Gut microbiota in hypertensive patients with versus without obstructive sleep apnea

We investigated the alteration of gut microbiota and the associated metabolic risks in hypertensive patients with obstructive sleep apnea (OSA) comorbidity. Fecal and blood samples were collected from 52 hypertensive patients, who were divided into three groups: A (controls, apnea‐hypopnea index[AHI] < 5, n = 15), B (mild OSA, 5 < AHI < 20, n = 17), and C (moderate‐to‐severe OSA, AHI > 20, n = 20). The composition of the gut microbiota was studied through 16s RNA sequencing of variable regions 3–4. Analysis of the results revealed that group C had a significant higher concentration of total cholesterol, low‐density lipoprotein, and IL‐1β compared with group A. The Shannon index showed that bacterial biodiversity was lower in OSA patients. At the phylum level, the ratio of Firmicutes to Bacteroidetes (F/B) was significantly higher in group C than in groups A and B. At the genus level, the relative abundance of short‐chain fatty acids (SCFA)‐producing bacteria (e.g., Bacteroides and Prevotella) was lower while the number of inflammation‐related bacteria (e.g., Lactobacillus) was increased in patients with OSA. We found that the IL‐1β level was negatively correlated with Bacteroidetes. The area under the receiver operating characteristic curve was .672 for F/B ratio in determining hypertensive patients with OSA. In patients with hypertension, OSA was associated with worse gut dysbiosis, as evidenced by decreased levels of short‐chain fatty acids‐producing bacteria and increased number of inflammation‐related bacteria. The differences in gut microbiota discriminate hypertensive patients with OSA from those without and may result in an enhanced inflammatory response and increase the risk of metabolic diseases.     

The impact of hydroxychloroquine–azithromycin combination on Tpeak‐to‐end and Tpeak‐to‐end/QT ratio during a short treatment course

BackgroundSince there was no proven treatment of coronavirus disease 2019 (COVID‐19), hydroxychloroquine–azithromycin (HCQ‐AZM) combination is being used in different countries as a treatment option. Many controversies exist related to the safety and effectiveness of this combination, and questions about how HCQ‐AZM combination affects the ventricular repolarization are still unknown.ObjectiveThe aim of the study was to show whether the hydroxychloroquine–azithromycin (HCQ‐AZM) combination prolonged Tpeak‐to‐end (TpTe) duration and TpTe/QT interval ratio or not.MethodsOne hundred and twenty‐six consequent COVID‐19(+) patients meeting the study criteria were enrolled in this study. Baseline ECGs were obtained immediately after hospitalization and before commencing the HCQ‐AZM combination. On‐treatment ECG was obtained 24–48 hr after the loading dose of HCQ/AZM. ECG parameters including PR interval, QRS duration, QT interval, QTc interval, TpTe duration, and TpTe/QT interval ratio were assessed. Demographic and laboratory findings were collected from an electronic recording system.ResultsECGs of 126 COVID‐19(+) patients who received HCQ‐AZM combination were assessed. Mean baseline QTc (by Fridericia formula), TpTe, and TpTe/QT ratio were 420.0 ± 26.5 ms, 82.43 ± 9.77 ms, and 0.22 ± 0.02, respectively. On‐treatment QTc, TpTe and TpTe/QT ratio were 425.7 ± 27.18 ms, 85.17 ± 11.17 ms, and 0.22 ± 0.03, respectively. No statistically significant acute impacts of HCQ‐AZM combination on TpTe duration and TpTe/QT interval ratio were observed compared with baseline values. No ventricular tachycardia/fibrillation and the significant conduction delays were seen during in‐hospital follow‐up.ConclusionHCQ‐AZM combination increased TpTe duration. However, no significant impact on TpTe/QT interval ratio was observed.     

Characteristics of hypertension and arterial stiffness in obstructive sleep apnea: A Scandinavian experience from a prospective study of 6408 normotensive and hypertensive patients

