tachycardia, ventricular extrasystoles, and first-degree atrioventricular block, were detected in the CTSL-deficient mice.
Familial dilated cardiomyopathy is a highly heterogeneous genetic disease. Thus, identification of disease-causing mutations is a challenging and time-consuming task. Genotype-phenotype associations ...may alleviate identification of the underlying mutation.
The purpose of this study was to investigate cardiac phenotypes within a family harboring a familial dilated cardiomyopathy-related mutation in the gene encoding phospholamban.
Complete genetic and clinical analyses were performed in a family with familial dilated cardiomyopathy due to the PLN-R14Del mutation. Family relatives were studied by ECG, Holter ECG, echocardiography, ECG body surface potential mapping, and cardiac magnetic resonance imaging.
A candidate gene approach resulted in identification of a heterozygous deletion of arginine 14 in the gene encoding phospholamban (PLN-R14Del) segregating with dilated cardiomyopathy in the family pedigree. Mutation carriers suffered from familial dilated cardiomyopathy associated with cardiac death between the ages of 26 and 50 years. Interestingly, all adult mutation carriers revealed strikingly attenuated R amplitudes on standard ECG, regardless of the absence or presence of echocardiographic abnormalities. Gadolinium-enhanced cardiac magnetic resonance imaging showed late enhancement in PLN-R14Del carriers with preserved ejection fraction. Late enhancement was regionally related to areas of most pronounced R-amplitude attenuation as assessed by body surface potential mapping.
Attenuated R amplitudes were identified as an early ECG phenotype in a family with familial dilated cardiomyopathy due to the PLN-R14Del mutation. All adults harboring PLN-R14Del had attenuated R waves irrespective of echocardiographic abnormalities. The study findings suggest a mutation-related remodeling process preceding ventricular dysfunction.
There is growing concern that antipsychotic drugs that prolong the QT interval almost always increase the risk for patients to develop life-threatening ventricular tachyarrhythmias (VTs) of the ...torsade de pointes type. We therefore sought to compare the electrophysiologic effects of the psychotropic agent sertindole, which prolongs cardiac repolarization by inhibiting the rapid component of the delayed rectifier potassium current (I(Kr)) but has a low torsadogenic potential to the antiarrhythmic agent dl-sotalol. In 18 Langendorff-perfused rabbit hearts, sotalol (10 microM, n = 8) and sertindole (0.5, 1.0, and 1.5 microM; n = 10) led to significant and comparable QT prolongation. In the presence of sotalol, torsade de pointes reproducibly occurred in atrioventricular node-blocked hearts after lowering the potassium concentration to 1.5 mM. High doses of sertindole (1.5 microM) only caused monomorphic VT (n = 4) and nonsustained polymorphic VT (n = 2) in the presence of QRS prolongation. Multiple simultaneous epi- and endocardial monophasic action potentials and a volume-conducted ECG demonstrated widening of the T/U wave, early afterdepolarizations, and increased dispersion of repolarization in the presence of dl-sotalol. In contrast to sotalol, QT and monophasic action potential prolongation were cycle length-independent in the presence of sertindole. Sertindole had no significant effect on transmural or interventricular dispersion of repolarization. Early afterdepolarizations did not occur. Despite comparable QT prolongation, sertindole did not display the proarrhythmic profile typical of other blockers of I(Kr) such as dl-sotalol. It is likely that a different mode of interaction between sertindole and the channel and/or additional pharmacological effects of sertindole, e.g., its ability to inhibit I(Na) and/or its ability to block alpha(1)-receptors, play a role.
Patients with Brugada syndrome present with characteristic ECG abnormalities (atypical right bundle-branch block and ST-segment elevation) and life-threatening ventricular tachyarrhythmias despite ...structurally normal hearts. Involvement of the autonomic nervous system is suggested by the occurrence of ventricular tachyarrhythmias and sudden death at rest or during sleep and by changes of typical ECG signs under pharmacological modulation of the myocardial autonomic tone.
