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.

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.

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.

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.

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.

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.

Normal ranges and potential modifiers of T-wave morphology parameters among healthy individuals: A meta-analysis.

BACKGROUND: T-wave morphology parameters, such as total cosine R-to-T (TCRT), T-wave loop dispersion (TWLD), T-wave morphology dispersion (TMD), and T-wave residuum (TWR), were suggested to be robust markers for adverse cardiovascular outcomes. Yet, the normal range of these parameters is unknown. This study aimed to evaluate the weighted normal values of T-wave morphology parameters of healthy individuals and study the effect of potential modifiers. METHODS: A systematic search of studies published in PubMed was conducted. Only those reporting on control groups of healthy individuals were included. Weighted means were calculated for TCRT, TWLD, TMD, and TWR. Linear regression analysis was conducted for age, percentage of males, heart rate, and QTc. RESULTS: The weighted TCRT was 0.40 ± 0.05, significantly higher than the various cutoffs previously suggested to identify high risk. There was some overlap between the results of weighted normal TMD (19.42 ± 6.77°), TWLD (38.51 ± 0.31), and relative TWR (0.118 ± 0.056%) and reports on the same parameters from patients with cardiovascular disease. Women were also characterized by higher TWLD, TMD, and relative TWR. TCRT was negatively correlated with age and heart rate, and positively correlated with QTc duration, although all associations were weak (R2  < 0.9). CONCLUSIONS: T-wave morphology parameters reported in the medical literature span a broad range of values in healthy individuals. Seemingly abnormal values of TWLD, TMD, and relative TWR were often reported in healthy adults. The variability between studies may stem from methodological issues. Therefore, standardizing the methodology for measuring T-wave morphology is imperative.

Evaluation of a Proarrhythmic Repolarization Marker (Total Cosine R to T) in Patients With Uncomplicated Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder characterized by recurrent attacks of fever and serous inflammation. The association between FMF and risk of cardiac arrhythmia is continuously questioned; some studies report abnormal cardiac repolarization, while others do not. Considering this controversy, we aim to perform in a large cohort of FMF patients a total cosine R to T (TCRT) analysis, a previously unexplored repolarization marker in this disorder. METHODS: The study group included 56 FMF patients without amyloidosis, diagnosed with FMF according to published criteria and 131 control subjects, unaffected with FMF. A 12-lead electrocardiogram (ECG) was performed according to strict standards. Electrocardiogram files were processed with Python-based computer software. Patients were followed for 10 to 12 years, and the rate of cardiac complications was evaluated. RESULTS: Other than FMF and prescription of colchicine, both groups had similar medical and demographic background. TCRT results were similar for a randomly selected beat (0.40 ± 0.06 vs 0.50 ± 0.04, p > 0.05) and for an averaged beat (0.39 ± 0.06 vs 0.50 ± 0.04, p > 0.05) in FMF patients and control subjects, respectively. Correction of average TCRT for heart rate also resulted in similar TCRTc values in patients and control groups (0.42 ± 0.07 s vs 0.51 ± 0.05 s, respectively, p > 0.05). During the follow-up period, none of the patients died, and no patient developed clinical symptoms suggestive of ventricular arrhythmias. CONCLUSIONS: Colchicine treated uncomplicated FMF patients have normal TCRT and TCRTc values, implying low risk for cardiac arrhythmias in this population. Future studies should evaluate the sensitivity and specificity of this marker in high-risk FMF populations, such as those who developed AA amyloidosis.

Normal Heart Rate Variability in Colchicine-Resistant Familial Mediterranean Fever Patients.

BACKGROUND: The relationship between autonomic nervous system (ANS) dysfunction and familial Mediterranean fever (FMF) is controversial. We recently reported normal heart rate variability (HRV), suggestive of normal ANS, in patients with uncomplicated FMF. OBJECTIVES: To evaluate ANS function in colchicine non-responders by using the HRV tool. METHODS: The study group comprised 24 FMF patients suffering from recurrent FMF attacks despite treatment with a maximal colchicine dose. Electrocardiogram was measured under strict conditions and HRV parameters were calculated. Results were compared with age- and gender-matched unaffected controls. RESULTS: No statistically significant difference was found between the groups in any of the HRV parameters: maximal RR, minimal RR and average RR intervals, standard deviation of RR interval, square root of the mean squared differences of successive RR intervals, HRV triangular index, NN50, pNN50, and power spectral analysis parameters. CONCLUSIONS: Although a small difference in HRV parameters in the current study cannot be entirely excluded, FMF patients in whom colchicine did not provide adequate symptomatic relief and who did not develop amyloidosis appear to have normal HRV parameters suggestive of normal ANS function, compared with healthy adults.

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.

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.

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.

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.

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.

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.

Normal late ventricular potentials in hospitalized patients with eating disorders.

