Ranolazine reduces repolarization heterogeneity in symptomatic patients with diabetes and non–flow‐limiting coronary artery stenosis

Background

Experimental evidence suggests that ranolazine decreases susceptibility to ischemia‐induced arrhythmias independent of effects on coronary artery blood flow.

Objective

In symptomatic diabetic patients with non–flow‐limiting coronary artery stenosis with diffuse atherosclerosis and/or microvascular dysfunction, we explored whether ranolazine reduces T‐wave heterogeneity (TWH), an electrocardiographic (ECG) marker of arrhythmogenic repolarization abnormalities shown to predict sudden cardiac death.

Methods

We studied all 16 patients with analyzable ECG recordings during rest and exercise tolerance testing before and after 4 weeks of ranolazine in the double‐blind, crossover, placebo‐controlled RAND‐CFR trial (NCT01754259). TWH was quantified without knowledge of treatment assignment by second central moment analysis, which assesses the interlead splay of T waves in precordial leads about a mean waveform. Myocardial blood flow (MBF) was measured by positron emission tomography.

Results

At baseline, prior to randomization, TWH during rest was 54 ± 7 μV and was not altered following placebo (47 ± 6 μV, p = .47) but was reduced by 28% (to 39 ± 5 μV, p = .002) after ranolazine. Ranolazine did not increase MBF at rest. Exercise increased TWH after placebo by 49% (to 70 ± 8 μV, p = .03). Ranolazine did not reduce TWH during exercise (to 75 ± 16 μV), and there were no differences among the groups (p = .95, ANOVA). TWH was not correlated with MBF at rest before (r² = .07, p = .36) or after ranolazine (r² = .23, p = .06).

Conclusions

In symptomatic diabetic patients with non‐flow‐limiting coronary artery stenosis with diffuse atherosclerosis and/or microvascular dysfunction, ranolazine reduced TWH at rest but not during exercise. Reduction in repolarization abnormalities appears to be independent of alterations in MBF.

     

Baseline fragmented QRS increases the risk of major arrhythmic events in Brugada syndrome: Systematic review and meta‐analysis

Background

Fragmented QRS reflects disturbances in the myocardium predisposing the heart to ventricular tachyarrhythmias. Recent studies suggest that fragmented QRS (fQRS) is associated with major arrhythmic events in Brugada syndrome. However, a systematic review and meta‐analysis of the literature has not been done. We assessed the association between fQRS and major arrhythmic events in Brugada syndrome by a systematic review of the literature and a meta‐analysis.

Methods

We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2017. Included studies were published prospective or retrospective cohort studies that compared major arrhythmic events (ventricular fibrillation, sustained ventricular tachycardia, sudden cardiac arrest, or sudden cardiac death) in Brugada syndrome with fQRS versus normal QRS. Data from each study were combined using the random‐effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals.

Results

Nine studies from January 2012 to May 2017 were included in this meta‐analysis involving 2,360 subjects with Brugada syndrome (550 fQRS and 1,810 non‐fQRS). Fragmented QRS was associated with major arrhythmic events (pooled risk ratio =3.36, 95% confidence interval: 2.09‐5.38, p < .001, I² = 50.9%) as well as fatal arrhythmia (pooled risk ratio =3.09, 95% confidence interval: 1.40‐6.86, p = .005, I² = 69.7%).

Conclusions

Baseline fQRS increased major arrhythmic events up to 3‐fold. Our study suggests that fQRS could be an important tool for risk assessment in patients with Brugada syndrome.

     

Baseline fragmented QRS increases the risk of major arrhythmic events in hypertrophic cardiomyopathy: Systematic review and meta‐analysis

Background

Fragmented QRS reflects disturbances in the myocardium predisposing the heart to ventricular tachyarrhythmias. Recent studies suggest that fragmented QRS (fQRS) is associated with worse major arrhythmic events in hypertrophic cardiomyopathy (HCM). However, a systematic review and meta‐analysis of the literature has not been done. We assessed the association between fQRS and major arrhythmic events in hypertrophic cardiomyopathy by a systematic review of the literature and a meta‐analysis.

