Cardiomyopathy Research Articles

Distribution and prognostic impact of different heart failure etiologies in patients with heart failure with mildly reduced ejection fraction

ObjectiveThe study investigates the characteristics and prognostic impact of different heart failure (HF) etiologies in patients with heart failure with mildly reduced ejection fraction (HFmrEF). BackgroundData regarding the characterization of patients with HFmrEF and their outcomes is scarce. MethodsConsecutive patients with HFmrEF (i.e., left ventricular ejection fraction 41–49 % and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. Patients with ischemic cardiomyopathy (ICM) were compared to patients without ischemic cardiomyopathy (non-ICM). The primary endpoint was all-cause mortality at 30 months (median follow-up). Statistical analyses included Kaplan-Meier, multivariable Cox proportional regression analyses and propensity score matching. ResultsFrom a total of 1,832 patients hospitalized with HFmrEF, ICM was the most common HF etiology in 68.7 %, followed by hypertensive (9.7 %) and primary non-ischemic cardiomyopathies (NICM) (8.1 %). Within the entire study cohort, the presence of ICM was not associated with the risk of all-cause mortality (HR = 0.864; 95 % CI 0.723 – 1.031), however after multivariable adjustment (HR = 0.792; 95 % CI 0.646 – 0.972; p = 0.026) and propensity score matching (25.7% vs. 31.4 %; log rank p = 0.050), the presence of ICM was associated with lower risk of all-cause mortality at 30 months compared to patients without ICM. ConclusionICM is the most common etiology of HF in HFmrEF and may be associated with favorable outcomes. This may be related to better adherence to pharmacological treatment and improved revascularization strategies for HFmrEF patients with ICM.

Undetected Neuromuscular Disease in Patients after Heart Transplantation.

(1) Heart transplantation (HTX) improves the overall survival and functional status of end-stage heart failure patients with cardiomyopathies (CMPs). The majority of CMPs have genetic causes, and the overlap between CMPs and inherited myopathies is well documented. However, the long-term outcome in skeletal muscle function and possibility of an undiagnosed underlying genetic cause of both a cardiac and skeletal pathology remain unknown. (2) Thirty-nine patients were assessed using open and standardized interviews on muscle function, a quality-of-life (EuroQol EQ-5D-3L) questionnaire, and a physical examination (Medical Research Council Muscle scale). Whole-exome sequencing was completed in three stages for those with skeletal muscle weakness. (3) Seven patients (17.9%) reported new-onset muscle weakness and motor limitations. Objective muscle weakness in the upper and lower extremities was seen in four patients. In three of them, exome sequencing revealed pathogenic/likely pathogenic variants in the genes encoding nexilin, myosin heavy chain, titin, and SPG7. (4) Our findings support a positive long-term outcome of skeletal muscle function in HTX patients. However, 10% of patients showed clinical signs of myopathy due to a possible genetic cause. The integration of genetic testing and standardized neurological assessment of motor function during the peri-HTX period should be considered.

Impact of Diabetes and Glycemia on Cardiac Improvement and Adverse Events Following Mechanical Circulatory Support.

Type 2 diabetes is prevalent in cardiovascular disease and contributes to excess morbidity and mortality. We sought to investigate the effect of glycemia on functional cardiac improvement, morbidity, and mortality in durable left ventricular assist device (LVAD) recipients. Consecutive patients with an LVAD were prospectively evaluated (n=531). After excluding patients missing pre-LVAD glycated hemoglobin (HbA1c) measurements or having inadequate post-LVAD follow-up, 375 patients were studied. To assess functional cardiac improvement, we used absolute left ventricular ejection fraction change (ΔLVEF: LVEF post-LVAD-LVEF pre-LVAD). We quantified the association of pre-LVAD HbA1c with ΔLVEF as the primary outcome, and all-cause mortality and LVAD-related adverse event rates (ischemic stroke/transient ischemic attack, intracerebral hemorrhage, gastrointestinal bleeding, LVAD-related infection, device thrombosis) as secondary outcomes. Last, we assessed HbA1c differences pre- and post-LVAD. Patients with type 2 diabetes were older, more likely men suffering ischemic cardiomyopathy, and had longer heart failure duration. Pre-LVAD HbA1c was inversely associated with ΔLVEF in patients with nonischemic cardiomyopathy but not in those with ischemic cardiomyopathy, after adjusting for age, sex, heart failure duration, and left ventricular end-diastolic diameter. Pre-LVAD HbA1c was not associated with all-cause mortality, but higher pre-LVAD HbA1c was shown to increase the risk of intracerebral hemorrhage, LVAD-related infection, and device thrombosis by 3 years on LVAD support (P<0.05 for all). HbA1c decreased from 6.68±1.52% pre-LVAD to 6.11±1.33% post-LVAD (P<0.001). Type 2 diabetes and pre-LVAD glycemia modify the potential for functional cardiac improvement and the risk for adverse events on LVAD support. The degree and duration of pre-LVAD glycemic control optimization to favorably affect these outcomes warrants further investigation.

