Trans-myocardial bipolar electrogram: A strategy for mapping and determining efficacy of bipolar ablation of deep foci.

Mapping and ablation of intramural ventricular tachycardia (VT) remain a challenge. We developed a trans-myocardial electrogram recording across distal tips of two separate ablation catheters placed on contralateral sides of the myocardium to record a trans-myocardial bipole and a novel pacing electrode configuration. This trans-myocardial bipole was applied during bipolar ablation in a patient with septal VT. Local activation in this trans-myocardial bipole was similar to the earliest activation recorded from detailed activation maps from both sides of the septum. Pacing from this trans-myocardial bipole resulted in a perfect morphology match. After bipolar ablation, the trans-myocardial bipolar voltage decreased by 82%, and pacing threshold increased by 800%. These findings correlated with VT noninducibility.

Minimalistic strategy for coronary sinus lead implant: A single tool capable of electrophysiological mapping, pressure measurement, and angiography.

BACKGROUND: Left ventricular (LV) lead implantation for cardiac resynchronization therapy (CRT) may be confounded by contrast load during attempted cannulation and lead dislodgement during guiding catheter splitting. An LV lead implant system with a steerable single catheter that completely avoids the use of guiding catheters when needed, acquires atrioventricular electrograms, measures intracardiac pressures, permits CS angiography, and has the ability to direct a coronary angioplasty wire that will lead the final delivery of LV lead into a CS tributary, may help limit contrast use and avoid lead dislodgement at CS guide sheath removal. METHODS AND RESULTS: In this article as a proof of concept, we describe the use of this minimalist technique as a first line approach in six patients who had standard indications for CRT. The LV lead was successfully implanted in a target vein in all patients without acute complications. Contrast was not used in half the group and the LV lead was successfully implanted without guiding catheter in four patients. The implantation technique evolved through the series and in the final patient, no guiding sheath or contrast was used. Postimplant lead positions on chest X-ray and lead parameters were stable in all patients at follow-up. CONCLUSION: In proof of concept paper, we describe a technique of LV lead implantation potentially without the use of contrast and standard CS guiding catheters. Once familiar, this approach may provide a less complicated strategy.

Syncope and presyncope in patients with COVID-19.

INTRODUCTION: Recent studies have described several cardiovascular manifestations of COVID-19 including myocardial ischemia, myocarditis, thromboembolism, and malignant arrhythmias. However, to our knowledge, syncope in COVID-19 patients has not been systematically evaluated. We sought to characterize syncope and/or presyncope in COVID-19. METHODS: This is a retrospective analysis of consecutive patients hospitalized with laboratory-confirmed COVID-19 with either syncope or presyncope. This "study" group (n = 37) was compared with an age and gender-matched cohort of patients without syncope ("control") (n = 40). Syncope was attributed to various categories. We compared telemetry data, treatments received, and clinical outcomes between the two groups. RESULTS: Among 1000 COVID-19 patients admitted to the Mount Sinai Hospital, the incidence of syncope/presyncope was 3.7%. The median age of the entire cohort was 69 years (range 26-89+ years) and 55% were men. Major comorbidities included hypertension, diabetes, and coronary artery disease. Syncopal episodes were categorized as (a) unspecified in 59.4% patients, (b) neurocardiogenic in 15.6% patients, (c) hypotensive in 12.5% patients, and (d) cardiopulmonary in 3.1% patients with fall versus syncope and seizure versus syncope in 2 of 32 (6.3%) and 1 of 33 (3.1%) patients, respectively. Compared with the "control" group, there were no significant differences in both admission and peak blood levels of d-dimer, troponin-I, and CRP in the "study" group. Additionally, there were no differences in arrhythmias or death between both groups. CONCLUSIONS: Syncope/presyncope in patients hospitalized with COVID-19 is uncommon and is infrequently associated with a cardiac etiology or associated with adverse outcomes compared to those who do not present with these symptoms.

Exit sites on the epicardium rarely subtend critical diastolic path of ischemic VT on the endocardium: Implications for noninvasive ablation.

