Nonobstructive Hypertrophic Cardiomyopathy Research Articles

2D speckle-tracking in assessment of myocardial strain in children with hypertrophic cardiomyopathy

Purpose: To assess the myocardial strain in children with hypertrophic cardiomyopathy (HCM).
 Methods: A total of 61 patients aged between 7 and 17 years with an asymmetric form of HCM underwent an ultrasound examination of the heart using standard techniques. An assessment of the left ventricular systolic function was performed using the two-dimensional (2D) speckle-tracking mode with analysis parameters that included global and segmental longitudinal, circumferential, and radial myocardial strains. Strain data for the subendocardial and subepicardial layers for each segment of the left ventricle, as well as their total values, were determined.
 Results: Global longitudinal strain and longitudinal strain rate were dec reased due to the impaired contractility of hypertrophied myocardial segments in 100% of cases of non-obstructive and obstructive HCM forms. A decrease in global, radial, and circumferential strain parameters and their rates has been observed in all children with an obstructive form of HCM and 39 (86.6%) patients with non-obstructive form. At the same time, there was a statistically significant difference between strains and strain rates in children with a non-obstructive form of HCM in comparison to those with an obstructive form of the disease.
 Conclusion: Changes in myocardial strains observed using the 2D speckle-tracking mode in children with HCM indicate early systolic dysfunction of the left ventricle. Longitudinal strain was the most sensitive compared to radial and circumferential types. It was statistically significantly different in children with an obstructive form of HCM compared to those with non-obstructive form of the disease. These results are important for early therapy initiation and, therefore, may improve prognosis in children with HCM.

HYPERTROPHIC CARDIOMYOPATHY SIMULATING AN ACUTE CORONARY SYNDROME

Hypertrophic cardiomyopathy corresponds to myocardial hypertrophy >15mm or >13mm in case of familial hypertrophic cardiomyopathy (HCM).We report the case of a 31-year-old patient with no cardiovascular risk factors and no notable history who was admitted to the emergency room for the management of prolonged resting chest pain associated with electrical changes in the electrocardiogram (EKG)given the clinical symptomatology and the overshift with the mirror image. A coronary angiography was performed and came back without any particularity. The diagnosis of non-obstructive septal HCM was made based on echocardiography and cardiac magnetic resonance imaging (MRI) findings.The patient stayed in the cardiac intensive care unit with a good clinical course, he was declared to be discharged under symptomatic treatment given the non-obstructive nature and the low risk of sudden death.

Prognostic Value of Apical Sparing of Longitudinal Strain in Patients with Symptomatic Aortic Stenosis.

Older patients with aortic stenosis (AS) have a higher incidence of wild-type transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to determine whether apical sparing of longitudinal strain (LS) could help diagnose ATTR-CA and provide useful prognostic information in symptomatic AS. We performed vendor-independent two-dimensional speckle-tracking analysis of regional and global left ventricular LS in 16 patients with ATTR-CA and 31 patients with non-obstructive hypertrophic cardiomyopathy to determine the best cutoff value of the apical sparing ratio (APSR) for diagnosing ATTR-CA. We then determined the prevalence in patients who had an APSR higher than the best cutoff value and investigated its prognostic value in 230 patients with symptomatic AS. To determine the natural history of symptomatic AS, patients who had aortic valve replacement were censored at the time of surgery. The best cutoff value of APSR was 0.76. APSR ≥ 0.76 was observed in 108 patients with symptomatic AS (48%). The prevalence was not different among the four AS subgroups. During a median follow-up period of 5.7 months, 47 patients had cardiac events. Cox proportional hazards analysis revealed that neither APSR nor APSR ≥ 0.76 was significantly associated with future cardiac events. Apical sparing was frequently observed in patients with symptomatic AS, and it was not a useful predictor of future adverse outcomes. Our results suggest that the underlying cause of apical sparing in AS may not be related to the presence of ATTR-CA.

Hypertrophic obstructive cardiomyopathy complicated with acute myocardial infarction and diffuse fibrosis: surgery or not?