Inpatient mortality and outcomes of COVID-19 among patients with non-ischemic cardiomyopathy: A propensity matched analysis

BackgroundPatients with chronic medical conditions, particularly cardiovascular diseases, are at a greater risk of adverse outcomes due to COVID-19. The effect of COVID-19 on patients with non-ischemic cardiomyopathy (NICM) is not known well. ObjectivesTo study the impact of COVID-19 infection on NICM hospital mortality and other outcomes. MethodsThis study included a cohort of patients from the 2020 and 2021 National Inpatient Sample databases. Patients hospitalized for COVID-19 with and without NICM were matched using a 1:1 propensity score-matching ratio. Outcomes analyzed were in-hospital mortality, rates of acute kidney injury (AKI), acute myocardial infarction (AMI), cardiogenic shock, cardiac arrest, mechanical ventilation, tracheal intubation, pulmonary embolism (PE), ventricular tachycardia (VT), ventricular fibrillation (VF), length of stay (LOS), and total hospitalization charges. ResultsA total of 2,532,652 patients met the inclusion criteria (1,199,008 females [47.3 %], predominantly white 1,456,203 (57.5 %); mean [SD] age 63 [5.4] years), including 64,155 (2.5 %) patients with a history of NICM. Following propensity matching, 10,258 COVID-19 patients with and without NICM were matched. Patients with NICM had higher rates of AMI (11.1 vs. 7.1 %, p < 0.001), cardiogenic shock (2 vs. 0.6 %, p < 0.001), cardiac arrest (4.4 vs. 3.2 %, p < 0.01), mechanical ventilation (13.7 vs 12 %, p < 0.01), VT (8.5 vs. 2.2 %, p < 0.001), and VF (1.0 vs 0.25 %, p < 0.001). The odds ratios for in-hospital mortality, AKI, and PE did not differ significantly. ConclusionA History of NICM does not affect COVID-19 mortality but increases the risk of cardiovascular complications.

Septal late enhancement by cardiac CT is associated with repeat ablation in nonischemic cardiomyopathy patients.

Scar substrate in nonischemic cardiomyopathy (NICM) patients is often difficult to identify. Advances in cardiac imaging, especially using late iodine-enhanced computed tomography (LIE-CT), allow better characterization of scars giving rise to ventricular tachycardia (VT). Currently, there are limited data on clinical correlates of CT-derived scar substrates in NICM. We sought assess the relationship between scar location on LIE-CT and outcomes after radiofrequency catheter ablation (RFCA) in NICM patients with VT. From 2020 to 2022, consecutive patients with NICM undergoing VT RFCA with integration of cardiac CT scar modeling (inHeart, Pessac, France) were included at two US tertiary care centers. The CT protocol included both arterial-enhanced imaging for anatomical modeling and LIE-CT for scar assessment. The distribution of substrate on CT was analyzed in relation to patient outcomes, with primary endpoints being VT recurrence and the need for repeat ablation procedure. Sixty patients were included (age 64 ± 12 years, 90% men). Over a median follow-up of 120 days (interquartile range [IQR]: 41-365), repeat ablation procedures were required in 32 (53%). VT recurrence occurred in 46 (77%), with a median time to recurrence of 40 days (IQR: 8-65). CT-derived total scar volume positively correlated with intrinsic QRS duration (r = .34, p = 0.008). Septal scar was found on CT in 34 (57%), and lateral scar in 40 (7%). On univariate logistic regression, septal scar was associated with increased odds of repeat ablation (odds ratio [OR]: 2.9 [1.0-8.4]; p = 0.046), while lateral scar was not (OR: 0.9 [0.3-2.7]; p = 0.855). Septal scar better predicted VT recurrence when compared to lateral scar, but neither were statistically significant (septal scar OR: 3.0 [0.9-10.7]; p = 0.078; lateral scar OR: 1.7 [0.5-5.9]; p = 0.391). In this tertiary care referral population, patients with NICM undergoing VT catheter ablation with septal LIE-CT have nearly threefold increased risk of need for repeat ablation.

