Serial Cardiac Magnetic Resonance Imaging in Patients with Mitral Valve Prolapse-A Single-Center Retrospective Registry.

Background: Mitral valve prolapse (MVP) and mitral annular disjunction (MAD) are common valvular abnormalities that have been associated with ventricular arrhythmias (VA). Cardiac magnetic resonance imaging (CMR) has a key role in risk stratification of VA, including assessment of late gadolinium enhancement (LGE). Methods: Single-center retrospective analysis of patients with MVP or MAD who had >1 CMR and >1 24 h Holter registration available. Data are presented in detail, including evolution of VA and presence of LGE over time. Results: A total of twelve patients had repeated CMR and Holter registrations available, of which in four (33%) patients, it was conducted before and after minimal invasive mitral valve repair (MVR). After a median of 4.7 years, four out of eight (50%) patients without surgical intervention had new areas of LGE. New LGE was observed in the papillary muscles and the mid to basal inferolateral wall. In four patients, presenting with syncope or high-risk non-sustained ventricular tachycardia (VT), programmed ventricular stimulation was performed and in two (50%), sustained monomorphic VT was easily inducible. In two patients who underwent MVR, new LGE was observed in the basal inferolateral wall of which one presented with an increased burden of VA. Conclusions: In patients with MVP and MAD, repeat CMR may show new LGE in a small subset of patients, even shortly after MVR. A subgroup of patients who presented with an increase in VA burden showed new LGE upon repeat CMR. VA in patients with MVP and MAD are part of a heterogeneous spectrum that requires further investigation to establish risk stratification strategies.

Landmark Evolutions in Time and Indication for Cardiac Resynchronization Therapy: Results from a Multicenter Retrospective Registry.

Background: Cardiac resynchronization therapy (CRT) has evolved into an established therapy for patients with chronic heart failure and a wide QRS complex. Data on long-term outcomes over time are scarce and the criteria for implantation remain a subject of investigation. Methods: An international, multicenter, retrospective registry includes 2275 patients who received CRT between 30 November 2000 and 31 December 2019, with a mean follow-up of 3.6 ± 2.7 years. Four time periods were defined, based on landmark trials and guidelines. The combined endpoint was a composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Results: The composite endpoint occurred in 656 patients (29.2%). The mean annual implantation rate tripled from 31.5 ± 17.4/year in the first period to 107.4 ± 62.4/year in the last period. In the adjusted Cox regression analysis, the hazard ratio for the composite endpoint was not statistically different between time periods. When compared to sinus rhythm with left bundle branch block (LBBB), a non-LBBB conduction pattern (sinus rhythm: HR 1.51, 95% CI 1.12-2.03; atrial fibrillation: HR 2.08, 95% CI 1.30-3.33) and a QRS duration below 130 ms (HR 1.64, 95% CI 1.29-2.09) were associated with a higher hazard ratio. Conclusions: Despite innovations, an adjusted regression analysis revealed stable overall survival over time, which can at least partially be explained by a shift in patient characteristics.

Investigating the Cost-Effectiveness of Telemonitoring Patients With Cardiac Implantable Electronic Devices: Systematic Review.