Methods

We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2017. Included studies were published prospective or retrospective cohort studies that compared major arrhythmic events (sustained ventricular tachycardia, sudden cardiac arrest, or sudden cardiac death) in HCM with fQRS versus non‐fQRS. Data from each study were combined using the random‐effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals.

Results

Five studies from January 2013 to May 2017 were included in this meta‐analysis involving 673 subjects with HCM (205 fQRS and 468 non‐fQRS). Fragmented QRS was associated with major arrhythmic events (pooled risk ratio = 7.29, 95% confidence interval: 4.00–13.29, p < .01, I² = 0%).

Conclusion

Baseline fQRS increased major arrhythmic events up to sevenfold. Our study suggests that fQRS could be an important tool for risk assessment in patients with HCM.

     

Prognostic value of T‐wave morphology parameters in coronary artery disease in current treatment era

Background

The prognostic value of T‐wave morphology parameters in coronary artery disease in the current treatment era is not well established.

Methods

The Innovation to reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study included 1,946 patients with angiographically verified coronary artery disease (CAD). The study patients underwent thorough examinations including 12‐lead digital electrocardiogram (ECG) at baseline.

Results

During a follow‐up period of 73 ± 22 months, a total of 201 (10.3%) patients died. Of the study patients, 95 (4.9%) experienced cardiac death (CD) consisting of 44 (2.3%) sudden cardiac deaths (SCD) and 51 (2.6%) nonsudden cardiac deaths (NSCD), and 106 (5.4%) patients experienced noncardiac death (NCD). T‐wave morphology dispersion (TMD), T‐wave area dispersion (TWAD), and total cosine R‐to‐T (TCRT) had a significant association with CD even after adjustment with relevant clinical risk markers in the Cox regression analysis (multivariate HRs: 1.015, 95% CI 1.007–1.023, p = .0003; 0.474, 95% CI 0.305–0.737, p = .0009; 0.598, 95% CI 0.412–0.866, p = .006, respectively). When including these parameters to the clinical risk model for CD, the C‐index increased from 0.810 to 0.823 improving the discrimination significantly (integrated discrimination index [IDI] = 0.0118, 95% CI 0.0028–0.0208, p = .01). These parameters were more closely associated with NSCD (multivariate p‐values from .016 to .001) than with SCD (univariate/multivariate p‐values for TMD .015/.197 and for TCRT .012/.43).

Conclusion

T‐wave morphology parameters describing repolarization heterogeneity improve the predictive power of the clinical risk model for CD in patients with CAD in the current treatment era.

     

Genotype–phenotype relationship and risk stratification in loss‐of‐function SCN5A mutation carriers

Introduction

Loss‐of‐function (LoF) mutations in the SCN5A gene cause multiple phenotypes including Brugada Syndrome (BrS) and a diffuse cardiac conduction defect. Markers of increased risk for sudden cardiac death (SCD) in LoF SCN5A mutation carriers are ill defined. We hypothesized that late potentials and fragmented QRS would be more prevalent in SCN5A mutation carriers compared to SCN5A‐negative BrS patients and evaluated risk markers for SCD in SCN5A mutation carriers.

Methods

We included all SCN5A loss‐of‐function mutation carriers and SCN5A‐negative BrS patients from our center. A combined arrhythmic endpoint was defined as appropriate ICD shock or SCD.

Results

Late potentials were more prevalent in 79 SCN5A mutation carriers compared to 39 SCN5A‐negative BrS patients (66% versus 44%, p = .021), while there was no difference in the prevalence of fragmented QRS. PR interval prolongation was the only parameter that predicted the presence of a SCN5A mutation in BrS (OR 1.08; p < .001). Four SCN5A mutation carriers, of whom three did not have a diagnostic type 1 ECG either spontaneously or after provocation with a sodium channel blocker, reached the combined arrhythmic endpoint during a follow‐up of 44 ± 52 months resulting in an annual incidence rate of 1.37%.

Conclusion

LP were more frequently observed in SCN5A mutation carriers, while fQRS was not. In SCN5A mutation carriers, the annual incidence rate of SCD was non‐negligible, even in the absence of a spontaneous or induced type 1 ECG. Therefore, proper follow‐up of SCN5A mutation carriers without Brugada syndrome phenotype is warranted.