Predictors of ventricular tachyarrhythmia in patients with a wearable cardioverter defibrillator: an international multicenter registry.

Wearable cardioverter defibrillator (WCD) can protect patients from sudden cardiac death due to ventricular tachyarrhythmias and serve as a bridge to decision of definite defibrillator implantation. The aim of this analysis from an international, multicenter WCD registry was to identify predictors of sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) in this population. One thousand six hundred seventy-five patients with WCD were included in a multicenter registry from 9 European centers, with a median follow-up of 440days (IQR 120-893). The primary study end point was the occurrence of sustained VT/VF. Sustained VT was detected by WCD in 5.4% and VF in 0.9% of all patients. Of the 30.3% of patients receiving ICD implantation during follow-up, sustained VT was recorded in 9.3% and VF in 2.6%. Non-ischemic cardiomyopathy (HR 0.5, p < 0.001), and medication with angiotensin-converting enzyme inhibitors (HR 0.7, p = 0.027) and aldosterone antagonists (HR 0.7, p = 0.005) were associated with a significantly lower risk of VT/VF. Patients who received WCD due to a transient increased risk of sudden cardiac death have a comparatively lower risk of VT/VF in the presence of non-ischemic cardiomyopathy. Of note, optimal medical treatment for heart failure not only results in an improvement in left ventricular ejection fraction but also in a reduction in the risk for VT/VF.

Potential prognostic impact of left-ventricular global longitudinal strain in analysis of whole-heart myocardial mechanics in nonischemic dilated cardiomyopathy

Cardiac magnetic resonance (CMR) feature-tracking (FT) has an important diagnostic role in non-ischemic dilated cardiomyopathy (NIDCM). To date, the relationship between whole-heart myocardial mechanics by CMR and early primary outcomes in NIDCM has not been elucidated. patients with NIDCM were eligible for this study. CMR-FT was used to analyze whole-heart myocardial mechanics. The primary outcomes were a composite of heart failure (HF) death, heart transplantation (HT), and hospitalization for HF worsening (WHF) after 1-year since diagnosis. 98 patients were included. During a 1-year follow-up, a worse prognosis occurred in 32 patients (30 hospitalizations for WHF, 8 deaths, and 3 HT). The left ventricular (LV) global longitudinal systolic strain (GLS), left ventricular global circumferential strain (LV GCS), strains of right ventricle and both atria were significantly reduced in patients with events vs. those without (GLS − 8.0 ± 3.4 vs. − 12.1 ± 4.5, p < 0.001; GCS − 13.0 ± 6.4 vs. − 18.3 ± 7.1, p < 0.001; right ventricular (RV) GLS − 12.1 ± 4.9 vs. − 17.4 ± 6.4, p < 0.001; left atrial longitudinal strain 7.5 ± 3.8 vs. 15.1 ± 12.3, p < 0.001; right atrial longitudinal strain 11.0 ± 6.7 vs. 17.2 ± 8.0, p < 0.001). Left ventricular ejection fraction (LVEF) was significantly higher in patients with better prognosis (22.7 ± 8.7 vs. 33.56 ± 10.4, p < 0.001). Multivariate regression analysis revealed LV GLS as an independent predictor of a worse prognosis (OR 0.787, CI 95% 0.697–0.890, p < 0.001). reduction of LV GLS showed the strongest predictive value for the composite outcome of WHF, HT, and HF death.Graphical abstract

Endoscopic Transclival Approach for Evacuation of Retroclival Hematoma: 2-Dimensional Operative Video.