BACKGROUND: Noninvasive electrocardiographic mapping of ventricular tachycardia (VT) and ablation using stereotactic radiotherapy was recently reported. This strategy does not directly evaluate the critical diastolic components and assumes that the epicardial exit site of VT subtends closely over the endocardial mid-diastolic isthmus. OBJECTIVE: To determine if the epicardial exit site of VT spatially corresponds to the critical diastolic components of ischemic scar-related VT. MATERIALS AND METHODS: Intraoperative simultaneous endocardial and epicardial mapping were performed during VT using a 112-bipole endocardial balloon and 112-bipole epicardial sock array. In eight patients, nine VTs having entire diastolic circuit mapped were included in the study. The diastolic path and VT-exit sites (epicardial and endocardial) were determined. RESULTS: The diastolic path was mapped in the endocardium for all nine VTs (median length, 50; interquartile range [IQR], 28 mm). The tachycardia cycle length ranged from 210-500 ms. The VT-exit site was early in the endocardium for six VTs and on the epicardium for three VTs. The mid-diastolic isthmus and endocardial exit site of the six endocardial VTs were spatially distant from their epicardial exit site by a median distance of 32 and 27 mm, respectively. For the three VTs with an early epicardial exit, the isthmus and endocardial exit sites were distant from the epicardial exit site by a median distance of 34 and 38 mm, respectively. CONCLUSION: The epicardial exit site and the mid-diastolic isthmus sites were spatially distant and discrepant. Surface electrocardiography (ECG)-derived strategy in identifying epicardial exit site to select noninvasive ablation targets is prone to identify epicardial exit sites and may not identify critical targets in ischemic scar VT.

Essential role of ryanodine receptor 2 phosphorylation in the effect of azumolene on ventricular arrhythmia vulnerability in a rabbit heart model.

INTRODUCTION: Following long-duration ventricular fibrillation (LDVF), reinitiation of ventricular fibrillation (VF) poses a major challenge during resuscitation. Ryanodine receptor 2 (RyR2) becomes dysfunctional following VF. The relationship between LDVF, RyR2 modulation, and ventricular refibrillation, as well as the role of RyR2 phosphorylation, remains unknown. METHODS: Langendorff-perfused rabbit hearts were subjected to global ischemia and treated with azumolene (or vehicle alone in controls) upon reperfusion. After electrical induction of an initial LDVF episode, each heart was further stimulated electrically to assess reinducibility of VF. Myocardial calcium dynamics were assessed by optical mapping. RyR2 phosphorylation in left ventricular tissue extracts was analyzed by Western blot analysis. RESULTS: Fewer episodes of refibrillation (lasting ≥ 10 seconds) were induced in azumolene-treated hearts than in controls (P = 0.01); however, this reduction in refibrillation was abrogated in the presence of the protein kinase A inhibitor H89. Spontaneous calcium elevation was significantly lower in azumolene-treated hearts than in control hearts ( P = 0.002) and in hearts pretreated with H89 before azumolene ( P = 0.01). RyR2 phosphorylation at Ser2808 was higher in hearts subjected to LDVF than in non-VF hearts ( P = 0.029), while no significant difference was found at Ser2814. Pretreatment with H89 led to significantly less RyR2 phosphorylation at Ser2808 ( P = 0.04) after LDVF, while pretreatment with KN93 or azumolene alone showed no effects on RyR2 phosphorylation. CONCLUSION: Ventricular refibrillation following LDVF was reduced by azumolene, which also improves calcium dynamics. RyR2 phosphorylation at Ser2808 is a prerequisite for the beneficial effects of azumolene.

Objective criteria for septal fibrosis in non-ischemic dilated cardiomyopathy: validation for the prediction of future cardiovascular events.

