Stress-Induced Proteasome Sub-Cellular Translocation in Cardiomyocytes Causes Altered Intracellular Calcium Handling and Arrhythmias.

The ubiquitin-proteasome system (UPS) is an essential mechanism responsible for the selective degradation of substrate proteins via their conjugation with ubiquitin. Since cardiomyocytes have very limited self-renewal capacity, as they are prone to protein damage due to constant mechanical and metabolic stress, the UPS has a key role in cardiac physiology and pathophysiology. While altered proteasomal activity contributes to a variety of cardiac pathologies, such as heart failure and ischemia/reperfusion injury (IRI), the environmental cues affecting its activity are still unknown, and they are the focus of this work. Following a recent study by Ciechanover's group showing that amino acid (AA) starvation in cultured cancer cell lines modulates proteasome intracellular localization and activity, we tested two hypotheses in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs, CMs): (i) AA starvation causes proteasome translocation in CMs, similarly to the observation in cultured cancer cell lines; (ii) manipulation of subcellular proteasomal compartmentalization is associated with electrophysiological abnormalities in the form of arrhythmias, mediated via altered intracellular Ca2+ handling. The major findings are: (i) starving CMs to AAs results in proteasome translocation from the nucleus to the cytoplasm, while supplementation with the aromatic amino acids tyrosine (Y), tryptophan (W) and phenylalanine (F) (YWF) inhibits the proteasome recruitment; (ii) AA-deficient treatments cause arrhythmias; (iii) the arrhythmias observed upon nuclear proteasome sequestration(-AA+YWF) are blocked by KB-R7943, an inhibitor of the reverse mode of the sodium-calcium exchanger NCX; (iv) the retrograde perfusion of isolated rat hearts with AA starvation media is associated with arrhythmias. Collectively, our novel findings describe a newly identified mechanism linking the UPS to arrhythmia generation in CMs and whole hearts.

Autonomic responses in young females with typical vasovagal syncope.

To determine whether young women who have experienced typical vasovagal syncope (tVVS) have altered autonomic response parameters, based on a battery of autonomic tests and maneuvers. Notably, previous studies including small cohorts and a partial list of tests yielded conflicting results. A total of 91 otherwise healthy women were included and divided according to those who had experienced tVVS (39 patients) or not (52 patients). Heart rate variability was evaluated at rest, under strict conditions, during 5 min of standing and during a deep breathing test. Response to Valsalva maneuver and Ewing maneuver were also quantified and compared. Both groups had similar clinical characteristics at baseline. No significant differences were found between the two groups in any of the autonomic parameters evaluated. Autonomic responses in young women who experienced typical vasovagal syncope at baseline were indistinguishable from those who did not. Thus, using non-tilt test autonomic screening tests does not seem to provide diagnostic benefits, and may not be useful in predicting recurrence in this patient population.

Normal baseline cardiac autonomic function and increased pupillary parasympathetic tone in patients with vasovagal syncope.

It is controversial whether people with vasovagal syncope (VVS) have abnormal autonomic responses at baseline and whether specific diagnostic manoeuvres have a diagnostic value. We investigated whether the pupillary light reflex and cardiac autonomic tests can be used to identify autonomic dysfunction in volunteers with a medical history of VVS. The study groups included 128 healthy volunteers, of whom 31 reported a history of typical VVS. The right pupil was evaluated using an automated, commercial infra-red pupillometer under strict conditions. In addition to miosis and mydriasis kinetics, pupil diameters were measured. Heart rate variability at rest and heart rate changes to standing were quantified with high-resolution electrocardiography and designated software. The demographic and clinical characteristics of both groups were statistically similar. Average constriction velocity (ACV) was significantly higher in VVS patients following a univariate analysis (3.83 ± 0.59 vs. 3.56 ± 0.73 mm/s, p = 0.042) and after correcting for potential confounders (p = 0.049). All other pupillometric and heart rate indices were comparable between groups. Patients with a history of VVS depict pupillary parasympathetic overactivity in response to light stimuli, manifested as increased ACV. The prognostic implications of this finding and the significance of using this simple clinical tool to identify patients who are at risk for developing frequent episodes of VVS or physical injuries following a syncope merits further study.

