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.

Adverse Histological Features of Differentiated Thyroid Cancer Are Commonly Found in Autopsy Studies: Implications for Treatment Guidelines.

Background: While the popularity of lobectomy for differentiated thyroid cancer (DTC) has increased since the 2015 ATA (American Thyroid Association) guidelines, recent studies reported that adverse histological features (minimal extrathyroidal extension [mETE], multifocality, vascular invasion, and lymph node [LN] metastases) may be found in 30-60% of lobectomy specimens, questioning the validity of this approach. Aim: To assess the prevalence adverse histological features in occult DTC detected in autopsy studies. Methods: Meta-analysis of autopsy studies of the thyroid in subjects without known history of thyroid cancer. Results: Twenty-nine studies including 8750 subjects fulfilled the inclusion criteria, with incidentally discovered DTC in 740 autopsies (8.5%). Age was reported in 17 studies, with a median age of 61 years (range 41-68 years). Multifocality was reported in 27 studies with a calculated event rate of 28.2% ([CI 23.1-33.8], I2 = 46.3%), with bilateral involvement in 18% [CI 12.6-25.1]. mETE was reported in 5 studies, with an event rate of 24.5% ([CI 9.3-50.7], I2 = 88.5%), and the presence of LN metastases were reported in 13 studies with an event rate of 11% ([CI 6.1-19.1], I2 = 69.5%). Vascular invasion was reported in seven studies with an event rate of 16% ([CI 4-47], I2 = 86.8%). Of 25 studies with whole body autopsies (722 subjects), 3 cases of distant metastases were reported, of which 2 had fatal metastatic disease (where thyroid origin was not diagnosed before death), and 1 had occult disease. Conclusions: Adverse histological features including mETE, LN metastases, multifocality, and vascular invasion are common in occult DTC. When minimal in size, these adverse histological features do not seem to be markers of aggressive disease and may not be an indication for completion thyroidectomy or radioiodine therapy.

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.

Benefits of a nurse-led home injection service for acromegaly patients treated with somatuline autogel.

AIM: The aim of this study is to assess the benefits of a nurse-led home injection service for somatuline autogel-treated patients with acromegaly, including the adherence to treatment and disease control. METHODS: Historical prospective data of all patients with acromegaly initiating somatuline autogel between November 14, 2000, and March 9, 2020, who voluntarily enrolled in the nurse-led home injection service between January 1, 2018 and June 30, 2020. Adherence to treatment was calculated as the number of administered injections divided by the number of expected injections during the follow-up period. Excellent adherence to treatment was defined when >90% of scheduled injections were administered, while low adherence was defined when patients received <80% of expected injections. The primary outcome was the adherence to treatment. RESULTS: The cohort included 88 patients (mean age ± SD, 59.8 ± 14.9 years, 53% men). Average adherence to treatment was 93 ± 8% (range 62-100%). Excellent adherence was documented in 65 participants (74%), of which 29 patients (33%) received all scheduled injections. Low adherence to treatment was recorded in seven patients (8%). Average adherence was high independent of gender, age, prior surgery, or radiation therapy, or whether somatuline autogel was used as monotherapy or in combination regimens. However, excellent adherence decreased with increased somatuline dose and with dosing interval of 21 days. Average adherence was slightly higher in patients with biochemically controlled acromegaly. CONCLUSIONS: A nurse-led home injection service for somatuline autogel injections is associated with high adherence to treatment. Establishing such a program globally may lead to better adherence to treatment and improved disease control.

T-wave morphology among medically treated patients with Anorexia Nervosa.