BackgroundHypertrophic cardiomyopathy with extreme hypertrophy, biventricular obstruction and diffuse myocardial fibrosis complicated by myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) is a rare phenotype. Evidence and guideline recommendations are still lacking for a treatment strategy.Case presentationEmergency coronary angiography was performed in a 38-year-old man with a 2-year history of nonobstructive hypertrophic cardiomyopathy (HCM) presenting with acute myocardial infarction. The coronary angiogram yielded no stenotic lesions but showed a diffusely dilated left descending artery with slow blood flow. All evidence from biomarker analysis, electrocardiography, echocardiography, and imaging supported the diagnosis of acute myocardial infarction in the left ventricular anterior wall. The echocardiogram demonstrated severe interventricular and apical hypertrophy, severe left ventricular outflow tract obstruction and mild right ventricular outflow tract obstruction. Cardiac magnetic resonance imaging showed a concentric morphological subtype of HCM with diffuse late gadolinium enhancement in the left ventricle. Extended septal myectomy was performed 1 month later, and the patient recovered well.ConclusionsHypertrophic obstructive cardiomyopathy with acute myocardial infarction is an indication for coronary angiography. Septal reduction surgery could be performed cautiously in HCM patients with extreme hypertrophy, biventricular obstruction and diffuse myocardial fibrosis complicated by MINOCA to improve the patient’s symptoms.

Blunted coronary flow velocity reserve is associated with impairment in systolic function and functional capacity in hypertrophic cardiomyopathy

BackgroundCoronary microvascular dysfunction constitutes an important pathophysiological feature in hypertrophic cardiomyopathy (HCM).We aimed to assess the association between impaired coronary flow velocity reserve (CFVR) and ventricular systolic function and functional capacity. MethodsEighty-three patients with HCM were enrolled in this prospective cohort study. Patients underwent echocardiogram to evaluate ventricular performance and CFVR in the left anterior descending artery (LAD) and posterior descending artery (PD). Diastolic coronary flow velocity was measured in basal conditions and in hyperemia. CFVR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. Functional capacity was evaluated by cardiopulmonary exercise testing (CPET). The link between CFVR and biventricular systolic function and peak VO2 was studied. ResultsAge was 55.0(14.4)years, 50 patients (60%) were male; 59 patients (71%) had nonobstructive HCM. Mean CFVR LAD was 1.81(0.49) and CFVR PD was 1.73(0.55). Lower CFVR PD was associated with impaired global longitudinal strain (GLS) 2D (β-estimate:-3.240,95%CI:-4.634;-1.846, p < 0.001), GLS 3D (β-estimate:-2.559,95%CI:-3.932;-1.186, p < 0.001) and area strain (β-estimate:-3.044,95%CI:-5.373;-0.716, p = 0.011). Lower values of CFVR PD related to worse global work index (β-estimate:267.824,95%CI:75.964;459.683, p = 0.007), global constructive work (β-estimate:217.300,95%CI:38.750;395.850, p = 0.018) and global work efficiency (β-estimate:5.656,95%CI:2.229;9.084, p = 0.002). Impaired CFVR LAD (β-estimate:2.826, 95%CI:0.913;4.739, p = 0.004) and CFVR PD (β-estimate:2.801,95%CI:0.657;4.945, p = 0.011) were associated with lower TAPSE. Lower values of CFVR LAD (β-estimate:2.580, 95%CI:0.169;4.991, p = 0.036) and CFVR PD (β-estimate:3.163, 95%CI: 0.721;5.606, p = 0.012) were associated with worse peak VO2. ConclusionLower CFVR was associated with impairment in biventricular systolic function parameters and functional capacity assessed by pVO2.

Cardiovascular evaluation of pregnant women with hypertrophic cardiomyopathy.

The effect of physiological circulatory changes during pregnancy on hypertrophic cardiomyopathy (HCM) has been reported with limited data. This study aimed to provide information regarding outcomes of pregnant women with HCM and to identify predictors of major adverse cardiac event (MACE). Atotal of 45pregnancies with HCM were retrospectively reviewed. The primary endpoint was aMACE that occurred within an 8‑week period after delivery, including maternal death, heart failure (HF), syncope, and malignant ventricular arrhythmias (VAs). Baseline and outcome data were analyzed for all patients. Patients with and without MACE were compared, and patients with obstructive HCM were compared with those who had non-obstructive HCM. The study population was divided into two subgroups of patients having or not having an implantable cardioverter defibrillator implantation (ICD). At least one MACE occurred in 11patients (24.4%); six patients developed HF (13.3%), six had aventricular tachyarrhythmia (13.3%), and two had syncope (4.4%). New York Heart Association functional class of ≥ II, presence of HF signs before pregnancy, increased left ventricular outflow tract (LVOT) gradient were significantly associated with MACE. Fatal VAs were seen during pregnancy inone of five HCM patients with ICD. In the ROC curve analysis, an LVOT gradient higher than 53.5 mm Hg predicted the presence of MACE with asensitivity of 90.9% and aspecificity of 73.5%. This study is the largest series in the literature representing pregnant women who had HCM and ICD. The current data suggest that HF and high LVOT gradients are important risk factors for the development of cardiac complications.