The impact of obstructive sleep apnea (OSA) on arterial stiffness is less studied. We aimed to investigate the prevalence and covariates of increased pulse pressure (PP), a surrogate marker of arterial stiffness, in the entire study population as well as in separate analyses in normotensive and hypertensive patients. Further, we also explored the impact of smoking on brachial BP in hypertensive patients. Between 2012 and 2019, a total of 6408 participants with suspected OSA underwent a standard out‐of‐center respiratory polygraphy. OSA was defined by an apnea‐hypopnea index (AHI) ≥15/h regardless of symptoms. PP ≥60 mmHg was used as a surrogate marker of increased arterial stiffness. Mean age was 49.3±13.7 years, 69.4% were male, and 34.5% had OSA. The prevalence of hypertension was 70.8% in OSA and 46.7% in No‐OSA (AHI < 15/h) controls (P < .0001). Hypertension was controlled (clinic BP < 140/90 mmHg) in 45.5% and uncontrolled in 54.5% (P < .001). Mean PP was 50±12 mmHg in smokers and 52±12 mmHg in non‐smokers (P = .001). Increased PP was found in 24.2% of the entire study population and was higher in patients with OSA compared to No‐OSA group (27.5% vs 22.4%, P < .0001). In an unadjusted logistic regression model, OSA was associated with a 1.3‐fold higher risk of having increased PP (95% CI 1.16‐1.48, P < .001). In a multivariable‐adjusted model, higher age, male sex, and history of hypertension, but not OSA (OR 0.89; 95% CI 0.77‐1.02, P = .104) were associated with increased PP. In this large study of nearly 6500 participants who were referred with suspected OSA, one‐third were diagnosed with OSA and a quarter had increased arterial stiffness by elevated brachial PP. Hypertension but not OSA per se was associated with increased arterial stiffness. Hypertension was highly prevalent and poorly controlled.     

Electrocardiographic markers of increased risk of sudden cardiac death in patients with COVID‐19 pneumonia

BackgroundLittle is known about the role of ECG markers of increased risk of sudden cardiac death during the acute period of coronavirus disease 2019 ( COVID‐19) pneumonia.ObjectivesTo evaluate ECG markers of sudden cardiac death on admission, including the index of cardiac electrophysiological balance (iCEB) (QTc/QRS) and transmural dispersion of repolarization (TDR) (T from peak to end (Tp‐e) interval and Tp‐e/QTc), in patients with COVID‐19 pneumonia.Patients and methodsThis cross‐sectional study included 63 patients with newly diagnosed COVID‐19 pneumonia who presented to the outpatient clinic or admitted to the respiratory care unit between August 20 and September 15, 2020. Forty‐six persons matched for sex and age were selected from data collected before COVID‐19 pandemic.ResultsQRS and QTc showed a significant prolongation in patients with COVID‐19 pneumonia compared to the controls (87 vs. 78, p < .00, and 429 versus. 400, p < .00, respectively). After categorization of patients with COVID‐19 pneumonia into 3 groups according to the severity of pneumonia as mild‐moderate, severe, and critical groups, a decreased values of QRS were observed in the critical COVID‐19 pneumonia group compared to severe and mild‐moderate COVID‐19 pneumonia groups (p = .04) while increased values of QTc and iCEB(QTc/QRS) were noted in critical COVID‐19 pneumonia group compared to other 2 groups(p < .00).ConclusionsPatients with COVID‐19 pneumonia showed significant changes in repolarization and conduction parameters compared to controls. Patients with mild to severe COVID‐19 pneumonia may be at low risk for torsades de pointes development.     

Therapeutic effect of laparoscopic sleeve gastrectomy on obstructive sleep apnea and relationship of type 2 diabetes in Japanese patients with severe obesity

Aims/IntroductionObstructive sleep apnea (OSA) is among the most important obesity‐related diseases, and offers the potential for accelerated the early onset and progression of type 2 diabetes. The aim of the present study was to clarify the therapeutic effect of laparoscopic sleeve gastrectomy on OSA in severely obese Japanese patients, and to find correlations between OSA improvements and β‐cell function (BCF).Materials and MethodsBetween September 2013 and December 2019, 61 patients who underwent laparoscopic sleeve gastrectomy were enrolled. The apnea–hypopnea index (AHI) was used to diagnose OSA. The tongue area, uvula area and other parameters were measured using cone‐beam computed tomography. Regarding BCF parameters, the homeostasis model assessment of β‐cell function, insulinogenic, Matsuda and disposition indexes were used to evaluate the improvement in BCF. Improvement of OSA was defined as AHI <15.ResultsThe improvement rate of OSA was 51.8% (29/56). The change in AHI was significantly correlated with the excess weight loss percentage (ρ = 0.501), changes in tongue area (ρ = 0.350) and uvula area (ρ = 0.341). Multivariate analysis showed that preoperative AHI and postoperative hemoglobin A1c were independent prognostic factors of OSA non‐improvement. The homeostasis model assessment of β‐cell function (P < 0.001), the insulinogenic index (P < 0.001) and the disposition index (P = 0.019) of patients with AHI of <15 were significantly higher than those in patients with AHI of ≥15.ConclusionsLaparoscopic sleeve gastrectomy is a promising procedure for severely obese patients with OSA. BCF recovery was found to be significantly higher in patients with OSA improvement.     

