Data of the COVID-19 mRNA-Vaccine V-Safe Surveillance System and Pregnancy Registry Reveals Poor Embryonic and Second Trimester Fetal Survival Rate. Comment on Stuckelberger et al. SARS-CoV-2 Vaccine Willingness among Pregnant and Breastfeeding Women during the First Pandemic Wave: A Cross-Sectional Study in Switzerland. Viruses 2021, 13, 1199.

Dr. Sarah Stuckelberger and her colleagues should be commended for their cross-sectional study assessing the willingness of Swiss pregnant and breastfeeding women to be vaccinated against SARS-CoV-2 [...].

Study of the time-relationship of the mechano-electrical interaction in an animal model of tetralogy of Fallot: implications for the risk assessment of ventricular arrhythmias.

OBJECTIVES: The long-term outcome of tetralogy of Fallot (TOF) is determined by progressive right ventricular (RV) dysfunction through pulmonary regurgitation (PR) and the risk of malignant arrhythmia. Although mechano-electrical coupling in TOF is well-known, its time effect on the inducibility of arrhythmia remains ill-defined. The goal of this study was to investigate the mechano-electrical properties at different times in animals with chronic PR. METHODS: PR was induced by a transannular patch with limited RV scarring in infant pigs. Haemodynamic assessment included biventricular pressure-volume loops after 3 (n = 8) and 6 months (n = 7) compared to controls (n = 5). The electrophysiological study included endocardial monophasic action potential registration, intraventricular conduction velocity and induction of ventricular arrhythmia by burst pacing. RESULTS: Progressive RV dilation was achieved at 6 months (RV end-diastolic volume 143 ± 13 ml/m2-RV end-systolic volume 96 ± 7 ml/m2; P < 0.001), in association with depressed RV contractility (preload recruitable stroke work-slope: 19 ± 1 and 11 ± 3 Mw.ml-1.s-1 for control and 6 m; P < 0.001) and left ventricular contractility (preload recruitable stroke work-slope: 60 ± 13 and 40 ± 11 Mw.ml-1.s-1 for control and 6 m; P = 0.005). Concomitant to QRS prolongation, monophasic action potential90-duration and dispersion at the RV and left ventricle were increased at 6 months. Intraventricular conduction was delayed only in the RV at 6 months (1.8 ± 0.2 and 2.4 ± 0.6 m/s for group 6M and the control group; P = 0.035). Sustained ventricular arrhythmias were not inducible. CONCLUSIONS: In animals yielding the sequelae of a contemporary operation for TOF, mechano-electrical alterations are progressive and affect predominantly the RV after midterm exposure of PR. Because ventricular arrhythmias were not inducible despite significant RV dilation, the data suggest that the haemodynamic RV deterioration effectively precedes the risk of inducing sustained arrhythmia after TOF repair and opens a window for renewed stratification of contemporary risk factors of ventricular arrhythmias in patients operated on with currently used pulmonary valve- and RV-related techniques.

Progression of incomplete toward complete left bundle branch block: A clinical and electrocardiographic analysis.

BACKGROUND: Complete left bundle branch block (cLBBB) is associated with increased cardiovascular mortality and heart failure. On the contrary, the clinical relevance of incomplete left bundle branch block (iLBBB) is less known. This study investigated the profile and outcome of iLBBB patients and assessed the risk of progression to cLBBB. METHODS: Patients diagnosed with iLBBB between July 2013 and April 2018 were retrospectively included. Subsequently, echo- and electrocardiographic examinations at time of iLBBB diagnosis and during follow-up, as well as progression to non-strict cLBBB and strict cLBBB, were evaluated. RESULTS: The study enrolled 321 patients (33% female, age 74 ± 11 years). During the follow-up of 21 (8;34) months, 33% of iLBBB patients evolved to non-strict cLBBB and 27% to strict cLBBB. iLBBB patients who evolved to non-strict or strict cLBBB were older, had more frequently reduced left ventricular ejection fraction, and had more often QRS notching/slurring in the lateral leads and inferior leads, compared to patients without progression to cLBBB. In multivariate analysis, only QRS notching/slurring in the lateral leads was independently associated with progression to non-strict cLBBB (odds ratio 4.64, p < .001) and strict cLBBB (odds ratio 9.6, p < .001). iLBBB patients with QRS notching/slurring had a progression rate to non-strict cLBBB of 52% and 49% to strict cLBBB. CONCLUSION: Among patients with iLBBB, up to one third of the patients progress to cLBBB within a period of 2 years. The presence of QRS notching/slurring in the lateral leads during iLBBB was the strongest predictor for progression toward cLBBB.