This study investigated the presynaptic cardiac neuronal reuptake of norepinephrine (uptake 1) in 17 patients with Brugada syndrome and 10 age-matched control subjects with the use of the norepinephrine analogue 123Im-iodobenzylguanidine (123I-MIBG), single-photon emission CT (SPECT), and quantitative 33-segment bull's-eye analysis. Regionally reduced 123I-MIBG uptake was present in 8 (47%) of 17 patients with Brugada syndrome but in none of the control subjects. Quantitative analysis showed segmental reduction of 123I-MIBG uptake in the inferior and septal left ventricular wall in patients with Brugada syndrome compared with control subjects (P<0.05). No correlation was found between the findings of 123I-MIBG-SPECT and clinical characteristics of the study patients.
The present study demonstrated an abnormal 123I-MIBG uptake in patients with Brugada syndrome, indicating presynaptic sympathetic dysfunction of the heart. These findings may have potential impact on the pathophysiology and arrhythmogenesis in patients with Brugada syndrome. Future quantitative investigations of the presynaptic and postsynaptic sympathetic and parasympathetic branches of the cardiac autonomic nervous system may clarify whether these observations represent a primary adrenergic dysfunction or an imbalance between sympathetic and parasympathetic innervation of the heart.
Background: Numerous noncardiovascular drugs prolong repolarization and thereby increase the risk for patients to develop life‐threatening tachyarrhythmias of the torsade de pointes (TdP) type. The ...development of TdP is an individual, patient‐specific response to a repolarization‐prolonging drug, depending on the repolarization reserve. The aim of the present study was to analyze the underlying mechanisms that discriminate hearts that will develop TdP from hearts that will not develop TdP. We therefore investigated the group of quinolone antibiotics that reduce repolarization reserve via IKr blockade in an intact heart model of proarrhythmia.
Methods and Results: In 47 Langendorff‐perfused, AV‐blocked rabbit hearts, ciprofloxacin (n = 10), ofloxacin (n = 14), levofloxacin (n = 10), and moxifloxacin (n = 13) in concentrations from 100 μM to 1,000 μM were infused. Eight monophasic action potentials (MAPs) and an ECG were recorded simultaneously. After incremental pacing at cycle lengths from 900 ms to 300 ms to compare the action potential duration, potassium concentration was lowered to provoke TdP. All antibiotics led to a significant increase in QT interval and MAP duration, and exhibited reverse‐use dependence. Eight simultaneously recorded MAPs demonstrated an increase in dispersion of repolarization in the presence of all antibiotics. MAP triangulation (ratio: MAP90/50) and fluctuation of consecutive action potentials were increased for all tested drugs at high concentrations. In the presence of low potassium concentration, all quinolones led to TdP: ciprofloxacin, 4 out of 10 (40%); ofloxacin, 3 out of 14 (21%); moxifloxacin, 9 out of 13 (69%); and levofloxacin, 2 out of 10 (20%). Hearts that developed TdP demonstrated a significant greater influence on dispersion of repolarization and on triangulation as compared with hearts without TdP.
Conclusion: Quinolone antibiotics may be proarrhythmic due to a significant effect on myocardial repolarization. The individual response of a heart to develop TdP in this experimental model is characterized by a greater effect on dispersion of repolarization and on triangulation of action potential as compared with hearts that do not develop TdP.
Voltage‐Guided Cavotricuspid Isthmus Ablation.
Introduction: The recently proposed “maximum voltage‐guided” (MVG) technique for radiofrequency catheter ablation of atrial flutter targets high‐voltage ...electrograms along cavotricuspid isthmus (CTI) to ablate the functionally important anatomic muscle bundles alone, without drawing a complete anatomic line across the CTI. This innovative approach may shorten ablation time and procedure duration.