Association of non‐invasive electrocardiographic risk factors with left ventricular systolic function in post‐myocardial infarction patients with mildly reduced or preserved ejection fraction: Insights from the PRESERVE‐EF study

BackgroundElectrocardiographic non‐invasive risk factors (NIRFs) have an important role in the arrhythmic risk stratification of post‐myocardial infarction (post‐MI) patients with preserved or mildly reduced left ventricular ejection fraction (LVEF). However, their specific relation to left ventricular systolic function remains unclear. We aimed to evaluate the association between NIRFs and LVEF in the patients included in the PRESERVE‐EF trial.MethodsWe studied 575 post‐MI ischemia‐free patients with LVEF≥40% (mean age: 57.0 ± 10.4 years, 86.2% men). The following NIRFs were evaluated: premature ventricular complexes, non‐sustained ventricular tachycardia (NSVT), late potentials (LPs), prolonged QTc, increased T‐wave alternans, reduced heart rate variability, and abnormal deceleration capacity with abnormal turbulence.ResultsThere was a statistically significant relationship between LPs (Chi‐squared = 4.975; p < .05), nsVT (Chi‐squared = 5.749, p < .05), PVCs (r= −.136; p < .01), and the LVEF. The multivariate linear regression analysis showed that LPs (p = .001) and NSVT (p < .001) were significant predictors of the LVEF. The results of the multivariate logistic regression analysis indicated that LPs (OR: 1.76; 95% CI: 1.02–3.05; p = .004) and NSVT (OR: 2.44; 95% CI: 1.18–5.04; p = .001) were independent predictors of the mildly reduced LVEF: 40%–49% versus the preserved LVEF: ≥50%.ConclusionLate potentials and NSVT are independently related to reduced LVEF while they are independent predictors of mildly reduced LVEF versus the preserved LVEF. These findings may have important implications for the arrhythmic risk stratification of post‐MI patients with mildly reduced or preserved LVEF.     

Depolarization and repolarization dynamics after His‐bundle pacing: Comparison with right ventricular pacing and native ventricular conduction

BackgroundThe current study aimed to evaluate changes in electrical depolarization and repolarization parameters after His‐bundle pacing (HBP) compared with right ventricular pacing (RVP) and its association with ventricular arrhythmia (VA).MethodsForty‐one patients (13 with HBP, 14 with RVP, and 14 controls [AAI mode]) were evaluated. After continuous pacing algorithm, QRS duration, QT interval, QTc, JT interval, T‐peak to T‐end (Tpe), and Tpe/QT ratio were measured on electrocardiography at baseline and 1 week, 1 month, and 6 months postoperatively. We investigated VA occurrence and adverse events after implantation.ResultsAt 6 months, QRS duration was significantly shorter in the HBP (121.6 ± 15.6 ms) than in the RVP (150.1 ± 14.9 ms) group. The QT intervals were lower in the HBP (424.0 ± 40.9 ms) and control (405.9 ± 23.0 ms) groups than in the RVP (453.0 ± 40.2 ms) group. The Tpe and Tpe/QT ratios at 6 months differed significantly between the HBP and RVP groups (Tpe, 69.8 ± 19.7 ms vs 87.4 ± 11.9 ms and Tpe/QT, 0.16 ± 0.03 vs 0.19 ± 0.02, respectively). The Tpe and Tpe/QT ratios were similarly shortened in the HBP and control groups. VA occurred less frequently in the HBP (15%) and control (7.1%) groups than in the RVP (50%) group (p = 0.020). The non‐RVP group showed significantly lower rates of VA and major adverse events than the RVP group. Patients with VA demonstrated significantly longer QRS duration, QT interval, Tpe, and Tpe/QT at 6 months than those without VA.ConclusionHBP showed better depolarization and repolarization stability than RVP.     

Single‐pill combination of cilnidipine,an l‐/n‐type calcium channel blocker,and valsartan reduces the day‐by‐day variability of morning home systolic blood pressure in patients with treated hypertension: A sub‐analysis of the HOPE‐combi survey

