Cause Of Left Ventricular Hypertrophy Research Articles

Fabry Disease: More than a Phenocopy of Hypertrophic Cardiomyopathy.

Fabry disease (FD) is a genetic lysosomal storage disease with frequent cardiovascular involvement, whose presence is a major determinant of adverse clinical outcomes. As a potentially treatable cause of left ventricular hypertrophy (LVH) and heart failure with preserved ejection fraction, the early recognition of FD is crucial to initiate enzyme replacement therapy and improve long-term prognosis. Multimodality imaging plays a central role in the evaluation of patients with FD and helps in the differential diagnosis of other conditions presenting with LVH. In the present review, we explore the current applications of multimodality cardiac imaging, in particular echocardiography and cardiovascular magnetic resonance, in the diagnosis, prognostic assessment, and follow-up of patients with FD.

Dissociation of LA volume and deformation is a hallmark of ATTR-CA

Abstract Background Transthyretin Cardiac amyloidosis (ATTR-CA) is associated with an infiltrative left atrial (LA) cardiomyopathy. Purpose We sought to identify unique characteristics of LA cardiomyopathy in CA compared to non-amyloid states of left ventricular hypertrophy (LVH). Methods In suspected patients, a diagnosis of ATTR-CA was made by a positive Tc-99m PYP in conjunction with negative serum/urine studies for a clonal plasma cell dyscrasia. Endomyocardial biopsy was performed when clinically indicated. All patients underwent complete transthoracic echocardiography (TTE) with speckle tracking strain imaging. Left ventricular (LV) strain, LA reservoir strain (LASr) and LA volume index (LAVI) were measured. LA stiffness index was estimated by the ratio (E/e’)/LASr. ATTR-CA patients were compared to patient with non- CA LVH (interventricular septal thickness > 1.2 cm). Atrial fibrillation (AF) during the TTE was noted. Logistic regression and Cox-regression analyses were performed to find the independent determinant of ATTR-CA and outcome predictors, respectively. Results We studied 98 patients with ATTR-CA (44 with AF) and 62 patients with non-CA LVH (35 with AF). ATTR-CA patients had a higher prevalence of relative apical sparing (RAS) (79% vs 20%, p<0.0001), reduced LASr (9.8±4.8% vs 14.0±7.2%; p<0.001) and high LA stiffness (2.5±0.2 vs 1.4±0.9; p<0.001) irrespective of AF. Surprisingly, LAVI of ATTR-CA patients was significantly lower than non- CA LVH patients (44±15 ml/m2 vs 51±24 ml/m2; p=0.046). Consequently, LAVI correlated strongly with LASr in non-amyloid LVH group (r= -0.52, p<0.001) whereas no correlation was observed in ATTR-CA (p<0.05) (Figure 1). Patients with ATTR-CA had the lowest LASr and highest LA stiffness regardless of AF (Figure 2). Importantly, LASr determined ATTR-CA among all study subjects independently of RAS (p<0.001) and emerged as a predictor of composite endpoint including all-cause mortality, hospitalization from heart failure and stroke in ATTR-CA patients (p=0.037). Conclusion ATTR-CA is characterized by severely reduced LASr and increased LA stiffness, yet LA dilatation is relatively less severe when compared to other causes of LVH. LASr seems promising to make the differential diagnosis of ATTR-CA and is of prognostic importance.Figure 1Figure 2

Abstract 17053: Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Mortality in Hypertrophic Cardiomyopathy: A Retrospective Study

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been demonstrated to improve outcomes in congestive heart failure (HF). However, their effect in hypertrophic cardiomyopathy (HCM) is unknown. Research Question: Can SGLT2i improve clinical outcomes in HCM patients? Methods: Using TriNetX Global Research Network from March 2013 to February 2021, patients diagnosed with HCM (ICD-10 codes I42.1, I42.2) were identified and categorized into 2 groups: those on SGLT2i vs. those who are not. To avoid inclusion of other causes of left ventricular hypertrophy, patients with aortic stenosis or systemic hypertension were excluded. Propensity score matching (PSM) was used to limit confounders. Primary outcome was all-cause mortality and secondary outcomes were HF exacerbation, all-cause hospitalization, and documented cardiovascular symptoms (chest pain, dyspnea, palpitations, or leg edema) over a 2-year follow-up period. Results: A total of 27,561 HCM patients were identified; 408 (1.5%) on SGLT2i and 27,153 (98.5%) were not. Patients on SGLT2i were older (55 ± 15 vs. 48 ± 19, p<0.01) and had more comorbidities, including a nearly 6-fold higher prevalence of diabetes mellitus (44% vs. 7%, p<0.01) and congestive HF (65% vs. 10%, p<0.01). After PSM, each group consisted of 355 patients. HCM patients on SGLT2i had lower rates of all-cause mortality (OR 0.22 [95% CI: 0.12, 0.39]; p<0.01), hospitalizations (OR 0.72 [95% CI: 0.53, 0.98]; p=0.04), and cardiovascular symptoms (OR 0.71 [95% CI: 0.52, 0.97]; p=0.029) when compared to patients not on SGLT2i. There was no statistical difference in the rate of HF exacerbation (OR 0.82 [95% CI: 0.54, 1.24]; p=0.3). Conclusion: In this large dataset, SGLT2i use in a select subset of HCM patients was associated with improved survival, less hospitalizations, and fewer cardiovascular symptoms. These data support future randomized trials to evaluate the efficacy and safety of SGLT2i in more diverse HCM patient populations.

A pragmatic clinical trial assessing the effect of a targeted notification and clinical support pathway on the diagnostic evaluation and treatment of individuals with left ventricular hypertrophy (NOTIFY-LVH)

Electronic health records contain vast amounts of cardiovascular data, including potential clues suggesting unrecognized conditions. One important example is the identification of left ventricular hypertrophy (LVH) on echocardiography. If the underlying causes are untreated, individuals are at increased risk of developing clinically significant pathology. As the most common cause of LVH, hypertension accounts for more cardiovascular deaths than any other modifiable risk factor. Contemporary healthcare systems have suboptimal mechanisms for detecting and effectively implementing hypertension treatment before downstream consequences develop. Thus, there is an urgent need to validate alternative intervention strategies for individuals with preexisting-but potentially unrecognized-LVH. Through a randomized pragmatic trial within a large integrated healthcare system, we will study the impact of a centralized clinical support pathway on the diagnosis and treatment of hypertension and other LVH-associated diseases in individuals with echocardiographic evidence of concentric LVH. Approximately 600 individuals who are not treated for hypertension and who do not have a known cardiomyopathy will be randomized. The intervention will be directed by population health coordinators who will notify longitudinal clinicians and offer to assist with the diagnostic evaluation of LVH. Our hypothesis is that an intervention that alerts clinicians to the presence of LVH will increase the detection and treatment of hypertension and the diagnosis of alternative causes of thickened myocardium. The primary outcome is the initiation of an antihypertensive medication. Secondary outcomes include new hypertension diagnoses and new cardiomyopathy diagnoses. The trial began in March 2023 and outcomes will be assessed 12 months from the start of follow-up. The NOTIFY-LVH trial will assess the efficacy of a centralized intervention to improve the detection and treatment of hypertension and LVH-associated diseases. Additionally, it will serve as a proof-of-concept for how to effectively utilize previously collected electronic health data to improve the recognition and management of a broad range of chronic cardiovascular conditions. NCT05713916.

Classifying hypertension mediated left ventricular hypertrophy phenotypes from the 12-lead electrocardiogram using machine learning

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Pat Merriman Clinical Research Training Fellowship Background Hypertension is the commonest cause of left ventricular hypertrophy (LVH), an established independent predictor of cardiovascular morbidity and mortality. Four distinct LVH phenotypes with varying prognostic implications have been reported using cardiac magnetic resonance (CMR) LV mass to volume ratio: normal LV, LV remodelling, eccentric LVH and concentric LVH. Current electrocardiogram (ECG) criteria can detect LVH but their ability to differentiate between hypertension mediated LVH phenotypes is unknown. Purpose The aim of this study was to classify hypertension mediated LVH phenotypes using 12-lead electrocardiogram (ECG) and clinical data for cost-effective patient stratification. Methods 24,535 hypertensive participants from UK Biobank imaging study were categorised into the CMR-defined LVH phenotypes. ECG biomarkers with a physiological association with LVH (including QRS biomarkers, Sokolow-Lyon and Cornell voltage) were extracted from the 12-lead ECG of each participant using in-house algorithms. Vascular risk factors known to be associated with LVH were also ascertained from the clinical data of each participant. Classification models integrating ECG biomarkers and clinical data were built using logistic regression, support vector machine (SVM) and random forest (RF). The dataset was split into 80% train and 20% test sets for performance measurement. Ten-fold cross validation was applied and the training set was downsampled to the minority class. Results Among the participants (mean age ± standard deviation 65.3 ± 7.4 years), 23,312 (95.0%) had normal LV, 900 (3.7%) LV remodelling, 220 (0.8%) eccentric LVH and 103 (0.4%) concentric LVH. R wave amplitude V5, S wave amplitude V3 and QT duration V6 (P<0.001) were the top ECG biomarkers and systolic blood pressure (p<0.001) the top clinical predictor of LVH phenotypes (Figure 1). Classification with logistic regression had an accuracy of 77% (sensitivity 55%, specificity 85%, Area under the receiver operator curve [AUC] 0.76), SVM 80% accuracy (sensitivity 61%, specificity 87%, AUC 0.75) and RF 75% accuracy (sensitivity 49%, specificity 83%, AUC 0.75). ECG biomarkers enhanced model performance of all classifiers, compared to using clinical data alone. Conclusion A combination of automatically extracted ECG biomarkers and clinical data were able to discriminate the hypertension mediated LVH phenotypes. An advanced classification approach improves selection of hypertensive patients with LVH, thereby adding prognostic value to traditional risk models. We are currently validating our findings in an external population and using deep learning for comparison.

Multi-channel deep learning model-based myocardial spatial–temporal morphology feature on cardiac MRI cine images diagnoses the cause of LVH

BackgroundTo develop a fully automatic framework for the diagnosis of cause for left ventricular hypertrophy (LVH) via cardiac cine images.MethodsA total of 302 LVH patients with cine MRI images were recruited as the primary cohort. Another 53 LVH patients prospectively collected or from multi-centers were used as the external test dataset. Different models based on the cardiac regions (Model 1), segmented ventricle (Model 2) and ventricle mask (Model 3) were constructed. The diagnostic performance was accessed by the confusion matrix with respect to overall accuracy. The capability of the predictive models for binary classification of cardiac amyloidosis (CA), hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD) were also evaluated. Additionally, the diagnostic performance of best Model was compared with that of 7 radiologists/cardiologists.ResultsModel 3 showed the best performance with an overall classification accuracy up to 77.4% in the external test datasets. On the subtasks for identifying CA, HCM or HHD only, Model 3 also achieved the best performance with AUCs yielding 0.895–0.980, 0.879–0.984 and 0.848–0.983 in the validation, internal test and external test datasets, respectively. The deep learning model showed non-inferior diagnostic capability to the cardiovascular imaging expert and outperformed other radiologists/cardiologists.ConclusionThe combined model based on the mask of left ventricular segmented from multi-sequences cine MR images shows favorable and robust performance in diagnosing the cause of left ventricular hypertrophy, which could be served as a noninvasive tool and help clinical decision.

Mitochondrial Cardiomyopathy: Distinctive Cardiac Phenotype Detected with Cardiovascular MRI

Left ventricular hypertrophy (LVH) has a broad differential diagnosis. Pathogenic variants of mitochondrial DNA are a rare cause of LVH, and cardiac MRI is a powerful technique that may aid in differentiating such rare causes. This case report presents three siblings with a pathogenic variant of the mitochondrially encoded tRNA isoleucine (MT-TI) gene. A distinctive cardiac phenotype was detected with cardiac MRI. Extensive LVH and dilatation and decreased ejection fraction were observed with a pattern of increased T2 signal and extensive late gadolinium enhancement, which was remarkably consistent among all three siblings. Keywords: Cardiomyopathies, MR Imaging, Hypertrophic Cardiomyopathy, Mitochondrial, Inherited Cardiomyopathy, Left Ventricular Hypertrophy, Cardiovascular MRI, Late Gadolinium Enhancement Supplemental material is available for this article. © RSNA, 2023.

Effect of the structural modification of Candesartan with Zinc on hypertension and left ventricular hypertrophy

Hypertension is the most common cause of left ventricular hypertrophy, contributing to heart failure progression. Candesartan (Cand) is an angiotensin receptor antagonist widely used for hypertension treatment. Structural modifications were previously performed by our group using Zinc (ZnCand) as a strategy for improving its pharmacological properties. The measurements showed that ZnCand exerts a stronger interaction with the angiotensin II receptor, type 1 (AT1 receptor), reducing oxidative stress and intracellular calcium flux, a mechanism implied in cell contraction. These results were accompanied by the reduction of the contractile capacity of mesangial cells. In vivo experiments showed that the complex causes a significant decrease in systolic blood pressure after 8 weeks of treatment in spontaneously hypertensive rats (SHR). The reduction of heart hypertrophy was evidenced by echocardiography, the histologic cross-sectional area of cardiomyocytes, collagen content, the B-type natriuretic peptide (BNP) marker and connective tissue growth factor (CTGF) and the matrix metalloproteinase 2 (MMP-2) expression. Besides, the complex restored the redox status. In this study, we demonstrated that the complexation with Zn(II) improves the antihypertensive and cardiac effects of the parental drug.

Current and emerging perspectives on pathophysiology, diagnosis, and management of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common genetically inherited cardiomyopathy with an autosomal dominant inheritance pattern. A disease-causing gene is found between 34% and >60% of the times and the two most frequently mutated genes, which encode sarcomeric proteins, are MYBPC3 and MYH7. HCM is a diagnosis of exclusion since secondary causes of left ventricular hypertrophy should first be ruled out. These include hypertension, aortic stenosis, infiltrative disease, metabolic and endocrine disorders, mitochondrial cardiomyopathies, neuromuscular disorders, malformation syndromes and some chronic drug use. The disease is characterized by great heterogeneity of its clinical manifestations, however diastolic dysfunction and increased ventricular arrhythmogenesis are commonly seen. Current HCM therapies focus on symptom management and prevention of sudden cardiac death. Symptom management includes the use of pharmacological agents, elimination of medication promoting outflow track obstruction, control of comorbid conditions and invasive procedures, whereas in the prevention of sudden cardiac death, implantable cardiac defibrillators and antiarrhythmic drugs are used. A targeted therapy for LVOTO represented by allosteric cardiac myosin inhibitors has been developed. In terms of sport participation, a more liberal approach is recently recommended, after careful evaluation and common-shared decision. The application of the current therapies has lowered HCM mortality rates to <1.0%/year, however it appears to have shifted focus to heart failure and atrial fibrillation, as the predominant causes of disease-related morbidity and mortality and, therefore, unmet treatment need. With improved understanding of the genetic and molecular basis of HCM, the present decade will witness novel treatments for disease prevention and modification.

Abstract P475: Left Ventricular Hypertrophy Prevalence by Electrocardiogram in Patients Presenting With Cerebrovascular Accident

Background: A strong association has been previously suggested between left ventricular hypertrophy (LVH) and stroke. The prevalence of LVH and hypertension, however, differs depending on demographic variables. In light of the most recent hypertension guidelines, more aggressive blood pressure control is called for to achieve the lower goals set forth. This will hopefully translate into lower incidence of LVH and stroke. Objectives: To examine the prevalence of left ventricular hypertrophy in patients receiving an electrocardiogram (EKG) for a diagnosis of stroke, transient ischemic attack, or cerebrovascular accident; all of which will be referred to as CVA. Methods: An EKG database from a university cardiology noninvasive lab was examined for the diagnosis of CVA over a one year period. The EKGs were evaluated for the presence of LVH or atrial fibrillation/flutter. The results were analyzed using Chi square test. Results: There was a total of 14,798 EKGs performed over one year. There were 272 EKGs with a diagnosis of CVA (1.7%); 2364 EKGs (16%) with diagnosis of LVH, and 481 (3.2%) with diagnosis of atrial fibrillation/flutter. Out of the 272 EKGs in patients with CVA diagnosis, there were 174 EKGs in sinus rhythm without LVH (64%), 78 EKGs in sinus rhythm with LVH (29%, P &lt; 0.05), and 20 EKGs in atrial fibrillation or atrial flutter (7.4%, P &lt; 0.05). Discussion: Stroke is a major health problem associated with increased mortality and morbidity. While atrial fibrillation and atrial flutter are well-established causes of stroke and were nearly twice as frequent in CVA patients as the general population in our cohort, LVH by EKG, in the absence of atrial fibrillation/flutter, was also nearly twice as prevalent, underscoring its importance as a potential marker for CVA. Hypertension is a well established risk factor for stroke in addition to cardiovascular events, and is a major cause of LVH on EKG. In our cohort nearly one third of patients with stroke were in sinus rhythm, but had left ventricular hypertrophy by EKG, a prevalence that was nearly four times that of atrial fibrillation/flutter. Since hypertension is the most common cause of left ventricular hypertrophy in our population, this places further significance on hypertension as a major modifiable risk factor and predictor of CVA and cardiovascular disease in general. In light of the most recent hypertension guidelines, aggressive blood pressure management to achieve the newly defined lower limits for a diagnosis of hypertension, with monitoring for signs of left ventricular hypertrophy by EKG, should be emphasized in order to decrease the incidence of stroke and other cardiovascular events.

Rapid progression of left ventricular hypertrophy caused by leukaemic infiltration of myocardium.

A man in his 40s was hospitalized due to recurrence of acute myeloid leukaemia. Echocardiography was performed because of negative T waves in the electrocardiogram. Severe and global left ventricular hypertrophy (LVH) was observed (Panels B and E, see Supplementary data online, Video S2), which was not found 15 months ago (Panels A and D, Supplementary data online, Video S1). Computed tomography scan also showed severe LVH (Panel H), which was not found 3 months ago (Panel G). Thus, it was confirmed that the rapid hypertrophic change occurred within 3 months. Low-dose Ara-C (cytosine arabinoside) and VP-16 (etoposide) therapy was administered for leukaemia. Echocardiography, after two weeks from the start of treatment, showed reduced LVH (Panels C and F). Therefore, the myocardial infiltration of leukaemia cells was considered as the cause of LVH. Unfortunately, 16 weeks later, the patient died by multiple organ failure. Autopsy showed that the cardiac wall thickened and numerous numbers of leukaemia cells infiltrated in the myocardium (Panels J and K). Distribution of the myocardial fibre was disarrayed but necrosis was not found. Infiltration of leukaemia cells was observed in multiple organs.

Mechanism of long-term high-dose prednisolone administration producing myocardial fibrosis in beagle dogs.

We previously reported that myocardial fibrosis may be one of the causes of left ventricular hypertrophy and cardiac dysfunction in dogs with hyperglucocorticism (HGC). The detailed mechanism by which myocardial fibrosis of the left ventricle occurs in dogs with HGC remains unclear. Th is study investigated the mechanism by which HGC causes fibrosis of the left ventricle. The impa cts of HGC on the heart by comparing samples obtained from high-dose glucocorticoid (GC)-treated (P) and untreated (C) dogs. The P group included healthy Beagle dogs (n = 6) treated with prednisolone (2 mg/kg, bid, po) for 84 days, and the C group included healthy Beagle dogs (n = 6) euthanized for unrelated reasons. In three of the P group dogs, serum was collected before the start of administration (Day 0) and on Day 84 to measure angiotensin II concentrations and oxidative stress markers (8-hydroxy-2'-deoxyguanosine (8OHdG), NADPH oxidase, and superoxide levels). Samples of the left ventricular free wall (LVFW), right ventricular free wall (RVFW), interventricular septum (IVS), and aortic root were harvested from both groups (n = 6 for each group). Using these tissue samples, angiotensin II type 1 receptor (AT1R), 8OHdG, and transforming growth factor β1 (TGFβ1) immunohistochemical stains were performed. The blood N ADPH oxidase concentration was significantly higher (p = 0.027) in the P group 84 days after initiation of the medication compared to that before prednisolone treatment. By contrast, there was no significant difference in serum angiotensin II (p = 0.450), 8OHdG (p = 0.068), and superoxide (p = 0.057) concentrations. The positive staining rates of AT1R, 8OHdG, and TGFβ1 in the heart (LVFW, RVFW, IVS, and aortic root) were significantly higher in the P group than those in the C group. Angiotensin II and oxidative stress in HGC may cause left ventricular fibrosis in dogs.

Fabry Disease, a Rare Disorder with Cardiac Manifestations. The Problem of Diagnosis and Treatment: a Literature Review

Fabry disease (FD) is an X-linked lysosomal storage disease caused by a mutation in the gene encoding α-galactosidase A and leads to reduced activity or complete absence of this enzyme, which causes the accumulation of globotriaosylceramide (Gb3) and its deacylated form (lyso-Gb3) in cells of the whole body. FD can occur both with multisystem manifestations, including damage to the nervous system, kidneys, and skin, and can affect only the heart. Cardiac involvement is a major cause of poor quality of life and death in patients with FD and an underrecognized cause of heart failure with preserved ejection fraction and ventricular arrhythmias in men over 30 years of age and women over 40 years of age. Cardiac damage begins at an early age, progresses subclinically until the appearance of significant symptoms, and usually manifests as leftventricular hypertrophy, mimicking hypertrophic cardiomyopathy.&#x0D; After the introduction of enzyme replacement therapy, early recognition of FD and differential diagnosis with other causes of leftventricular hypertrophy have become crucial to limit the progression of the disease. Recent advances in the understanding of cardiac pathophysiology and imaging have improved diagnostic and therapeutic approaches to the cardiac manifestations of this pathology.&#x0D; Modern achievements in the study of cardiac manifestations of FD have made it possible to significantly improve diagnostic and therapeutic approaches, in particular, in relation to the identification of pathogenetic mechanisms of organ damage and early disruption of their function. A better understanding of secondary pathogenic pathways, such as myocardial inflammation, may influence future therapeutic strategies and timely diagnosis of FD.&#x0D; Delay in diagnosis and untimely initiation of treatment remain critical problems for many patients with FD, especially for patients with late-onset cardiovascular manifestations, in whom treatment effects may be more limited and ineffective.&#x0D; Cooperation between specialists in genetic diseases and cardiologists remains important to identify patients before the appearance of cardiac symptoms in order to obtain maximum therapeutic effects.

Development and validation of a smartphone based app to support the differential diagnosis in patients with primary left ventricular hypertrophy

Abstract Introduction Patients presenting with primary Left Ventricular Hypertrophy (LVH) suffers from a diagnostic delay quantified in years. They are often misdiagnosed because of both physician-related and disease-related reasons including fragmented knowledge among different specialties and rarity of the conditions. Purpose We developed and validate a free digital support tool in the form of an App to provide support and to guide the physician in the differential diagnostic process of patients presenting with primary LVH. Methods We studied 210 consecutively genotyped patients (54±21 years, 118 (56% males) referred to our center for the suspicion of primary LVH. A systematic literature analysis was conducted to classify disease specific red-flags (RFs) associated with sarcomeric and non sarcomeric hypertrophic cardiomyopathy (HCM). RFs were categorized into two subgroups: extremely specific RFs (features only described associated to the given disease) and specific RF (characteristics typical for the disease but also associated with other conditions). Pre-specified RF were categorized into four domains: family history; signs/symptoms; electrocardiography and imaging. The outcome of the digital support tool was categorized as follows: (a) most likely diagnosis (if contemplated age range for the condition, at least 1 extremely specific RFs or more than 1 specific RF were satisfied); (b) possible diagnosis (if contemplated age range for the condition, 1 specific RF were satisfied); (c) less likely diagnosis (outside age range for disease and no RF selected). Results Of the 210 patients, 84 (40%) were diagnosed with sarcomeric HCM, 56 (27%) with TTR amyloidosis, 44 (21%) with Fabry disease (FD), 7 (4%) with a mitochondrial disease, 4 (2%) with Pompe disease, 4 (2%) with PRKAG2 cardiomyopathy, 3 (1%) with Noonan, 3 (1%) with Friederich's Ataxia, 3 (1%) with LEOPARD and 2 (1%) with Danon disease. A total of 942 RFs has been identified in the cohort, of which 327 were extremely specific RFs (41 from family history; 107 from signs/symptoms; 111 from electrocardiography and 113 from imaging sections). Non-sarcomeric causes of HCM were the most prevalent in ages &amp;lt;1yo and &amp;gt;55yo. One-hundred-ninety-five patients (92%) were correctly categorized in the most likely and possible diagnosis section. The App proved to be sensible for sarcomeric HCM, FD (0.99 and 0.91, NPV 0.98 and 0.83) and extremely capable in the identification of rare causes of LVH (Danon, Friederich's ataxia, LEOPARD, Pompe, Noonan and PRKAG2 diseases). By design, specificity was not high, in particular for sarcomeric HCM and FD. Conclusions The present free digital support tool in the form of an App proved to be extremely sensible in providing the support to the screening of different causes of primary LVH in patients presenting with a HCM phenotype. Further external and multicenter validation is warranted. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amicus therapeutics

Cardiac Magnetic Resonance in Fabry Disease: Morphological, Functional, and Tissue Features.

Fabry disease (FD) is an X-linked inheritable storage disease caused by a deficiency of alpha-galactosidase causing lysosomal overload of sphingolipids. FD cardiomyopathy is characterized by left ventricular (LV) hypertrophy and should be considered in differential diagnosis with all the other causes of LV hypertrophy. An early diagnosis of FD is very important because the enzyme replacement therapy (ERT) may change the fate of patients by blocking both cardiac and systemic involvement and improving prognosis. Diagnosis may be relatively easy in young patients with the typical signs and symptoms of FD, but in male patients with late onset of disease and in females, diagnosis may be very challenging. Morphological and functional aspects are not specific to FD, which cannot be diagnosed or excluded by echocardiography. Cardiac magnetic resonance (CMR) with tissue characterization capability is an accurate technique for the differential diagnosis of LV hypertrophy. The finding of decreased myocardial T1 value in LV hypertrophy is specific to FD. Late gadolinium enhancement (LGE) is found in the late stage of the disease, but it is useful to predict the cardiac response to ERT and to stratify the prognosis.

Evaluation of demographic, clinical, and aetiological data of patients admitted to cardiology clinics and diagnosed with left ventricular hypertrophy in Turkish population (LVH-TR)

Background Left ventricular hypertrophy (LVH) is potentially modifiable cardiovascular risk factor often overlooked in clinical practice. For this reason, we planned to LVH-TR (Left Ventricular Hypertrophy in Turkish Population) trial to determine the aetiological causes and demographic characteristics of LVH patients. Methods Our study was a multicentre, national, observational study and included 886 patients who applied to the cardiology clinics in 22 centres between February 2020 and August 2021. In the initial evaluation, the Fabry disease (FD) and cardiac amyloidosis (CA) algorithm was followed in patients whose definitive etiologic cause(s) could not be identified. Results The most common aetiological causes of LVH in our study were hypertension with a rate of 56.6%, heart valve disease with 8.2%, and hypertrophic cardiomyopathy with 7.5%. Athlete’s heart was detected in eight patients, LV non-compaction was detected in four patients. The rate of LVH of unknown cause was 18.8%. FD was suspected in 143 patients, and CA was suspected in 16 patients. There were 43 (4.85%) patients with low α-galactosidase A enzyme levels. GLA gene mutation analysis was positive in 1.58% of all patients, and these patients were diagnosed with FD, and 15 (1.69%) patients were diagnosed with CA by endomyocardial biopsy method. Conclusion In the aetiology of LVH, the rate of LVH of unknown cause was high. FD and CA should be considered primarily in this patient group. Early diagnosis of the disease by following the schemes leading to FD and CA was essential in starting treatment before the progression of the disease.

Development and validation of a smartphone based app to support the differential diagnosis in patients with primary left ventricular hypertrophy

Abstract Introduction Patients presenting with primary Left Ventricular Hypertrophy (LVH) suffers from a diagnostic delay quantified in years. They are often misdiagnosed because of both physician-related and disease-related reasons including fragmented knowledge among different specialties and rarity of the conditions. Purpose We developed and validate a free digital support tool in the form of an App to provide support and to guide the physician in the differential diagnostic process of patients presenting with primary LVH. Methods We studied 210 consecutively genotyped patients (54±21 years, 118 (56% males) referred to our center for the suspicion of primary LVH. A systematic literature analysis was conducted to classify disease specific red-flags (RFs) associated with sarcomeric and non sarcomeric hypertrophic cardiomyopathy (HCM). RFs were categorized into two subgroups: extremely specific RFs (features only described associated to the given disease) and specific RF (characteristics typical for the disease but also associated with other conditions). Pre-specified RF were categorized into four domains: family history; signs/symptoms; electrocardiography and imaging. The outcome of the digital support tool was categorized as follows: (a) most likely diagnosis (if contemplated age range for the condition, at least 1 extremely specific RFs or more than 1 specific RF were satisfied); (b) possible diagnosis (if contemplated age range for the condition, 1 specific RF were satisfied); (c) less likely diagnosis (outside age range for disease and no RF selected). Results Of the 210 patients, 84 (40%) were diagnosed with sarcomeric HCM, 56 (27%) with TTR amyloidosis, 44 (21%) with Fabry disease (FD), 7 (4%) with a mitochondrial disease, 4 (2%) with Pompe disease, 4 (2%) with PRKAG2 cardiomyopathy, 3 (1%) with Noonan, 3 (1%) with Friederich's Ataxia, 3 (1%) with LEOPARD and 2 (1%) with Danon disease. A total of 942 RFs has been identified in the cohort, of which 327 were extremely specific RFs (41 from family history; 107 from signs/symptoms; 111 from electrocardiography and 113 from imaging sections). Non-sarcomeric causes of HCM were the most prevalent in ages &amp;lt;1yo and &amp;gt;55yo. One-hundred-ninety-five patients (92%) were correctly categorized in the most likely and possible diagnosis section. The App proved to be sensible for sarcomeric HCM, FD (0.99 and 0.91, NPV 0.98 and 0.83) and extremely capable in the identification of rare causes of LVH (Danon, Friederich's ataxia, LEOPARD, Pompe, Noonan and PRKAG2 diseases). By design, specificity was not high, in particular for sarcomeric HCM and FD. Conclusions The present free digital support tool in the form of an App proved to be extremely sensible in providing the support to the screening of different causes of primary LVH in patients presenting with a HCM phenotype. Further external and multicenter validation is warranted. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amicus therapeutics

