Unlocking the Enigma: Investigating I-Cell Disease in a Newborn Through Placental Pathology.

I-cell disease (Mucolipidosis Type II) is a rare lysosomal storage disorder caused by GNPTAB gene defects, leading to severe morbidity and mortality. The authors present the case of a neonate born at 38 wk gestational age, with suspected skeletal dysplasia during pregnancy and a complex clinical and laboratory presentation after birth. This is a rare case, and its diagnosis was made through placental pathology, which revealed the condition called mucolipidosis Type II. To the best of authors' knowledge, this is one of the few cases diagnosed in the neonatal period with placental pathology globally and the first in Canada, highlighting the significance of placental pathology for the diagnosis of these rare conditions and future counseling of the parents. In conclusion, mucolipidosis Type II is a rare condition in neonates. Early diagnosis in neonates can be made through placental pathology for parental counseling.

Echocardiographic Evaluation of Diastolic Function in Special Populations.

Left ventricular (LV) diastolic dysfunction results from a combination of impaired relaxation, reduced restoring forces, and increased chamber stiffness. Noninvasive assessment of diastology uses a multiparametric approach involving surrogate markers of increased filling pressures, which include mitral inflow, septal and lateral annular velocities, tricuspid regurgitation velocity, and left atrial volume index. However, these parameters must be used cautiously. This is because the traditional algorithms for evaluating diastolic function and estimation of LV filling pressures (LVFPs), as recommended by the American Society of Echocardiography and European Association of Cardiovascular Imaging 2016 guidelines, do not apply to unique patients with underlying cardiomyopathies, significant valvular disease, conduction abnormalities, arrhythmias, LV assist devices, and heart transplants, which alter the relation between the conventional indexes of diastolic function and LVFP. The purpose of this review is to provide solutions for evaluating LVFP through illustrative examples of these special populations, incorporating supplemental Doppler indexes, such as isovolumic relaxation time, mitral deceleration time, and pulmonary venous flow analysis, as needed to formulate a more comprehensive approach.

Update on cardiogenic shock: from detection to team management.

PURPOSE OF REVIEW: The following review is intended to provide a summary of contemporary cardiogenic shock (CS) profiling and diagnostic strategies, including biomarker and hemodynamic-based (invasive and noninvasive) monitoring, discuss clinical differences in presentation and trajectory between acute myocardial infarction (AMI)-CS and heart failure (HF)-CS, describe transitions to native heart recovery and heart replacement therapies with a focus on tailored management and emerging real-world data, and emphasize trends in team-based initiatives and interventions for cardiogenic shock including the integration of protocol-driven care. RECENT FINDINGS: This document provides a broad overview of contemporary scientific consensus statements as well as data derived from randomized controlled clinical trials and observational registry working groups focused on cardiogenic shock management. SUMMARY: This review highlights the increasingly important role of pulmonary artery catheterization in AMI-CS and HF-CS cardiogenic shock and advocates for routine application of algorithmic approaches with interdisciplinary care pathways. Cardiogenic shock algorithms facilitate the integration of clinical, hemodynamic, and imaging data to determine the most appropriate patient hemodynamic support platform to achieve adequate organ perfusion and decongestion.

Quantification of Significant Aortic Stenosis by Echocardiography versus Four-Dimensional Cardiac Computed Tomography: A Multi-Modality Imaging Study.