Haemodynamic management of patients with left ventricular assist devices using echocardiography: the essentials.

Mechanical circulatory support with continuous-flow left ventricular assist devices (LVADs) has emerged as a viable treatment modality for patients with advanced heart failure. LVAD support results in unique haemodynamic and echocardiographic alterations that must be understood to provide optimal care for these patients. In this review, we propose essential echocardiographic and haemodynamic elements for the assessment of optimal LVAD function based on the literature and the use of simulation software. A key element of LVAD physiology remains the interaction between an unloaded left ventricle and a loaded right ventricle. The echocardiographic assessment and treatment of the pathophysiology of the right-sided part of the heart remains critical to maintaining optimal LVAD support.

Failure to detect life-threatening arrhythmias in ICDs using single-chamber detection criteria.

BACKGROUND: There are anecdotal reports of sudden death despite a functional implantable cardioverter defibrillator (ICD). We sought to describe scenarios leading to fatal or near-fatal outcome due to inappropriately inhibited ICD therapy in devices programmed with single-chamber detection criteria. METHODS: Programmed settings, episode lists, and intracardiac electrograms from 24 patients with a life-threatening event (n = 12) or fatal outcome (n = 12) related to failed ventricular arrhythmia detection were used to clarify the underlying scenario. RESULTS: Fifty episodes of failed ventricular arrhythmia detection were identified and categorized into six scenarios: (1) spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) with a rate below the detection limits, (2) misclassification of polymorphic VT (PVT) or VF as supraventricular tachycardia (SVT), (3) misclassification of VT/VF as cluster of nonsustained VT episodes, (4) misclassification of monomorphic VT (MVT) as SVT, (5) inappropriate shock abortion, and (6) false termination detection. These scenarios occurred respectively 6, 9, 3, 9, 8, and 15 times. In 9/9 (100%) patients with PVT/VF classified as SVT, rate stability was active for rates ranging from 222 to 250 beats/min. MVT detected as SVT was due to the sudden onset criterion in 7/9 (78%) patients and twice a consequence of the rate stability criterion active for rates ranging from 200 to 250 beats/min. CONCLUSION: We describe six scenarios leading to failure of ventricular arrhythmia detection in a single-chamber detection setting withholding life-saving therapy. These scenarios are more likely to occur with high-rate programming and long detection times, especially if combined with rate stability and sudden onset.

Gender differences in electro-mechanical characteristics of left bundle branch block: Potential implications for selection and response of cardiac resynchronization therapy.

BACKGROUND: Female patients are underrepresented in cardiac resynchronization therapy (CRT) trials, although they show better CRT response compared to males and at shorter QRS durations. We hypothesized that differences in left bundle branch block (LBBB) characteristics and mechanical dyssynchrony might explain this gender disparity. METHODS: Patients presenting with true LBBB-morphology (including mid-QRS notching) on surface electrocardiograms (ECG) were selected. LBBB QRS duration (QRSDLBBB) was measured automatically on the ECG. Left ventricular dimensions were assessed by two-dimensional echocardiography. Mechanical dyssynchrony was assessed by the presence of septal flash (SF) on echocardiography. RESULTS: The study enrolled 1037 patients (428 females). Female LBBB patients had smaller QRSDLBBB compared to male LBBB patients (142 [22]ms versus 156 [24]ms, p<0.001). In a multivariate analysis, sex and left ventricular end-diastolic diameter (LVEDD) were independent predictors of QRSDLBBB. QRSDLBBB can be corrected for sex and LVEDD using a simplified formula: corrected-QRSDLBBB=QRSDLBBB+0.5×(50-LVEDD)-10 (if male). SF was more prevalent in females compared to males (60% versus 43%, p<0.001). Women revealed significantly more SF in narrow QRSDLBBB groups compared to men: 65% versus 13% (p<0.001) with QRSDLBBB 120-129ms, 66% versus 18% (p<0.001) with QRSDLBBB 130-139ms and 63% versus 31% (p<0.001) with QRSDLBBB 140-149ms. At QRSDLBBB>150ms, there were no differences in SF prevalence between females and males. CONCLUSION: Female patients show true LBBB morphology at shorter QRSD and have more frequent mechanical dyssynchrony at shorter QRSD compared to males. This might explain the better CRT response rates at shorter QRSD in females.

Relation between electrical and mechanical dyssynchrony in patients with left bundle branch block: An electro- and vectorcardiographic study.