Retroclival hematomas are a rare entity, presenting anteriorly to the brainstem in the epidural, subdural, or subarachnoid space. Although those that develop in the epidural space often arise from trauma, subdural retroclival hematomas frequently occur spontaneously in the setting of coagulopathy, aneurysm rupture, or pituitary apoplexy, with many cases having an unknown etiology.1-4 Although most are treated with conservative management, surgical intervention is preferred for those presenting with evidence of brainstem compression, hydrocephalus, worsening neurological deficits, and clinical deterioration.5 In this report, we present the case of a 75-year-old woman with a medical history of mitral regurgitation, nonischemic cardiomyopathy, and atrial fibrillation on warfarin presenting with 4 days of temporoparietal headaches and double vision. On examination, the patient demonstrated right abducens and hypoglossal nerve palsies. Computed tomography revealed a subdural hemorrhage within the retroclival cistern, extending into the dorsal inferior aspect of the C2 vertebral body, resulting in posterior displacement of the pons, medulla, and proximal cervical spinal cord. Spinal and cerebral angiograms did not show evidence of any vascular malformation. An endoscopic transclival approach was selected for hematoma evacuation. Key surgical steps included harvesting of nasoseptal flap, endoscopic transnasal approach to the sellar/subsellar space, transclival drilling, retroclival hematoma evacuation, and clival reconstruction. The patient tolerated the procedure well and was discharged 15 days postoperatively with resolution of prior cranial nerve deficits. Postoperative computed tomography imaging revealed complete retroclival hematoma evacuation. At her 3-month follow-up, the patient remained neurologically intact with imaging confirming no residual subdural hematoma. Institutional Review Board approval was obtained for this submission (2018-9379). Patient consent was not obtained as personal identifying information was kept confidential, following guidelines set forth by Institutional Review Board requirements.

Percutaneous mechanical support in catheter ablation of ventricular arrhythmias: hype or hope?

Catheter ablation (CA) has become an established treatment strategy for managing recurrent ventricular tachycardias (VTs) in patients with structural heart disease. In recent years, percutaneous mechanical circulatory support (PMCS) devices have been increasingly used intra-operatively to improve the ablation outcome. One indication would be rescue therapy for patients who develop haemodynamic deterioration during the ablation. However, more efforts are focused on identifying subjects who are at high risk of such deterioration and could benefit from the pre-emptive use of the PMCS. The third reason to use PMCS could be the inability to identify diffuse substrate, especially in non-ischaemic cardiomyopathy. This paper reviews available experiences using various types of PMCS in different clinical scenarios. Although PMCS allows mapping during VT, it does not significantly influence acute outcomes and not convincingly long-term outcomes. On the contrary, the complication rate appears to be higher in PMCS cohorts. Our data suggest that even in patients with severe left ventricular dysfunction, the substrate modification can be performed without the need for general anaesthesia and risk of haemodynamic decompensation. In end-stage heart failure associated with the electrical storm, implantation of a left ventricular assist device (or PMCS with a transition to the left ventricular assist device) might be the preferred strategy before CA. In high-risk patients who are not potential candidates for these treatment options, radiotherapy could be considered as a bail-out treatment of recurrent VTs. These approaches should be studied in prospective trials.

Efficacy, usage and adverse effects of furosemide in cardiovascular diseases

Cardiovascular diseases can be caused by numerous beginning conditions. The underpinning causes may include heart/ myocardial inflammation, cardio myopathy, coronary vascular complaint (CAD), dyslipidemia, hypertension, pulmonary hypertension, and arrhythmia, which may eventually affect heart and liver failure. The study was aimed to determine the efficacy, usage and adverse effects of furosemide in diseased heart conditions. Furosemide is prescribed in the treatment of various cardiovascular illnesses, including monitoring the effects in various age groups, gender and body weights. Considering all the primary parameters of drug dose and secondary parameters of dose duration and their certain categories, we evaluate the results based on the effectiveness of furosemide. The collected and gathered data is analyzed by the suitable statistical methods (Central tendency methods) like Arithmetic mean. The effectiveness of furosemide is rapid and strong in the age group of 39-69yrs with the sodium levels of 132.8mEq/L and the urine output of 2.23L/day. The drug shows potential adverse effects like Ototoxicity, skin irritations and stomach cramps, in people with existing heart conditions. The usage of furosemide is beneficial in heart patients however some people show some potential adverse effects. The drug poses its potential side effects only when the usage is high or in unauthorized dose and also depends on previously existed disease conditions. Keywords: furosemide; cardiovascular diseases; heart failure; ototoxicity; skin irritations; arithmetic mean; hepatic failure

Six-minute walk test as clinical end point in cardiomyopathy clinical trials, including ATTR-CM: a systematic literature review.

Aim: The six-minute walk test (6MWT) is acommon measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy (CM) trials, including transthyretin-mediated amyloidosis with CM (ATTR-CM), are often limited to hospitalization and mortality. Objective: To investigate the relationship between the 6MWT and hospitalization or mortality in CM, including ATTR-CM. Method: A PRISMA-guided systematic literature review was conducted using search terms for CM, 6MWT, hospitalization and mortality. Results: Forty-one studies were identified that reported 6MWT data and hospitalization or mortality data for patients with CM. The data suggest that a greater 6MWT distance is associated with a reduced risk of hospitalization or mortality in CM. Conclusion: The 6MWT is an accepted alternative end point in CM trials, including ATTR-CM.

Left ventricular mass as a modulator of ventricular arrhythmia risk and sex differences after CRT for nonischemic cardiomyopathy and LBBB

BackgroundThe risk of ventricular arrhythmias (VAs) after cardiac resynchronization therapy (CRT) has been associated with ischemic disease/scar, sex, and possibly left ventricular mass (LVM). ObjectiveThe purpose of this study was to evaluate sex differences and baseline/postimplant change in LVM on VA risk after CRT implantation in patients with nonischemic cardiomyopathy and left bundle branch block. MethodsIn patients meeting the criteria, baseline and follow-up echocardiographic images were obtained for LVM assessment. VA events were reported from device diagnostics and therapies. VA risk was stratified by receiver operating characteristic (Youden index cutoff point) for baseline LVM and baseline/postimplant change in LVM. Multivariate Cox regression model was also used for VA risk stratification. ResultsOne hundred eighteen patients (71 female patients [60.2%]; mean age 60.5 ± 11.3 years; left ventricular ejection fraction 19.2% ± 7.0%; QRS duration 165.6 ± 20 ms; LVM 313.9 ± 108.8 g) were enrolled and followed up for a median of 90 months (interquartile range 44–158 months). Thirty-five patients (29.6%) received appropriate shocks or antitachycardia pacing at a median of 73.5 months (interquartile range 25–130 months) postimplantation. Males had a higher VA incidence (male patients 18 of 47 [38.3%] vs female patients 17 of 71 [23.9%]; P = .02). Baseline LVM > 308.9 g separated patients with higher VA risk (P = .001). Less than a 20% decrease in LVM increased VA risk (P < .001). Baseline LVM was the only baseline characteristic predicting VA events in the Cox regression model (hazard ratio 1.01; 95% confidence interval 1.001–1.009; log-rank, P = .003). Sex differences in VA risk were eliminated by the baseline LVM parameters. ConclusionVA risk after CRT implantation in nonischemic cardiomyopathy was associated with baseline LV > 308.9 g and a decrease in LVM ≤ 20%, without sex differences.

Inflammatory Myocardial Disease Case Report Following COVID-19 Infection: Giant Cell Myocarditis versus Cardiac Sarcoidosis: To Be or Not to Be

Abstract COVID-19 can induce cardiac involvement, which can include myocardial infarction, various types of arrhythmia, atrioventricular block, myocarditis, acute heart failure, and sudden cardiac death, in approximately 30% of infected patients. There are some reports on the triggering of sarcoid-like reactions and inflammatory myocardial processes by various types of infections. However, little is known about the relationship between COVID-19 and inflammatory cardiomyopathies such as cardiac sarcoidosis (CS) and giant cell myocarditis (GCM). Herein, we describe the clinical course, management, and follow-up of an unmasked inflammatory cardiomyopathy in a 57-year-old Iranian woman, who presented with ventricular arrhythmia 4 months after mild COVID-19 infection. The onset of symptomatic inflammatory myocardial disorders such as CS or GCM may be triggered by COVID-19 infection. The best approach to the management of myocardial inflammatory COVID-19 should probably be individualized based on the patient’s clinical presentation and severity of cardiac involvement.

Echocardiography-Derived Hemodynamic Forces Are Associated with Clinical Outcomes in Patients with Non-Ischemic Dilated Cardiomyopathy.