Anorexia nervosa (AN) has the highest rate of mortality of any psychiatric disorder, and cardiovascular complications occur in up to 80% of patients with AN and account for up to 30% of mortality. A controversy exists as to whether patients with AN are prone to develop electrocardiographic abnormalities related to repolarization. We aim to study previously unexplored T wave morphology markers in medically-treated patients with AN. Fifty-eight patients with AN (32 with restricting type and 26 with binge-eating/purging type) and 82 healthy controls were included in the study. ECGs were conducted under strict conditions and total cosine R-to-T (TCRT) and T-wave morphology dispersion (TMD) were computed according to accepted standards for a random beat and for an averaged beat. Forty-six AN patients were hospitalized (79.3%) during the study for a mean duration of 1.5 ± 1.1 months. AN patients had comparable QTc, TCRT, mean TMD, TMDpre, TMDpost and TCRTc values to those of healthy adults. Flattened T wave occurred slightly more often among AN patients than in controls (1.57 ± 1.23 leads affected compared with 1.11 ± 0.80 leads, respectively, p = 0.017). QTc, TCRT and TMD parameters' values were unaffected by the clinical type of AN. In conclusion, weight-restored AN patients are characterized by T wave flattening, but normal other T wave morphology parameters, which seemingly reflects an overall low risk of repolarization-associated ventricular arrhythmias. Long-term follow-up studies should be conducted to evaluate the prognostic significance of these novel repolarization markers in untreated patients or early in the refeeding phase.

Reliability of ultrashort electrocardiographic indices in hypertension: the quest for a clinically applicable prognostic marker.

Heart rate variability (HRV) is an accepted clinical tool for evaluating autonomic nervous system function and a marker of adverse cardiac outcome. Although 5 min long HRV recordings are considered methodologically acceptable, it remains impractical in most clinical settings. Also, while some ultrashort HRV (usHRV) parameters were found useful in healthy individuals, their applicability to patients with cardiovascular risk factors is largely unknown. Therefore, our goal was to evaluate the reliability of ultrashort ECG (usECG) indices for HRV among patients with hypertension. One-hundred and two patients with essential hypertension were included. HRV was recorded for 5 min in strictly monitored settings. HRV parameters from randomly chosen 1 min and 10 s series were analyzed. Excellent correlations were found between 1 min SD of RR interval (SDNN) (intraclass correlation coefficient (ICC) 0.973), 10 s SDNN (ICC 0.92) and 5 min SDNN results. An excellent correlation was also found between 1 min root mean square of successive differences in RR intervals (RMSSD) (ICC 0.992), 10 s RMSSD (ICC 0.982) and 5 min RMSSD. Logarithmic transformation of ultrashort 1 min HRV-triangular index using the natural logarithm (Ln) also had excellent correlation with 5 min measurements (ICC 0.9). Also, excellent correlations were found between 10 s and 1 min Ln(RMSSD), 10 s Ln(RMSSD) and 5 min measurements. Other HRV parameters measured from 1 min and 10 s periods showed lower correlations. In conclusion, evaluation of SDNN, RMSSD or Ln(RMSSD) from 10 s ECG recordings can be used to estimate autonomic nervous system function in patients with hypertension. These appealing markers can be readily calculated from any standard ECG tracing. The prognostic significance of ultrashort SDNN and ultrashort RMSSD in patients with cardiovascular risk factors needs to be determined in future prospective cohort studies.

The association between red cell distribution width and poor outcomes in hospitalized patients with influenza.

PURPOSE: To examine an association between red blood cell distribution width (RDW) and the prognosis of influenza patients. METHODS: We conducted a retrospective analysis of patients hospitalized with influenza during 2012-2015 in the internal medicine wards of one medical center. RDW measurements during hospitalization were analyzed. Primary outcome was complicated hospitalization (defined as at least one of: length of stay ≥7days, need for mechanical ventilation, septic shock, transfer to intensive-care, or 30-day mortality). Secondary outcome was 30-day mortality. RESULTS: 153 patients were included, mean age: 62.5±1, 82 (54%) male; 84 (55%) had a high RDW value (>14.5%) during hospitalization. Patients with high and low RDW (≤14.5%) had similar age and comorbidity profiles, but those with high RDW had lower hemoglobin and higher creatinine levels. Patients with high RDW had a higher rate of complicated hospitalization (32.5% vs. 10.3%, p<0.01) and a trend for increased 30-day mortality. In a multivariate regression model, high RDW was a predictor of complicated hospitalization (OR 5.03, 95% CI 1.81-13.93, p<0.01). Each 1-point increase in RDW was associated with a 29% increase in the risk for the primary outcome. CONCLUSION: RDW>14.5% was a predictor of severe hospital complications in patients with influenza.