Effect of ischaemic postconditioning on markers of myocardial injury in ST-elevation myocardial infarction: a meta-analysis.

OBJECTIVES: This study aimed to perform a meta-analysis of the short-term impact of ischaemic postconditioning (IPoC) on myocardial injury in ST elevation myocardial infarction (STEMI) using surrogate cardiac biomarkers. METHODS: Eligible studies were identified using several article databases. Randomised controlled trials published between 1 January 2000 and 1 December 2021 comparing IPoC to standard of therapy in STEMI patients were included in the search. Outcomes included surrogates of myocardial injury, specifically peak troponin, creatine-kinase (CK) and CK myoglobin binding (CK-MB) enzyme levels. RESULTS: 11 articles involving 1273 patients reported on CK-MB and 8 studies involving 505 patients reported on CK. Few studies used troponin as an outcome, thus, a subanalysis of troponin dynamics was not performed. Meta-regression analysis demonstrated no significant effect of IPoC on peak CK-MB (effect size -0.41, 95% CI -1.15 to 0.34) or peak CK (effect size -0.42, 95% CI -1.20 to 0.36). Linear regression analysis demonstrated a significant correlation between a history of smoking and CK-MB in the IPoC group (p=0.038). CONCLUSIONS: IPoC does not seem to protect against myocardial injury in STEMI, except possibly in smokers. These results resonate with some studies using imaging techniques to ascertain myocardial damage. More research using troponin and cardiac imaging should be pursued to better assess the effects of IPoC on cardiovascular outcomes in STEMI.

Ischemic Postconditioning Confers No Benefit to Left Ventricular Systolic Function: A Meta-Analysis of Cardiac Magnetic Resonance Imaging Results.

Ischemic postconditioning (IPoC) is a technique suggested to reduce reperfusion injury in patients suffering acute ST-elevation myocardial infarction (STEMI), although its use is highly controversial. This meta-analysis aimed to evaluate the effect of IPoC with percutaneous coronary intervention in patients with acute STEMI, as measured by follow-up left ventricular ejection fraction (LVEF) on cardiac magnetic resonance imaging. The investigators searched PubMed, Embase, and Web of Science for all randomized controlled trials published during the last 2 decades. After the removal of duplicates, 2,021 articles from online databases had been identified using relevant search criteria. The included randomized controlled trials had studied patients with acute STEMI and Thrombolysis in Myocardial Infarction flow 0 to 1 at presentation and had measured follow-up LVEF using cardiac magnetic resonance imaging. Overall, 11 studies (n = 1,339 patients) qualified for inclusion. In each study, the control group did not differ significantly from the experimental group. The pooled data from included studies were analyzed using standardized mean difference between IPoC and control groups, and the 95% confidence interval for LVEF; the results were visualized using a forest plot. Bivariate regression analyses and 1-way analyses of LVEF coefficient ratios were done to isolate for various clinical and procedural parameters. An analysis of pooled data of the IPoC (n = 674) and control (n = 665) groups showed that IPoC did not significantly impact follow-up LVEF (using standardized mean difference 0.10, 95% confidence interval 0.00 to 0.21). Further analysis showed that IPoC did not improve follow-up LVEF when isolating for relevant clinical and procedural parameters. In conclusion, the use of IPoC as an adjunctive therapy to percutaneous coronary intervention seemingly provides no benefit to left ventricular systolic function, as quantified with cardiac magnetic resonance imaging, in patients with acute STEMI with Thrombolysis in Myocardial Infarction flow 0 to 1.