Introduction: Non-ischemic dilated cardiomyopathy (NIDCM) is characterized by a reduced left ventricular (LV) ejection fraction (LVEF, <50%) and a high risk for heart failure (HF) and death. Echocardiography-derived hemodynamic forces (HDFs) may provide important information on LV mechanics, but their prognostic value is unknown. Aim: To explore the features of echocardiography-derived HDFs in NIDCM and their association with clinical endpoints. Methods: Asymptomatic, non-hospitalized NIDCM patients free from coronary artery disease and moderate or severe valvular heart disease were included in this single-center observational retrospective longitudinal study. Those with atrial fibrillation and a follow-up <12 months were excluded. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death, HF hospitalization, and ambulatory intravenous diuretics administration. LV HDFs were analyzed with a prototype software. Apex-base (HDFs-ab), lateral-septal (HDFs-ls), and HDFs-angle were computed. Results: Ninety-seven patients were included, sixty-seven (69%) were males, mean age was 62 ± 14 years, and mean LVEF was 39.2 ± 8.6%. During a median follow-up of 4.2 (3.1-5.1) years, 19 (20%) patients experienced MACE. These patients had a higher HDFs-angle (71.0 (67.0-75.0) vs. 68.0 (63.0-71.0)°, p = 0.005), lower HDFs-ls (1.36 (1.01-1.85) vs. 1.66 ([1.28-2.04])%, p = 0.015), but similar HDFs-ab (5.02 (4.39-6.34) vs. 5.66 (4.53-6.78)%, p = 0.375) compared to those without MACE. in a Cox regression analysis, HDFs-angle (HR 1.16 (95%-CI 1.04-1.30), p = 0.007) was associated with MACE, while other conventional echocardiography parameters, including LVEF and LV longitudinal strain, were not. Conclusions: HDFs-angle is associated with clinical endpoints in NIDCM. A higher HDFs-angle may be a marker of impaired myocardial performance in patients with reduced LVEF.

Deriving phenotype-representative left ventricular flow patterns by reduced-order modeling and classification

BackgroundExtracting phenotype-representative flow patterns and their associated numerical metrics is a bottleneck in the clinical translation of advanced cardiac flow imaging modalities. We hypothesized that reduced-order models (ROMs) are a suitable strategy for deriving simple and interpretable clinical metrics of intraventricular flow suitable for further assessments. Combined with machine learning (ML) flow-based ROMs could provide new insight to help diagnose and risk-stratify patients. MethodsWe analyzed 2D color-Doppler echocardiograms of 81 non-ischemic dilated cardiomyopathy (DCM) patients, 51 hypertrophic cardiomyopathy (HCM) patients, and 77 normal volunteers (Control). We applied proper orthogonal decomposition (POD) to build patient-specific and cohort-specific ROMs of LV flow. Each ROM aggregates a low number of components representing a spatially dependent velocity map modulated along the cardiac cycle by a time-dependent coefficient. We tested three classifiers using deliberately simple ML analyses of these ROMs with varying supervision levels. In supervised models, hyperparameter grid search was used to derive the ROMs that maximize classification power. The classifiers were blinded to LV chamber geometry and function. We ran vector flow mapping on the color-Doppler sequences to help visualize flow patterns and interpret the ML results. ResultsPOD-based ROMs stably represented each cohort through 10-fold cross-validation. The principal POD mode captured >80 % of the flow kinetic energy (KE) in all cohorts and represented the LV filling/emptying jets. Mode 2 represented the diastolic vortex and its KE contribution ranged from <1 % (HCM) to 13 % (DCM). Semi-unsupervised classification using patient-specific ROMs revealed that the KE ratio of these two principal modes, the vortex-to-jet (V2J) energy ratio, is a simple, interpretable metric that discriminates DCM, HCM, and Control patients. Receiver operating characteristic curves using V2J as classifier had areas under the curve of 0.81, 0.91, and 0.95 for distinguishing HCM vs. Control, DCM vs. Control, and DCM vs. HCM, respectively. ConclusionsModal decomposition of cardiac flow can be used to create ROMs of normal and pathological flow patterns, uncovering simple interpretable flow metrics with power to discriminate disease states, and particularly suitable for further processing using ML.