BACKGROUND: Telemonitoring patients with cardiac implantable electronic devices (CIEDs) can improve their care management. However, the results of cost-effectiveness studies are heterogeneous. Therefore, it is still a matter of debate whether telemonitoring is worth the investment. OBJECTIVE: This systematic review aims to investigate the cost-effectiveness of telemonitoring patients with CIEDs, focusing on its key drivers, and the impact of the varying perspectives. METHODS: A systematic review was performed in PubMed, Web of Science, Embase, and EconLit. The search was completed on July 7, 2022. Studies were included if they fulfilled the following criteria: patients had a CIED, comparison with standard care, and inclusion of health economic evaluations (eg, cost-effectiveness analyses and cost-utility analyses). Only complete and peer-reviewed studies were included, and no year limits were applied. The exclusion criteria included studies with partial economic evaluations, systematic reviews or reports, and studies without standard care as a control group. Besides general study characteristics, the following outcome measures were extracted: impact on total cost or income, cost or income drivers, cost or income drivers per patient, cost or income drivers as a percentage of the total cost impact, incremental cost-effectiveness ratios, or cost-utility ratios. Quality was assessed using the Consensus Health Economic Criteria checklist. RESULTS: Overall, 15 cost-effectiveness analyses were included. All studies were performed in Western countries, mainly Europe, and had primarily a male participant population. Of the 15 studies, 3 (20%) calculated the incremental cost-effectiveness ratio, 1 (7%) the cost-utility ratio, and 11 (73%) the health and cost impact of telemonitoring. In total, 73% (11/15) of the studies indicated that telemonitoring of patients with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy ICDs was cost-effective and cost-saving, both from a health care and patient perspective. Cost-effectiveness results for telemonitoring of patients with pacemakers were inconclusive. The key drivers for cost reduction from a health care perspective were hospitalizations and scheduled in-office visits. Hospitalization costs were reduced by up to US $912 per patient per year. Scheduled in-office visits included up to 61% of the total cost reduction. Key drivers for cost reduction from a patient perspective were loss of income, cost for scheduled in-office visits and transport. Finally, of the 15 studies, 8 (52%) reported improved quality of life, with statistically significance in only 1 (13%) study (P=.03). CONCLUSIONS: From a health care and patient perspective, telemonitoring of patients with an ICD or a cardiac resynchronization therapy ICD is a cost-effective and cost-saving alternative to standard care. Inconclusive results were found for patients with pacemakers. However, telemonitoring can lead to a decrease in providers' income, mainly due to a lack of reimbursement. Introducing appropriate reimbursement could make telemonitoring sustainable for providers while still being cost-effective from a health care payer perspective. TRIAL REGISTRATION: PROSPERO CRD42022322334; https://tinyurl.com/puunapdr.

Case report: accidental finding of mobile pacemaker lead structures.

We present a case of a 79-year-old man on apixaban for atrial fibrillation who suffered multiple ischaemic strokes and was found to have mobile structures attached to his pacemaker lead on transesophageal echocardiography. Based on the Modified Duke Criteria, there was no evidence of infectious endocarditis. Since there were no signs of a patent foramen ovale or arteriovenous malformations in the lungs, the mobile structures probably were not the cause of the ischaemic strokes. After the visualisation of the mobile structures, apixaban was switched to dabigatran with a clear decrease in the size of the structures. Blood cultures remained negative and there was no fever or increase in inflammatory parameters. It was therefore suspected that the structures were thrombus material rather than vegetations of infectious endocarditis.There is uncertainty surrounding the clinical relevance and indication for treatment of incidentally found mobile structures on pacemaker leads. Multiple studies with different imaging modalities show a significant difference in the prevalence of thrombi. More studies with longer follow-ups are needed to investigate the prevalence and need for treatment of these incidentally found structures on pacemaker leads.

Artificial intelligence electrocardiogram as a novel screening tool to detect a newly abnormal left ventricular ejection fraction after anthracycline-based cancer therapy.

AIMS: Cardiotoxicity is a serious side effect of anthracycline treatment, most commonly manifesting as a reduction in left ventricular ejection fraction (EF). Early recognition and treatment have been advocated, but robust, convenient, and cost-effective alternatives to cardiac imaging are missing. Recent developments in artificial intelligence (AI) techniques applied to electrocardiograms (ECGs) may fill this gap, but no study so far has demonstrated its merit for the detection of an abnormal EF after anthracycline therapy. METHODS AND RESULTS: Single centre consecutive cohort study of all breast cancer patients with ECG and transthoracic echocardiography (TTE) evaluation before and after (neo)adjuvant anthracycline chemotherapy. Patients with HER2-directed therapy, metastatic disease, second primary malignancy, or pre-existing cardiovascular disease were excluded from the analyses as were patients with EF decline for reasons other than anthracycline-induced cardiotoxicity. Primary readout was the diagnostic performance of AI-ECG by area under the curve (AUC) for EFs < 50%. Of 989 consecutive female breast cancer patients, 22 developed a decline in EF attributed to anthracycline therapy over a follow-up time of 9.8 ± 4.2 years. After exclusion of patients who did not have ECGs within 90 days of a TTE, 20 cases and 683 controls remained. The AI-ECG model detected an EF < 50% and ≤ 35% after anthracycline therapy with an AUC of 0.93 and 0.94, respectively. CONCLUSION: These data support the use of AI-ECG for cardiotoxicity screening after anthracycline-based chemotherapy. This technology could serve as a gatekeeper to more costly cardiac imaging and could enable patients to monitor themselves over long periods of time.