     

Impact of ST‐segment resolution on clinical outcome in patients with ST‐segment elevation myocardial infarction and preserved left ventricular function

Background

Patients with successful reperfusion and preserved left ventricular ejection fraction (LVEF) after ST‐segment myocardial infarction (STEMI)have always been thought to have low risk for adverse events. Great interest is focused on finding simple, noninvasive tools to refine risk stratification among them.

Objectives

We hypothesized that degree of ST‐segment resolution (STR) after STEMI can identify high‐risk group among patients with LVEF ≥ 50% following STEMI.

Methods

During the period from January to July 2017, patients with successful reperfusion of STEMI and LVEF ≥ 50% were prospectively included. Patients were divided into two groups based on the percent of ST segment resolution using single lead STR method; group I (complete STR ≥ 70%) and group II (partial STR 50%–70%). The endpoint was a composite of cardiovascular mortality, re‐hospitalization for heart failure and urgent revascularization at 30‐day.

Results

After exclusion, 110 patients were left for final analysis. No significant differences in all baseline characteristics were found between both groups. The primary endpoint occurred in seven patients (12.7%) of group I versus 17 patients (30.9%) of group II (Relative risk = 2.43, 95%CI = 1.1–5.4, p = 0.021) driven by a significant reduction in rates of re‐hospitalization due to heart failure. A multivariate logistic regression analysis showed incomplete STR to be a significant independent predictor for 30‐dayMACEs (OR 3.25, 95% CI1.2–8.83, p = 0.02) even after adjustment for location of infarction.

Conclusion

Complete STR predicts 30‐day outcome in patients with preserved LVEF following successful reperfusion of STEMI.

     

Use of fragmented QRS in prognosticating clinical deterioration and mortality in pulmonary embolism: A meta‐analysis

Background

Fragmented QRS (fQRS) on electrocardiography is potentially valuable in prognosticating acute pulmonary embolism (PE). ECG is one of the first tests performed in the emergency department, quickly interpretable, noninvasive, inexpensive, and available in remote areas. We aimed to review fQRS's role in PE prognostication.

Methods

We searched MEDLINE, EMBASE, Google Scholar, Web of Science, abstracts, conference proceedings, and reference lists until October 2017. Eligible studies used fQRS to prognosticate patients for the main outcomes of death and clinical deterioration or escalation of therapy. Two authors independently selected studies, with disagreement resolved by consensus. Ad hoc piloted forms were used to extract data and assess risk of bias. We used a random‐effects model to pool relevant data in meta‐analysis with odds ratios (OR) and 95% confidence intervals (CI), while all other data were synthesized qualitatively. Statistical heterogeneity was assessed using the I² index.

Results

We included five studies (1,165 patients). There was complete agreement in study selection. fQRS significantly predicted in‐hospital mortality (OR [95% CI], 2.92 [1.73–4.91]; p < .001), cardiogenic shock (OR [95% CI], 4.71 [1.61–13.70]; p = .005), and total mortality at 2‐year follow‐up (OR [95% CI], 4.42 [2.57–7.60]; p < .001). Adjusted analyses were generally consistent with these results.

Conclusion

Although few studies have explored the current study's question, they showed that fQRS is potentially valuable in PE prognostication. fQRS should be considered as an entry, along with other clinical and ECG findings, in a PE risk score.

     

Propensity score matching analysis of the impact of Syntax score and Syntax score II on new onset atrial fibrillation development in patients with ST segment elevation myocardial infarction

Background

New‐onset atrial fibrillation (NOAF) is a common complication in the setting of ST segment elevation myocardial infarction (STEMI), and worsened short/long‐term prognosis. Several clinical parameters have already been associated with NOAF development. However, relationship between NOAF and coronary artery disease (CAD) severity in STEMI patients is unclear. This study evaluates the relationship between NOAF and CAD severity using Syntax score (SS) and Syntax score II (SSII) in STEMI patients who were treated with primary percutaneous coronary intervention (pPCI).

Method

We enrolled 1,565 consecutive STEMI patients who were treated with pPCI. Patients with NOAF were compared to patients without NOAF in the entire study population and in a matched population defined by propensity score matching.