Prognostic implications of ultra-short heart rate variability indices in hospitalized patients with infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is a disease that poses a serious health risk. It is important to identify high-risk patients early in the course of their treatment. In the current study, we evaluated the prognostic value of ultra-short heart-rate variability (HRV), an index of vagal nerve activity, in IE. METHODS: Retrospective analysis was performed on adult patients admitted to a tertiary hospital due to IE. A logistic regression (LR) was used to determine whether clinical, laboratory, and HRV parameters were predictive of specific clinical features (valve type, staphylococcal infection) or severe short-term complications (cardiac, metastatic infection, and death). The accuracy of the model was evaluated through the measurement of the area under the curve (AUC) of the receiver operating characteristic curve (ROC). An analysis of survival was conducted using Cox regression. A number of HRV indices were calculated, including the standard deviation of normal heart-beat intervals (SDNN) and the root mean square of successive differences (RMSSD). RESULTS: 75 patients, aged 60.3(±18.6) years old, were examined. When compared with published age- and gender-adjusted HRV norms, SDNN and RMSSD were found to be relatively low in our cohort (75%-76% lower than the median; 33%-41% lower than the 2nd percentile). 26(34.6%) patients developed a metastatic infection, with RMSSD<7.03ms (adjusted odds ratio (aOR) 9.340, p = 0.002), incorporated in a multivariate LR model (AUC 0.833). Furthermore, 27(36.0%) patients were diagnosed with Staphylococcus IE, with SDNN<4.92ms (aOR 5.235, p = 0.004), a major component of the multivariate LR model (AUC 0.741). Multivariate Cox regression survival model, included RMSSD (HR 1.008, p = 0.012). CONCLUSION: SDNN, and particularly RMSSD, derived from ultra-short ECG recordings, may provide prognostic information about patients presenting with IE.

Ambient circulation surrounding an ablation catheter tip affects ablation lesion characteristics.

INTRODUCTION: The association between ambient circulating environments (CEs) and ablation lesions has been largely underexplored. METHODS: Viable bovine myocardium was placed in a saline bath in an ex vivo endocardial model. Radiofrequency (RF) ablation was performed using three different ablation catheters: 3.5 mm open irrigated (OI), 4, and 8 mm. Variable flow rates of surrounding bath fluids were applied to simulate standard flow, high flow, and no flow. For in vivo epicardial ablation, 24 rats underwent a single OI ablation and performed with circulating saline (30 ml/min; n = 12), versus those immersed in saline without circulation (n = 12). RESULTS: High flow reduced ablation lesion volumes for all three catheters. In no-flow endocardial CE, both 4 mm and OI catheters produced smaller lesions compared with standard flow. However, the 8 mm catheter produced the largest lesions in a no-flow CE. Ablation performed in an in vivo model with CE resulted in smaller lesions compared with ablation performed in a no-flow environment. No statistically significant differences in steam pops were found among the groups. CONCLUSION: A higher endocardial CE flow can decrease RF effectiveness. Cardiac tissue subjected to no endocardial CE flow may also limit RF for 4 mm catheters, but not for OI catheters; these findings may have implications for RF ablation safety and efficacy, especially in the epicardial space without circulating fluid or in the endocardium under varying flow conditions.

Needle-Tipped Catheter Ablation of Papillary Muscle Results in Deeper and Larger Ablation Lesions.

Ventricular tachycardia associated with papillary muscle (PM) is often refractory to standard radiofrequency ablation (RFA). The needle-tipped ablation catheter (NT-AC) has been used to treat deep intramyocardial substrates, but its use for PM has not been characterized. Using an ex vivo experimental platform, both 3 mm and 6 mm NT-AC created larger ablation lesion volumes and depths than open-irrigated ablation catheter did (OI-AC; e.g., 57.12 ± 9.70mm3 and 2.42 ± 0.22 mm, respectively; p < 0.01 for all comparisons). Longer NT-AC extension (6 mm) resulted in greater ablation lesion volumes and maximum depths (e.g., 333.14 ± 29.13mm3 and 6.46 ± 0.29 mm, respectively, compared to the shorter 3 mm NT-AC extension, 143.33 ± 12.77mm3, and 4.46 ± 0.14 mm; both p < 0.001). There were no steam pops. In conclusion, for PM ablation, the NT-AC was able to achieve ablation lesions that were larger and deeper than with conventional OI-AC. Ablation of PM may be another application for needle-tip ablation. Further studies are warranted to establish long-term safety and efficacy in human studies.

