Long QT: Good, bad or indifferent?

A survey of current literature suggests an increasing interest in both the desirable and undesirable implications of a prolonged QT interval, the former perceived to be the beneficial effect of antiarrhythmic drugs that prolong the duration of ventricular action potential, and the latter considered to be a potential marker for sudden cardiac death in patients with ischemic heart disease. In addition, there has been an increasing interest in the congenital long QT syndrome associated with an apparent dysfunction of the autonomic nervous system and serious, potentially lethal ventricular arrhythmias. Circumstantial evidence suggests that these arrhythmias are due to increased dispersion of repolarization which may be aggravated by psychologic and emotional perturbations.In this review, the associations between the long QT interval, autonomic nervous system, dispersion of repolarization, antiarrhythmic drugs and ventricular arrhythmias are examined. Attention is directed to the difficulties of accurate QT measurement, problems related to the correction of the QT interval for heart rate and sex (QTC), the wide range of normal values and the modest QT alterations after various manipulations of the autonomic nervous system. Clinical conditions as- sociated with marked, moderate and occasional QT lengthening are listed and discussed briefly in relation to the disturbances of nervous system, dispersion of ventricular repolarization and ventricular arrhythmias.It is proposed that the absence of relevant animal models of neurogenic or psychogenic QT prolongation hinders the investigation of the neurogenic factors associated with QT lengthening. QT prolongation is most often induced by antiarrhythmic drugs and ischemic heart disease. However, it is not known whether the occurrence of torsade de pointes type of ventricular tachycardia in patients treated with antiarrhythmic drugs is related to a critical drug dose or a critical degree of QTC prolongation. There is no conclusive evidence that QT lengthening has any predictive value either during the acute phase or during convalescence after myocardial infarction. Also, a serious deficiency in current knowledge is the lack of an established relation between the prolonged QT interval and the dispersion of ventricular repolarization. It is concluded that the number of unanswered questions discussed in this review still makes it difficult to judge when a prolonged QT interval is good, bad or indifferent

T Wave Alternans in high arrhythmic risk patients: Analysis in time and frequency domains: A pilot study

BACKGROUND: T wave alternans (TA) is a repolarisation phenomenon manifesting as a microvolt beat to beat change in the amplitude of the T wave and ST segment. TA has been shown to be a predictor of arrhythmic risk in unselected myocardial infarction populations. TA has not been used to differentiate risk within the ischaemic cardiomyopathy population. METHODS: The subjects investigated comprised, Group 1: 7 stable patients with remote (>20 months) extensive myocardial scarring and no arrhythmic events (NYHA 3 and 4). Group2: 9 post infarction patients with malignant arrhythmia and implantable defibrillator. During breath holding, 20 continuous QRST complexes from each patients X, Y and Z leads were digitally recorded. Time domain, resultant absolute difference vectors (ATA), were calculated for alternate resultant T wave sequences. Group differences between the magnitude and temporal distribution of mean ATAs and their spectral and cross-spectral analysis were compared. RESULTS: Group 1 v Group 2 mean ATAs were 10.7 (7.17) v 11.7 (8.48) respectively, not significant. Each group had a homogenous temporal distribution of ATAs. Both group's largest mean ATA frequency components were between 0 to 25 Hz, the largest ATA component being at the DC frequency. Cross spectral analysis showed no significant differences in group ATA frequency content. CONCLUSION: The frequency content and microvolt magnitude of T wave alternans was not significantly different in these two groups. The specificity of T wave alternans for differentiating arrhythmic risk in post infarction scarring and heart failure needs investigation

Identification of a novel zinc metalloprotease through a global analysis of clostridium difficile extracellular proteins

Clostridium difficile is a major cause of infectious diarrhea worldwide. Although the cell surface proteins are recognized to be important in clostridial pathogenesis, biological functions of only a few are known. Also, apart from the toxins, proteins exported by C. difficile into the extracellular milieu have been poorly studied. In order to identify novel extracellular factors of C. difficile, we analyzed bacterial culture supernatants prepared from clinical isolates, 630 and R20291, using liquid chromatography-tandem mass spectrometry. The majority of the proteins identified were non-canonical extracellular proteins. These could be largely classified into proteins associated to the cell wall (including CWPs and extracellular hydrolases), transporters and flagellar proteins. Seven unknown hypothetical proteins were also identified. One of these proteins, CD630_28300, shared sequence similarity with the anthrax lethal factor, a known zinc metallopeptidase. We demonstrated that CD630_28300 (named Zmp1) binds zinc and is able to cleave fibronectin and fibrinogen in vitro in a zinc-dependent manner. Using site-directed mutagenesis, we identified residues important in zinc binding and enzymatic activity. Furthermore, we demonstrated that Zmp1 destabilizes the fibronectin network produced by human fibroblasts. Thus, by analyzing the exoproteome of C. difficile, we identified a novel extracellular metalloprotease that may be important in key steps of clostridial pathogenesis