Diazoxide-Associated Pulmonary Hypertension in Patient with Hyperinsulinemic Hypoglycemia

Background: Congenital hyperinsulinism (CHI) is the most common of persistent hypoglycemia in infancy characterized by inappropriate insulin secretion in the presence of hypoglycemia. Objective: This case report evaluates the effect of Diazoxide treatmentin inducing pulmonary hypertension in a patient with hyperinsulinemic hypoglycemia. Case findings: A full-term baby male, birth weight 4.3kg, was born at 41 weeks gestation by emergency caesarean section due to fetal distress born in Al-Dawadmi Hospital. He developed convulsions started postnatally loaded with phenobarbitone then shifted to AL-Yamammah hospital as lifesaving case to be admitted in Neonatal ICU. He was found to have hyperinsulinemic hypoglycemia and started on Diazoxide. The patient readmitted in Pediatric ICUat age of 2 month with hypoxic respiratory failure. After evidence of pulmonary hypertension by Echocardiography, Diazoxide was held at 2nd day of admission but he developed recurrent attacks of hypoglycemia required Octreotide with intermittent glucagon. After 14 days, Echocardiographic study repeated and showed findings of non-obstructive hypertrophic cardiomyopathy with good systolic function and no evidences of pulmonary hypertension (PH). Conclusions: Pulmonary hypertension may be developed during Diazoxide therapy. Pulmonaryhypertension was evaluated by echocardiography at regular intervals. This complicationresolved once diazoxide has been withdrawn.

Apical Myectomy in HCM: Time to Let the Rubber of the Operation Meet the Road of a Randomized Trial

In the context of the Batista operation, Mark Ratcliffe1 suggested that success of remodeling the left ventricle (LV) depends on how it affects both end-systolic pressure-volume (elastance) and diastolic pressure-volume (compliance) relationships. In this manuscript and in a 2020 manuscript, the authors suggest that in patients with nonobstructive hypertrophic cardiomyopathy (nHCM), an apical myectomy alters the LV diastolic properties by augmenting LV volume while decreasing LV end-diastolic pressure, thus increasing stroke volume.

Myocardial work in hypertrophic cardiomyopathy - a new non-invasive parameter for segmental myocardial function?

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): DFG Introduction Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease. Alcohol septal ablation (PTSMA) is an established treatment option for patients with intracavitary obstruction. In non-obstructive patients, measurement of myocardial work (MW) using pressure strain loops was introduced as a new non-invasive tool to estimate myocardial performance. Purpose In this preliminary study, we compared global constructive work (GCW) and global wasted work (GWW) as well as the respective values for the septal- and lateral-basal segments in HOCM after successful PTSMA and non-obstructive HCM. Methods We included 12 patients (4 women, mean age 59.1 ± 17.6 years) with non-obstructive (maximal left ventricular gradient &amp;lt;30 mmHg; mean 10.6 ± 6.2 mmHg) HCM. 7 (58%) patients (subgroup A) had successful gradient reduction by PTSMA ≥3 months before analysis, whereas 5 patients had non-obstructive HCM (subgroup B). Using echocardiographic measurements of longitudinal strain and non-invasive measurements of peripheral- and calculated (PWA) central blood pressure (BP) as left ventricular systolic pressure (LVSP), we estimated and compared GCW and GWW as well as constructive work (CW) and wasted work (WW) of septal-basal and lateral-basal segments. Results In subgroup B, NTproBNP was significant higher than in subgroup A (2050 ± 1957 vs. 552 ± 845 pg/ml; p &amp;lt; 0.05). There were no differences between both subgroups in maximal septal thickness (20.7 ± 2.9 mm (A) vs. 22.2 ± 3.6 mm) and left atrial volume (91.6 ± 33.0 (A) vs. 114.0 ± 49.8 ml (B)). Using the measured peripheral BP as LVSP, GCW (1653 ± 347 (A) mmHg% vs 1641 ± 698mmHg%) and GWW (171 ± 89mmHg% (A) vs. 200 ± 126 mmHg%) showed no differences between both subgroups. Compared to published data of a healthy population, values of GCW were lower and values of GWW higher in HCM. Comparison in segmental analysis in subgroup A showed lower CW in septal-basal than in lateral-basal segments (1032 ± 385mmHg% vs. 1929 ± 699 mmHg%). In the subgroup B the finding was the same pattern (1024 ± 504mmHg% vs. 2301 ± 1069 mmHg%). In contrast, WW showed no difference between basal-septal and lateral-basal segments in both subgroups. Conclusions Our preliminary data show decreased GCW and increased GWW in HCM patients without obstruction at rest. As expected, we found lower CW in septal-basal segments than lateral-basal in patients after PTSMA with basal-septal-induced therapeutic infarction. Surprisingly, we found the same pattern in non-obstructive HCM patients. This finding might be one pathophysiological reason for not developing LVOT obstruction, which should be investigated in further detail.

Assessment of myocardial work: a promising tool in obstructive and nonobstructive hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Myocardial work is a novel dynamic non-invasive method for assessing myocardial deformation providing incremental information to left ventricular ejection fraction (LVEF) and strain imaging. The aim of this study was to assess left ventricular myocardial work in hypertrophic cardiomyopathy (HCM) and compare patients with obstructive HCM (oHCM) and nonobstructive HCM (nHCM). Methods Prospective assessment of HCM patients’ myocardial strain parameters with 2D speckle-tracking echocardiography, stratified according to LV segments (basal, midcavity and apical regions). Results were compared between oHCM and nHCM patients. Results 83 patients with HCM, 60% male, 33% oHCM (with a LVOT gradient of 89 ± 60 mmHg). There was no significant difference between groups in mean age (56 ± 13 years vs. 55 ± 15 years, p = 0.719), LV mass index (186 ± 75 g/m2 vs. 158 ± 65 g/m2, p = 0.103), maximum wall thickness (21 ± 4 mm vs. 19 ± 5 mm, p = 0.425) or left ventricular ejection fraction (LVEF) (68 ± 8% vs. 67 ± 11%, p = 0.584). Regarding global work index (GWI) there was no significant difference between oHCM and nHCM (1206 ± 431 mmHg% vs. 1384 ± 437 mmHg%, p = 0.090), although oHCM patients had a significantly inferior GWI in the basal (921 ± 383 mmHg% vs. 1364 ± 419 mmHg%, p &amp;lt; 0.001) and midcavity (1049 ± 456 mmHg% vs. 1288 ± 492 mmHg%, p = 0.038) segments (Figure 1). No significant difference was noted in the apical segments (1680 ± 653 mmHg% vs. 1519 ± 770 mmHg%, p = 0.335). Myocardial work index in the basal segments showed inverse correlation with resting LVOT gradient (r=-0.242, p = 0.032) and maximum provoked LVOT gradient (r=-0.291, p = 0.010). Furthermore, patients with septal hypertrophy pattern showed significantly impaired basal myocardial work index compared with apical hypertrophy patients (1090 ± 428 mmHg% vs 1537 ± 389 mmHg%, p &amp;lt; 0.001). Global constructive work (GCW) (1443 ± 449 mmHg% vs. 1604 ± 426 mmHg%, p = 0.123) and global wasted work (GWW) (197 ± 140 mmHg% vs. 154 ± 107 mmHg%, p = 0.137) were not significantly different between groups. Global work efficiency (GWE) was significantly reduced in oHCM patients vs. nHCM (84.1 ± 7% vs. 88.3 ± 7.3%, p = 0.017), particularly in the basal (80.2 ± 11.2% vs. 88.3±.7.2%, p = 0.033) and midcavity segments (85.4 ± 9.2% vs. 90.0 ± 8.5%, p = 0.044) (Figure 2). No significant difference was noted in the apical segments (88.2 ± 9.9% vs. 87.0 ± 12%, p = 0.679). Myocardial work efficiency in the basal segments showed inverse correlation with resting LVOT gradient (r=-0.389, p = 0.002) and maximum provoked LVOT gradient (r=-0.446, p &amp;lt; 0.001). Moreover, patients with septal hypertrophy pattern showed significantly reduced basal myocardial work efficiency versus apical hypertrophy patients (83 ± 9% vs 92 ± 3%, p &amp;lt; 0.001). Conclusion Myocardial work is a promising tool to evaluate myocardial function in patients with oHCM and nHCM. oHCM patients had a significantly inferior GWI and GWE particularly in the basal and midcavity segments versus nHCM patients. Abstract Figure 1: Myocardial Work Index Abstract Figure 2: Myocardial Work Efficiency

New Genetic finding in a Combination of Long QT Syndrome and Hypertrophic Cardiomyopathy in a Single Patient

In 2000 the description of a family (a mother and three sons) with a typical long QT ECG and echocardiographic diagnosis of classical hypertrophic non-obstructive cardiomyopathy was published [1]. The ECG of three family members was characterised by typical long QT syndrome (QTc intervals between 460 up to nearly 500 msec), but without signs of left ventricular hypertrophy, pathologic Q-wave and T-wave abnormalities as shown in ECG figures [1]. The mother of the family developed atypical angina; coronary angiography revealed slight coronary abnormalities. One of her sons had pre-syncope. In the later follow-up the mother developed severe ventricular arrhythmias; the implantation of an ICD has been discussed.