Catheter Ablation for Atrial Fibrillation in Adult Congenital Heart Disease: An International Multicenter Registry Study.

BACKGROUND: Data on atrial fibrillation (AF) ablation and outcomes are limited in patients with congenital heart disease (CHD). We aimed to investigate the characteristics of patients with CHD presenting for AF ablation and their outcomes. METHODS: A multicenter, retrospective analysis was performed of patients with CHD undergoing AF ablation between 2004 and 2020 at 13 participating centers. The severity of CHD was classified using 2014 Pediatric and Congenital Electrophysiology Society/Heart Rhythm Society guidelines. Clinical data were collected. One-year complete procedural success was defined as freedom from atrial tachycardia or AF in the absence of antiarrhythmic drugs or including previously failed antiarrhythmic drugs (partial success). RESULTS: Of 240 patients, 127 (53.4%) had persistent AF, 62.5% were male, and mean age was 55.2±13.3 years. CHD complexity categories included 147 (61.3%) simple, 68 (28.3%) intermediate, and 25 (10.4%) severe. The most common CHD type was atrial septal defect (n=78). More complex CHD conditions included transposition of the great arteries (n=14), anomalous pulmonary veins (n=13), tetralogy of Fallot (n=8), cor triatriatum (n=7), single ventricle physiology (n=2), among others. The majority (71.3%) of patients had trialed at least one antiarrhythmic drug. Forty-six patients (22.1%) had reduced systemic ventricular ejection fraction <50%, and mean left atrial diameter was 44.1±8.2 mm. Pulmonary vein isolation was performed in 227 patients (94.6%); additional ablation included left atrial linear ablations (40%), complex fractionated atrial electrogram (19.2%), and cavotricuspid isthmus ablation (40.8%). One-year complete and partial success rates were 45.0% and 20.5%, respectively, with no significant difference in the rate of complete success between complexity groups. Overall, 38 patients (15.8%) required more than one ablation procedure. There were 3 (1.3%) major and 13 (5.4%) minor procedural complications. CONCLUSIONS: AF ablation in CHD was safe and resulted in AF control in a majority of patients, regardless of complexity. Future work should address the most appropriate ablation targets in this challenging population.

Diabetes without Overt Cardiac Disease Is Associated with Markers of Abnormal Repolarization: A Case-Control Study.

Patients with diabetes mellitus (DM) are prone to advanced atherosclerosis, microvascular disease, and tissue fibrosis. Despite the increased risk for arrhythmias, little is known about cardiac repolarization abnormalities in DM. We aimed to determine whether abnormal T-wave morphology markers are common among patients with DM and no known cardiac disease. Patients were recruited and classified as having DM or impaired fasting glucose (IFG) according to accepted guidelines. Total cosine R to T (TCRT) and T-wave morphology dispersion (TMD) were computed with custom-designed software for randomly selected and averaged beats. Among 124 patients recruited; 47 were diagnosed with DM and 3 IFG. DM patients and the control group had similar clinical characteristics, other than statins and anti-diabetic drugs, which were more common among DM patients. Patients with DM/IFG had decreased TCRT values computed from a random beat (0.06 ± 0.10 vs. 0.43 ± 0.07, p < 0.01) and an average beat (0.08 ± 0.09 vs. 0.44 ± 0.06, p < 0.01), when compared with the control group. TMD parameters did not differ. In conclusion, TCRT is reduced in patients with DM and no known cardiac diseases. Further research is required to investigate whether repolarization-associated changes in DM are the consequence of subclinical atherosclerosis, diabetic cardiomyopathy, or a combination of the two.