We examined the effects of a fixed‐dose single‐pill combination of cilnidipine (10 mg), an L‐/N‐type calcium channel blocker, and valsartan (80 mg) (SPC of Cil/Val) on the day‐by‐day variability of morning home systolic blood pressure (MHSBP) in 616 patients with treated hypertension for 12 months as a sub‐analysis of the HOPE‐Combi survey, multicentral, post‐marketing, and prospective observational survey. The SPC of Cil/Val was administrated once a day in the morning. The SPC of Cil/Val decreased the standard deviation (SD, from 6.3 ± 4.8 to 5.1 ± 3.8 mmHg, p < .01), coefficient of variation (from 4.3 ± 3.2 to 3.8 ± 2.9%, p < .05), average real variability (ARV, from 7.9 ± 6.6 to 6.3 ± 5.1 mmHg, p < .01), and the difference between maximum and minimum (MMD, from 11.9 ± 9.2 to 9.7 ± 7.2 mmHg, p < .01) of MHSBP. The variability of MHSBP increased with age; however, this was not increased in patients ≥70 years at the baseline. In elderly patients (≥70 years, N = 283), the SPC of Cil/Val decreased the SD (from 6.9 ± 5.6 to 5.6 ± 4.4 mmHg, p < .01), ARV (from 8.6 ± 7.7 to 6.9 ± 5.7 mmHg, p < .05), and MMD (from 13.2 ± 10.7 to 10.7 ± 8.3 mmHg, p < .01) of MHSBP at 12 months; the reduction in these MHSBP variability parameters was comparable to that in adults <70 years. These results suggest that the SPC of Cil/Val is effective in reducing day‐by‐day variability of MHSBP in elderly patients.     

T‐wave heterogeneity in standard resting 12‐lead ECGs is associated with 90‐day cardiac mortality in women following emergency department admission: A nested case–control study

BackgroundWe investigated whether T‐wave heterogeneity (TWH) can identify patients who are at risk for near‐term cardiac mortality.MethodsA nested case–control analysis was performed in the 888 patients admitted to the Emergency Department (ED) of our medical center in July through September 2018 who had ≥2 serial troponin measurement tests within 6 hr for acute coronary syndrome evaluation to rule‐in or rule‐out the presence of acute myocardial infarction. Patients who died from cardiac causes during 90 days after ED admission were considered cases (n = 20; 10 women) and were matched 1:4 on sex and age with patients who survived during this period (n = 80, 40 women). TWH, that is, interlead splay of T waves, was automatically assessed from precordial leads by second central moment analysis.ResultsTWH_V4‐6 was significantly elevated at ED admission in 12‐lead resting ECGs of female patients who died of cardiac causes during the following 90 days compared to female survivors (100 ± 14.9 vs. 40 ± 3.6 µV, p < .0001). TWH_V4‐6 generated areas under the receiver‐operating characteristic (ROC) curve (AUC) of 0.933 in women (p < .0001) and 0.573 in men (p = .4). In women, the ROC‐guided 48‐µV TWH_V4‐6 cut point for near‐term cardiac mortality produced an adjusted odds ratio of 121.37 (95% CI: 2.89–6,699.84; p = .02) with 100% sensitivity and 82.5% specificity. In Kaplan–Meier survival analysis, TWH_V4‐6 ≥ 48 µV predicted cardiac mortality in women during 90‐day follow‐up with a hazard ratio of 27.84 (95% CI: 7.29–106.36, p < .0001).ConclusionElevated TWH_V4‐6 is associated with near‐term cardiac mortality among women evaluated for acute coronary syndrome.     

QT and Tpeak‐Tend interval variability: Predictive electrical markers of hospital stay length and mortality in acute decompensated heart failure. Preliminary data

BackgroundAs previously reported, an increased repolarization temporal imbalance induces a higher risk of total/cardiovascular mortality.HypothesisThe aim of this study was to assess if the electrocardiographic short period markers of repolarization temporal dispersion could be predictive of the hospital stay length and mortality in patients with acutely decompensated chronic heart failure (CHF).MethodMean, standard deviation (SD), and normalized variance (VN) of QT (QT) and Tpeak‐Tend (Te) were obtained on 5‐min ECG recording in 139 patients hospitalized for acutely decompensated CHF, subgrouping the patients for hospital length of stay (LoS): less or equal 1 week (≤1 W) and those with more than 1 week (>1 W).ResultsWe observed an increase of short‐period repolarization variables (TeSD and TeVN, p < .05), a decrease of blood pressure (p < .05), lower ejection fraction (p < .05), and higher plasma level of biomarkers (NT‐proBNP, p < .001; Troponin, p < .05) in >1 W LoS subjects. 30‐day deceased subjects reported significantly higher levels of QTSD (p < .05), Te mean (p < .001), TeSD (p < .05), QTVN (p < .05) in comparison to the survivors. Multivariable Cox regression analysis reported that TeVN was a risk factor for longer hospital stay (hazard ratio: 1.04, 95% confidence limit: 1.01–1.08, p < .05); whereas, a longer Te mean was associated with higher mortality risk (hazard ratio: 1.02, 95% confidence limit: 1.01–1.03, p < .05).ConclusionA longer hospital stay is considered a clinical surrogate of CHF severity, we confirmed this finding. Therefore, these electrical and simple parameters could be used as noninvasive, transmissible, inexpensive markers of CHF severity and mortality.     