Single Nucleus RNA-sequencing Reveals Altered Intercellular Communication and Dendritic Cell Activation in Nonobstructive Hypertrophic Cardiomyopathy.

End stage, nonobstructive hypertrophic cardiomyopathy (HCM) is an intractable condition with no disease-specific therapies. To gain insights into the pathogenesis of nonobstructive HCM, we performed single nucleus RNA-sequencing (snRNA-seq) on human HCM hearts explanted at the time of cardiac transplantation and organ donor hearts serving as controls. Differential gene expression analysis revealed 64 differentially expressed genes linked to specific cell types and molecular functions. Analysis of ligand-receptor pair gene expression to delineate potential intercellular communication revealed significant reductions in expressed ligand-receptor pairs likely affecting the extracellular matrix, growth factor binding, peptidase regulator activity, platelet-derived growth factor binding and protease binding in the HCM tissue. Changes in Integrin-β1 receptor expression were responsible for many observed changes related to extracellular matrix interactions, by increasing in dendritic, smooth muscle and pericyte cells while decreasing in endothelial and fibroblast cells, suggesting potential mechanisms for fibrosis and microvascular disease in HCM and a potential role for dendritic cells. In contrast, there was an increase in ligand-receptor pair expression associated with adenylate cyclase binding, calcium channel molecular functions, channel inhibitor activity, ion channel inhibitor activity, phosphatase activator activity, protein kinase activator activity and titin binding, suggesting important shifts in various signaling cascades in nonobstructive, end stage HCM.

How to build a successful hypertrophic cardiomyopathy team and ensure training the next generation of myectomy surgeons.

Transaortic extended septal myectomy is the most reliable method for septal reduction for symptomatic patients with obstructive hypertrophic cardiomyopathy. In addition, surgical management of nonobstructive hypertrophic cardiomyopathy is possible for selected patients with diastolic heart failure and small left ventricular end-diastolic cavity dimensions. These procedures, however, are performed infrequently in many centers, and trainees may not be exposed to the preoperative evaluation and intraoperative management of patients with hypertrophic cardiomyopathy. In this paper, we review what we believe are the central features for creating a successful program for septal myectomy and detail our strategies to optimize instruction in these techniques for residents and fellows.

The Impact of Ischemia Assessed by Magnetic Resonance on Functional, Arrhythmic, and Imaging Features of Hypertrophic Cardiomyopathy

Aims: The aim of the study is to investigate the association between the degree of ischemia due to coronary microvascular dysfunction (CMD) and the left ventricular (LV) tissue characteristics, systolic performance, and clinical manifestations in hypertrophic cardiomyopathy (HCM).Methods and Results: This prospective study enrolled 75 patients with HCM without obstructive epicardial coronary artery disease. Each patient underwent cardiovascular magnetic resonance (CMR) including parametric mapping, perfusion imaging during regadenoson-induced hyperemia, late gadolinium enhancement (LGE) and three-dimensional longitudinal, circumferential, and radial strains analysis. Electrocardiogram, 24-h Holter recording, and cardiopulmonary exercise testing (CPET) were performed to assess arrhythmias and functional capacity. In total, 47 (63%) patients were men with the mean age of 54.6 (14.8) years, 51 (68%) patients had non-obstructive HCM, maximum wall thickness (MWT) was 20.2 (4.6) mm, LV ejection fraction (LVEF) was 71.6 (8.3%), and ischemic burden was 22.5 (16.9%) of LV. Greater MWT was associated with the severity of ischemia (β-estimate:1.353, 95% CI:0.182; 2.523, p = 0.024). Ischemic burden was strongly associated with higher values of native T1 (β-estimate:9.018, 95% CI:4.721; 13.315, p < 0.001). The association between ischemia and LGE was significant in following subgroup analyses: MWT 15–20 mm (β-estimate:1.941, 95% CI:0.738; 3.143, p = 0.002), non-obstructive HCM (β-estimate:1.471, 95% CI:0.258; 2.683, p = 0.019), women (β-estimate:1.957, 95% CI:0.423; 3.492, p = 0.015) and age <40 years (β-estimate:4.874, 95% CI:1.155; 8.594, p = 0.016). Ischemia in ≥21% of LV was associated with LGE >15% (AUC 0.766, sensitivity 0.724, specificity 0.659). Ischemia was also associated with atrial fibrillation or flutter (AF/AFL) (OR-estimate:1.481, 95% CI:1.020; 2.152, p = 0.039), but no association was seen for non-sustained ventricular tachycardia. Ischemia was associated with shorter time to anaerobic threshold (β-estimate: −0.442, 95% CI: −0.860; −0.023, p = 0.039).Conclusion: In HCM, ischemia associates with morphological markers of severity of disease, fibrosis, arrhythmia, and functional capacity.