Perpendicular catheter orientation during papillary muscle ablation results in larger, deeper lesions.

INTRODUCTION: Ablation of papillary muscles (PMs) for refractory ventricular arrhythmias can often be challenging. The catheter approach and orientation during ablation may affect optimal radiofrequency (RF) delivery. Yet, no previous study investigated the association between catheter orientation and PM lesion size. We evaluated ablation lesion characteristics with various catheter orientations relative to the PM tissue during open irrigated ablation, using a standardized, experimental setting. METHODS: Viable bovine PM was positioned on a load cell in a circulating saline bath. RF ablation was performed over PM tissue at 50 W, with the open irrigated catheter positioned either perpendicular or parallel to the PM surface. Applied force was 10 g. Ablation lesions were sectioned and underwent quantitative morphometric analysis. RESULTS: A catheter position oriented directly perpendicular to the PM tissue resulted in the largest ablation lesion volumes and depths compared with ablation with the catheter parallel to PM tissue (75.26 ± 8.40 mm3 vs. 34.04 ± 2.91 mm3 , p < .001) and (3.33 ± 0.18 mm vs. 2.24 ± 0.10 mm, p < .001), respectively. There were no significant differences in initial impedance, peak voltage, peak current, or overall decrease in impedance among groups. Parallel catheter orientation resulted in higher peak temperature (41.33 ± 0.28°C vs. 40.28 ± 0.24°C, p = .003), yet, there were no steam pops in either group. CONCLUSION: For PM ablation, catheter orientation perpendicular to the PM tissue achieves more effective and larger ablation lesions, with greater lesion depth. This may have implications for the chosen ventricular access approach, the type of catheter used, consideration for remote navigation, and steerable sheaths.

Repolarization in systemic sclerosis: a meta-analysis.

OBJECTIVES: Systemic sclerosis (SSc) is a rare connective tissue disease characterized by immune dysregulation, vascular damage, and increased deposition of extracellular matrix. In SSc, cardiac manifestations are common and account for 14% of deaths. Numerous studies have examined electrocardiographic findings in SSc patients yielding conflicting reports regarding QTc duration. We conducted a systematic review and meta-analysis of existing studies to investigate whether QTc duration may aid in diagnosis and risk stratification of SSc patients. METHODS: Two electronic databases (PubMed and Embase) were searched for case-control and cohort studies assessing QTc duration in SSc patients published before March 1, 2021. A random-effects model was used to meta-analyze the results, and included studies were tested for heterogeneity. Linear regression was performed to determine correlations between comorbidities, and QTc duration. RESULTS: Ninety-six studies, abstracts, and posters were identified. After abstract review and duplicate removal, 23 manuscripts remained. After application of the inclusion and exclusion criteria, 10 studies remained which were quantitatively analyzed. The weighted mean QTc was found to be 422.21 ms for SSc patients and 411.43 ms for control subjects. A significant increase in QTc duration among SSc patients was found, with a standardized mean difference of 0.59 (p < 0.01, 95% CI 0.27-0.92). No significant correlation was found between underlying traits and QTc values. Substantial heterogeneity was found between the studies (I2 = 83%, p < 0.01). CONCLUSION: A significant increase in QTc duration is observed in SSc patients, though the absolute prolongation is not extreme. Therefore, the clinical utility of this finding is unclear and merits large prospective observations. Key Points • A statistically significant prolongation of the QTc interval exists in patients with systemic sclerosis. • Absolute QTc differences between healthy controls and scleroderma patients are not extreme, and, as such, may be of limited clinical utility. • When assessing the underlying traits of systemic sclerosis patients, no statistically significant correlations were found between underlying parameters and QTc duration.

Venous capacitance and venous return in young adults with typical vasovagal syncope: a cross-sectional study.