Transthoracic echocardiography (TTE) grading of aortic stenosis (AS) is challenging when parameters are discrepant, and four-dimensional cardiac computed tomography (4D-CCT) is increasingly utilized for transcatheter intervention workup. We compared TTE and 4D-CCT measures contributing to AS quantification. AS patients (n = 80, age 86 ± 10 years, 71% men) referred for transcatheter replacement in 2014−2017 were retrospectively studied, 20 each with high-gradient AS (HG-AS), classical and paradoxical low-flow low-gradient AS (CLFLG-AS and PLFLG-AS), and normal-flow low-gradient AS (NFLG-AS). Correlation and Bland−Altman analyses were performed between TTE and 4D-CCT parameters. There were moderate-to-high TTE versus 4D-CCT correlations for left ventricular volumes, function, mass, and outflow tract dimensions (r = 0.51−0.88), though values were mostly significantly higher by 4D-CCT (p < 0.001). Compared with 4D-CCT planimetry of aortic valve area (AVA), TTE estimates had modest correlation (r = 0.37−0.43) but were significantly lower (by 0.15−0.32 cm2). The 4D-CCT estimate of LVSVi lead to significant reclassification of AS subtype defined by TTE. In conclusion, 4D-CCT quantified values were higher than TTE for the left ventricle and AVA, and the AS subtype was reclassified based on LVSVi by 4D-CCT, warranting further research to establish its clinical implications and optimal thresholds in severe AS management.

Imaging and haemodynamic parameters associated with clinical outcomes following isolated tricuspid valve surgery.

INTRODUCTION: Isolated tricuspid valve surgery (TVS) may be associated with high morbidity and mortality. The aim of this study was to investigate the association of preoperative imaging and haemodynamic data derived from echocardiography (ECHO), cardiac magnetic resonance (CMR) and right heart catheterisation (RHC) with postoperative outcomes following TVS. METHODS: In a retrospective cohort study, patients who underwent isolated TVS at our institution between 2012 and 2020 were screened and followed up to 1 year. We only included those who had all three tests before surgery: ECHO, CMR and RHC. Patients with congenital heart disease, infective endocarditis and those who underwent concomitant valve or pericardial surgery were excluded. The primary outcome was a composite of mortality and congestive heart failure at 1 year. Time-to-event analyses at 1 year and Cox proportional hazards regression analyses were performed. RESULTS: A total of 60 patients were included (mean age of 60±14 years, 63% women), of whom 67% underwent TV repair. The primary outcome occurred in 16 patients (27%) with a 1-year mortality of 7%. It was associated with ECHO-derived right ventricular (RV) free wall strain and RHC-derived RV systolic and diastolic as well as mean pulmonary pressures. On multivariable Cox regression analysis, only RV systolic and diastolic pressures were significantly associated with the primary outcome at 1 year (HRs=5.9 and 3.4, respectively, p<0.05). CONCLUSION: Baseline invasive haemodynamic assessment could have a strong association with clinical outcomes and help risk-stratify patients undergoing isolated TVS.

Impact of elevated left ventricular filling pressure on long-term outcomes after transcatheter aortic valve replacement.

BACKGROUND: Increase in left ventricular filling pressure (FP) and diastolic dysfunction are established consequences of progressive aortic stenosis (AS). However, the impact of elevated FP as detected by pretranscatheter aortic valve replacement (TAVR) echocardiogram on long-term outcomes after TAVR remains unclear. OBJECTIVE: To understand the impact of elevated FP in patients with severe AS who undergo TAVR. METHODS: This was a retrospective study of all patients who underwent TAVR between 1 January 2014 and 31 December 2017. The presence of elevated FP was determined in accordance with the latest guidelines using the last available comprehensive echocardiogram prior to TAVR. RESULTS: Of 983 patients who were included in our study, 422 patients (43%) were found to have elevated FP and 561 patients (57%) had normal FP prior to TAVR. Patients with elevated FP had a mean age of 81.2±8.6 years and were more likely to be males (62%), diabetic (41% vs 35%, p=0.046), and have a higher prevalence of atrial fibrillation (Afib) (53% vs 39%, p<0.001). The 5-year all-cause mortality after TAVR was significantly higher in patients with elevated FP when compared with patients with normal FP (32% vs 24%, p=0.006). The presence of elevated FP, history of Afib and prior PCI emerged as independent predictors of long-term mortality after TAVR. CONCLUSION: Elevated FP is associated with increased mortality in patients with severe AS undergoing TAVR. Assessment of FP should be incorporated into the risk assessment of AS patients to identify those who may benefit from early intervention.