Normal atrial conduction in medically treated patients with bulimia nervosa.

BACKGROUND: Bulimia nervosa (BN) patients are characterized by binge eating followed by compensatory behaviors. Ingestion of emetic substances, characteristic to some BN patients, has been reported to be associated with supraventricular arrhythmias. AIMS: To evaluate atrial electrocardiographic markers for supraventricular arrhythmias in patients with BN. METHOD: The cohort included 31 patients with BN and sex- and age-matched controls. Twelve-lead electrocardiography was conducted on all participants under strict standards. P wave length and P wave dispersion in each patient were computed from a randomly selected beat and an averaged beat constructed from 7-12 beats, included in a 10-s ECG. RESULTS: No statistically significant differences were found between the groups for minimal, maximal, and average P wave duration and P wave dispersion, calculated either from a random beat or averaged beats. CONCLUSION: BN patients who are medically monitored and treated, have normal P wave parameters and P wave dispersion, and therefore do not appear to have an increased risk for developing supraventricular arrhythmias. Future research should focus on evaluating the effect of acute ingestion of emetic drugs on resting ECG of BN patients, as well as using signal averaging techniques and prolonged ECG-Holter monitoring.

Evaluating reliability of ultra-short ECG indices of heart rate variability in diabetes mellitus patients.

Our aim was to investigate the reliability of ultra-short HRV in patients with DM. A good correlation was found between the 1 minute and 5 minute parameters for maximal-RR, minimal-RR, average-RR, SDNN, RMSSD, pNN50, and total power. Also, a good correlation between 10 second and 5 minute parameters was found for maximal-RR, minimal-RR, average-RR, and RMSSD. We suggest that certain ultra-short HRV parameters can be used efficiently in DM patients for autonomic evaluation.

Medically treated anorexia nervosa is associated with normal P wave parameters.

Anorexia nervosa (AN) is an increasingly common medical condition. Some studies have demonstrated an increased prevalence of atrial premature contractions and anatomical changes in AN patients. Our aim was to investigate P wave parameters and P wave dispersion, an electrocardiographic marker for supraventricular arrhythmias, and its effect on AN. The study group included 48 patients with AN, most hospitalized for a few weeks, and a matched control group. All participants underwent 12-lead electrocardiography (ECG) under strict standards. P wave length and P wave dispersion in each patient were computed from a randomly selected beat and an averaged beat, constructed from 7 to 12 beats, included in a 10-s ECG. There were no statistically significant differences found between the groups for minimal, maximal, average P wave duration and P wave dispersion, calculated either from a random beat or averaged beats. In conclusion, medically treated AN patients who have gained weight have normal P wave parameters, and therefore do not appear to have an increased electrocardiographic risk for atrial fibrillation compared with healthy controls. Further studies are required to evaluate the influence of different disease stages, electrolyte imbalance and other medical complications on P wave parameters and risk for supraventricular arrhythmias in AN patients.

QT interval variability in familial Mediterranean fever: a study in colchicine-responsive and colchicine-resistant patients.

The association between familial Mediterranean fever (FMF), early atherosclerosis, and electrocardiographic markers for arrhythmias remains controversial. There are conflicting results as to the occurrence of high QT dispersion in FMF. The aim of the present study was to further investigate repolarization dynamics and other repolarization-associated pro-arrhythmogenic markers in FMF patients. To explore repolarization in FMF, patients who responded well to colchicine and patients who had not responded to colchicine, yet were amyloidosis-free, were included. We aimed to evaluate whether increased inflammatory burden, a characteristic of non-responsive patients, was specifically associated with abnormal repolarization. Included in the study were 53 FMF patients (27 colchicine non-responders) and 53 age- and sex-matched control subjects. Electrocardiograms were performed under strict standards. QT variability parameters were computed with custom-made computer software. No significant difference in any of the QT dynamic parameters was found in either FMF group compared with the healthy controls. Mean values of QT variability index, regardless of colchicine response, were similar to previously published results for healthy persons. In conclusion, patients with FMF who are continuously treated with colchicine and have not developed amyloidosis, regardless of their clinical response, have normal QT variability parameters, indicating normal repolarization dynamics and suggesting no increased risk of repolarization-associated cardiac arrhythmias.