Impact of P‐wave indices in prediction of atrial fibrillation—Insight from loop recorder analysis

BackgroundSeveral P‐wave indices are associated with the development of atrial fibrillation (AF). However, previous studies have been limited in their ability to reliably diagnose episodes of AF. Implantable loop recorders allow long‐term, continuous, and therefore more reliable detection of AF.HypothesisThe aim of this study is to identify and evaluate ECG parameters for predicting AF by analyzing patients with loop recorders.MethodsThis study included 366 patients (mean age 62 ± 16 years, mean LVEF 61 ± 6%, 175 women) without AF who underwent loop recorder implantation between 2010–2020. Patients were followed up on a 3 monthly outpatient interval.ResultsDuring a follow‐up of 627 ± 409 days, 75 patients (20%) reached the primary study end point (first detection of AF). Independent predictors of AF were as follows: age ≥68 years (hazard risk [HR], 2.66; 95% confidence interval [CI], 1.668–4.235; p < .001), P‐wave amplitude in II <0.1 mV (HR, 2.11; 95% CI, 1.298–3.441; p = .003), P‐wave terminal force in V₁ ≤ −4000 µV × ms (HR, 5.3; 95% CI, 3.249–8.636; p < .001, and advanced interatrial block (HR, 5.01; 95% CI, 2.638–9.528; p < .001). Our risk stratification model based on these independent predictors separated patients into 4 groups with high (70%), intermediate high (41%), intermediate low (18%), and low (4%) rates of AF.ConclusionsOur study indicated that P‐wave indices are suitable for predicting AF episodes. Furthermore, it is possible to stratify patients into risk groups for AF using simple ECG parameters, which is particularly important for patients with cryptogenic stroke.     

Continuous multi‐day tracking of post‐myocardial infarction recovery of cardiac electrical stability and autonomic tone using electrocardiogram patch monitors

BackgroundSudden cardiac death (SCD) risk is elevated following acute myocardial infarction (MI). The time course of SCD susceptibility post‐MI requires further investigation.MethodsIn this observational cohort study, we employed state‐of‐the‐art noninvasive ECG techniques to track the daily time course of cardiac electrical instability and autonomic function following ST‐segment elevation myocardial infarction (STEMI) and non‐STEMI (NSTEMI). Preventice BodyGuardian MINI‐EL Holters continuously recorded ECGs for 7 days at hospital discharge and at 40 days for STEMI (N = 5) or at 90 days for NSTEMI patients (N = 5). Cardiac electrical instability was assessed by T‐wave alternans (TWA) and T‐wave heterogeneity (TWH); autonomic tone was determined by rMSSD‐heart rate variability (HRV).ResultsTWA was severely elevated (≥60 μV) in STEMI patients (80 ± 10.3 μV) at discharge and throughout the first recording period but declined by 50% to 40 ± 2.3 μV (p = .03) by Day 40 and remained in the normal range (<47 μV). TWH, a related phenomenon analyzed from 12‐lead ECGs, was reduced by 63% in the five STEMI patients from discharge to normal (<80 μV) at follow‐up (105 ± 27.3 to 39 ± 3.3 μV, p < .04) but increased by 65% in a STEMI case (89 to 147 μV), who received a wearable defibrillator vest and later implantable cardioverter defibrillator. In NSTEMI patients, TWA was borderline abnormal (47 ± 3.3 μV) at discharge and declined by 19% to normal (38 ± 1.2 μV) by Day 90 (p = .05). An overall reciprocal increase in rMSSD‐HRV suggested recovery of vagal tone.ConclusionsThis study provides proof‐of‐principle for tracking post‐MI SCD risk in individual patients with implications for personalized therapy.     

Management and outcome across the spectrum of high‐risk patients with myocardial infarction according to the thrmobolysis in myocardial infarction (TIMI) risk‐score for secondary prevention