Association Between Atrial Uptake on Cardiac Scintigraphy With Technetium-99m-Pyrophosphate Labeled Bone-Seeking Tracers and Atrial Fibrillation.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disease, in which atrial fibrillation (AF) has been shown to be prevalent. Cardiac scintigraphy with technetium-99m-pyrophosphate (99mTc-PyP) labeled bone-seeking tracers is used to noninvasively make the diagnosis of ATTR-CA, based on ventricular myocardial uptake. Assessment of atrial wall uptake (AU) on 99mTc-PyP is currently not used in the clinical setting Methods: We analyzed a cohort of patients referred for 99mTc-PyP scan at a tertiary center to explore AU and associations between any and incident AF, ATTR-CA, and all-cause mortality. RESULTS: Among 580 patients included, 296 patients (51%) had a diagnosis of AF; 164 patients (28%) had scans consistent with ATTR-CA while 117 patients (20%) had AU. Of 117 patients with AU, 107 (91%) had any AF. In contrast, of 463 patients without AU 191(41%) had any AF. Of those with AU, 59/117(50%) patients had a 99mTc-PyP diagnosis of ATTR-CA while 58/117(50%) patients did not have such a diagnosis (P=1.00). Patients with AU had significantly more any AF (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04]; P<0.001), independent of ATTR-CA diagnosis and sex. On multivariable Cox proportional hazards analyses adjusting for age, AU, ATTR-CA diagnosis, sex, smoking, hypertension, diabetes, left ventricular ejection fraction, and coronary artery disease, both age (HR, 1.03 [95% CI, 1.02-1.04]; P<0.0001) and AU (HR, 2.68 [95% CI, 2.11-3.41]; P<0.0001) were independently associated with the development of any AF. Freedom from incident AF at 1-year was significantly lower in patients with AU, both in patients with and without ATTR-CA respectively (HR, 2.27 [95% CI, 1.37-3.78]; P<0.0001 versus HR, 2.21 [95% CI, 1.46-3.34]; P<0.0001). CONCLUSIONS: In a consecutive cohort of patients undergoing 99mTc-PyP scans, 20% had AU, which was statistically associated with any AF, independently of ATTR-CA diagnosis and sex. AU was associated with significantly lower freedom from incident AF at 1-year. Overlooking AU on 99mTc-PyP scans could potentially miss an earlier disease manifestation, or an additional risk factor for any/incident AF.

The role of multimodality imaging in patients with heart failure with reduced and preserved ejection fraction.

PURPOSE OF REVIEW: The burden of clinical heart failure, both heart failure with a reduced ejection fraction (HFrEF) and with a preserved ejection fraction (HFpEF), continues to increase both nationally and globally. This review summarizes the expanding role of multimodality imaging techniques in the evaluation and management these patients. RECENT FINDINGS: Echocardiographic assessment for heart failure continues to expand and should include a robust hemodynamic and strain assessment. Nuclear techniques have also continued to evolve and advances including computed tomography attenuation correction for single photon emission-computed tomography positron-emission tomography increase diagnostic accuracy as well as provide information such as myocardial blood flow and viability assessment. Computed tomography imaging, already well established in the assessment of coronary and valvular disease, has increasing utility in the characterization of myopathy, and cardiac magnetic resonance imaging (MRI) continues to expand its role in tissue characterization to a wider breadth of diseases, including right ventricular cardiomyopathy and left ventricle noncompaction. SUMMARY: Although heart failure remains a clinical diagnosis based on history and examination, early imaging is critical for further assessment. Due to its widespread availability, affordability, and safety, transthoracic echocardiography has long been the mainstay tool for both initial evaluation as well as for periodic surveillance of heart failure patients, but advances in multimodality imaging are occurring at a rapid pace and promise to provide an increasing wealth of data to help manage such patients.

SARS-CoV-2 Myocarditis: Insights Into Incidence, Prognosis, and Therapeutic Implications.