BACKGROUND: Expert subjective reporting of mid-wall septal fibrosis on late gadolinium enhancement (LGE) images has been shown to predict major cardiovascular outcomes in patients with non-ischemic dilated cardiomyopathy (NIDCM). This study aims to establish objective criteria for non-experts to report clinically relevant septal fibrosis and compare its performance by such readers versus experts for the prediction of cardiovascular events. METHODS: LGE cardiovascular magnetic resonance (CMR) was performed in 118 consecutive patients with NIDCM (mean age 57 ± 14, 42 % female) and the presence of septal fibrosis scored by expert readers. CMR-naive readers performed signal threshold-based LGE quantification by referencing mean values of remote tissue and applying these to a pre-defined anatomic region to measure septal fibrosis. All patients were followed for the primary composite outcome of cardiac mortality or appropriate implantable cardioverter-defibrillator (ICD) therapy. RESULTS: The mean LVEF was 32 ± 12 %. At a median follow-up of 1.9 years, 20 patients (17 %) experienced a primary composite outcome. Expert visual scoring identified 55 patients with septal fibrosis. Non-expert septal fibrosis quantification was highly reproducible and identified mean septal fibrosis burden for three measured thresholds as follows; 5SD: 2.9 ± 3.6 %, 3SD: 6.9 ± 6.3 %, and 2SD: 11.1 ± 7.5 % of the left ventricular (LV) mass, respectively. By ROC analysis, optimal thresholds for prediction of the primary outcome were; 5SD: 2.74 % (HR 8.7, p < 0.001), 3SD: 6.63 % (HR 5.7, p = 0.001) and 2SD: 10.15 % (HR 6.1, p = 0.001). By comparison, expert visual scoring provided a HR of 5.3 (p = 0.001). In adjusted analysis, objective quantification by a novice reader (>5SD threshold) was the strongest independent predictor of the primary outcome (HR 8.7) and provided improved risk reclassification beyond LVEF alone (NRI 0.54, 95 % CI 0.16-0.92, p = 0.005). CONCLUSIONS: Novice readers were able to achieve superior risk prediction for future cardiovascular events versus experts using objective criteria for septal fibrosis in patients with NIDCM. Patients with a septal fibrosis burden >2.74 % of the LV mass (>5SD threshold) were at a 9-fold higher risk of cardiac death or appropriate ICD therapy versus those not meeting this criteria. As such, this study validates reproducible criteria applicable to all levels of expertise to identify NIDCM patients at high risk of future cardiovascular events.

Use of Wearable Technology and Deep Learning to Improve the Diagnosis of Brugada Syndrome.

BACKGROUND: The diagnosis of Brugada syndrome by 12-lead electrocardiography (ECG) is challenging because the diagnostic type 1 pattern is often transient. OBJECTIVES: This study sought to improve Brugada syndrome diagnosis by using deep learning (DL) to continuously monitor for Brugada type 1 in 24-hour ambulatory 12-lead ECGs (Holters). METHODS: A convolutional neural network was trained to classify Brugada type 1. The training cohort consisted of 10-second standard/high precordial leads from 12-lead ECGs (n = 1,190) and 12-lead Holters (n = 380) of patients with definite and suspected Brugada syndrome. The performance of the trained model was evaluated in 2 testing cohorts of 10-second standard/high precordial leads from 12-lead ECGs (n = 474) and 12-lead Holters (n = 716). RESULTS: DL achieved a receiver-operating characteristic area under the curve of 0.976 (95% CI: 0.973-0.979) in classifying Brugada type 1 from 12-lead ECGs and 0.975 (95% CI: 0.966-0.983) from 12-lead Holters. Compared with cardiologist reclassification of Brugada type 1, DL had similar performance and produced robust results in experiments evaluating scalability and explainability. When DL was applied to consecutive 10-second, clean ECGs from 24-hour 12-lead Holters, spontaneous Brugada type 1 was detected in 48% of patients with procainamide-induced Brugada syndrome and in 33% with suspected Brugada syndrome. DL detected no Brugada type 1 in healthy control patients. CONCLUSIONS: This novel DL model achieved cardiologist-level accuracy in classifying Brugada type 1. Applying DL to 24-hour 12-lead Holters significantly improved the detection of Brugada type 1 in patients with procainamide-induced and suspected Brugada syndrome. DL analysis of 12-lead Holters may provide a robust, automated screening tool before procainamide challenge to aid in the diagnosis of Brugada syndrome.

Statins Protect Against Early Stages of Doxorubicin-induced Cardiotoxicity Through the Regulation of Akt Signaling and SERCA2.