Vasovagal syncope (VVS) has a high prevalence in the general population and is associated with potential complications. There is limited information on the possible association between venous capacitance (VC) and venous return (VR), important determinants of preload and VVS. Since the tilt test was reported to yield a high rate of false positive results, the aim of this study was to evaluate whether abnormal VC and VR at baseline could predispose individuals to VVS.To this end, 88 young, healthy volunteers were recruited and classified to 26 (29.5%) who experienced typical VVS and 62 (70.5%) who did not. VC and VR were evaluated with a commercial device and plethysmography applied to the elevated legs. Maximum venous outflow (MVO), segmental venous capacitance (SVC) and MVO/SVC ratio were calculated and averaged.No significant differences between MVO (5.0±0.5 vs 5.6±0.8, p>0.05), SVC (6.0±0.5 vs 6.3±0.8, p>0.05) or MVO/SVC ratio (0.83±0.02 vs 0.86±0.03, p>0.05) were observed for the non-VVS and VVS volunteers, respectively. There was a significant association between a higher MVO and SVC values and a larger decrease in diastolic blood pressure with standing, although correlations were weak (R2=0.0582 and 0.0681, respectively).In conclusion, at baseline, VC and VR are not impaired in healthy volunteers with a history of VVS. It remains unknown if similar results would be found in patients with cardiovascular comorbidities. Also, the sensitivity of VC and VR evaluations to identify a predisposition for VVS following physiological provocations merits further study.

Association between T wave morphology parameters and abnormal cardiac SPECT imaging.

BACKGROUND: T-wave morphology dispersion (TMD) described the electrocardiographic T-wave heterogeneity during a single cardiac cycle. Total cosine R-to-T (TCRT) is the average of the cosines of the angles between the QRS and T vectors on the ECG. We examine the predictive value of TMD and TCRT calculation to assess abnormal myocardial perfusion. METHODS: Retrospective single center cohort study including all patients referred for evaluation of ischemia by myocardial SPECT scanning with no known history of ischemic heart disease, from 1 January 2019 to 31 December 2019. Study endpoint was the correlation between the calculated TMD and TCRT values and detection of myocardial injury or ischemia by myocardial SPECT. RESULTS: Among 606 patients, calculated TCRT was 0.401 ± 0.53 for the normal group and 0.283 ± 0.62 for the abnormal group (p = 0.007). Measured TMD was 22.9 ± 16.6 degrees (p < 0.001) in the normal group, compared to 31.5 ± 22.8 degrees (p < 0.001) for the abnormal group. CONCLUSIONS: The results demonstrate a correlation between the decreased TCRT values and increase TMD and myocardial ischemia seen in SPECT results. The TCRT and TMD can be used as simple and non-invasive markers to predict abnormal SPECT results and ischemic heart disease in patients with no known cardiac history.

Ultra Short Heart Rate Variability Predicts Clinical Outcomes in Patients with a Clinical Presentation Consistent with Myocarditis: A Derivation Cohort Analysis.

Myocarditis prognosis varies substantially, hence identification of novel prognostic factors is crucial. The prognostic role of ultra-short heart-rate variability (HRV) in myocarditis remains unknown. In a retrospective study, adult patients admitted to a tertiary hospital due to clinically suspected myocarditis were included. Clinical, laboratory and HRV parameters were assessed as predictors of severe short term complications (heart failure (HF), dilated cardiomyopathy­DCM, ventricular arrhythmia­VA and death), utilizing logistic regression (LR). Accuracy was evaluated with receiver operating characteristic (ROC) curve area under the curve (AUC). HRV indices included standard deviation of normal beat intervals (SDNN) and root mean square of successive differences (RMSSD). 115 patients, aged 34 (±13) years old, were examined. Six patients (5%) developed severe HFrEF. RMSSD was included in a multivariate LR model (RMSSD < 10.72 ms adjusted odds ratio (AOR) 14.056, p-value 0.024). Model classification accuracy was very good, with an AUC of 86%. Eight patients (7%) developed DCM. RMSSD < 10.72 ms was included in a multivariate classification model (AOR 8.826, p-value 0.013); model classification AUC of 82%. HRV did not predict development of VA or death. SDNN and especially RMSSD may be prognostic indicators in myocarditis.