A Case Report and Literature Review of New-Onset Myasthenia Gravis after COVID-19 Infection

Myasthenia gravis (MG) is an autoimmune disorder affecting the neuromuscular junction caused by a B-cell-mediated, T-cell-dependent immunologic attack at the end plate of the postsynaptic membrane. Attack on muscle acetylcholine receptors (AChR) of the postsynaptic membrane due to the AChR, muscle-specific tyrosine kinase, or lipoprotein receptor-related peptide 4 antibodies lead to symptoms of painless, fluctuating weakness of muscle groups and often begins with ocular signs and symptoms. Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus closely related to SARS-CoV. Serious neurologic complications are infrequent and diverse with reported cases of stroke, encephalitis/meningitis, Guillain-Barré syndrome, acute disseminated encephalomyelitis, ataxia, and unspecified limb weakness. MG is a rarely reported sequela of COVID-19 infection. To date, there are 15 reported cases of post-COVID-19 MG. In this article, we present a case of post-COVID-19 MG and a concise review of other reported cases. An 83-year-old Caucasian male with a medical history of atrial fibrillation status post-ablation and non-ischemic cardiomyopathy was initially admitted for COVID-19 pneumonia. He was treated with remdesivir, convalescent plasma, and supplemental oxygen therapy but did not require invasive mechanical intubation. One month after discharge, he started experiencing fatigue with muscle weakness and progressive dyspnea. He progressed to develop dysphonia, especially at the end of the day. After extensive workup, he was diagnosed with MG with a positive antibody against the AChR. The chronological events of developing slowly worsening muscular weakness after recovering from COVID-19 infection and positive AChR antibody led to the diagnosis of post-COVID-19 new-onset MG. Post-COVID-19 fatigue, long-term use of steroids, and intensive care unit-related physical deconditioning ....

Multimodal explainable artificial intelligence identifies patients with non-ischaemic cardiomyopathy at risk of lethal ventricular arrhythmias

The efficacy of an implantable cardioverter-defibrillator (ICD) in patients with a non-ischaemic cardiomyopathy for primary prevention of sudden cardiac death is increasingly debated. We developed a multimodal deep learning model for arrhythmic risk prediction that integrated late gadolinium enhanced (LGE) cardiac magnetic resonance imaging (MRI), electrocardiography (ECG) and clinical data. Short-axis LGE-MRI scans and 12-lead ECGs were retrospectively collected from a cohort of 289 patients prior to ICD implantation, across two tertiary hospitals. A residual variational autoencoder was developed to extract physiological features from LGE-MRI and ECG, and used as inputs for a machine learning model (DEEP RISK) to predict malignant ventricular arrhythmia onset. In the validation cohort, the multimodal DEEP RISK model predicted malignant ventricular arrhythmias with an area under the receiver operating characteristic curve (AUROC) of 0.84 (95% confidence interval (CI) 0.71–0.96), a sensitivity of 0.98 (95% CI 0.75–1.00) and a specificity of 0.73 (95% CI 0.58–0.97). The models trained on individual modalities exhibited lower AUROC values compared to DEEP RISK [MRI branch: 0.80 (95% CI 0.65–0.94), ECG branch: 0.54 (95% CI 0.26–0.82), Clinical branch: 0.64 (95% CI 0.39–0.87)]. These results suggest that a multimodal model achieves high prognostic accuracy in predicting ventricular arrhythmias in a cohort of patients with non-ischaemic systolic heart failure, using data collected prior to ICD implantation.