Artificial intelligence electrocardiogram can be used to screen for an abnormal heart function after anthracycline chemotherapy, opening the door to new ways of cost-effective screening of cancer survivors at risk of cardiotoxicity over long periods of time.

QRS complex and T wave planarity for the efficacy prediction of automatic implantable defibrillators.

OBJECTIVE: To test the hypothesis that in recipients of primary prophylactic implantable cardioverter-defibrillators (ICDs), the non-planarity of ECG vector loops predicts (a) deaths despite ICD protection and (b) appropriate ICD shocks. METHODS: Digital pre-implant ECGs were collected in 1948 ICD recipients: 21.4% females, median age 65 years, 61.5% ischaemic heart disease (IHD). QRS and T wave three-dimensional loops were constructed using singular value decomposition that allowed to measure the vector loop planarity. The non-planarity, that is, the twist of the three-dimensional loops out of a single plane, was related to all-cause mortality (n=294; 15.3% females; 68.7% IHD) and appropriate ICD shocks (n=162; 10.5% females; 87.7% IHD) during 5-year follow-up after device implantation. Using multivariable Cox regression, the predictive power of QRS and T wave non-planarity was compared with that of age, heart rate, left ventricular ejection fraction, QRS duration, spatial QRS-T angle, QTc interval and T-peak to T-end interval. RESULTS: QRS non-planarity was significantly (p<0.001) associated with follow-up deaths despite ICD protection with HR of 1.339 (95% CI 1.165 to 1.540) but was only univariably associated with appropriate ICD shocks. Non-planarity of the T wave loop was the only ECG-derived index significantly (p<0.001) associated with appropriate ICD shocks with multivariable Cox regression HR of 1.364 (1.180 to 1.576) but was not associated with follow-up mortality. CONCLUSIONS: The analysed data suggest that QRS and T wave non-planarity might offer distinction between patients who are at greater risk of death despite ICD protection and those who are likely to use the defibrillator protection.

Long-term outcome after upgrade to cardiac resynchronization therapy: A propensity score-matched analysis.

AIM: Cardiac resynchronization therapy (CRT) is a cornerstone in the management of chronic heart failure in patients with a broad or paced QRS. However, data on long-term outcome after upgrade to CRT are scarce. METHODS AND RESULTS: This international, multicentre retrospective registry included 2275 patients who underwent a de novo or upgrade CRT implantation with a mean follow-up of 3.6 ± 2.7 years. The primary composite endpoint included all-cause mortality, heart transplantation, or ventricular assist device implantation. The secondary endpoint was first heart failure admission. Multivariable Cox regression and propensity score matching (PSM) analyses were performed. Patients who underwent CRT upgrade (n = 605, 26.6%) were less likely female (19.7% vs. 28.8%, p < 0.001), more often had ischeemic cardiomyopathy (49.8% vs. 40.2%, p < 0.001), and had worse renal function (median estimated glomerular filtration rate 50.3 ml/min/1.73 m2 [35.8-69.5] vs. 59.9 ml/min/1.73 m2 [43.0-76.5], p < 0.001). The incidence rate of the composite endpoint was 10.8%/year after CRT upgrade versus 7.1%/year for de novo implantations (p < 0.001). PSM for the primary endpoint resulted in 488 pairs. After propensity score matching, upgrade to CRT was associated with a higher chance to reach the composite endpoint (multivariable hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.08-1.70), for both upgrade from pacemaker (multivariable HR 1.33, 95% CI 1.03-1.70) and implantable cardioverter-defibrillator (ICD) (multivariable HR 1.40, 95% CI 1.01-1.95). PSM for the secondary endpoint resulted in 277 pairs. After PSM, upgrade to CRT was associated with a higher chance for heart failure admission (HR 1.74, 95% CI 1.26-2.41). CONCLUSION: In this retrospective analysis, the outcome of patients who underwent upgrades to CRT differed significantly from patients who underwent de novo CRT implantation, particularly for upgrades from ICD. Importantly, this difference in outcome does not imply a causal relation between therapy and outcome but rather a difference between two different patient populations.