Results

Patients with NOAF had significantly higher SS and SSII than those without, both in the matched population (18.6 ± 4 vs 16.75 ± 3.6; p < .001 and 42 ± 13.4 vs 35.1 ± 13.1; p < .001, respectively), and in all study population (18.6 ± 4 vs 16.5 ± 4.6; p < .001 and 42 ± 13.3 vs 31.5 ± 11.9; p < .001 respectively). SSII, compared to its components, was the only independent predictor of NOAF (OR: 1,041 95% CI: 1.015–1.068; p = .002). In the long‐term follow‐up, all‐cause long‐term mortality was significantly higher in patients with NOAF than those without NOAF (23.3% vs. 11%; p = .032).

Conclusion

This is the first study to comprehensively examine the relationship between NOAF development and CAD severity using SS and SSII. We demonstrated that, in STEMI patients, high SSII was significantly related to NOAF and was an independent predictor of NOAF. Furthermore, patients with NOAF were associated with poor prognosis.

     

Coronary sinus lead delay index for optimization of coronary sinus lead placement

Aim

Optimization of coronary sinus (CS) lead position to the latest activated left ventricular (LV) area is important to increase cardiac resynchronization therapy (CRT) response. We aimed to detect the relationship between coronary sinus lead delay index (CSDI) and echocardiographic, electrocardiographic response to CRT treatment.

Methods

We prospectively included 137 consecutive patients with heart failure (HF) diagnosis, QRS ≥ 120 ms, left bundle branch block (LBBB), New York Heart Association score (NYHA) II–IV, LV ejection fraction (LVEF) <35% and scheduled for CRT (84 male, 53 female; mean age 65.1 ± 10.1 years). Echocardiographic CRT response was defined as ≥15% reduction in LV end‐systolic volume (LVESV). CS lead sensing delay was calculated as the time interval from the onset of surface QRS wave to the onset of depolarization wave recorded from the CS lead by using the CS pacing lead as a bipolar electrode. CSDI was calculated by dividing the CS lead sensing delay by the QRS duration.

Results

LVESV reduction was associated with baseline QRS width (r = .257, p = .002), QRS narrowing (r = .396, p < .001), CSDI (r = .357, p < .001), and NT‐proBNP (r = ?0.213, p = .022) in bivariate analysis. In logistic regression analysis, CSDI was found to be only independent parameter for predicting significant LVESV reduction (Beta = 0.318, p < .001). CSDI was also found to be significantly associated with LVEF increase (r = .244, p = .004) and QRS narrowing (r = .178, p = .046).

Conclusion

CSDI may be used as a marker to predict the favorable response to CRT. It may be useful to integrate CSDI to CRT implantation procedure in order to minimize nonresponders.

     

Narrowing filtered QRS duration on signal‐averaged electrocardiogram predicts outcomes in cardiac resynchronization therapy patients with nonischemic heart failure

Background

To evaluate the impact of changes in the filtered QRS duration (fQRS) on signal‐averaged electrocardiograms (SAECGs) from pre‐ to postimplantation on the clinical outcomes in nonischemic heart failure (HF) patients under cardiac resynchronization therapy (CRT).

Methods

We studied 103 patients with nonischemic HF and sinus rhythm who underwent CRT implantation. SAECGs were obtained within 1 week before and 1 week after implantation and narrowing fQRS was defined as a decrease in fQRS from pre‐ to postimplantation. Echocardiography was performed before and 6 months after CRT implantation. The primary outcome was death from any cause. The secondary outcomes were hospitalization due to worsened HF and occurrence of ventricular tachyarrhythmias.

Results

Of the 103 CRT patients, 53 (51%) showed narrowing fQRS. Left ventricular end‐diastolic volume and end‐systolic volume were significantly reduced (both p < .001), and the left ventricular ejection fraction was significantly increased (p < .001) after CRT in patients with narrowing fQRS, but not in patients with nonnarrowing fQRS. During a median follow‐up period of 33 months, patients with narrowing fQRS exhibited better survival than patients with nonnarrowing fQRS (p = .007). A lower incidence of hospitalization due to worsened HF (p < .001) and a lower occurrence of ventricular tachyarrhythmias (p = .071) were obtained in patients with narrowing fQRS. After adjusting for confounding variables, narrowing fQRS was associated with a low risk of mortality (HR 0.27, p = .006).