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.

QT variability among weight-restored patients with anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) may be complicated by cardiac arrhythmias and sudden death. A single study reported an increased QT variability index (QTVI), a marker for cardiac arrhythmogenicity, in AN patients. The aim of the current study was to further evaluate repolarization dynamics in a large cohort of patients with AN without electrolyte abnormalities and to evaluate previously unreported repolarization dynamics parameters. METHODS: Forty-three AN patients and 45 age- and sex-matched controls were included in the study. Twenty-nine AN patients were hospitalized for a mean time of 1.5±1.1 months. The rest were ambulatory AN patients. Electrocardiograms were conducted under strict standards. QT variability index, normalized QT variability (QTVN) and power spectral analysis of QT dynamics were conducted with designated computer software. RESULTS: None of the patients had an electrolyte imbalance. Although mean QT was higher in AN patients compared with controls, QTc results were similar following corrections for RR interval. There was no significant difference in QTVI, QTVN and power spectral analysis parameters among groups. The results of QTVI and QTVN were comparable to those previously published for healthy individuals. During 3 years of follow-up, no patient developed arrhythmias or suddenly died. CONCLUSIONS: Medically treated AN patients who gained weight and had normal serum electrolytes appeared to have normal QTc and QT variability indexes, reflecting a nonincreased risk for cardiac arrhythmias. We suggest that weight normalization, medical treatment and lack of electrolyte abnormalities are responsible in part for these results. Further evaluation of the prognostic significance of QTVI and QTVN in AN is warranted.

The efficiency of 10-second resting heart rate for the evaluation of short-term heart rate variability indices.

BACKGROUND: High values of resting heart rate were found to be correlated with adverse outcomes in various patient groups. Heart rate variability (HRV) is a reliable technique in determining autonomic nervous system function. Our aim was to evaluate whether a 10-second resting heart rate obtained from a resting electrocardiogram (ECG), could be used as a reliable evaluation of short-term HRV. METHODS: Seventy-nine healthy volunteers were included in the study. All participants underwent a 10-second ECG, and 5-minute HRV measurement under strict criteria. RESULTS: A significantly negative correlation was found between resting heart rate and 5-minute max-RR, min-RR, standard deviation of normal RR intervals (SDNN), root mean square of successive differences of RR intervals (RMSSD), HRV triangular index, number of intervals differing by 50 milliseconds from the preceding interval (NN50), pNN50, standard deviation of the points perpendicular to the line of identity (SD1), standard deviation along the line of identity (SD2), and high frequency spectral component (HF). A significant positive correlation was found between resting heart rate and a 5-minute low frequency spectral component (LF) and LF/HF ratio. Specifically, max-RR and min-RR were found to have the best correlation with resting heart rate. CONCLUSIONS: Resting heart rate obtained from a 10-second ECG can be used for crude estimation of all HRV results in healthy individuals who do not take medications, with variable efficacy depending on the measured parameter. Resting heart rate was especially efficient in predicting max-RR and min-RR. Further research should focus on assessing the reliability of a resting heart rate for HRV evaluation, in patients with autonomic dysfunction and high-risk cardiac patients.

Normal autonomic nervous system responses in uncomplicated familial Mediterranean fever: a comparative case-control study.

There is a paucity of knowledge regarding the autonomic nervous system function in patients with familial Mediterranean fever (FMF). Therefore, our aim was to evaluate autonomic responses in patients with FMF using complementary tests. The study groups included 33 patients with uncomplicated FMF and 39 control subjects. Autonomic function was evaluated by measuring responses to metronomic breathing, the Valsalva maneuver, and the Ewing maneuver. Autonomic parameters were computed from electrocardiograms with designated computer software. There were no statistically significant differences in any of the measured parameters of autonomic function between the patient and control group. The measured autonomic parameters of both groups were similar to those previously reported in healthy individuals. In conclusion, patients with FMF who did not develop amyloidosis due to continuous colchicine treatment appeared to have normal autonomic function, as reflected by the normal response to physiological autonomic stimuli.