Background: Doxorubicin-induced cardiomyopathy (DICM) is one of the complications that can limit treatment for a significant number of cancer patients. In animal models, the administration of statins can prevent the development of DICM. Therefore, the use of statins with anthracyclines potentially could enable cancer patients to complete their chemotherapy without added cardiotoxicity. The precise mechanism mediating the cardioprotection is not well understood. The purpose of this study is to determine the molecular mechanism by which rosuvastatin confers cardioprotection in a mouse model of DICM. Methods: Rosuvastatin was intraperitoneally administered into adult male mice at 100 µg/kg daily for 7 days, followed by a single intraperitoneal doxorubicin injection at 10 mg/kg. Animals continued to receive rosuvastatin daily for an additional 14 days. Cardiac function was assessed by echocardiography. Optical calcium mapping was performed on retrograde Langendorff perfused isolated hearts. Ventricular tissue samples were analyzed by immunofluorescence microscopy, Western blotting, and quantitative polymerase chain reaction. Results: Exposure to doxorubicin resulted in significantly reduced fractional shortening (27.4% ± 1.11% vs 40% ± 5.8% in controls; P < 0.001) and re-expression of the fetal gene program. However, we found no evidence of maladaptive cardiac hypertrophy or adverse ventricular remodeling in mice exposed to this dose of doxorubicin. In contrast, rosuvastatin-doxorubicin-treated mice maintained their cardiac function (39% ± 1.26%; P < 0.001). Mechanistically, the effect of rosuvastatin was associated with activation of Akt and phosphorylation of phospholamban with preserved sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 (SERCA2)-mediated Ca2+ reuptake. These effects occurred independently of perturbations in ryanodine receptor 2 function. Conclusions: Rosuvastatin counteracts the cardiotoxic effects of doxorubicin by directly targeting sarcoplasmic calcium cycling.

Contexte: La cardiomyopathie induite par la doxorubicine (CMID) est l'une des complications pouvant limiter le traitement d'un nombre considérable de patients atteints de cancer. Dans des modèles animaux, l'administration de statines peut prévenir l'apparition d'une CMID. Ainsi, l'utilisation de statines avec les anthracyclines pourrait vraisemblablement permettre aux patients de compléter leur chimiothérapie en évitant une cardiotoxicité supplémentaire. Le mécanisme précis qui sous-tend cet effet cardioprotecteur n'est pas entièrement élucidé. Cette étude a pour objectif de déterminer dans un modèle murin de CMID le mécanisme moléculaire par lequel la rosuvastatine confère une cardioprotection. Méthodologie: La rosuvastatine a été administrée par voie intrapéritonéale à des souris adultes mâles à une dose de 100 µg/kg par jour pendant sept jours, suivie d'une dose unique de doxorubicine de 10 mg/kg administrée par injection intrapéritonéale. Les animaux poursuivaient ensuite le traitement par la rosuvastatine une fois par jour pendant 14 jours supplémentaires. La fonction cardiaque a été mesurée par échocardiographie. Une cartographie optique du calcium a été réalisée sur des cœurs isolés soumis à une perfusion rétrograde selon la méthode de Langendorff. Des échantillons de tissu ventriculaire ont été analysés par microscopie en immunofluorescence, par buvardage de western et par mesure quantitative de l'amplification en chaîne par polymérase. Résultats: L'exposition à la doxorubicine a entraîné une diminution significative de la fraction de raccourcissement (27,4 % ± 1,11 % vs 40 % ± 5,8 % dans le groupe témoin; p < 0,001) et la réexpression du programme génique fœtal. Toutefois, aucune hypertrophie cardiaque inadaptée ni aucun remodelage ventriculaire indésirable n'ont été observés chez les souris ayant été exposées à la dose de doxorubicine étudiée. En revanche, la fonction cardiaque a été préservée chez les souris traitées par l'association rosuvastatine-doxorubicine (39 % ± 1,26 %; p < 0,001). Sur le plan du mode d'action, l'effet de la rosuvastatine a été associé à une activation de l'Akt et à une phosphorylation du phospholambane, avec préservation du recaptage de Ca2+ médié par la pompe SERCA2 (sarcoplasmic/endoplasmic reticulum Ca 2+ transporting 2). Ces effets sont survenus indépendamment des perturbations de la fonction du récepteur RyR2 (ryanodine receptor 2). Conclusions: La rosuvastatine neutralise les effets cardiotoxiques de la doxorubicine en ciblant directement la circulation sarcoplasmique du calcium.

Cardioprotective effects of dantrolene in doxorubicin-induced cardiomyopathy in mice.