BACKGROUND: Current guidelines select patients for cardiac resynchronization therapy (CRT) mainly on electrocardiographic parameters like QRS duration and left bundle branch block (LBBB). However, among those LBBB patients, heterogeneity in mechanical dyssynchrony occurs and might be a reason for nonresponse to CRT. This study assesses the relation between electrocardiographic characteristics and presence of mechanical dyssynchrony among LBBB patients. METHODS: The study included patients with true LBBB (including mid-QRS notching) on standard 12-lead electrocardiograms. Left bundle branch block-induced mechanical dyssynchrony was assessed by the presence of septal flash on two-dimensional echocardiography. Previously reported electro- and vectorcardiographic dyssynchrony markers were analyzed: global QRS duration (QRSDLBBB ), left ventricular activation time (QRSDLVAT ), time to intrinsicoid deflection (QRSDID ), and vectorcardiographic QRS areas in the 3D vector loop (QRSA3D ). RESULTS: The study enrolled 545 LBBB patients. Septal flash (SF) is present in 52% of patients presenting with true LBBB. Patients with SF are more frequent female, have less ischemic heart disease and smaller left ventricular dimensions. In multivariate analysis longer QRSDLBBB , QRSDLVAT and larger QRSA3D were independently associated with SF. Of all parameters, QRSA3D has the best accuracy to predict SF, although overall accuracy remains moderate (59% sensitivity, 58% specificity). The predictive value of QRSA3D remained constant in both sexes, irrespective of ischemic heart disease, ejection fraction and even when categorizing for QRSDLBBB . CONCLUSION: In LBBB patients, large QRS areas correlate better with mechanical dyssynchrony compared to wide QRSD intervals. However, the overall accuracy to predict mechanical dyssynchrony by electrocardiographic dyssynchrony markers, even when using complex vectorcardiographic parameters, remains low.

Accuracy of computer-calculated and manual QRS duration assessments: Clinical implications to select candidates for cardiac resynchronization therapy.

BACKGROUND: QRS duration (QRSD) plays a key role in the field of cardiac resynchronization therapy (CRT). Computer-calculated QRSD assessments are widely used, however inter-manufacturer differences have not been investigated in CRT candidates. METHODS: QRSD was assessed in 377 digitally stored ECGs: 139 narrow QRS, 140 LBBB and 98 ventricular paced ECGs. Manual QRSD was measured as global QRSD, using digital calipers, by two independent observers. Computer-calculated QRSD was assessed by Marquette 12SL (GE Healthcare, Waukesha, WI, USA) and SEMA3 (Schiller, Baar, Switzerland). RESULTS: Inter-manufacturer differences of computer-calculated QRSD assessments vary among different QRS morphologies: narrow QRSD: 4 [2-9] ms (median [IQR]), p=0.010; LBBB QRSD: 7 [2-10] ms, p=0.003 and paced QRSD: 13 [6-18] ms, p=0.007. Interobserver differences of manual QRSD assessments measured: narrow QRSD: 4 [2-6] ms, p=non-significant; LBBB QRSD: 6 [3-12] ms, p=0.006; paced QRSD: 8 [4-18] ms, p=0.001. In LBBB ECGs, intraclass correlation coefficients (ICCs) were comparable for inter-manufacturer and interobserver agreement (ICC 0.830 versus 0.837). When assessing paced QRSD, manual measurements showed higher ICC compared to inter-manufacturer agreement (ICC 0.902 versus 0.776). Using guideline cutoffs of 130ms, up to 15% of the LBBB ECGs would be misclassified as <130ms or ≥130ms by at least one method. Using a cutoff of 150ms, this number increases to 33% of ECGs being misclassified. However, by combining LBBB-morphology and QRSD, the number of misclassified ECGs can be decreased by half. CONCLUSION: Inter-manufacturer differences in computer-calculated QRSD assessments are significant and may compromise adequate selection of individual CRT candidates when using QRSD as sole parameter. Paced QRSD should preferentially be assessed by manual QRSD measurements.

The electrocardiographic characteristics of septal flash in patients with left bundle branch block.

AIMS: In patients with systolic heart failure and left bundle branch block (LBBB), septal flash (SF) movement has been described by echocardiography. We evaluated the prevalence of SF in LBBB and non-LBBB patients and evaluated whether specific electrocardiographic (ECG) characteristics within LBBB are associated with the presence of SF on echocardiography. METHODS AND RESULTS: One hundred and four patients with probable LBBB on standard 12-lead ECG were selected, 40 patients with non-LBBB served as controls. Left bundle branch block and non-LBBB were defined, according to the most recent guidelines. The presence of SF was assessed by echocardiography. Strict LBBB criteria were met in 93.3% of the patients. Septal flash was present in 45.2% of LBBB patients and was not present in non-LBBB patients. This was more prevalent in patients without anterior ischaemic cardiomyopathy (ICMP) compared with those with anterior ICMP (P = 0.008). The duration of QRS was longer in SF patients compared with that of non-SF patients (P < 0.05). The presence of a mid-QRS notching in more than two consecutive leads was a good predictor for the presence of SF (P = 0.01), and when combined with an absent R-wave in lead V1, the presence of SF is very likely (P = 0.001). CONCLUSION: Our data show that SF is present in 45.2% of LBBB patients, whereas it was absent in patients with non-LBBB. Patients with SF fulfilled more LBBB criteria compared with LBBB patients without SF. Our findings raise the provocative question of whether the presence of SF identifies patients with 'true LBBB' and whether this echocardiographic finding might be considered as a selection parameter in cardiac resynchronization therapy.

Biventricular Paced QRS Area Predicts Acute Hemodynamic CRT Response Better Than QRS Duration or QRS Amplitudes.

INTRODUCTION: Vectorcardiographic (VCG) QRS area of left bundle branch block (LBBB) predicts acute hemodynamic response in cardiac resynchronization therapy (CRT) patients. We hypothesized that changes in QRS area occurring with biventricular pacing (BV) might predict acute hemodynamic CRT response (AHR). METHODS AND RESULTS: VCGs of 624 BV paced electrocardiograms (25 LBBB patients with 35 different pacing configurations) were calculated according to Frank's orthogonal lead system. Maximum QRS vector amplitudes (XAmpl , YAmpl , ZAmpl , and 3DAmp ) and QRS areas (XArea , YArea , ZArea , and 3DArea ) in the orthogonal leads (X, Y, and Z) and in 3-dimensional projection were measured. Volume of the 3D vector loop and global QRS duration (QRSD) on the surface electrocardiogram were assessed. Differences (Δ) in VCG parameters between BV paced and LBBB QRS complexes were calculated. An increase of 10% in dP/dt max was considered as AHR. LBBB conduction is characterized by a large ZArea (109 µVs, interquartile range [IQR]:75;135), significantly larger than XArea (22 µVs, IQR:10;57) and YArea (44 µVs, IQR:32;62, P < 0.001). Overall, QRS duration, amplitudes, and areas decrease significantly with BV pacing (P < 0.001). Of all VCG parameters, 3DAmpl , Δ3DAmpl , ZArea, ΔZArea , Δ3DArea , and ΔQRSD differentiate AHR response from nonresponse (P < 0.05). ΔZArea predicted best positive AHR (area under the curve = 0.813) and outperformed any other VCG parameter or QRSD measurement. CONCLUSION: Of all VCG parameters, reduction in QRS area, calculated in Frank's Z lead, predicts acute hemodynamic response best. This method might be an easy, noninvasive tool to guide CRT implantation and optimization.

Different Methods to Measure QRS Duration in CRT Patients: Impact on the Predictive Value of QRS Duration Parameters.

BACKGROUND: Measurements of QRS duration (QRSD) in patients undergoing cardiac resynchronization therapy (CRT) are not standardized. We hypothesized that both the measurement of QRSD and its predictive value on CRT response are sensitive to the method by which QRSD is measured. METHODS: Electrocardiograms (ECGs) pre- and post-CRT from 52 CRT patients (66 ± 12 years, 65% male) were retrospectively analyzed. Custom-made software was developed to measure global QRSD (QRSDglobal ) and lead-specific QRSD (QRSDI,II,III,aVR,aVL,aVF,V1,V2,V3,V4,V5,V6 ). QRSD was also assessed automatic by a routinely used ECG device. For each method we measured QRSD pre- and post-CRT and shortening of QRSD (∆QRSD). Response to CRT at 6 months was defined as an improvement of ≥1 class in New York Heart Association classification and an increase by >7.5% in left ventricular ejection fraction. RESULTS: The CRT response rate was 77% (n = 40). Different methods to measure QRSD show divergent nominal values before (median range 152-172 ms, P < 0.001) and after CRT (130-152 ms, P < 0.001). The predictive value of QRSD measurements for CRT response also varies significantly according to the method used (range AUC pre-CRT QRSD 0.400-0.580, P < 0.05; AUC post-CRT QRSD 0.447-0.768, P < 0.05; AUC ΔQRSD 0.540-0.858, P < 0.05). Global QRSD measurements revealed lower variability compared to lead-specific QRSD. CONCLUSION: Different methods to measure QRSD yield not only different nominal values but also influence the value of QRSD in predicting CRT response. Measuring QRSD by a global method can help to standardize QRSD measurements in future studies.