PURPOSE OF REVIEW: In coronavirus disease 2019 (COVID-19), myocardial injury occurs frequently in severe or critically ill hospitalized patients, yet myocarditis is much less common. In this context, revisiting the definition of myocarditis is appropriate with a specific focus on diagnostic and management considerations in patients infected with SARS-CoV-2. RECENT FINDINGS: Pathologic cardiac specimens from patients with COVID-19 suggest a mixed inflammatory response involving lymphocytes and macrophages, and importantly, cellular injury occurs predominantly at the level of pericytes and endothelial cells, less often involving direct myocyte necrosis. In COVID-19, the diagnosis of myocarditis has understandably been based predominantly on clinical criteria, and the number of patients with clinically suspected myocarditis who would meet diagnostic histological criteria is unclear. Echocardiography and cardiac magnetic resonance are important diagnostic tools, although the prognostic implications of abnormalities are still being defined. Importantly, SARS-CoV2 myocarditis should be diagnosed within an appropriate clinical context and should not be based on isolated imaging findings. Therapies in COVID-19 have focused on the major clinical manifestation of pneumonia, but the promotion of viral clearance early in the disease could prevent the development of myocarditis, and further study of immunosuppressive therapies once myocarditis has developed are indicated. A strict and uniform approach is needed to diagnose myocarditis due to SARS-CoV-2 to better understand the natural history of this disease and to facilitate evaluation of potential therapeutic interventions. A methodological approach will also better inform the incidence of COVID-19 associated myocarditis and potential long-term health effects.

Strain evaluation for mitral annular disjunction by echocardiography and magnetic resonance imaging: A case-control study.

BACKGROUND: Mitral annular disjunction (MAD) is an increasingly recognized entity associated with mitral valve prolapse (MVP), ventricular arrhythmias and death. Few studies have investigated the utility of myocardial deformation analysis in MAD. We compared chamber quantification including strain by transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) between MVP patients with and without MAD. METHODS: Forty-two patients with MVP (21 with MAD, 21 without MAD) and 21 controls were studied. Global, basal and basal inferolateral (BIL) segmental strains were measured and compared using velocity-vector imaging TTE and feature-tracking CMR. RESULTS: Mean age was 54 ± 17 years, 19 (46%) were female, and 19 (46%) underwent surgical mitral valve repair with no deaths during follow-up in the 2 groups with MVP. Patients with MAD and MVP had lower basal longitudinal strain by TTE than those with MVP without MAD. Those with MAD and MVP had lower magnitude in BIL and basal segments by circumferential and radial strain by CMR compared to those with MVP without MAD and controls. Amongst global strain parameters, CMR-derived global circumferential strain was independently associated with MAD diagnosis odds ratio 1.49 (per 1%), 95% confidence interval 1.09-2.05, P = 0.014, with optimal threshold of -18.0% having 76% sensitivity and specificity for MAD. CONCLUSION: Abnormal circumferential and radial strain patterns in the basal segments by CMR may be useful for identifying regional LV dysfunction associated with MAD.

Recurrent pericarditis associated with human coronavirus (HKU1) infection in a patient with systemic lupus erythematosus (SLE).

The presence of human coronavirus HKU1 infection associated with pericardial inflammation is not reported. We are reporting a young woman with systemic lupus erythematosus, who was positive for HKU1 during her pericarditis flare. Diagnostic imaging demonstrated pericardial effusion, edema, and late gadolinium enhancement on cardiac magnetic resonance imaging and echocardiography. She was on multiple anti-inflammatory medications and achieved remission with anakinra. Her management and a brief literature review is also presented.

Double-blind randomized proof-of-concept trial of canakinumab in patients with COVID-19 associated cardiac injury and heightened inflammation.