Circumferential myocardial strain in cardiomyopathy with and without left bundle branch block

<p>Abstract</p> <p>Background</p> <p>Cardiac resynchronization therapy (CRT) has been shown to decrease mortality in 60-70% of advanced heart failure patients with left bundle branch block (LBBB) and QRS duration > 120 ms. There have been intense efforts to find reproducible non-invasive parameters to predict CRT response. We hypothesized that different left ventricular contraction patterns may exist in LBBB patients with depressed systolic function and applied tagged cardiovascular magnetic resonance (CMR) to assess circumferential strain in this population.</p> <p>Methods</p> <p>We determined myocardial circumferential strain at the basal, mid, and apical ventricular level in 35 subjects (10 with ischemic cardiomyopathy, 15 with non-ischemic cardiomyopathy, and 10 healthy controls). Patterns of circumferential strain were analyzed. Time to peak systolic circumferential strain in each of the 6 segments in all three ventricular slices and the standard deviation of time to peak strain in the basal and mid ventricular slices were determined.</p> <p>Results</p> <p>Dyskinesis of the anterior septum and the inferior septum in at least two ventricular levels was seen in 50% (5 out of 10) of LBBB patients while 30% had isolated dyskinesis of the anteroseptum, and 20% had no dyskinesis in any segments, similar to all of the non-LBBB patients and healthy controls. Peak circumferential strain shortening was significantly reduced in all cardiomyopathy patients at the mid-ventricular level (LBBB 9 ± 6%, non-LBBB 10 ± 4% vs. healthy 19 ± 4%; both p < 0.0001 compared to healthy), but was similar among the LBBB and non-LBBB groups (p = 0.20). The LBBB group had significantly greater dyssynchrony compared to the non-LBBB group and healthy controls assessed by opposing wall delays and 12-segment standard deviation (LBBB 164 ± 30 ms vs. non-LBBB 70 ± 17 ms (p < 0.0001), non-LBBB vs. healthy 65 ± 17 ms (p = 0.47)).</p> <p>Conclusions</p> <p>Septal dyskinesis exists in some patients with LBBB. Myocardial circumferential strain analysis enables detailed characterization of contraction patterns, strengths, and timing in cardiomyopathy patients with and without LBBB.</p

QRS pattern and improvement in right and left ventricular function after cardiac resynchronization therapy: a radionuclide study

Predicting response to cardiac resynchronization therapy (CRT) remains a challenge. We evaluated the role of baseline QRS pattern to predict response in terms of improvement in biventricular ejection fraction (EF)

Incidence of first primary central nervous system tumors in California, 2001–2005

We examined the incidence of first primary central nervous system tumors (PCNST) in California from 2001–2005. This study period represents the first five years of data collection of benign PCNST by the California Cancer Registry. California’s age-adjusted incidence rates (AAIR) for malignant and benign PCNST (5.5 and 8.5 per 100,000, respectively). Malignant PCNST were highest among non-Hispanic white males (7.8 per 100,000). Benign PCNST were highest among African American females (10.5 per 100,000). Hispanics, those with the lowest socioeconomic status, and those who lived in rural California were found to be significantly younger at diagnosis. Glioblastoma was the most frequent malignant histology, while meningioma had the highest incidence among benign histologies (2.6 and 4.5 per 100,000, respectively). This study is the first in the US to compare malignant to benign PCNST using a population-based data source. It illustrates the importance of PCNST surveillance in California and in diverse communities

Clinical Outcomes of Thirteen Patients with Acute Chagas Disease Acquired through Oral Transmission from Two Urban Outbreaks in Northeastern Brazil

Chagas disease is caused by a parasitic protozoan transmitted to humans by the contaminated feces of blood-feeding assassin bugs from the Triatominae subfamily. It may also be transmitted from mother to baby during pregnancy, by breastfeeding, blood transfusion or organ transplant. In rare cases, the disease can also be caused by accidental ingestion of contaminated food (sugar cane or açaí juice, drinking water, etc.). Acute Chagas disease often presents itself as a mononucleosis-like syndrome, with symptoms including fever, lymph node enlargement and muscle pain. The mortality rate of acute Chagas disease is high, mainly due to heart failure as a consequence of cardiac fiber lesions. There are few studies describing clinical outcomes and the disease progression of patients who receive therapeutic treatment, especially with regard to cardiac exam findings. In this report, the authors describe clinical findings from two micro-outbreaks occurring in impoverished towns in northeastern Brazil. Prior to receiving treatment, patient mortality rate was 28.6% in one of the outbreaks, and one pregnant woman experienced a spontaneous abortion due to the disease in the other outbreak. Most patients complained of fever, dyspnea, myalgia and periorbital edema. After receiving a two-month course of treatment, clinical symptoms improved and the number of abnormalities in cardiac exams decreased