Pheochromocytoma leading to Takotsubo and Ogilvie syndrome, a pathophysiological triad.

Takotsubo syndrome (TTS) is a transient left ventricle dysfunction usually caused by a stressful trigger (emotional or physical). We report the case of a 77 year-old female patient who presented with TTS caused by a pheochromocytoma, a catecholamine-producing neuroendocrine tumour. Diagnosis was facilitated by acute kidney injury prompting renal ultrasound, recurrence of TTS and symptoms of episodic palpitations, profuse sweating and labile blood pressure. Furthermore, during her hospitalisation the patient also developed an Ogilvie syndrome, an acute colonic pseudo-obstruction, due to the catecholamine-excess. Treatment consisted of betablocker and angiotensin-converting enzyme inhibitor for TTS, neostigmine for Ogilvie syndrome, in combination with alpha-blocker and surgical removal of the tumour after recuperation of left ventricular function and colonic pseudo-obstruction. To our knowledge, this is the first case report of the pathophysiological triad of pheochromocytoma leading to Takotsubo and Ogilvie syndrome in a single patient.

Reduced Ejection Fraction in Elite Endurance Athletes: Clinical and Genetic Overlap With Dilated Cardiomyopathy.

BACKGROUND: Exercise-induced cardiac remodeling can be profound, resulting in clinical overlap with dilated cardiomyopathy, yet the significance of reduced ejection fraction (EF) in athletes is unclear. The aim is to assess the prevalence, clinical consequences, and genetic predisposition of reduced EF in athletes. METHODS: Young endurance athletes were recruited from elite training programs and underwent comprehensive cardiac phenotyping and genetic testing. Those with reduced EF using cardiac magnetic resonance imaging (defined as left ventricular EF <50%, or right ventricular EF <45%, or both) were compared with athletes with normal EF. A validated polygenic risk score for indexed left ventricular end-systolic volume (LVESVi-PRS), previously associated with dilated cardiomyopathy, was assessed. Clinical events were recorded over a mean of 4.4 years. RESULTS: Of the 281 elite endurance athletes (22±8 years, 79.7% male) undergoing comprehensive assessment, 44 of 281 (15.7%) had reduced left ventricular EF (N=12; 4.3%), right ventricular EF (N=14; 5.0%), or both (N=18; 6.4%). Reduced EF was associated with a higher burden of ventricular premature beats (13.6% versus 3.8% with >100 ventricular premature beats/24 h; P=0.008) and lower left ventricular global longitudinal strain (-17%±2% versus -19%±2%; P<0.001). Athletes with reduced EF had a higher mean LVESVi-PRS (0.57±0.13 versus 0.51±0.14; P=0.009) with athletes in the top decile of LVESVi-PRS having an 11-fold increase in the likelihood of reduced EF compared with those in the bottom decile (P=0.034). Male sex and higher LVESVi-PRS were the only significant predictors of reduced EF in a multivariate analysis that included age and fitness. During follow-up, no athletes developed symptomatic heart failure or arrhythmias. Two athletes died, 1 from trauma and 1 from sudden cardiac death, the latter having a reduced right ventricular EF and a LVESVi-PRS >95%. CONCLUSIONS: Reduced EF occurs in approximately 1 in 6 elite endurance athletes and is related to genetic predisposition in addition to exercise training. Genetic and imaging markers may help identify endurance athletes in whom scrutiny about long-term clinical outcomes may be appropriate. REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374976&isReview=true; Unique identifier: ACTRN12618000716268.

Evolution of ventricular and valve function in patients with right ventricular pacing - A randomized controlled trial comparing leadless and conventional pacing.

BACKGROUND: Leadless pacemakers (PMs) were recently introduced to overcome lead-related complications. They showed high safety and efficacy profiles. Prospective studies assessing long-term safety on cardiac structures are still missing. OBJECTIVE: The purpose of this study was to compare the mechanical impact of Micra with conventional PM on heart function. METHODS: We conducted a non-inferiority trial in patients with an indication for single chamber ventricular pacing. Patients were 1:1 randomized to undergo implantation of either Micra or conventional monochamber ventricular pacemaker (PM). Patients underwent echocardiography at baseline, 6 and 12 months after implantation. Analysis included left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and valve function. N-terminal-pro hormone B-type natriuretic peptide (NT-pro-BNP) levels were measured at baseline and 12 months. RESULTS: Fifty-one patients (27 in Micra group and 24 in conventional group) were included. Baseline characteristics were similar for both groups. At 12 months, (1) the left ventricular function as assessed by LVEF and GLS worsened similarly in both groups (∆LVEF -10 ± 7.3% and ∆GLS +5.7 ± 6.4 in Micra group vs. -13.4 ± 9.9% and +5.2 ± 3.2 in conventional group) (p = 0.218 and 0.778, respectively), (2) the severity of tricuspid valve regurgitation was significantly lower with Micra than conventional pacing (p = 0.009) and (3) median NT-pro-BNP was lower in Micra group (970 pg/dL in Micra group versus 1394 pg/dL in conventional group, p = 0.041). CONCLUSION: Micra is non inferior to conventional PMs concerning the evolution of left ventricular function at 12-month follow-up. Our data suggest that Micra has a comparable mechanical impact on the ventricular systolic function but resulted in less valvular dysfunction.

Mechanical Dyssynchrony Combined with Septal Scarring Reliably Identifies Responders to Cardiac Resynchronization Therapy.

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74-0.88) and 0.86 (95%CI: 0.79-0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12-0.67) to 0.20 (95%CI: 0.08-0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine.

Effectiveness of the risk stratification proposed by the 2022 European Heart Rhythm Association Expert Consensus statement on arrhythmic mitral valve prolapse.

BACKGROUND: Recently, an expert consensus statement proposed indications where implantation of a primary prevention implantable cardioverter-defibrillator (ICD) may be reasonable in patients with mitral valve prolapse (MVP). The objective was to evaluate the proposed risk stratification by the expert consensus statement. METHODS: Consecutive patients with MVP without alternative arrhythmic substrates with cardiac magnetic resonance imaging (CMR) were included in a single-center retrospective registry. Arrhythmic MVP (AMVP) was defined as a total premature ventricular complex burden ≥5%, non-sustained ventricular tachycardia (VT), VT, or ventricular fibrillation. The end point was a composite of SCD, VT, inducible VT, and appropriate ICD shocks. RESULTS: In total, 169 patients (52.1% male, median age 51.4 years) were included and 99 (58.6%) were classified as AMVP. Multivariate logistic regression identified the presence of late gadolinium enhancement (OR 2.82, 95%CI 1.45-5.50) and mitral annular disjunction (OR 1.98, 95%CI 1.02-3.86) as only predictors of AMVP. According to the EHRA risk stratification, 5 patients with AMVP (5.1%) had a secondary prevention ICD indication, while in 69 patients (69.7%) the implantation of an ICD may be reasonable. During a median follow-up of 8.0 years (IQR 5.0-15.6), the incidence rate for the composite arrhythmic end point was 0.3%/year (95%CI 0.1-0.8). CONCLUSION: More than half of MVP patients referred for CMR met the AMVP diagnostic criteria. Despite low long-term event rates, in 70% of patients with AMVP the implantation of an ICD may be reasonable. Risk stratification of SCD in MVP remains an important knowledge gap and requires urgent investigation.

Electric Field-Based Spatial Analysis of Noncontact Unipolar Electrograms to Map Regional Activation-Repolarization Intervals.

BACKGROUND: Spatial heterogeneity in repolarization plays an important role in generating and sustaining cardiac arrhythmias. Reliable determination of repolarization times remains challenging. OBJECTIVES: The goal of this study was to improve processing of densely sampled noncontact unipolar electrograms to yield reliable high-resolution activation and repolarization maps. METHODS: Endocardial noncontact unipolar electrograms were both simulated and recorded in pig left ventricle. Electrical activity on the endocardial surface was processed in terms of a pseudo-electric field. Activation and repolarization times were calculated by using an amplitude-weighted average on QRS and T waves (ie, the E-field method). This was compared vs the conventional Wyatt method on unipolar electrograms. Timing maps were validated against timing on endocardial action potentials in a simulation study. In vivo, activation and repolarization times determined by using this alternative E-field method were validated against simultaneously recorded endocardial monophasic action potentials (MAPs). RESULTS: Simulation showed that the E-field method provides viable measurements of local endocardial action potential activation and repolarization times. In vivo, correlation of E-field activation times with MAP activation times (rE = 0.76; P < 0.001) was similar to those of Wyatt (rWyatt = 0.80, P < 0.001; P[h1:rE > rWyatt] = 0.82); for repolarization times, correlation improved significantly (rE = 0.96, P < 0.001; rWyatt = 0.82, P < 0.001; P[h1:rE > rWyatt] < 0.00001). This resulted in improved correlations of activation-repolarization intervals to endocardial action potential duration on MAP (rE = 0.96, P < 0.001; rWyatt = 0.86, P < 0.001; P[h1:rE > rWyatt] < 0.00001). Spatial beat-to-beat variation of repolarization could only be calculated by using the E-field methodology and correlated well with the MAP beat-to-beat variation of repolarization (rE = 0.76; P = 0.001). CONCLUSIONS: The E-field method substantially enhances information from endocardial noncontact electrogram data, allowing for dense maps of activation and repolarization times and derived parameters.

Exercise-induced myocardial T1 increase and right ventricular dysfunction in recreational cyclists: a CMR study.

PURPOSE: Although cardiac troponin I (cTnI) increase following strenuous exercise has been observed, the development of exercise-induced myocardial edema remains unclear. Cardiac magnetic resonance (CMR) native T1/T2 mapping is sensitive to the pathological increase of myocardial water content. Therefore, we evaluated exercise-induced acute myocardial changes in recreational cyclists by incorporating biomarkers, echocardiography and CMR. METHODS: Nineteen male recreational participants (age: 48 ± 5 years) cycled the 'L'étape du tour de France" (EDT) 2021' (175 km, 3600 altimeters). One week before the race, a maximal graded cycling test was conducted to determine individual heart rate (HR) training zones. One day before and 3-6 h post-exercise 3 T CMR and echocardiography were performed to assess myocardial native T1/T2 relaxation times and cardiac function, and blood samples were collected. All participants were asked to cycle 2 h around their anaerobic gas exchange threshold (HR zone 4). RESULTS: Eighteen participants completed the EDT stage in 537 ± 58 min, including 154 ± 61 min of cycling time in HR zone 4. Post-race right ventricular (RV) dysfunction with reduced strain and increased volumes (p < 0.05) and borderline significant left ventricular global longitudinal strain reduction (p = 0.05) were observed. Post-exercise cTnI (0.75 ± 5.1 ng/l to 69.9 ± 41.6 ng/l; p < 0.001) and T1 relaxation times (1133 ± 48 ms to 1182 ± 46 ms, p < 0.001) increased significantly with no significant change in T2 (p = 0.474). cTnI release correlated with increase in T1 relaxation time (p = 0.002; r = 0.703), post-race RV dysfunction (p < 0.05; r = 0.562) and longer cycling in HR zone 4 (p < 0.05; r = 0.607). CONCLUSION: Strenuous exercise causes early post-race cTnI increase, increased T1 relaxation time and RV dysfunction in recreational cyclists, which showed interdependent correlation. The long-term clinical significance of these changes needs further investigation. TRIAL REGISTRATION NUMBERS AND DATE: NCT04940650 06/18/2021. NCT05138003 06/18/2021.

A unified framework for multi-lead ECG characterization using Laplacian Eigenmaps.

Background.The analysis of multi-lead electrocardiographic (ECG) signals requires integrating the information derived from each lead to reach clinically relevant conclusions. This analysis could benefit from data-driven methods compacting the information in those leads into lower-dimensional representations (i.e. 2 or 3 dimensions instead of 12).Objective.We propose Laplacian Eigenmaps (LE) to create a unified framework where ECGs from different subjects can be compared and their abnormalities are enhanced.Approach.We conceive a normal reference ECG space based on LE, calculated using signals of healthy subjects in sinus rhythm. Signals from new subjects can be mapped onto this reference space creating a loop per heartbeat that captures ECG abnormalities. A set of parameters, based on distance metrics and on the shape of loops, are proposed to quantify the differences between subjects.Main results.This methodology was applied to find structural and arrhythmogenic changes in the ECG. The LE framework consistently captured the characteristics of healthy ECGs, confirming that normal signals behaved similarly in the LE space. Significant differences between normal signals, and those from patients with ischemic heart disease or dilated cardiomyopathy were detected. In contrast, LE biomarkers did not identify differences between patients with cardiomyopathy and a history of ventricular arrhythmia and their matched controls.Significance.This LE unified framework offers a new representation of multi-lead signals, reducing dimensionality while enhancing imperceptible abnormalities and enabling the comparison of signals of different subjects.

Regional beat-to-beat variability of repolarization increases during ischemia and predicts imminent arrhythmias in a pig model of myocardial infarction.

Ventricular arrhythmia (VT/VF) can complicate acute myocardial ischemia (AMI). Regional instability of repolarization during AMI contributes to the substrate for VT/VF. Beat-to-beat variability of repolarization (BVR), a measure of repolarization lability increases during AMI. We hypothesized that its surge precedes VT/VF. We studied the spatial and temporal changes in BVR in relation to VT/VF during AMI. In 24 pigs, BVR was quantified on 12-lead electrocardiogram recorded at a sampling rate of 1 kHz. AMI was induced in 16 pigs by percutaneous coronary artery occlusion (MI), whereas 8 underwent sham operation (sham). Changes in BVR were assessed at 5 min after occlusion, 5 and 1 min pre-VF in animals that developed VF, and matched time points in pigs without VF. Serum troponin and ST deviation were measured. After 1 mo, magnetic resonance imaging and VT induction by programmed electrical stimulation were performed. During AMI, BVR increased significantly in inferior-lateral leads correlating with ST deviation and troponin increase. BVR was maximal 1 min pre-VF (3.78 ± 1.36 vs. 5 min pre-VF, 1.67 ± 1.56, P < 0.0001). After 1 mo, BVR was higher in MI than in sham and correlated with the infarct size (1.43 ± 0.50 vs. 0.57 ± 0.30, P = 0.009). VT was inducible in all MI animals and the ease of induction correlated with BVR. BVR increased during AMI and temporal BVR changes predicted imminent VT/VF, supporting a possible role in monitoring and early warning systems. BVR correlated to arrhythmia vulnerability suggesting utility in risk stratification post-AMI.NEW & NOTEWORTHY The key finding of this study is that BVR increases during AMI and surges before ventricular arrhythmia onset. This suggests that monitoring BVR may be useful for monitoring the risk of VF during and after AMI in the coronary care unit settings. Beyond this, monitoring BVR may have value in cardiac implantable devices or wearables.

Individualized QT interval (QTi) is a powerful diagnostic tool in long QT syndrome: results from a large validation study.

Aims: Diagnosis of Long QT syndrome (LQTS) is based on prolongation of the QT interval corrected for heart rate (QTc) on surface ECG and genotyping. However, up to 25% of genotype positive patients have a normal QTc interval. We recently showed that individualized QT interval (QTi) derived from 24 h holter data and defined as the QT value at the intersection of an RR interval of 1,000 ms with the linear regression line fitted through QT-RR data points of each individual patient was superior over QTc to predict mutation status in LQTS families. This study aimed to confirm the diagnostic value of QTi, fine-tune its cut-off value and evaluate intra-individual variability in patients with LQTS. Methods: From the Telemetric and Holter ECG Warehouse, 201 recordings from control individuals and 393 recordings from 254 LQTS patients were analysed. Cut-off values were obtained from ROC curves and validated against an in house LQTS and control cohort. Results: ROC curves indicated very good discrimination between controls and LQTS patients with QTi, both in females (AUC 0.96) and males (AUC 0.97). Using a gender dependent cut-off of 445 ms in females and 430 ms in males, a sensitivity of 88% and specificity of 96% were achieved, which was confirmed in the validation cohort. No significant intra-individual variability in QTi was observed in 76 LQTS patients for whom at least two holter recordings were available (483 ± 36 ms vs. 489 ± 42 ms, p = 0.11). Conclusions: This study confirms our initial findings and supports the use of QTi in the evaluation of LQTS families. Using the novel gender dependent cut-off values, a high diagnostic accuracy was achieved.

Heterogeneity of Repolarization and Cell-Cell Variability of Cardiomyocyte Remodeling Within the Myocardial Infarction Border Zone Contribute to Arrhythmia Susceptibility.