Aims: In coronavirus disease 2019 (COVID-19), myocardial injury is associated with systemic inflammation and higher mortality. Our aim was to perform a proof of concept trial with canakinumab, a monoclonal antibody to interleukin-1ß, in patients with COVID-19, myocardial injury, and heightened inflammation. Methods and results: This trial required hospitalization due to COVID-19, elevated troponin, and a C-reactive protein concentration more than 50 mg/L. The primary endpoint was time to clinical improvement at Day 14, defined as either an improvement of two points on a seven-category ordinal scale or discharge from the hospital. The secondary endpoint was mortality at Day 28. Forty-five patients were randomly assigned to canakinumab 600 mg (n = 15), canakinumab 300 mg (n = 14), or placebo (n = 16). There was no difference in time to clinical improvement compared to placebo [recovery rate ratio (RRR) for canakinumab 600 mg 1.15, 95% confidence interval (CI) 0.46-2.91; RRR for canakinumab 300 mg 0.61, 95% CI 0.23-1.64]. At Day 28, 3 (18.8%) of 15 patients had died in the placebo group, compared with 3 (21.4%) of 14 patients with 300 mg canakinumab, and 1 (6.7%) of 15 patients with 600 mg canakinumab. There were no treatment-related deaths, and adverse events were similar between groups. Conclusion: There was no difference in time to clinical improvement at Day 14 in patients treated with canakinumab, and no safety concerns were identified. Future studies could focus on high dose canakinumab in the treatment arm and assess efficacy outcomes at Day 28.

Founder Mutation in N Terminus of Cardiac Troponin I Causes Malignant Hypertrophic Cardiomyopathy.

BACKGROUND: Cardiac troponin I (TNNI3) gene mutations account for 3% of hypertrophic cardiomyopathy and carriers have a heterogeneous phenotype, with increased risk of sudden cardiac death (SCD). Only one mutation (p.Arg21Cys) has been reported in the N terminus of the protein. In model organisms, it impairs PKA (protein kinase A) phosphorylation, increases calcium sensitivity, and causes diastolic dysfunction. The phenotype of this unique mutation in patients with hypertrophic cardiomyopathy remains unknown. METHODS: We sequenced 29 families with hypertrophic cardiomyopathy enriched for pediatric-onset disease and identified 5 families with the TNNI3 p.Arg21Cys mutation. Using cascade screening, we studied the clinical phenotype of 57 individuals from the 5 families with TNNI3 p.Arg21Cys-related cardiomyopathy. We performed survival analysis investigating the age at first SCD in carriers of the mutation. RESULTS: All 5 families with TNNI3 p.Arg21Cys were from South Lebanon. TNNI3 p.Arg21Cys-related cardiomyopathy manifested a malignant phenotype-SCD occurred in 30 (53%) of 57 affected individuals at a median age of 22.5 years. In select carriers without left ventricular hypertrophy on echocardiogram, SCD occurred, myocyte disarray was found on autopsy heart, and tissue Doppler and cardiac magnetic resonance imaging identified subclinical disease features such as diastolic dysfunction and late gadolinium enhancement. CONCLUSIONS: The TNNI3 p.Arg21Cys mutation has a founder effect in South Lebanon and causes malignant hypertrophic cardiomyopathy with early SCD even in the absence of hypertrophy. Genetic diagnosis with this mutation may be sufficient for risk stratification for SCD.

Update on MRI Techniques for Evaluation of Pericardial Disease.

PURPOSE OF REVIEW: Cardiovascular magnetic resonance (CMR) provides the most comprehensive imaging assessment of pericardial disease, providing a three-dimensional assessment of the pericardium, functional assessment of its impact on cardiac contractility, and pericardial tissue/fluid characterization. This review presents an update on the utility of CMR imaging in a wide variety of pericardial diseases. RECENT FINDINGS: CMR provides both qualitative and quantitative assessment of the pericardium through various imaging techniques. It can also be used as a guide therapy and delineate response to treatment in pericarditis. CMR is also useful for the assessment of rare congenital disorders and in defining pericardial tumors and differentiating some non-invasively. CMR is a powerful non-invasive diagnostic tool for evaluating and characterizing pericardial diseases. Ongoing optimization of imaging techniques allows for differentiation of subtypes of disease as well as progression. Ongoing research demonstrates continued expanding role of CMR in both the diagnosis and management of pericardial and cardiovascular disease.

Multi-modality imaging of cardiac amyloidosis: Contemporary update.