587 Exercise induced pulmonary hypertension in hypertrophic cardiomyopathy: a combined cardiopulmonary exercise test-echocardiographic study

Abstract Aims Pulmonary arterial hypertension (PAH) has been described in patients with hypertrophic cardiomyopathy (HCM) and it was associated with a worse prognosis. Nevertheless in most HCM patients, despite normal pulmonary pressures at rest, congestive symptoms are elicited by exercise. In the present study, combining cardiopulmonary exercise test (CPET) with echocardiography, we aimed to evaluate the presence of exercise-induced pulmonary hypertension (EiPAH) its role in functional limitation and its prognostic significance in a cohort of patients with obstructive and non-obstructive HCM. Methods and results 182 HCM patients (35% females, mean age 47.5 ± 15.9) undergoing CPET. During CPET, LVOT velocities and trans-tricuspid gradient were measured. Thirty-seven patients (20%) developed sPAP &amp;gt; 40 mmHg at peak exercise (EiPAH). EiPAH was associated with an lower exercise performance, larger left atrial volumes, higher left ventricular gradient and higher VE/VCO2 slope .At multivariable model baseline sPAP (P &amp;lt; 0.0001) and baseline left ventricular obstruction (LVOT) (P = 0.028) were significantly associated with EiPAH .Kaplan-Meier curve analysis showed EiPAH was a significant predictor of HCM –related morbidity (hazards ratio: 6.21, 95% CI: 1.47–26.19; P = 0.05; 4.21, 95% CI: 1.94–9.12; P &amp;lt; 0.001) for the primary and the secondary endpoint respectively. Conclusions EiPAH was present in about one fifth of HCM patients without evidence of elevated pulmonary pressures at rest, and was associated with adverse clinical outcome. Diagnosing EiPAH by exercise echo/CPET may help physicians to detect early stage of PAH requiring a closer clinical monitoring and individualized treatment strategies.

816 UNA Diagnosi . . . Incidentale

Hypertrophic cardiomyopathy (HCM) is the most frequent genetic disease of the myocardium, with a prevalence of 1:500 cases in the general population. The salient feature is a hypertrophy, symmetrical or not, of the walls of the left ventricle (mainly the septum, but also less typical locations, such as the apex or the infero-lateral wall), not linked to abnormal load conditions. HCM is mostly an autosomal dominant inherited disease with incomplete penetrance and variable expressivity, mainly linked to mutations in genes coding for sarcomeric proteins. Several studies have shown an up-regulation of the ACE-2 gene, perhaps indicative of a compensatory anti-hypertrophic and anti-fibrotic response of the myocardium, in hypertrophic cardiomyopathy. Being the ACE-2 receptor target of the Sars-CoV-2 virus, these patients may have an increased risk of infection and a worse outcome. A 47-year-old man, with no known comorbidities, was hospitalized in our Emergency Medicine Department for bilateral Sars-CoV-2 pneumonia. Noninvasive mechanical ventilation c-PAP (FiO2 60%, PEEP 7.5 cmH20) was started for hypoxemic respiratory failure and an ECG showed diffuse ventricular repolarization abnormalities suggestive of left overload (asymmetric negative T waves V4 to V6, in I, II and aVL, flat in aVF. Figure 1), with a deep Q wave in III. The patient was asymptomatic for chest pain and equivalents and D-dimer and indices of myocardionecrosis were normal. Echocardiographic evaluation was performed, with evidence of marked asymmetric concentric hypertrophy of the left ventricle (interventricular septum: 16 mm), without significant anomalies in segmental kinetics, noteworthy valvulopathies and pericardial effusion. The family and personal medical history were negative for syncope, sudden cardiac death and resuscitated cardiac arrest and the estimated risk of sudden cardiac death at five years (HCM Risk-SCD) was <4% (1.33%). The diagnostic hypothesis of non-obstructive hypertrophic cardiomyopathy was advanced. During hospitalization, ECG monitoring showed no sustained ventricular arrhythmias and the patient remained asymptomatic for dyspnoea, chest pain and equivalents. Subsequent echocardiograms showed no new changes. A progressive weaning from oxygen support was carried out and, after thirty days, the patient was discharged to home fiduciary isolation, with optimal cardiological therapy and indication to study with cardiac magnetic resonance to the negativization of the nasal swab for Sars-CoV-2. MRI, performed about two months later, confirmed the suspicion of hypertrophic cardiomyopathy, with no signs of late enhancement in T1-weighted sequences (Figure 2). The patient was then referred to a genetic study and cardiological follow-up, still in progress. 816 Figure 1816 Figure 1