BACKGROUND: After myocardial infarction, the infarct border zone (BZ) is the dominant source of life-threatening arrhythmias, where fibrosis and abnormal repolarization create a substrate for reentry. We examined whether repolarization abnormalities are heterogeneous within the BZ in vivo and could be related to heterogeneous cardiomyocyte remodeling. METHODS: Myocardial infarction was induced in domestic pigs by 120-minute ischemia followed by reperfusion. After 1 month, remodeling was assessed by magnetic resonance imaging, and electroanatomical mapping was performed to determine the spatial distribution of activation-recovery intervals. Cardiomyocytes were isolated and tissue samples collected from the BZ and remote regions. Optical recording allowed assessment of action potential duration (di-8-ANEPPS, stimulation at 1 Hz, 37 °C) of large cardiomyocyte populations while gene expression in cardiomyocytes was determined by single nuclear RNA sequencing. RESULTS: In vivo, activation-recovery intervals in the BZ tended to be longer than in remote with increased spatial heterogeneity evidenced by a greater local SD (3.5±1.3 ms versus remote: 2.0±0.5 ms, P=0.036, npigs=5). Increased activation-recovery interval heterogeneity correlated with enhanced arrhythmia susceptibility. Cellular population studies (ncells=635-862 cells per region) demonstrated greater heterogeneity of action potential duration in the BZ (SD, 105.9±17.0 ms versus remote: 73.9±8.6 ms; P=0.001; npigs=6), which correlated with heterogeneity of activation-recovery interval in vivo. Cell-cell gene expression heterogeneity in the BZ was evidenced by increased Euclidean distances between nuclei of the BZ (12.1 [9.2-15.0] versus 10.6 [7.5-11.6] in remote; P<0.0001). Differentially expressed genes characterizing BZ cardiomyocyte remodeling included hypertrophy-related and ion channel-related genes with high cell-cell variability of expression. These gene expression changes were driven by stress-responsive TFs (transcription factors). In addition, heterogeneity of left ventricular wall thickness was greater in the BZ than in remote. CONCLUSIONS: Heterogeneous cardiomyocyte remodeling in the BZ is driven by uniquely altered gene expression, related to heterogeneity in the local microenvironment, and translates to heterogeneous repolarization and arrhythmia vulnerability in vivo.

Apical papillary muscle displacement is a prevalent feature and a phenotypic precursor of apical hypertrophic cardiomyopathy.

AIMS: Papillary muscle (PM) abnormalities are considered part of the phenotypic spectrum of hypertrophic cardiomyopathy (HCM). The aim of this study was to evaluate the presence and frequency of PM displacement in different HCM phenotypes. METHODS AND RESULTS: We retrospectively analysed cardiovascular magnetic resonance (CMR) findings in 156 patients (25% females, median age 57 years). Patients were divided into three groups: septal hypertrophy (Sep-HCM, n = 70, 45%), mixed hypertrophy (Mixed-HCM, n = 48, 31%), and apical hypertrophy (Ap-HCM, n = 38, 24%). Fifty-five healthy subjects were enrolled as controls. Apical PM displacement was observed in 13% of controls and 55% of patients, which was most common in the Ap-HCM group, followed by the Mixed-HCM and Sep-HCM groups (respectively: inferomedial PM 92 vs. 65 vs. 13%, P < 0.001; anterolateral PM 61 vs. 40 vs. 9%, P < 0.001). Significant differences in PM displacement were found when comparing healthy controls with patients with Ap- and Mixed-HCM subtypes but not when comparing them with patients with the Sep-HCM subtype. T-wave inversion in the inferior and lateral leads was more frequent in patients with Ap-HCM (100 and 65%, respectively) when compared with Mixed-HCM (89 and 29%, respectively) and Sep-HCM (57 and 17%, respectively; P < 0.001 for both). Eight patients with Ap-HCM had prior CMR examinations because of T-wave inversion [median interval 7 (3-8) years], and in the first CMR study, none showed apical hypertrophy [median apical wall thickness 8 (7-9) mm], while all of them presented with apical PM displacement. CONCLUSION: Apical PM displacement is part of the phenotypic Ap-HCM spectrum and may precede the development of hypertrophy. These observations suggest a potential pathogenetic, mechanical link between apical PM displacement and Ap-HCM.