Methods and Results:
Within the multicenter AURUM 8 study, which compared 8‐mm gold‐ and Pt‐Ir‐tip catheters in atrial flutter ablation, we made a post hoc comparison of procedural data from 72 patients treated with MVG technique with data from 281 patients undergoing anatomic CTI ablation (unmatched) and with data from 72 patients selected from among those 281 patients such that they were matched with the MVG group with respect to selected baseline parameters and catheter type (matched). The MVG technique markedly reduced (P < 0.001) ablation time (mean 6.9 minutes vs 10.9/9.7 minutes unmatched/matched), number of lesions (8.3 vs 13.7/12.9), fluoroscopy time (9.5 minutes vs 20.6/17.9 minutes), procedure duration (59 minutes vs 93/86 minutes), and energy delivered (19 kJ vs 34/30 kJ) compared with anatomic CTI ablation. The incidence of charring was higher for MVG than for anatomic ablation technique (31.9% vs 18.5/15.3%, P < 0.05), where Pt‐Ir tip catheters were 6‐fold more susceptible to charring than gold‐tip catheters (P < 0.001), likely because of a lower thermal conductivity of the Pt‐Ir material. The acute success rate was slightly better for MVG than for anatomic ablation technique (97.2% vs 92.2/91.7%, P = n.s.).
Conclusion:
Major procedural parameters are remarkably improved with MVG technique. Gold‐tip catheters are substantially less susceptible to charring and may therefore be preferred over Pt‐Ir‐tip catheters for MVG ablation technique.
(J Cardiovasc Electrophysiol, Vol. 23, pp. 479‐485, May 2012)
Brugada Syndrome and Supraventricular Tachyarrhythmias.
Introduction: The Brugada syndrome is a distinct form of idiopathic ventricular fibrillation characterized by a unique ECG pattern consisting ...of a right bundle branch block‐like aspect and ST segment elevation in leads V1 to V3. As a high induction rate of ventricular tachyarrhythmias has been reported in Brugada syndrome, we hypothesized that this also may be true for supraventricular tachycardias in these patients.
Methods and Results: Between January 1995 and December 2000, we identified 35 consecutive patients with Brugada syndrome; 26 had a history of cardiac arrest or syncope and 9 were asymptomatic. All patients underwent electrophysiologic study, including an atrial and ventricular stimulation protocol. Ten patients (29%) were found to have supraventricular tachyarrhythmias (SVT) in addition to the Brugada syndrome. These 10 patients presented with aborted sudden cardiac death (n = 3) and/or a family history of sudden cardiac death (n = 4), syncope (n = 4), or primarily with a Brugada typical ECG, a positive family history, and palpitations (n = 2). Eight of them underwent genetic testing, but only 1 had a mutation in the SCN5A gene. In 6 patients, an AV nodal reentrant tachycardia was easily and reproducibly inducible. Two patients had clinical documented and inducible episodes of an atrial tachycardia (1 in addition to an AV nodal reentrant tachycardia). One patient had paroxysmal atrial fibrillation alternating with sinus rhythm, and 2 patients with accessory pathways were identified.
Conclusion: This is the first description of an association of the Brugada syndrome with SVT. Thus, the arrhythmogenic substrate in Brugada syndrome may not be restricted to the ventricular level. Palpitations in this syndrome should raise the possibility of SVT. Conversely, in patients with SVT and aborted sudden cardiac death or syncope not related to SVT, the Brugada syndrome should be considered a possible additional electrophysiologic abnormality.
Since the 1960s, physicians have been aware of electrocardiographic (ECG) abnormalities and cases of sudden death associated with the use of antipsychotic drugs in patients with schizophrenia. ...Explanations for such deaths have traditionally focused on drug-induced prolongation of the QT interval leading to the development of life-threatening ventricular arrhythmias such as torsade de pointes (TdP). It is now apparent that most conventional and atypical antipsychotics can cause dose-related prolongation of the corrected QT interval (QTc), although there are important differences in the potency of individual agents. This review discusses potential mechanisms underlying QTc prolongation and arrhythmogenesis and examines the evidence for a relationship between antipsychotic drugs and prolongation of the QTc interval. New electrophysiological and epidemiological data are presented which suggest there may not be a clear-cut cause–effect relationship between QTc prolongation and the development of ventricular tachyarrhythmias for all atypical antipsychotics. For at least one of these agents (sertindole), counterbalancing mechanisms may act to reduce the risk of proarrhythmic activity arising as a result of QTc prolongation.