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.

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.

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.

A Complicated Case of Transient Constrictive Pericarditis Secondary to Rivaroxaban-Associated Hemopericardium.

A 72-year-old man on rivaroxaban developed effusive constrictive pericarditis secondary to hemopericardium. His condition improved with anti-inflammatory therapy supporting a diagnosis of transient constrictive pericarditis. On follow-up, residual constriction developed requiring surgical pericardiectomy. Although many cases with transient constrictive pericarditis resolve with medical management, some may progress and require pericardiectomy. (Level of Difficulty: Advanced.).

A speckle-tracking strain-based artificial neural network model to differentiate cardiomyopathy type.

Objectives. In heart failure, invasive angiography is often employed to differentiate ischaemic from non-ischaemic cardiomyopathy. We aim to examine the predictive value of echocardiographic strain features alone and in combination with other features to differentiate ischaemic from non-ischaemic cardiomyopathy, using artificial neural network (ANN) and logistic regression modelling. Design. We retrospectively identified 204 consecutive patients with an ejection fraction <50% and a diagnostic angiogram. Patients were categorized as either ischaemic (n = 146) or non-ischaemic cardiomyopathy (n = 58). For each patient, left ventricular strain parameters were obtained. Additionally, regional wall motion abnormality, 13 electrocardiographic (ECG) features and six demographic features were retrieved for analysis. The entire cohort was randomly divided into a derivation and a validation cohort. Using the parameters retrieved, logistic regression and ANN models were developed in the derivation cohort to differentiate ischaemic from non-ischaemic cardiomyopathy, the models were then tested in the validation cohort. Results. A final strain-based ANN model, full feature ANN model and full feature logistic regression model were developed and validated, F1 scores were 0.82, 0.79 and 0.63, respectively. Conclusions. Both ANN models were more accurate at predicting cardiomyopathy type than the logistic regression model. The strain-based ANN model should be validated in other cohorts. This model or similar models could be used to aid the diagnosis of underlying heart failure aetiology in the form of the online calculator (https://cimti.usj.edu.lb/strain/index.html) or built into echocardiogram software.

Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension.

BACKGROUND: Pulmonary hypertension (PH) remains one of the rarest and deadliest diseases. Pulmonary Capillary Hemangiomatosis (PCH) is one of the sub-classes of PH. It was identified using histological and molecular tools and is characterized by the proliferation of capillaries into the alveolar septae. Mutations in the gene encoding the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) have recently been linked to this particular subgroup of PH. METHODS: In our effort to unveil the genetic basis of idiopathic and familial cases of PH in Lebanon, we have used whole exome sequencing to document known and/or novel mutations in genes that could explain the underlying phenotype. RESULTS: We showed bi-allelic mutations in EIF2AK4 in two non-consanguineous families: a novel non-sense mutation c.1672C > T (p.Q558*) and a previously documented deletion c.560_564drlAAGAA (p.K187Rfs9*). Our histological analysis coupled with the CT-scan results showed that the two patients with the p.Q558* mutation have PH. In contrast, only one of the individuals harboring the p.K187Rfs9* variant has a documented PCH while his older brother remains asymtomatic. Differential analysis of the variants in the genes of the neighboring network of EIF2AK4 between the two siblings identified a couple of interesting missense mutations that could account for this discrepancy. CONCLUSION: These findings represent a novel documentation of the involvement of EIF2AK4 in the different aspects of pulmonary hypertension. The absence of a molecular mechanism that relates the abrogated function of the protein to the phenotype is still a major hurdle in our understanding of the disease.

A New Index for Pre-Operative Cardiovascular Evaluation.