BackgroundPatients with myocardial infarction (MI) are at increased risk for recurrent cardiovascular events, yet some patients, such as the elderly and those with prior comorbidities, are particularly at the highest risk. Whether these patients benefit from contemporary management is not fully elucidated.MethodsIncluded were consecutive patients with MI who underwent percutaneous coronary intervention (PCI) in a large tertiary medical center. Patients were stratified according to the thrombolysis in myocardial infarction (TIMI) risk score for secondary prevention (TRS2°P) to high (TRS2°P = 3), very high (TRS2°P = 4), or extremely high‐risk (TRS2°P = 5–9). Excluded were low and intermediate‐risk patients (TRS2°P < 3). Outcomes included 30‐day/1‐year major adverse cardiac events (MACE) and 1‐year mortality. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time‐periods.ResultsAmong 2053 patients, 50% were high‐risk, 30% very high‐risk and 20% extremely high‐risk. Extremely high‐risk patients were older (age 74 ± 10 year) and had significant comorbidities (chronic kidney disease 68%, prior CABG 40%, heart failure 78%, peripheral artery disease 29%). Drug‐eluting stents and potent antiplatelets were more commonly used over time in all risk‐strata. Over time, 30‐day MACE rates have decreased, mainly attributed to the very high (11.3% to 5.1%, p = .006) and extremely high‐risk groups (15.9% to 8.0%, p = .016), but not the high‐risk group, with similar quantitative results for 1‐year MACE. The rates of 1‐year mortality remained unchanged in either group.ConclusionWithin a particularly high‐risk cohort of MI patients who underwent PCI, the implementation of guideline‐recommended therapies has improved over time, with the highest‐risk groups demonstrating the greatest benefit in outcomes.     

Insulin–glucagon‐like peptide‐1 receptor agonist relay and glucagon‐like peptide‐1 receptor agonist first regimens in individuals with type 2 diabetes: A randomized,open‐label trial study

Aims/IntroductionGlucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) might be less effective in patients with severe hyperglycemia, because hyperglycemia downregulated the GLP‐1 receptor in an animal study. To examine this hypothesis clinically, we compared the glucose‐lowering effects of GLP‐1 receptor agonist liraglutide with and without prior glycemic control.Materials and MethodsIn an open‐label, parallel trial, participants with poorly controlled type 2 diabetes were recruited and randomized to receive once‐daily insulin therapy, degludec (Insulin–GLP‐1 RA relay group, mean 16.8 ± 11.4 IU/day), for 12 weeks and then liraglutide for 12 weeks or subcutaneous injections of GLP‐1 RA, liraglutide (GLP‐1 RA first group, 0.9 mg), for 24 weeks. The primary efficacy end‐points consisted of changes in the levels of fasting plasma glucose and glycated hemoglobin (HbA1c).ResultsThe median fasting plasma glucose and HbA1c before the study were 210.0 mg/dL and 9.8%, respectively. The levels of fasting plasma glucose and HbA1c significantly decreased in the Insulin–GLP‐1 RA relay group (P < 0.001) and GLP‐1 RA first group (P < 0.001) by week 24, although no intergroup differences were observed. The reduction of HbA1c in the Insulin–GLP‐1 RA relay group tended to be larger than that in the GLP‐1 RA first group in the lowest CPR (C‐peptide immunoreactivity) quartile (P = 0.072). The adverse events consisted of gastrointestinal problems, followed by hypoglycemia.ConclusionsThe GLP‐1 receptor agonist is overall effective without prior glycemic control with insulin in participants with poorly controlled type 2 diabetes. However, in participants with insulinopenic type 2 diabetes, prior glycemic control with insulin might overcome glucose toxicity‐induced GLP‐1 resistance.     

Night‐to‐night variability of sleep apnea detected by cyclic variation of heart rate during long‐term continuous ECG monitoring

BackgroundSleep apnea is common in patients with cardiovascular disease and is a factor that worsens prognosis. Holter 24‐h ECG screening for sleep apnea is beneficial in the care of these patients, but due to high night‐to‐night variability of sleep apnea, it can lead to misdiagnosis and misclassification of disease severity.MethodsTo investigate the long‐term dynamic behavior of sleep apnea, seven‐day ECGs recorded with a patch ECG recorder in 120 patients were analyzed for the cyclic variation of heart rate (CVHR) during sleep periods as determined by a built‐in three‐axis accelerometer.ResultsThe frequency of CVHR (Fcv) showed considerable night‐to‐night variability (coefficient of variance, 66 ± 35%), which was consistent with the night‐to‐night variability in apnea‐hypopnea index and oxygen desaturation index reported in earlier studies. In patients with presumed moderate‐to‐severe sleep apnea (Fcv > 15 cph at least one night), it was missed on 62% of nights, and on at least one night in 88% of patients. The CV of Fcv was negatively correlated with the average of Fcv, suggesting that patients with mild sleep apnea show greater night‐to‐night variability and would benefit from long‐term assessment. The average Fcv was higher in the supine position, but the night‐to‐night variability was not explained by the night‐to‐night variability of time spent in the supine position.ConclusionsCVHR analysis of long‐term ambulatory ECG recordings is useful for improving the reliability of screening for sleep apnea without placing an extra burden on patients with cardiovascular disease and their care.     