Autonomic Nervous System Indices in Patients with Systemic Sclerosis without Overt Cardiac Disease.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease that may affect the heart and the autonomic nervous system (ANS). There is little knowledge regarding the degree of ANS involvement in SSc patients with unknown cardiac disease. OBJECTIVES: To evaluate cardiac and pupillary autonomic functions in patients before cardiac involvement has emerged. METHODS: The study comprised 19 patients with SSc and 29 healthy controls. Heart rate variability (HRV) analysis for time and frequency domains, as well as deep breathing test and Ewing maneuvers, were performed in all patients. Automated pupillometry for the evaluation of pupillary diameter and pupillary light reflex was completed in 8 SSc patients and 21 controls. RESULTS: Both groups had similar characteristics, except for medications that were more commonly or solely prescribed for SSc patients. Compared with control subjects, the SSc patients had significantly lower HRV parameters of NN50 (15.8 ± 24.4 vs. 33.9 ± 33.1, P = 0.03), pNN50 (4.9 ± 7.4% vs.10.8 ± 10.8%, P = 0.03), and triangular index (11.7 ± 3.4 vs. 15.7 ± 5.8, P = 0.02). Abnormal adaptive responses in heart rate changes were recorded during deep breathing tests and Ewing maneuvers. There was no significant difference in any of the pupillometric indices or other HRV parameters within groups. CONCLUSIONS: SSc patients may manifest cardiac autonomic dysfunction, while their autonomic pupillary function is seemingly spared. The role of certain medications, the significance of differential organ involvement, as well as the prognostic value of our findings should be evaluated in future studies.

Repolarization dispersion in patients with systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is associated with increased cardiac morbidity and mortality. Whether some electrocardiographic markers of arrhythmias predispose to early cardiogenic death in SSc remains controversial. This study evaluated the occurrence of previously reported as well as unstudied markers of repolarization in patients with SSc and assessed their prognostic implications. METHODS: A total of 21 patients with SSc and 31 unaffected controls were included in this prospective study. Electrocardiograms were conducted under strict standards. Repolarization and dispersion parameters and markers of late ventricular potentials were determined using designated computer software. Results of multiple beats were averaged. RESULTS: There were no significant differences between the SSc and control groups in average QT intervals, average corrected QT intervals, average QT interval dispersion (QTd), average QT corrected dispersion (QTcd), and QT dispersion ratio. However, average QT apex dispersion, average JT dispersion, average JT corrected dispersion, and Tpeak-Tend corrected were significantly higher in patients with SSc than in controls. Late ventricular potentials were not found in patients with SSc or in controls. Increased QTd and QTcd were recorded in 1 patient who experienced ventricular arrhythmia before inclusion in the study. None of the remaining patients with SSc or the controls developed arrhythmia during the 9-year follow-up. CONCLUSION: Abnormal repolarization parameters may be observed in patients with SSc. However, their prognostic significance with regard to increased risk for repolarization-associated ventricular arrhythmias and increased cardiac death could not be determined in this study. Our findings endorse additional studies on this matter.

T-wave morphology descriptors in patients with bulimia nervosa.