BACKGROUND: Doxorubicin (Dox) is a potent chemotherapeutic agent, but its usage is limited by dose-dependent cardiotoxicity. Intracellular calcium dysregulation has been reported to be involved in doxorubicin-induced cardiomyopathy (DICM). The cardioprotective role of RyR stabilizer dantrolene (Dan) on the calcium dynamics of DICM has not yet been explored. OBJECTIVE: To evaluate the effects of dantrolene on intracellular calcium dysregulation and cardiac contractile function in a DICM model. METHODS: Adult male C57BL/6 mice were randomized into 4 groups: (1) Control, (2) Dox Only, (3) Dan Only, and (4) Dan + Dox. Fractional shortening (FS) and left ventricular ejection fraction (LVEF) were assessed by echocardiography. In addition, mice were sacrificed 2 weeks after doxorubicin injection for optical mapping of the heart in a Langendorff setup. RESULTS: Treatment with Dox was associated with a reduction in both FS and LVEF at 2 weeks (P < .0001) and 4 weeks (P < .006). Dox treatment was also associated with prolongation of calcium transient durations CaTD50 (P = .0005) and CaTD80 (P < .0001) and reduction of calcium amplitude alternans ratio (P < .0001). Concomitant treatment with Dan prevented the Dox-induced decline in FS and LVEF (P < .002 at both 2 and 4 weeks). Dan also prevented Dox-induced prolongation of CaTD50 and CaTD80 and improved the CaT alternans ratio (P < .0001). Finally, calcium transient rise time was increased in the doxorubicin-treated group, indicating RyR2 dyssynchrony, and dantrolene prevented this prolongation (P = .02). CONCLUSION: Dantrolene prevents cardiac contractile dysfunction following doxorubicin treatment by mitigating dysregulation of calcium dynamics.

Atrial Fibrillation in Patients Hospitalized With COVID-19: Incidence, Predictors, Outcomes, and Comparison to Influenza.

OBJECTIVES: The goal of this study is to determine the incidence, predictors, and outcomes of atrial fibrillation (AF) or atrial flutter (AFL) in patients hospitalized with coronavirus disease-2019 (COVID-19). BACKGROUND: COVID-19 results in increased inflammatory markers previously associated with atrial arrhythmias. However, little is known about their incidence or specificity in COVID-19 or their association with outcomes. METHODS: This is a retrospective analysis of 3,970 patients admitted with polymerase chain reaction-positive COVID-19 between February 4 and April 22, 2020, with manual review performed of 1,110. The comparator arm included 1,420 patients with influenza hospitalized between January 1, 2017, and January 1, 2020. RESULTS: Among 3,970 inpatients with COVID-19, the incidence of AF/AFL was 10% (n = 375) and in patients without a history of atrial arrhythmias it was 4% (n = 146). Patients with new-onset AF/AFL were older with increased inflammatory markers including interleukin 6 (93 vs. 68 pg/ml; p < 0.01), and more myocardial injury (troponin-I: 0.2 vs. 0.06 ng/ml; p < 0.01). AF and AFL were associated with increased mortality (46% vs. 26%; p < 0.01). Manual review captured a somewhat higher incidence of AF/AFL (13%, n = 140). Compared to inpatients with COVID-19, patients with influenza (n = 1,420) had similar rates of AF/AFL (12%, n = 163) but lower mortality. The presence of AF/AFL correlated with similarly increased mortality in both COVID-19 (relative risk: 1.77) and influenza (relative risk: 1.78). CONCLUSIONS: AF/AFL occurs in a subset of patients hospitalized with either COVID-19 or influenza and is associated with inflammation and disease severity in both infections. The incidence and associated increase in mortality in both cohorts suggests that AF/AFL is not specific to COVID-19, but is rather a generalized response to the systemic inflammation of severe viral illnesses.

Fall-Related Hospitalizations in Nursing Home Residents Co-Prescribed a Cholinesterase Inhibitor and Beta-Blocker.