Proenkephalin and the risk of new‐onset heart failure: data from prevention of renal and vascular end‐stage disease

BackgroundEnkephalins of the opioid system exert several cardiorenal effects. Proenkephalin (PENK), a stable surrogate, is associated with heart failure (HF) development after myocardial infarction and worse cardiorenal function and prognosis in patients with HF. The association between plasma PENK concentrations and new‐onset HF in the general population remains to be established.HypothesisWe hypothesized that plasma PENK concentrations are associated with new‐onset HF in the general population.MethodsWe included 6677 participants from the prevention of renal and vascular end‐stage disease study and investigated determinants of PENK concentrations and their association with new‐onset HF (both reduced [HFrEF] and preserved ejection fraction [HFpEF]).ResultsMedian PENK concentrations were 52.7 (45.1–61.9) pmol/L. Higher PENK concentrations were associated with poorer renal function and higher NT‐proBNP concentrations. The main determinants of higher PENK concentrations were lower estimated glomerular filtration rate (eGFR), lower urinary creatinine excretion, and lower body mass index (all p < .001). After a median 8.3 (7.8–8.8) years follow‐up, 221 participants developed HF; 127 HFrEF and 94 HFpEF. PENK concentrations were higher in subjects who developed HF compared with those who did not, 56.2 (45.2–67.6) versus 52.7 (45.1–61.6) pmol/L, respectively (p = .003). In competing‐risk analyses, higher PENK concentrations were associated with higher risk of new‐onset HF (hazard ratio [HR] = 2.09[1.47–2.97], p < .001), including both HFrEF (HR = 2.31[1.48–3.61], p < .001) and HFpEF (HR = 1.74[1.02–2.96], p = .042). These associations were, however, lost after adjustment for eGFR.ConclusionsIn the general population, higher PENK concentrations were associated with lower eGFR and higher NT‐proBNP concentrations. Higher PENK concentrations were not independently associated with new‐onset HFrEF and HFpEF and mainly confounded by eGFR.     

Prevalence and impact of diabetes in hospitalized COVID‐19 patients: A systematic review and meta‐analysis

BackgroundDiabetes is a cardiometabolic comorbidity that may predispose COVID‐19 patients to worse clinical outcomes. This study sought to determine the prevalence of diabetes in hospitalized COVID‐19 patients and investigate the association of diabetes severe COVID‐19, rate of acute respiratory distress syndrome (ARDS), mortality, and need for mechanical ventilation by performing a systematic review and meta‐analysis.MethodsIndividual studies were selected using a defined search strategy, including results up until July 2021 from PubMed, Embase, and Cochrane Central Register of Controlled Trials. A random‐effects meta‐analysis was performed to estimate the proportions and level of association of diabetes with clinical outcomes in hospitalized COVID‐19 patients. Forest plots were generated to retrieve the odds ratios (OR), and the quality and risk assessment was performed for all studies included in the meta‐analysis.ResultsThe total number of patients included in this study was 10 648, of whom 3112 had diabetes (29.23%). The overall pooled estimate of prevalence of diabetes in the meta‐analysis cohort was 31% (95% CI, 0.25‐0.38; z = 16.09, P < .0001). Diabetes significantly increased the odds of severe COVID‐19 (OR 3.39; 95% CI, 2.14‐5.37; P < .0001), ARDS (OR 2.55; 95% CI, 1.74‐3.75; P = <.0001), in‐hospital mortality (OR 2.44; 95% CI, 1.93‐3.09; P < .0001), and mechanical ventilation (OR 3.03; 95% CI, 2.17‐4.22; P < .0001).ConclusionsOur meta‐analysis demonstrates that diabetes is significantly associated with increased odds of severe COVID‐19, increased ARDS rate, mortality, and need for mechanical ventilation in hospitalized patients. We also estimated an overall pooled prevalence of diabetes of 31% in hospitalized COVID‐19 patients.     

Comparison of coronary atherosclerotic disease burden between ST‐elevation myocardial infarction and non‐ST‐elevation myocardial infarction: Non‐culprit Gensini score and non‐culprit SYNTAX score

BackgroundPatients with non‐ST‐elevation myocardial infarction (NSTEMI) have worse long‐term prognoses than those with ST‐elevation myocardial infarction (STEMI).HypothesisIt may be attributable to more extended coronary atherosclerotic disease burden in patients with NSTEMI.MethodsThis study consisted of consecutive 231 patients who underwent coronary intervention for myocardial infarction (MI). To assess the extent and severity of atherosclerotic disease burden of non‐culprit coronary arteries, two scoring systems (Gensini score and synergy between percutaneous coronary intervention with Taxus and cardiac surgery [SYNTAX] score) were modified by subtracting the score of the culprit lesion: the non‐culprit Gensini score and the non‐culprit SYNTAX score.ResultsPatients with NSTEMI had more multi‐vessel disease, initial thrombolysis in myocardial infarction (TIMI) flow grade 2/3, and final TIMI flow grade 3 than those with STEMI. As compared to STEMI, patients with NSTEMI had significantly higher non‐culprit Gensini score (16.3 ± 19.8 vs. 31.2 ± 25.4, p < 0.001) and non‐culprit SYNTAX score (5.8 ± 7.0 vs. 11.1 ± 9.7, p < 0.001).ConclusionsPatients with NSTEMI had more advanced coronary atherosclerotic disease burden including non‐obstruction lesions, which may at least in part explain higher incidence of cardiovascular events in these patients.     