OBJECTIVE: Eating disorders, in particular anorexia nervosa (AN), are associated with cardiovascular complications and risk of arrhythmias. In a recent published study, it was found that patients with eating disorders, especially those affected by bulimia nervosa (BN) and a history of AN have abnormal late ventricular potentials (LPs). LPs are electrocardiographic markers used in detecting abnormal depolarization and increased risk of arrhythmias. Given the paucity of knowledge regarding the affects of eating disorders on cardiac depolarization, our aim was to further explore LPs in patients with eating disorders. METHOD: The study group included 30 hospitalized patients with eating disorders (14 with AN, 10 with BN with no history of AN, and 6 with BN and history of AN). Signal averaged electrocardiography was conducted on all patients using the Frank corrected orthogonal lead system. RESULTS: No patient with either eating disorder tested positive for LPs. DISCUSSION: Hospitalized patients with eating disorders, medically monitored and treated for several weeks, had normal serum electrolytes, started to normalize their weight, and did not appear to be prone to arrhythmias associated with abnormal depolarization. The prognostic significance of LPs in risk stratification of patients with eating disorders should be further evaluated by large cohort studies and longer follow-up studies.

Meta-analysis of p-wave dispersion values in healthy individuals: the influence of clinical characteristics.

BACKGROUND: P-wave dispersion (Pd) is an appealing marker for predicting the risk of developing atrial fibrillation. At present, no definitive cutoff value has been determined as to the diagnosis of high-risk patients. Our aims were to evaluate P-wave parameters of healthy subjects published in the literature, determine normal range and weighted means of Pd and P-wave parameters, and investigate the influences of gender, age, and BMI on the weighted results. METHODS: A systematic search of studies published in PubMed was conducted. Only studies which included control groups of healthy individuals were included. RESULTS: Of the 657 studies initially identified, 80 were eligible for inclusion. The total number of participants was 6,827. The highest reported Pd values were 58.56 ± 16.24 ms; the lowest were 7 ± 2.7 ms. The weighted mean was 33.46 ± 9.65 ms; weighted median was 32.2 ms. Gender and age were not found to be associated with significant influences on P-wave parameter values. High-normal BMI was not found to be associated with increased P-wave parameter values. CONCLUSIONS: Pd, Pmax, and Pmin span a wide range of values in healthy individuals. Seemingly, abnormal values were often reported in healthy adults. The high variability of P-wave parameters in healthy individuals, and overlapping of the results with those reported for patients with increased risk for atrial fibrillation, might suggest that this technique has limited sensitivity and specificity. The variability between studies may stem from methodological issues and, therefore, there is a definite need for methodological standardization of Pd measurements.

QT dispersion in amyloidosis due to familial Mediterranean fever.

Cardiac amyloid deposition in FMF may cause increased QT dispersion (QTd), a marker for cardiac arrhythmias. The aim of this study was to further evaluate repolarization dispersion in familial Mediterranean fever (FMF) with amyloidosis. Findings on 12-lead electrocardiography were compared between 18 patients with FMF-amyloidosis and 18 age- and sex-matched control subjects. Repolarization and dispersion parameters were computed with designated computer software, and results of the 5 beats were subsequently averaged. There were no statistically significant differences between the groups as to average corrected QT interval length, average QTd interval, average QT corrected dispersion, or QT dispersion ratio. JT dispersion and JT corrected dispersion were also similar in both groups. In conclusion, patients with FMF-amyloidosis seem to have QT and JT dispersion parameters similar to those of healthy subjects. Future research and longer follow-ups should be conducted in order to evaluate the prognostic importance of repolarization dispersion parameters in amyloidosis of FMF.

QT variability in amyloidosis of familial Mediterranean fever.

BACKGROUND: The association between familial Mediterranean fever (FMF) and increased risk for ventricular arrhythmias is controversial, and data on this subject are meager. OBJECTIVES: To evaluate QT variability index (QTVI) and other repolarization markers associated with arrhythmogenity in patients with amyloidosis of FMF. METHODS: The study group comprised 12 FMF patients with amyloidosis, and 14 age and gender-matched healthy subjects served as the control group. QT measurements were conducted according to accepted procedure, using computerized software for recording and analysis. RESULTS: No differences were found in clinical and demographic parameters in the study and control groups, except for hypertension which was more common in the FMF amyloidosis group. QTc and power spectral analysis of QT variability parameters were similar in both groups. Nevertheless, QTVI values in FMF amyloidosis patients were significantly higher than in healthy individuals (-1.02 +/- 0.38, vs. -1.36 +/- 0.32 respectively, P = 0.02). CONCLUSIONS: Compared with healthy controls, amyloidosis of FMF is associated with increased QTVI. It remains unknown whether this finding is solely amyloidosis related and whether it has any prognostic significance.

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.