PURPOSE: Bulimia nervosa (BN) is associated with increased risk of cardiovascular disease and arrhythmias. Some reports found abnormal electrocardiographic markers of arrhythmias in BN, while others did not. This study investigated novel parameters of T-wave morphology that were reported to be associated with adverse cardiovascular outcomes in other patient groups, among patients with BN under medical care. METHOD: Thirty-five BN patients and 76 healthy controls were included. Total cosine R to T (TCRT) and T-wave Morphology Dispersion (TMD) parameters were computed according to accepted standards for an average beat and a random beat. Patients were followed for 11.1 ± 0.1 years for the emergence of arrhythmias or events of sudden death. RESULTS: Twenty-five (71.4%) BN patients were hospitalized when enrolled, for a mean duration of 1.1 ± 0.2 months. The rest were ambulatory patients. The BN group had lower blood pressure, more smokers, and used antidepressants, neuroleptic drugs and benzodiazepines more than controls did. Other demographic parameters were comparable between groups. TCRT and TMD parameters were statistically similar and within the normal ranges reported by other research groups. None of the BN patients had prolonged QTc interval or electrolyte abnormalities on inclusion. During the follow-up period, no clinical symptoms suggestive of arrhythmias were reported, and no cardiovascular-related hospitalizations or deaths occurred in either group. CONCLUSION: Medically treated BN patients have normal T-wave morphology parameters and hence, low risk for repolarization-associated malignant ventricular arrhythmias. The prognostic importance of these novel repolarization parameters remains to be explored among untreated patients, those who ingest emetic substances and patients with electrolyte imbalance. LEVEL OF EVIDENCE: Level III.

Familial tendency for hypertension is associated with increased vascular stiffness.

OBJECTIVE: Hypertension is the leading cause of cardiovascular disease and premature death. New methods for early detection of hypertension and its consequences can reduce complications arising from uncontrolled hypertension. Pulse-wave velocity (PWV), a measure of arterial stiffness, has been recognized as a valuable tool in assessing risk for cardiovascular complications, although its use in clinical practice is currently limited. Here we examine whether brachial--ankle PWV (baPWV) and femoral--ankle PWV (faPWV) are elevated in nonhypertensive volunteers, with and without a history of familial hypertension. METHODS: Volunteers were recruited and questioned as to their medical background and family history. Participants were divided into two groups based on history of familial hypertension and were measured for baPWV and faPWV. Carotid--femoral PWV was computed from these measurements. RESULTS: A total of 82 healthy nonhypertensive volunteers (mean age 31.4 ±â€Š9.6) were recruited. Among the study cohort, 43.7% had a history of familial hypertension. There were no between-group differences in any other clinical or demographic characteristics. Both baPWV and faPWV were significantly elevated in volunteers with a history of familial hypertension (10.86 ±â€Š1.69 vs. 9.68 ±â€Š1.52 m/s, P < 0.004, and 7.01 ±â€Š1.65 vs. 6.28 ±â€Š1.26 m/s, P < 0.028, respectively). CONCLUSION: Volunteers with a history of familial hypertension present with elevated baPWV and faPWV. This is suggestive of increased central and peripheral arterial stiffness in susceptible individuals before the onset of hypertension. Routine measurement of these parameters may allow for early intervention and risk stratification, especially in persons with a history of familial hypertension.

Effects of Cigarette Smoking on Cardiac Autonomic Responses: A Cross-Sectional Study.

It has been suggested that some of the adverse, long-term cardiovascular outcomes of smoking are mediated by impaired autonomic nervous system (ANS) activity. Yet, this association is currently inconclusive. Heart rate variability (HRV) and the deep breathing test (DBT) represent common quantitative markers of ANS activity due to their simplicity and reliability. This large cross-sectional study was designed to assess the effect of active smoking on ANS function as manifested by HRV or DBT abnormalities. Electrocardiograms were recorded at rest for 5 min and during forced metronomic breathing. HRV and DBT were calculated according to accepted standards. Participants were divided into two groups based on current smoking status. The study included 242 healthy volunteers (196 nonsmokers and 46 smokers). There were no significant differences in age, sex, and BMI between groups. Cumulative smoking exposure burden (CSEB) for the study group was 5.3 ± 1.3 pack-years. Comparative analysis of HRV and DBT parameters according to smoking status revealed no significant differences between groups. Significant (p < 0.05), yet weak or moderate correlations (r < 0.7) were found between CSEB and abnormal change in HRV parameters consistent with sympathetic overactivity and decreased parasympathetic tone. In conclusion, smoking for a relatively short period in healthy adults does not seem to lead to significant impairment in ANS function. Yet, the consequences of smoking seem to be amplified when cumulative exposure burden increases.