Mitral valve abnormalities in decedents of sudden cardiac death due to hypertrophic cardiomyopathy and idiopathic left ventricular hypertrophy

Abstract Background The sole identification of left ventricular hypertrophy (LVH) in a young individual that died suddenly may often lead to an erroneous diagnosis of hypertrophic cardiomyopathy (HCM). Emerging data suggests that idiopathic LVH (ILVH) and HCM may be separate entities. Aim We aimed to report on the prevalence and nature of mitral valve (MV) abnormalities, in a cohort of sudden cardiac death (SCD) victims with a post-mortem examination consistent with HCM and ILVH. Methods We reviewed 6860 consecutive cases of SCD referred to our specialist cardiac pathology centre between 1994 and 2020. SCD was defined as death from a cardiovascular cause within 12 hours of apparent well-being. HCM was defined by the presence of LVH, in the absence of abnormal loading conditions and characterised by myocyte disarray at histology. ILVH was defined as unexplained LVH (heart weight &amp;gt;500 g in males and &amp;gt;400 g in females) and left ventricular (LV) wall thickness &amp;gt;15mm, in the absence of myocardial disarray or secondary causes of LVH. The MV was examined for patency, circumference, thickening, nodularity, ballooning, bulging between cords, perforation, and the presence of impact lesions in the LV outflow tract (LVOT) and aortic outlet. Results Of the total cases of SCD, 264 (4%) were due to HCM (mean age 41±18 years, 78% males, LV maximal wall thickness 19±6 mm) (Figure 1). Ante-mortem symptoms were reported in 44 (17%) cases and for the majority (n=217, 82%) HCM was established at post-mortem. Death was attributed to ILVH in 253 (3%) cases (mean age 43±16 years, 80% males, LV maximal wall thickness 18±4 mm). MV abnormalities were found in 58 (22%) decedents with HCM (mean age 38±17 years; 72% males) and in 13 (5%) decedents with ILVH (mean age 55±15 years; 77% male), p&amp;lt;0.001. Amongst the 58 (22%) cases with HCM and MV abnormalities, 15 (6%) cases had multiple MV abnormalities. These included impact lesions associated with thickening of the anterior leaflet of the MV (n=39) and degenerative changes (n=34) such as bulging and ballooning; and thickening and nodularity. Decedents with HCM exhibiting MV abnormalities were younger than decedents with a normal MV (38±17 versus 45±19 years; p=0.08). Among the 253 decedents with ILVH, 13 (5%) cases exhibited MV abnormalities, which largely included degenerative changes (n=12). Among decedents with HCM and ILVH exhibiting MV abnormalities, the former was significantly younger (38±17 versus 55±15; p=0.001). Myocardial fibrosis was observed in 162 (61%) cases of HCM and 99 (39%) cases of ILVH, p&amp;lt;0.001. Conclusions MV abnormalities are over four-fold more common in individuals with HCM than those with ILVH and may be considered as additional macroscopic features to differentiate between these two entities. Furthermore, the inherent descriptive terminologies used when assessing the MV, support a greater emphasis on the standardisation and quantification of MV abnormalities as part of the autopsy in victims of SCD. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Acknowledgements: We thank the charitable organisation, Cardiac Risk in the Young (CRY) who fund and support the CRY Cardiovascular Pathology Unit and CRY database.

Mitral valve abnormalities in decedents of sudden cardiac death due to hypertrophic cardiomyopathy and idiopathic left ventricular hypertrophy.

Mitral valve abnormalities in decedents of sudden cardiac death due to hypertrophic cardiomyopathy and idiopathic left ventricular hypertrophy.

Left Ventricular Myocardial Work to Differentiate Cardiac Amyloidosis From Hypertrophic Cardiomyopathy

Cardiac amyloidosis (CA) is a progressive disorder with a reported median survival of 2.5 to 3.5 years after diagnosis.1 Novel treatment options are emerging that could improve prognosis but seem most efficient when started at an early stage of the disease, underscoring the importance of early diagnosis. Echocardiography is the first-line imaging technique for the assessment of cardiac structure and function and might raise suspicion of CA. Although “relative apical sparing” of speckle-tracking-derived left ventricular (LV) longitudinal strain (LS) measurements was suggested to help diagnose CA,2 differentiating CA from other causes of LV hypertrophy remains difficult.