Diagnostic accuracy of a novel method for detection of acute transmural myocardial ischemia based upon a self-applicable 3-lead configuration.

BACKGROUND: Delayed medical attendance is a leading cause of death in patients with ST elevation myocardial infarction (STEMI). METHODS: We aimed to introduce, develop, and validate a novel method (RELF method) for detection of transmural ischemia based on a new and easy-to-use 3-lead configuration and orthonormalization of ST reference vectors (STDVN). The study included 60 patients undergoing coronary artery occlusion (CAO) during balloon inflation and 30 healthy subjects. RESULTS: STDVN was significantly different and an optimal discriminator between CAO patients and healthy subjects (respectively 8.00±4.50 vs. 1.90±0.86 normalized units, p<0.001). Compared to the 12-lead ECG, the RELF method was sensitive (90 vs. 73%, p=0.13) and more specific (91 vs. 75%, p<0.001). CONCLUSIONS: The RELF method is highly accurate for early detection of acute occlusion related ischemia and it outperforms the conventional 12-lead ECG criteria for STEMI. This method provides a platform for self-detection of CAO with handheld devices or smart phones.

Alternans of the Ventricular Electrogram in Patients with an Implanted Cardioverter-Defibrillator.

BACKGROUND: The occurrence and significance of alternans of the ventricular electrogram (VEGM) in patients with an implanted cardioverter-defibrillator (ICD) has been rarely reported. OBJECTIVES AND METHODS: This report describes our observations of VEGM alternans documented in nine patients with an ICD (seven new cases and two previously published cases for comparison). RESULTS: We found seven new cases of near-field VEGM alternans and added two of our previously reported examples. Catecholaminergic polymorphic ventricular tachycardia (CPVT) was diagnosed in one patient based on ICD recordings. Alternans occurred during ventricular tachycardia (VT) in eight patients. A fast sinus tachycardia could not be ruled out in one patient. Stable cycle length alternans was found in five patients. QRS alternans of the left ventricular (LV) electrogram (EGM) was recorded in all five patients who had a device for cardiac resynchronization therapy capable of sensing by the LV channel. These five cases exhibited corresponding alternans of the right ventricular (RV) EGM in three cases, none in one patient, and a questionable recording in another. Alternans of the far-field (FF) VEGM occurred simultaneously with RV EGM alternans in all four patients whose device provided an FF tracing. CONCLUSION: Ventricular alternans may be more common than realized in ICD patients with VT. The correlation of VEGM alternans with the surface electrocardiogram remains unknown. Although QRS alternans itself as an electrical pattern is generally benign, its cause may not be, as illustrated in our patient with CPVT. Furthermore, associated cycle length alternans or undersensing of the smaller alternans component may complicate ICD therapy.

Variability in interpretation of the electrocardiogram in young athletes: an unrecognized obstacle for electrocardiogram-based screening protocols.

AIMS: To assess in young athletes (i) the variability in the percentage of abnormal electrocardiograms (ECGs) using different criteria and (ii) the variability in ECG interpretation among cardiologists and sport physicians. METHODS AND RESULTS: Electrocardiograms of 138 athletes were categorized by seven cardiologists according to the original European Society of Cardiology (ESC) criteria by Corrado (C), subsequently modified by Uberoi (U), Marek (M), and the Seattle criteria (S); seven sports physicians only used S criteria. The percentage of abnormal ECGs for each physician was calculated and the percentage of complete agreement was assessed. For cardiologists, the median percentage of abnormal ECGs was 14% [interquartile range (IQR) 12.5-20%] for C, 11% (IQR 9.5-12.5%) for U [not significant (NS) compared with C], 11% (IQR 10-13%) for M (NS compared with C), and 7% (IQR 5-8%) for S (P < 0.005 compared with C); complete agreement in interpretation was 64.5% for C, 76% for U (P < 0.05 compared with C), 74% for M (NS compared with C), and 84% for S (P < 0.0005 compared with C). Sport physicians classified a median of 7% (IQR 7-11%) of ECGs as abnormal by S (P = NS compared with cardiologists using S); complete agreement was 72% (P < 0.05 compared with cardiologists using S). CONCLUSION: Seattle criteria reduced the number of abnormal ECGs in athletes and increased agreement in classification. However, variability in ECG interpretation by cardiologists and sport physicians remains high and is a limitation for ECG-based screening programs.