527 An incidental diagnosis in a patient with SARS-CoV-2 pneumonia

Hypertrophic cardiomyopathy (HCM) is the most frequent genetic disease of the myocardium, with a prevalence of 1:500 cases in the general population. The salient feature is a hypertrophy, symmetrical or not, of the walls of the left ventricle (mainly the septum, but also less typical locations, such as the apex or the infero-lateral wall), not linked to abnormal load conditions. HCM is mostly an autosomal dominant inherited disease with incomplete penetrance and variable expressivity, mainly linked to mutations in genes coding for sarcomeric proteins. Several studies have shown an up-regulation of the ACE-2 gene, perhaps indicative of a compensatory anti-hypertrophic and anti-fibrotic response of the myocardium, in hypertrophic cardiomyopathy. Being the ACE-2 receptor target of the SARS-CoV-2 virus, these patients may have an increased risk of infection and a worse outcome.A 47-year-old man, with no known comorbidities, was hospitalized in our Emergency Medicine Department for bilateral SARS-CoV-2 pneumonia. Noninvasive mechanical ventilation c-PAP (FiO2 60%, PEEP 7.5 cmH2O) was started for hypoxemic respiratory failure and an ECG showed diffuse ventricular repolarization abnormalities suggestive of left overload (asymmetric negative T waves V4–V6, in I, II, and aVL, flat in aVF. Figure 1), with a deep Q wave in III. The patient was asymptomatic for chest pain and equivalents and D-dimer and indices of myocardionecrosis were normal. Echocardiographic evaluation was performed, with evidence of marked asymmetric concentric hypertrophy of the left ventricle (interventricular septum: 16 mm), without significant anomalies in segmental kinetics, noteworthy valvulopathies, and pericardial effusion. The family and personal medical history were negative for syncope, sudden cardiac death, and resuscitated cardiac arrest and the estimated risk of sudden cardiac death at 5 years (HCM Risk-SCD) was <4% (1.33%). The diagnostic hypothesis of non-obstructive hypertrophic cardiomyopathy was advanced. During hospitalization, ECG monitoring showed no sustained ventricular arrhythmias and the patient remained asymptomatic for dyspnoea, chest pain, and equivalents. Subsequent echocardiograms showed no new changes. A progressive weaning from oxygen support was carried out and, after 30 days, the patient was discharged to home fiduciary isolation, with optimal cardiological therapy and indication to study with cardiac magnetic resonance to the negativization of the nasal swab for SARS-CoV-2. MRI, performed about 2 months later, confirmed the suspicion of hypertrophic cardiomyopathy, with no signs of late enhancement in T1-weighted sequences (Figure 2). The patient was then referred to a genetic study and cardiological follow-up, still in progress.

Role of global longitudinal strain in discriminating variant forms of left ventricular hypertrophy and predicting mortality.