Cardiac amyloidosis is a heterogeneous and challenging diagnostic disease with poor prognosis that is now being altered by introduction of new therapies. Echocardiography remains the first-line imaging tool, and when disease is suspected on echocardiography, cardiac magnetic resonance imaging and nuclear imaging play critical roles in the non-invasive diagnosis and evaluation of cardiac amyloidosis. Advances in multi-modality cardiac imaging allowing earlier diagnosis and initiation of novel therapies have significantly improved the outcomes in these patients. Cardiac imaging also plays important roles in the risk stratification of patients presenting with cardiac amyloidosis. In the current review, we provide a clinical and imaging focused update, and importantly outline the imaging protocols, diagnostic and prognostic utility of multimodality cardiac imaging in the assessment of cardiac amyloidosis.

Canakinumab to reduce deterioration of cardiac and respiratory function in SARS-CoV-2 associated myocardial injury with heightened inflammation (canakinumab in Covid-19 cardiac injury: The three C study).

BACKGROUND: In patients with Covid-19, myocardial injury and increased inflammation are associated with morbidity and mortality. We designed a proof-of-concept randomized controlled trial to evaluate whether treatment with canakinumab prevents progressive respiratory failure and worsening cardiac dysfunction in patients with SARS-CoV2 infection, myocardial injury, and high levels of inflammation. HYPOTHESIS: The primary hypothesis is that canakiumab will shorten time to recovery. METHODS: The three C study (canakinumab in Covid-19 Cardiac Injury, NCT04365153) is a double-blind, randomized controlled trial comparing canakinumab 300 mg IV, 600 mg IV, or placebo in a 1:1:1 ratio in hospitalized Covid-19 patients with elevations in troponin and C-reactive protein (CRP). The primary endpoint is defined as the time in days from randomization to either an improvement of two points on a seven category ordinal scale or discharge from the hospital, whichever occurs first up to 14 days postrandomization. The secondary endpoint is mortality at day 28. A total of 45 patients will be enrolled with an anticipated 5 month follow up period. RESULTS: Baseline characteristics for the first 20 randomized patients reveal a predominantly male (75%), elderly population (median 67 years) with a high prevalence of hypertension (80%) and hyperlipidemia (75%). CRPs have been markedly elevated (median 16.2 mg/dL) with modest elevations in high-sensitivity troponin T (median 21 ng/L), in keeping with the concept of enrolling patients with early myocardial injury. CONCLUSIONS: The three C study will provide insights regarding whether IL-1ß inhibition may improve outcomes in patients with SARS-CoV2 associated myocardial injury and increased inflammation.

AUB-HAS2 Cardiovascular Risk Index: Performance in Surgical Subpopulations and Comparison to the Revised Cardiac Risk Index.

Background The American University of Beirut (AUB)-HAS2 Cardiovascular Risk Index is a newly derived index for preoperative cardiovascular evaluation. It is based on 6 data elements: history of heart disease; symptoms of angina or dyspnea; age ≥75 years; hemoglobin <12 mg/dL; vascular surgery; and emergency surgery. In this study we analyze the performance of this new index and compare it with that of the Revised Cardiac Risk Index in a broad spectrum of surgical subpopulations. Methods and Results The study population consisted of 1 167 278 noncardiac surgeries registered in the American College of Surgeons National Surgical Quality Improvement Program database. Each patient was given an AUB-HAS2 score of 0, 1, 2, 3, or >3, depending on the number of data elements present. The performance of the AUB-HAS2 index was studied in 9 surgical specialty groups and in 8 commonly performed site-specific surgeries. Receiver operating characteristic curves were constructed for the AUB-HAS2 and Revised Cardiac Risk Index measures, and the areas under the curve were compared. The outcome measure was death, myocardial infarction, or stroke at 30 days after surgery. The AUB-HAS2 score was able to stratify risk in all surgical subgroups (P<0.001). In the majority of surgeries, patients with an AUB-HAS2 score of 0 had an event rate of <0.5%. The performance of the AUB-HAS2 index was superior to that of the Revised Cardiac Risk Index in all surgical subgroups (P<0.001). Conclusions This study extends the validation of the AUB-HAS2 index to a broad spectrum of surgical subpopulations and demonstrates its superior discriminatory power compared with the commonly utilized Revised Cardiac Risk Index.