Rare and Common Genetic Variation Underlying Atrial Fibrillation Risk

Atrial fibrillation (AF) has a substantial genetic component. The importance of polygenic risk is well established, while the contribution of rare variants to disease risk warrants characterization in large cohorts. To identify rare predicted loss-of-function (pLOF) variants associated with AF and elucidate their role in risk of AF, cardiomyopathy (CM), and heart failure (HF) in combination with a polygenic risk score (PRS). This was a genetic association and nested case-control study. The impact of rare pLOF variants was evaluated on the risk of incident AF. HF and CM were assessed in cause-specific Cox regressions. End of follow-up was July 1, 2022. Data were analyzed from January to October 2023. The UK Biobank enrolled 502 480 individuals aged 40 to 69 years at inclusion in the United Kingdom between March 13, 2006, and October 1, 2010. UK residents of European ancestry were included. Individuals with prior diagnosis of AF were excluded from analyses of incident AF. Rare pLOF variants and an AF PRS. Risk of AF and incident HF or CM prior to and subsequent to AF diagnosis. A total of 403 990 individuals (218 489 [54.1%] female) with a median (IQR) age of 58 (51-63) years were included; 24 447 were diagnosed with incident AF over a median (IQR) follow-up period of 13.3 (12.4-14.0) years. Rare pLOF variants in 6 genes (TTN, RPL3L, PKP2, CTNNA3, KDM5B, and C10orf71) were associated with AF. Of these, TTN, RPL3L, PKP2, CTNNA3, and KDM5B replicated in an external cohort. Combined with high PRS, rare pLOF variants conferred an odds ratio of 7.08 (95% CI, 6.03-8.28) for AF. Carriers with high PRS also had a substantial 10-year risk of AF (16% in female individuals and 24% in male individuals older than 60 years). Rare pLOF variants were associated with increased risk of CM both prior to AF (hazard ratio [HR], 3.13; 95% CI, 2.24-4.36) and subsequent to AF (HR, 2.98; 95% CI, 1.89-4.69). Rare and common genetic variation were associated with an increased risk of AF. The findings provide insights into the genetic underpinnings of AF and may aid in future genetic risk stratification.

Two-Year Outcomes of Primary Prophylactic Use of Defibrillators for Ischemic and Non-Ischemic Cardiomyopathy - Propensity Score-Matched Analysis From the Nippon Storm Study.

In 2016, the DANISH study reported negative results regarding the efficacy of implantable cardioverter-defibrillators (ICDs) in patients with non-ischemic cardiomyopathy (NICM) and reduced left ventricular ejection fraction (LVEF). In this study we determined the efficacy of using ICDs for primary prophylaxis in patients with NICM.Methods and Results: We selected 1,274 patients with underlying cardiac disease who were enrolled in the Nippon Storm Study. We analyzed the data of 451 patients with LVEF ≤35% due to NICM or ischemic cardiomyopathy (ICM) who underwent ICD implantation for primary prophylaxis (men, 78%; age, 65±12 years; LVEF, 25±6.4%; cardiac resynchronization therapy, 73%; ICM, 33%). After propensity score matching, we compared the baseline covariates between groups: NICM (132 patients) and ICM (132 patients). The 2-year appropriate ICD therapy risks were 27.7% and 12.2% in the NICM and ICM groups, respectively (hazard ratio, 0.390 [95% confidence interval, 0.218-0.701]; P=0.002). This subanalysis of propensity score-matched patients from the Nippon Storm Study revealed that the risk of appropriate ICD therapy was significantly higher in patients with NICM than in those with ICM.

Necropsy findings in heart transplant recipients with or without primary graft dysfunction

BackgroundPrimary graft dysfunction (PGD) is the leading cause of death in the first year after heart transplant (HT), but pathophysiology and histology are not completely understood. This study describes and compares morphological findings of hearts of patients with and without PGD. MethodsWe included adult patients submitted to HT in a single center who died within the first 14 days after HT and were submitted to necropsy. Clinical and histological data were recorded retrospectively. All heart slides were reviewed by a blinded pathologist. We categorized patients in two groups (PGD and non-PGD) and compared findings between them. ResultsAmong 322 HTs, 26 patients were included. Median age was 51.5 years, 57.7% were male, 46.1% had non-ischemic cardiomyopathy, 30.8% Chagas cardiomyopathy and 23% ischemic cardiomyopathy. Eleven patients presented PGD, while 15 patients did not. PGD was severe in 72.7% of cases and moderate in 27.3%. PGD group had longer ischemic time (p=0.08), higher incidence of mechanical circulatory support (p=0.004), lower post-transplant biventricular ejection fraction (p=0.005). However, necropsy findings were similar between groups. Necrosis was detected in 80.7% of all cases (p=0.907 comparing groups), taking ≥ 10% of myocardial area in 46.1% of them, and 4 types of necrosis were found either in patients with and without PGD. ConclusionCardiac pathological findings were similar in HT patients with or without PGD who died within 14 days after the transplant and necrosis was frequent in both groups, raising the hypothesis necrosis is not the cause of cardiac dysfunction in PGD.