BACKGROUND/OBJECTIVES: To examine the association between hospitalization for a fall-related injury and the co-prescription of a cholinesterase inhibitor (ChEI) among persons with dementia receiving a beta-blocker, and whether this potential drug-drug interaction is modified by frailty. DESIGN: Nested case-control study using population-based administrative databases. SETTING: All nursing homes in Ontario, Canada. PARTICIPANTS: Persons with dementia aged 66 and older who received at least one beta-blocker between April 2013 and March 2018 following nursing home admission (n = 19,060). MEASUREMENTS: Cases were persons with dementia with a hospitalization (emergency department visit or acute care admission) for a fall-related injury with concurrent beta-blocker use. Each case (n = 3,038) was matched 1:1 to a control by age (±1 year), sex, cohort entry year, frailty, and history of fall-related injuries. The association between fall-related injury and exposure to a ChEI in the 90 days prior was examined using multivariable conditional logistic regression. Secondary exposures included ChEI type, daily dose, incident versus prevalent use, and use in the prior 30 days. Subgroup analyses considered frailty, age group, sex, and history of hospitalization for fall-related injuries. RESULTS: Exposure to a ChEI in the prior 90 days occurred among 947 (31.2%) cases and 940 (30.9%) controls. In multivariable models, no association was found between hospitalization for a fall-related injury and prior exposure to a ChEI in persons with dementia dispensed beta-blockers (adjusted odds ratio = .96, 95% confidence interval = .85-1.08). Findings were consistent across secondary exposures and subgroup analyses. CONCLUSION: Among nursing home residents with dementia receiving beta-blockers, co-prescription of a ChEI was not associated with an increased risk of hospitalization for a fall-related injury. However, we did not assess for its association with falls not leading to hospitalization. This finding could inform clinical guidelines and shared decision making between persons with dementia, caregivers, and clinicians concerning ChEI initiation and/or discontinuation.

Direct and indirect mapping of intramural space in ventricular tachycardia.

BACKGROUND: The ventricular tachycardia (VT) circuit is often assumed to be located in the endocardium or epicardium. The plateauing success rate of VT ablation warrants reevaluation of this mapping paradigm. OBJECTIVE: The purpose of this study was to resolve the intramural components of VT circuits by mapping in human hearts. METHODS: Panoramic simultaneous endocardial-epicardial mapping (SEEM) during intraoperative mapping (IOM) was performed in human subjects. In explanted hearts (EH), SEEM and intramural multielectrode plunge needle mapping (NM) of the left ventricle were performed. Overall, 37 VTs (26 ischemic cardiomyopathy [ICM], 11 nonischemic cardiomyopathy [NICM]) were studied in 32 patients. Intraoperative SEEM was performed in 16 patients (16 ICM). Additionally, 16 explanted myopathic human hearts (9 NICM, 7 ICM) were studied in a Langendorff setup. Predominant intramural location of the VT was imputed by the absence of significant endocardial-epicardial activation during IOM (using SEEM and no NM) or by the presence of intramural activation spanning the entire cycle length (including mid-diastole) in EH (SEEM and NM). RESULTS: By IOM (SEEM), predominant endocardial activation (entire tachycardia cycle length including mid-diastolic activation) was present in 10 of 18 VTs (55%). In 8 of 18 VTs (44%), the VT circuit was presumed to be intramural due to incomplete diastolic activation in endocardium and epicardium. In EH (SEEM and NM), VT location was predominantly intramural, endocardial, and epicardial in 8 of 19 (42%), 5 of 19 (26%), and 1 of 19 VTs (5%), respectively. CONCLUSION: In a significant proportion of both ischemic and nonischemic ventricular tachycardias, the predominant activation was located in the intramural space.

Malignant Arrhythmias in Patients With COVID-19: Incidence, Mechanisms, and Outcomes.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) who develop cardiac injury are reported to experience higher rates of malignant cardiac arrhythmias. However, little is known about these arrhythmias-their frequency, the underlying mechanisms, and their impact on mortality. METHODS: We extracted data from a registry (NCT04358029) regarding consecutive inpatients with confirmed COVID-19 who were receiving continuous telemetric ECG monitoring and had a definitive disposition of hospital discharge or death. Between patients who died versus discharged, we compared a primary composite end point of cardiac arrest from ventricular tachycardia/fibrillation or bradyarrhythmias such as atrioventricular block. RESULTS: Among 800 patients with COVID-19 at Mount Sinai Hospital with definitive dispositions, 140 patients had telemetric monitoring, and either died (52) or were discharged (88). The median (interquartile range) age was 61 years (48-74); 73% men; and ethnicity was White in 34%. Comorbidities included hypertension in 61%, coronary artery disease in 25%, ventricular arrhythmia history in 1.4%, and no significant comorbidities in 16%. Compared with discharged patients, those who died had elevated peak troponin I levels (0.27 versus 0.02 ng/mL) and more primary end point events (17% versus 4%, P=0.01)-a difference driven by tachyarrhythmias. Fatal tachyarrhythmias invariably occurred in the presence of severe metabolic imbalance, while atrioventricular block was largely an independent primary event. CONCLUSIONS: Hospitalized patients with COVID-19 who die experience malignant cardiac arrhythmias more often than those surviving to discharge. However, these events represent a minority of cardiovascular deaths, and ventricular tachyarrhythmias are mainly associated with severe metabolic derangement. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04358029.