Conclusion

Our results suggested that narrowing fQRS on SAECG after CRT implantation predicts LV reverse remodeling and long‐term outcomes in nonischemic HF patients.

     

Marked exercise‐induced T‐wave heterogeneity in symptomatic diabetic patients with nonflow‐limiting coronary artery stenosis

Background

T‐wave heterogeneity (TWH) independently predicted cardiovascular mortality in Health Survey 2000 based on 12‐lead ECGs recorded at rest. We investigated whether TWH is elevated during exercise tolerance testing (ETT) in symptomatic diabetic patients with nonflow‐limiting coronary artery stenosis compared to control subjects without diabetes.

Methods

Cases were all patients (n = 20) with analyzable ECG recordings during both rest and ETT who were enrolled in the Effects of Ranolazine on Coronary Flow Reserve (CFR) in Symptomatic Patients with Diabetes and Suspected or Known Coronary Artery Disease (RAND‐CFR) study (NCT01754259); median CFR was 1.44; 80% of cases had CFR <2. Control subjects (n = 9) were nondiabetic patients who had functional flow reserve (FFR) >0.8, a range not associated with inducible ischemia. TWH was analyzed from precordial leads V₄, V₅, and V₆ by second central moment analysis, which assesses the interlead splay of T‐waves about a mean waveform.

Results

During exercise to similar rate‐pressure products (p = .31), RAND‐CFR patients exhibited a 49% increase in TWH during exercise (rest: 49 ± 5 μV; exercise: 73 ± 8 μV, p = .003). By comparison, in control subjects, TWH was not significantly altered (rest: 52 ± 11 μV; ETT: 38 ± 5 μV, p = .19). ETT‐induced ST‐segment depression >1 mm (p = .11) and T_peak‐T_end (p = .18) and QTc intervals (p = .80) failed to differentiate cases from controls.

Conclusions

TWH is capable of detecting latent repolarization abnormalities, which are present during ETT in diabetic patients with nonflow‐limiting stenosis but not in control subjects. The technique developed in this study permits TWH analysis from archived ECGs and thereby enables mining of extensive databases for retrospective studies and hypothesis testing.

     

S‐R difference in V1‐V2 is a novel criterion for differentiating the left from right ventricular outflow tract arrhythmias

Aim

The correct estimation of the VA origin as RVOT or LVOT results in reduced ablation duration reduced radiation exposure and decreased number of vascular access. In our study, we aimed to detect the predictive value of S‐R difference in V1‐V2 for differentiating the left from right ventricular outflow tract arrhythmias.

Methods

We included 123 patients with symptomatic frequent premature ventricular outflow tract contractions who underwent successful catheter ablation (70 male, 53 female; mean age 46.2 ± 13.9 years, 61 RVOT, 62 LVOT origins). S‐R difference in V1‐V2 was calculated with this formula on the 12‐lead surface ECG: (V1S + V2S) – (V1R + V2R). Conventional ablation was performed in 101 (82.1%) patients, CARTO electroanatomic mapping system was used in 22 (17.9%) patients.

Results

V1‐2 SRd was found to be significantly lower for LVOT origins than RVOT origins (p < .001). The cutoff value of V1‐2 SRd obtained by ROC curve analysis was 1.625 mV for prediction of RVOT origin (sensitivity: 95.1%, specificity: 85.5%, positive predictive value: 86.5%, negative predictive value: 94.5%). The area under the curve (AUC) was 0.929 (p < .001).

Conclusion

S‐R difference in V1‐V2 is a novel and simple electrocardiographic criterion for accurately differentiating RVOT from LVOT sites of ventricular arrhythmia origins. The use of this simple ECG measurement could improve the accuracy of OTVA localization, could be beneficial for decreasing ablation duration and radiation exposure. Further studies with larger patient population are needed to verify the results of this study.

     

Thrombus aspiration in late presenters with ST‐elevation myocardial infarction: A single‐center randomized trial

Objectives

To examine whether routine thrombus aspiration (TA) is associated with improved myocardial salvage in patients with ST‐elevation myocardial infarction (STEMI) presenting ≥12 h after onset of symptoms.

Background

TA is a recognized treatment option in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) especially in the setting of heavy thrombus burden. However, data on the role of TA in STEMI patients presenting late after onset of symptoms are limited.

Methods

In this single‐center prospective randomized study, patients with subacute STEMI presenting ≥12 and ≤48 h after symptom onset were randomized to primary PCI with or without manual TA in a 1:1 ratio. The primary endpoint was the myocardial salvage index assessed with Single Photon Emission Computed Tomography (SPECT) on admission and 4 days later.

Results

A total of 60 patients underwent randomization. Baseline characteristics were comparable between groups. TA was associated with improved myocardial salvage index compared with control group (60.1 ± 11.1% vs 28.1 ± 21.3%; P = <0.001). Furthermore, TA was associated with improved post‐procedural TIMI flow (2.9 ± 0.3 vs 2.5 ± 0.6; P = 0.003), myocardial blush grade (2.9 ± 0.3 vs 2.2 ± 0.8, P = <0.001), and reduction in left ventricular end‐diastolic dimensions (50.4 ± 4.3 mm vs 54.4 ± 5.8 mm, P = 0.004) compared with the control group. Clinical outcomes at 30 days and 6 months were similar between both groups.

Conclusions

TA might be associated with improved reperfusion and myocardial salvage especially in STEMI patients presenting after 12 h from symptom onset who are likely to have a heavy thrombus burden.

     

The prognostic significance of early and late right precordial lead (V4R) ST‐segment elevation in patients with acute anterior myocardial infarction

Background

The predictive significance of ST‐segment elevation (STE) in lead V₄R in patients with anterior ST‐segment elevation myocardial infarction (STEMI) has not been well‐understood. In this study, we evaluated the prognostic value of early and late STE in lead V₄R in patients with anterior STEMI.

Methods

A total 451 patients with anterior STEMI who treated with primary percutaneous coronary intervention (PPCI) were prospectively enrolled in this study. All patients were classified according to presence of STE (>1 mm) in lead V₄R at admission and/or 60 min after PPCI. Based on this classification, all patients were divided into three subgroups as no V₄R STE (Group 1), early but not late V₄R STE (Group 2) and late V₄R STE (Group 3).

Results

In‐hospital mortality had higher rates at group 2 and 3 and that had 2.1 and 4.1‐times higher mortality than group 1. Late V₄R STE remained as an independent risk factor for cardiogenic shock (odds ratio [OR] 2.6; 95% confidence interval [CI] 1.9–4.3; p < .001) and in‐hospital mortality (OR 2.3; 95% CI 1.8–4.1; p < .001). The 12‐month overall survival for group 1, 2, and 3 were 91.1%, 82.4%, and 71.4% respectively. However, the long‐term mortality also had the higher rate at group 3; late V₄R STE did not remain as an independent risk factor for long‐term mortality (OR 1.5; 95% CI 0.8–4.1; p: .159).

Conclusion

Late V₄R STE in patients with anterior STEMI is strongly associated with poor prognosis. The record of late V₄R in patients with anterior STEMI has an important prognostic value.

     

Heart rate recovery fast‐to‐slow phase transition: Influence of physical fitness and exercise intensity

Background

Postexercise heart rate (HR) recovery presents an exponential decay, with two distinct phases: a fast phase, characterized by abrupt decay of HR, and determined by parasympathetic reactivation; and a slow phase, characterized by gradual decay of HR, and predominantly determined by sympathetic withdrawal. Although several methods have been proposed to assess postexercise HR recovery, none of those methods selectively assesses the time of transition from the fast to the slow phase of the HR recovery curve (HRR_PT), and the magnitude of decay prior to (HRR_FP) and after this point (HRR_SP). Therefore, the aim of the present study was to propose a method to identify HRR_PT, HRR_FP, and HRR_SP and to verify the effects of exercise intensity and physical fitness on such parameters.

Methods

Ten healthy young participants (24 ± 3 years; 23.6 ± 1.7 kg/m²) randomly underwent two exercise sessions (30 min of cycling), at moderate (MI) and high intensity (HI); followed by 5 min of inactive recovery. HR was continuously recorded during the sessions. The algorithm for HRR_PT analysis was written in Python and is freely available online.

Results

HRR_PT and HRR_SP were increased in HI session compared with MI (81 ± 24 vs. 60 ± 20 s; 8 ± 10 vs. 1 ± 5 bpm; p = .04), and there was no difference in HRR_FP between sessions (49 ± 15 vs. 46 ± 10 bpm; p = .17). In addition, HRR_PT for MI exercise session was significantly and negatively associated with VO_2max (r = ‐0.85, p < .05).

Conclusion

The method herein presented was sensitive to exercise intensity, and partially responsive to aerobic fitness. Next studies should perform the pharmacological and clinical validations of the method.

     

Diagnostic value of the cardiac electrical biomarker,a novel ECG marker indicating myocardial injury,in patients with symptoms suggestive of non‐ST‐elevation myocardial infarction

Background

The cardiac electrical biomarker (CEB) is a novel electrocardiographic (ECG) marker quantifying the dipolar activity of the heart with higher levels indicating myocardial injury.

Methods

We prospectively enrolled 1097 patients presenting with suspected non‐ST‐elevation myocardial infarction (NSTEMI) to the emergency department (ED). Digital 12‐lead ECGs were recorded at presentation and the CEB values were calculated in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. The prognostic endpoint was all‐cause mortality during 2 years of follow‐up.

Results

NSTEMI was the final diagnosis in 14% of patients. CEB levels were higher in patients with NSTEMI compared to other causes of chest pain (median 44 (IQR 21–98) vs. 30 (IQR 16–61), p < .001). A weak but significant correlation between levels of high‐sensitivity cardiac troponin T (hs‐cTnT) at admission to the ED and the CEB was found (r = .23, p < .001). The use of the CEB in addition to conventional ECG criteria improved the diagnostic accuracy for the diagnosis of NSTEMI as quantified by the area under the receiver operating characteristics curve from 0.66 to 0.71 (p < .001) and the sensitivity improved from 43% to 79% (p < .001).

Conclusion

In conclusion, the CEB, an ECG marker of myocardial injury, significantly improves the accuracy and sensitivity of the ECG for the diagnosis of NSTEMI.

     

Unshielded magnetocardiography: Repeatability and reproducibility of automatically estimated ventricular repolarization parameters in 204 healthy subjects

Background

Magnetocardiographic mapping (MCG) provides quantitative assessment of the magnetic field (MF) induced by cardiac ionic currents, is more sensitive to tangential currents, and measures vortex currents undetectable by ECG, with higher reported sensitivity of MCG ventricular repolarization (VR) parameters for earlier detection of acute myocardial ischemia. Aims of this study were to validate the feasibility of in‐hospital unshielded MCG and to assess repeatability and reproducibility of quantitative VR parameters, considering also possible gender‐ and age‐related variability.

Methods

MCG of 204 healthy subjects [114 males—mean age 43.4 ± 17.3 and 90 females—mean age 40.2 ± 15.7] was retrospectively analyzed, with a patented proprietary software automatically estimating twelve VR parameters derived from the analysis of the dynamics of the T‐wave MF extrema (five parameters) and from the inverse solution with the effective magnetic dipole model giving the effective magnetic vector components (seven parameters). MCG repeatability was calculated as coefficient of variation (CV) ±standard error of the mean (SEM). Reproducibility was assessed as intraclass correlation coefficient (ICC).

Results

The repeatability of all MCG parameters was 16 ± 1.2 (%) (average CV ± SEM). Optimal (ICC > 0.7) reproducibility was found for 11/12 parameters (mean values) and in 8/12 parameters (single values). No significant gender‐related difference was observed; six parameters showed a strong/moderate correlation with age.

Conclusion

Reliable MCG can be performed into an unshielded hospital ambulatory, with repeatability and reproducibility of quantitative assessment of VR adequate for clinical purposes. Wider clinical use is foreseen with the development of multichannel optical magnetometry.

     

The effect of head‐up tilt upon markers of heart rate variability in patients with atrial fibrillation

Background

Heart rate variability (HRV) analysis is uncommonly undertaken in patients with atrial fibrillation (AF) due to an assumption that ventricular response is random. We sought to determine the effects of head‐up tilt (HUT), a stimulus known to elicit an autonomic response, on HRV in patients with AF; we contrasted the findings with those of patients in sinus rhythm (SR).