BACKGROUND: Currently used indices for pre-operative cardiovascular evaluation are either powerful, but complex, or simple, but with weak discriminatory power. OBJECTIVES: This study sought to prospectively derive and validate a simple powerful index that can stratify the cardiovascular risk of patients undergoing noncardiac surgery. METHODS: The derivation cohort consisted of 3,284 prospectively enrolled adult patients undergoing noncardiac surgery at the American University of Beirut Medical Center. The validation cohort consisted of 1,167,414 patients registered in the American College of Surgeons National Surgical Quality Improvement Program database. The primary outcome measure was death, myocardial infarction, or stroke at 30 days after surgery. RESULTS: The primary outcome occurred in 38 patients (1.2%) in the derivation cohort. Multivariate logistic regression analysis in the derivation cohort identified 6 data elements to be included in the prediction model: age ≥75 years, history of heart disease, symptoms of angina or dyspnea, hemoglobin <12 mg/dl, vascular surgery, and emergency surgery. Each patient was assigned a Cardiovascular Risk Index (CVRI) of 0, 1, 2, 3, and >3 based on the number of data elements present. The incidence of the primary outcome increased steadily across the CVRI groups in both the derivation (0%, 0.5%, 2.0%, 5.6%, and 15.7%, respectively; p < 0.0001) and validation (0.3%, 1.6%, 5.6%, 11.0%, and 17.5%, respectively; p < 0.0001) cohorts. The discriminatory power of the new CVRI was further confirmed by constructing a receiver-operating characteristic curve that had an area under the curve of 0.90 in the derivation cohort and 0.82 in the validation dataset. CONCLUSIONS: This study reports a new index for pre-operative cardiovascular evaluation which has a strong discriminatory power that can effectively stratify patients into low- (CVRI 0 to 1), intermediate- (CVRI 2 to 3), and high-risk (CVRI >3) groups. This has important implications for the efficient triage and management of patients scheduled for noncardiac surgery.

High Precision Digitization of Paper-Based ECG Records: A Step Toward Machine Learning.

INTRODUCTION: The electrocardiogram (ECG) plays an important role in the diagnosis of heart diseases. However, most patterns of diseases are based on old datasets and stepwise algorithms that provide limited accuracy. Improving diagnostic accuracy of the ECG can be done by applying machine learning algorithms. This requires taking existing scanned or printed ECGs of old cohorts and transforming the ECG signal to the raw digital (time (milliseconds), voltage (millivolts)) form. OBJECTIVES: We present a MATLAB-based tool and algorithm that converts a printed or scanned format of the ECG into a digitized ECG signal. METHODS: 30 ECG scanned curves are utilized in our study. An image processing method is first implemented for detecting the ECG regions of interest and extracting the ECG signals. It is followed by serial steps that digitize and validate the results. RESULTS: The validation demonstrates very high correlation values of several standard ECG parameters: PR interval 0.984 +/-0.021 (p-value < 0.001), QRS interval 1+/- SD (p-value < 0.001), QT interval 0.981 +/- 0.023 p-value < 0.001, and RR interval 1 +/- 0.001 p-value < 0.001. CONCLUSION: Digitized ECG signals from existing paper or scanned ECGs can be obtained with more than 95% of precision. This makes it possible to utilize historic ECG signals in machine learning algorithms to identify patterns of heart diseases and aid in the diagnostic and prognostic evaluation of patients with cardiovascular disease.

Clinical and genetic characteristics of pulmonary arterial hypertension in Lebanon.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an incidence rate of 2-6 cases per million per year. Our knowledge of the disease in the Middle East and North Africa (MENA) region is limited by the small number of clinical studies and the complete absence of genetic studies. METHODS: Our aim was to shed light on the clinical and genetic characteristics of PAH in Lebanon and the region by using exome sequencing on PAH patients referred to the American University of Beirut Medical Center (AUBMC). Twenty-one idiopathic, hereditary and Congenital Heart Disease (CHD) PAH patients were prospectively recruited, their clinical data summarized, and sequencing performed. RESULTS: The mean age at diagnosis was 33 years with a female preponderance of 70%. The mean pulmonary artery pressure at the time of diagnosis was 55. Genetic testing showed that 5 out of 19 idiopathic and Congenital Heart Disease PAH patients had Bone Morphogenetic Protein Receptor 2 (BMPR2) mutations at 25% prevalence, with 2 of these patients exhibiting a novel mutation. It also showed the presence of 1 BMPR2 mutation with 100% penetrance in a heritable PAH family. In the remaining cases, the lack of a complete genotype/phenotype correlation entailed a multigenic inheritance; suspected interactions involved previously associated genes T-box transcription factor 4 (TBX4), Bone Morphogenic Protein 10 (BMP10) and Growth Differentiation Factor 2 (GDF2). CONCLUSIONS: This is the first study that looks into the genetic causes of PAH, including known and new BMPR2 mutations, in the MENA region. It is also the first study to characterize the clinical features of the disease in Lebanon.