Molecular, microbiological and clinical characterization of Clostridium difficile isolates from tertiary care hospitals in Colombia

In Colombia, the epidemiology and circulating genotypes of Clostridium difficile have not yet been described. Therefore, we molecularly characterized clinical isolates of C.difficile from patients with suspicion of C.difficile infection (CDI) in three tertiary care hospitals. C.difficile was isolated from stool samples by culture, the presence of A/B toxins were detected by enzyme immunoassay, cytotoxicity was tested by cell culture and the antimicrobial susceptibility determined. After DNA extraction, tcdA, tcdB and binary toxin (CDTa/CDTb) genes were detected by PCR, and PCR-ribotyping performed. From a total of 913 stool samples collected during 2013–2014, 775 were included in the study. The frequency of A/B toxins-positive samples was 9.7% (75/775). A total of 143 isolates of C.difficile were recovered from culture, 110 (76.9%) produced cytotoxic effect in cell culture, 100 (69.9%) were tcdA+/tcdB+, 11 (7.7%) tcdA-/tcdB+, 32 (22.4%) tcdA-/tcdB- and 25 (17.5%) CDTa+/CDTb+. From 37 ribotypes identified, ribotypes 591 (20%), 106 (9%) and 002 (7.9%) were the most prevalent; only one isolate corresponded to ribotype 027, four to ribotype 078 and four were new ribotypes (794,795, 804,805). All isolates were susceptible to vancomycin and metronidazole, while 85% and 7.7% were resistant to clindamycin and moxifloxacin, respectively. By multivariate analysis, significant risk factors associated to CDI were, staying in orthopedic service, exposure to third-generation cephalosporins and staying in an ICU before CDI symptoms; moreover, steroids showed to be a protector factor. These results revealed new C. difficile ribotypes and a high diversity profile circulating in Colombia different from those reported in America and European countries

Restitution analysis of alternans and its relationship to arrhythmogenicity in hypokalaemic Langendorff-perfused murine hearts

Alternans and arrhythmogenicity were studied in hypokalaemic (3.0 mM K+) Langendorff-perfused murine hearts paced at high rates. Epicardial and endocardial monophasic action potentials were recorded and durations quantified at 90% repolarization. Alternans and arrhythmia occurred in hypokalaemic, but not normokalaemic (5.2 mM K+) hearts (P < 0.01): this was prevented by treatment with lidocaine (10 μM, P < 0.01). Fourier analysis then confirmed transition from monomorphic to polymorphic waveforms for the first time in the murine heart. Alternans and arrhythmia were associated with increases in the slopes of restitution curves, obtained for the first time in the murine heart, while the anti-arrhythmic effect of lidocaine was associated with decreased slopes. Thus, hypokalaemia significantly increased (P < 0.05) maximal gradients (from 0.55 ± 0.14 to 2.35 ± 0.67 in the epicardium and from 0.67 ± 0.13 to 1.87 ± 0.28 in the endocardium) and critical diastolic intervals (DIs) at which gradients equalled unity (from −2.14 ± 0.52 ms to 50.93 ± 14.45 ms in the epicardium and from 8.14 ± 1.49 ms to 44.64 ± 5 ms in the endocardium). While treatment of normokalaemic hearts with lidocaine had no significant effect (P > 0.05) on either maximal gradients (0.78 ± 0.27 in the epicardium and 0.83 ± 0.45 in the endocardium) or critical DIs (6.06 ± 2.10 ms and 7.04 ± 3.82 ms in the endocardium), treatment of hypokalaemic hearts with lidocaine reduced (P < 0.05) both these parameters (1.05 ± 0.30 in the epicardium and 0.89 ± 0.36 in the endocardium and 30.38 ± 8.88 ms in the epicardium and 31.65 ± 4.78 ms in the endocardium, respectively). We thus demonstrate that alternans contributes a dynamic component to arrhythmic substrate during hypokalaemia, that restitution may furnish an underlying mechanism and that these phenomena are abolished by lidocaine, both recapitulating and clarifying clinical findings