Methods

Consecutive, clinically indicated tilt tests were examined for 207 patients: 176 in SR, 31 in AF. Patients in AF were compared to an age‐matched SR cohort (n = 69). Five minute windows immediately before and after tilting were analyzed using time‐domain, frequency‐domain and nonlinear HRV parameters. Continuous, noninvasive assessment of blood pressure, heart rate and stroke volume were available in the majority of patients.

Results

There were significant differences at baseline in all HRV parameters between AF and age matched SR. HUT produced significant hemodynamic changes, regardless of cardiac rhythm. Coincident with these hemodynamic changes, patients in AF had a significant increase in median [quartile 1, 2] DFA‐α2 (+0.14 [?0.03, 0.32], p < .005) and a decrease in sample entropy (?0.17 [?0.50, ?0.01], p < .005).

Conclusion

In the SR cohort, increasing age was associated with fewer HRV changes on tilting. Patients with AF had blunted HRV responses to tilting, mirroring those seen in an age matched SR group. It is feasible to measure HRV in patients with AF and the changes observed on HUT are comparable to those seen in patients in sinus rhythm.

     

Ultra‐short heart rate variability recording reliability: The effect of controlled paced breathing

Background

Recent studies have reported that Heart Rate Variability (HRV) indices remain reliable even during recordings shorter than 5 min, suggesting the ultra‐short recording method as a valuable tool for autonomic assessment. However, the minimum time‐epoch to obtain a reliable record for all HRV domains (time, frequency, and Poincare geometric measures), as well as the effect of respiratory rate on the reliability of these indices remains unknown.

Methods

Twenty volunteers had their HRV recorded in a seated position during spontaneous and controlled respiratory rhythms. HRV intervals with 1, 2, and 3 min were correlated with the gold standard period (6‐min duration) and the mean values of all indices were compared in the two respiratory rhythm conditions.

Results

rMSSD and SD1 were more reliable for recordings with ultra‐short duration at all time intervals (r values from 0.764 to 0.950, p < 0.05) for spontaneous breathing condition, whereas the other indices require longer recording time to obtain reliable values. The controlled breathing rhythm evokes stronger r values for time domain indices (r values from 0.83 to 0.99, p < 0.05 for rMSSD), but impairs the mean values replicability of domains across most time intervals. Although the use of standardized breathing increases the correlations coefficients, all HRV indices showed an increase in mean values (t values from 3.79 to 14.94, p < 0.001) except the RR and HF that presented a decrease (t = 4.14 and 5.96, p < 0.0001).

Conclusion

Our results indicate that proper ultra‐short‐term recording method can provide a quick and reliable source of cardiac autonomic nervous system assessment.

     

Nasal valve evaluation in the Mexican‐Hispanic (mestizo) nose

Background

Our aim in this study was to determine the angle of the internal nasal valve in Mexican patients with the “mestizo nose” feature and without nasal obstructive symptoms. The work was prospective, comparative, and observational in nature and included patients >14 years of age who were seen in the Otolaryngology Department at the Los Angeles Lomas Hospital between April and May 2016.

Methods

The angle of the internal nasal valve was measured in 30 patients without obstructive symptoms. Endoscopic examination was performed with a 0° endoscope framed with tape at a 13‐mm distance from the endoscope's tip, and digital photographs of the internal nasal valve were taken. The measurement of the angle of the internal nasal valve was made in sexagesimal degrees using Golden Ratio v3.1 (2012) software. Statistical analysis was performed using Excel v15.13.3.

Results

The angles of the internal nasal valve of the patients were (mean ± standard deviation) 24.07 ± 4.8° for the right nasal cavity and 25.07 ± 5.0° for the left nasal cavity, wider than the angle reported in the normal Caucasian nose established in the literature.

Conclusions

According to our results, the Mexican‐Hispanic mestizo nose has a wider angle in the internal nasal valve than that considered normal in the literature (10°‐15°). We believe it is necessary to undertake a second study and add an airflow resistance measurement with a rhinomanometry procedure so we can compare the results with those in the Caucasian population.