Serum tumor necrosis factor‐α, interleukin‐1β, interleukin‐6, and interleukin‐17 relate to anxiety and depression risks to some extent in non‐small cell lung cancer survivor

IntroductionInflammatory cytokines are proposed as modulators for the pathogenesis of anxiety and depression (anxiety/depression), and anxiety/depression are frequently existed in non‐small cell lung cancer (NSCLC) survivors. However, no published study has explored the association of inflammation cytokines with anxiety/depression in NSCLC survivors.ObjectivesWe aimed to evaluate serum tumor necrosis factor‐α (TNF‐α), interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6), interleukin‐17 (IL‐17) levels, and their correlations with anxiety/depression in NSCLC survivors.MethodsTotally, 217 NSCLC survivors and 200 controls were recruited. Then, inflammatory cytokines in serum samples were detected by enzyme‐linked immunosorbent assay (ELISA). Besides, their anxiety/depression status was assessed by Hospital Anxiety and Depression Scale (HADS).ResultsHADS‐anxiety score, anxiety rate, anxiety severity, HADS‐depression score, depression rate, and depression severity were all increased in NSCLC survivors compared with controls (all P < 0.001). Regarding inflammatory cytokines, TNF‐α, IL‐1β, and IL‐17 levels were higher (all P < 0.01), while IL‐6 (P = 0.105) level was of no difference in NSCLC survivors compared with controls. Furthermore, TNF‐α, IL‐1β, IL‐6, and IL‐17 were all positively associated with HADS‐A score (all P < 0.05), anxiety occurrence (all P < 0.05), HADS‐D score (all P < 0.05), and depression occurrence (all P < 0.05) in NSCLC survivors, while the correlation‐coefficients were weak. Additionally, multivariate logistic regression analyses disclosed that TNF‐α (both P < 0.05) and IL‐1β (both P < 0.001) were independently correlated with increased anxiety and depression risks in NSCLC survivors.ConclusionSerum TNF‐α, IL‐1β, IL‐6, and IL‐17 are related to increased anxiety and depression risks to some extent in NSCLC survivors.     

Prognostic implications of ST‐segment elevation in lead aVR in patients with acute coronary syndrome: A meta‐analysis

BackgroundST‐segment elevation (STE) in lead aVR is a useful tool in recognizing patients with left main or left anterior descending coronary obstruction during acute coronary syndrome (ACS). The prognostic implication of STE in lead aVR on outcomes has not been established.MethodsWe performed a systematic search for clinical studies about STE in lead aVR in four databases including PubMed, EMBASE, Cochrane Library, and Web of Science. Primary outcome was in‐hospital mortality. Secondary outcomes included in‐hospital (re)infarction, in‐hospital heart failure, and 90‐day mortality.ResultsWe included 7 studies with a total of 7,700 patients. The all‐cause in‐hospital mortality of patients with STE in lead aVR during ACS was significantly higher than that of patients without STE (OR: 4.37, 95% CI 1.63 to 11.68, p = .003). Patients with greater STE (>0.1 mV) in lead aVR had a higher in‐hospital mortality when compared to lower STE (0.05–0.1 mV) (OR: 2.00, 95% CI 1.11–3.60, p = .02), However, STE in aVR was not independently associated with in‐hospital mortality in ACS patients (OR: 2.72, 95% CI 0.85–8.63, p = .09). The incidence of in‐hospital myocardial (re)infarction (OR: 2.77, 95% CI 1.30–5.94, p = .009), in‐hospital heart failure (OR: 2.62, 95% CI 1.06–6.50, p = .04), and 90‐day mortality (OR: 10.19, 95% CI 5.27–19.71, p < .00001) was also noted to be higher in patients STE in lead aVR.ConclusionsThis contemporary meta‐analysis shows STE in lead aVR is a poor prognostic marker in patients with ACS with higher in‐hospital mortality, reinfarction, heart failure and 90‐day mortality. Greater magnitude of STE portends worse prognosis. Further studies are needed to establish an independent predictive role of STE in aVR for these adverse outcomes.