In this study, we aimed to compare the functional adaptations of the left ventricle in variant forms of left ventricular hypertrophy (LVH) and to evaluate the use of two-dimensional speckle tracking echocardiography (2D-STE) in differential diagnosis and prognosis. This was a prospective cohort study of 68 patients with LVH, including 20 patients with non-obstructive hypertrophic cardiomyopathy (HCM), 23 competitive top-level athletes free of cardiovascular disease, and 25 patients with hypertensive heart disease (HHD). All the subjects underwent 2D transthoracic echocardiography (TTE) and 2D-STE. The primary endpoint was all-cause mortality. Global longitudinal strain (GLS) below -12.5% was defined as severely reduced strain, -12.5% to -17.9% as mildly reduced strain, and above -18% as normal strain. The mean LV-GLS value was higher in athletes than in patients with HCM and HHD with the lowest value being in the HCM group (HCM: -11.4±2.2%; HHD: -13.6±2.6%; and athletes: -15.5±2.1%; p<0.001 among groups). LV-GLS below -12.5% distinguished HCM from others with 65% sensitivity and 77% specificity [area under curve (AUC)=0.808, 95% confidence interval (CI): 0.699-0.917, p<0.001]. The median follow-up duration was 6.4±1.1 years. Overall, 11 patients (16%) died. Seven of these were in the HHD group, and four were in the HCM group. The mean GLS value in patients who died was -11.8±1.5%. LV-GLS was significantly associated with mortality after adjusting age and sex via multiple analysis (RR=0.723, 95% CI: 0.537-0.974, p=0.033). Patients with GLS below -12.5% had a higher risk of all-cause mortality compared with that of patients with GLS above -12.5% according to Kaplan-Meier survival analysis for 7 years (29% vs. 9%; p=0.032). The LV-GLS value predicts mortality with 64% sensitivity and 70% specificity with a cut-off value of -12.5 (AUC=0.740, 95% CI: 0.617-0.863, p=0.012). The 2D-STE provides important information about the longitudinal systolic function of the myocardium. It may enable differentiation variable forms of LVH and predict prognosis.

The Echocardiographic Parameters of Systolic Function Are Associated with Specific Metabolomic Fingerprints in Obstructive and Non-Obstructive Hypertrophic Cardiomyopathy.

The purpose of this study was to assess whether metabolomics, associated with echocardiography, was able to highlight pathophysiological differences between obstructive (OHCM) or non-obstructive (NOHCM) hypertrophic cardiomyopathy. Thirty-one HCM patients underwent standard and advanced echocardiography; a plasma sample was collected for metabolomic analysis. Results. Patients with OHCM compared with subjects with NOHCM had higher values of 2DLVEF (66.5 ± 3.3% vs. 60.6 ± 1.8%, p < 0.01), S wave (7.6 ± 1.1 vs. 6.3 ± 0.7 cm/s, p < 0.01) and 3D global longitudinal strain (17.2 ± 4.2%, vs. 13.4 ± 1.3%, p < 0.05). A 2-group PLS-Discriminant Analysis was performed to verify whether the two HCM groups differed also based on the metabolic fingerprint. A clear clustering was shown (ANOVA p = 0.014). The most discriminating metabolites resulted as follows: in the NOHCM Group, there were higher levels of threitol, aminomalonic acid, and sucrose, while the OHCM Group presented higher levels of amino acids, in particular those branched chains, of intermediates of glycolysis (lactate) and the Krebs cycle (fumarate, succinate, citrate), of fatty acids (arachidonic acid, palmitoleic acid), of ketone bodies (2-OH-butyrate). Our data point out a different systolic function related to a specific metabolic activity in the two HCM phenotypic forms, with specific metabolites associated with better contractility in OHCM.

Transcatheter mitral valve repair for the treatment of severe mitral regurgitation and exertional pre-syncope in a patient with non-obstructive hypertrophic cardiomyopathy: a case report

BackgroundHypertrophic cardiomyopathy (HCM) has a complex pathophysiology and heterogeneous phenotypic expression. In obstructive HCM with significant mitral regurgitation (MR), MitraClip device implantation reduces MR severity and symptoms. There are no data regarding MitraClip implantation in patients with non-obstructive HCM and significant MR.Case summaryA 78-year-old woman with non-obstructive HCM and significant functional MR (3+) was admitted to our centre for dyspnoea and episodes of pre-syncope under light stress. Transthoracic and transoesophageal echocardiography showed a normal left ventricular ejection fraction and normal right heart pressures, an inverted mitral filling pattern, and a central prevalent jet (A2-P2 origin) of MR. Exercise echocardiography performed to verify exercise tolerance was interrupted at the 50-W stage due to severe hypotension and pre-syncope. After transcatheter edge-to-edge repair using the MitraClip system, the patient exhibited a reduction in MR Grade from 3+ to 1+. Follow-up up to 1-year post-procedure revealed noticeable improvements in exercise tolerance and symptoms. There were no further episodes of pre-syncope.DiscussionIn non-obstructive HCM, the pathophysiological role of MR in symptom generation is unknown. In this patient, we speculated that significant MR contributed to the mechanisms responsible for severe hypotension and pre-syncope during exercise. A reduction in MR after MitraClip implantation was associated with symptomatic improvements. Our findings further highlight the potential utility of the exercise stress test in therapeutic decision-making for patients with non-obstructive HCM and MR.