Right Ventricular Ejection Fraction Is Incremental to Left Ventricular Ejection Fraction for the Prediction of Future Arrhythmic Events in Patients With Systolic Dysfunction.

BACKGROUND: Left ventricular ejection fraction remains the primary risk stratification tool used in the selection of patients for implantable cardioverter defibrillator therapy. However, this solitary marker fails to identify a substantial portion of patients experiencing sudden cardiac arrest. In this study, we examined the incremental value of considering right ventricular ejection fraction for the prediction of future arrhythmic events in patients with systolic dysfunction using the gold standard of cardiovascular magnetic resonance. METHODS AND RESULTS: Three hundred fourteen consecutive patients with ischemic cardiomyopathy or nonischemic dilated cardiomyopathy undergoing cardiovascular magnetic resonance were followed for the primary outcome of sudden cardiac arrest or appropriate implantable cardioverter defibrillator therapy. Blinded quantification of left ventricular and right ventricular (RV) volumes was performed from standard cine imaging. Quantification of fibrosis from late gadolinium enhancement imaging was incrementally performed. RV dysfunction was defined as right ventricular ejection fraction ≤45%. Among all patients (164 ischemic cardiomyopathy, 150 nonischemic dilated cardiomyopathy), the mean left ventricular ejection fraction was 32±12% (range, 6-54%) with mean right ventricular ejection fraction of 48±15% (range, 7-78%). At a median of 773 days, 49 patients (15.6%) experienced the primary outcome (9 sudden cardiac arrest, 40 appropriate implantable cardioverter defibrillator therapies). RV dysfunction was independently predictive of the primary outcome (hazard ratio=2.98; P=0.002). Among those with a left ventricular ejection fraction >35% (N=121; mean left ventricular ejection fraction, 45±6%), RV dysfunction provided an adjusted hazard ratio of 4.2 (P=0.02). CONCLUSIONS: RV dysfunction is a strong, independent predictor of arrhythmic events. Among patients with mild to moderate LV dysfunction, a cohort greatly contributing to global sudden cardiac arrest burden, this marker provides robust discrimination of high- versus low-risk subjects.

Prevalence of myocardial fibrosis patterns in patients with systolic dysfunction: prognostic significance for the prediction of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy.

BACKGROUND: Late gadolinium enhancement-cardiac magnetic resonance is increasingly performed in patients with systolic dysfunction. Numerous patterns of fibrosis are commonly reported among this population. However, the relative prevalence and prognostic significance of these findings remains uncertain. METHODS AND RESULTS: Three hundred eighteen consecutive patients referred for late gadolinium enhancement-cardiac magnetic resonance and a left ventricular ejection fraction <55% were followed up for the primary end point of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy. Late gadolinium enhancement images were blindly interpreted for the presence of 6 distinct pattern(s) of myocardial fibrosis in addition to signal threshold-based quantification of total fibrosis volume. The mean age and left ventricular ejection fraction of participants were 62.0±12.9 years and 32.6±11.9%, respectively. Any pattern of myocardial fibrosis was seen in 248 patients (78%) with ≥2 patterns present in 25% of patients. During follow-up (median of 467 days), 49 patients (15%) had a primary outcome. After adjustment for left ventricular ejection fraction, cardiomyopathy pathogenesis, and total fibrosis volume, the presence of a midwall striae pattern of fibrosis was an independent predictor of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy with a hazard ratio of 2.4 (95% confidence interval, 1.2-4.6; P=0.01); this finding is present in 30% of patients with nonischemic and 15% of patients with ischemic cardiomyopathy. Cumulative event rate was significantly higher among those with midwall striae, particularly among those with a left ventricular ejection fraction >35% (40% versus 6%; P=0.005). CONCLUSIONS: Patients with systolic dysfunction frequently demonstrate multiple patterns of myocardial fibrosis. Of these, a midwall striae pattern of fibrosis is the strongest independent predictor of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy.