Mild Hypertrophic Cardiomyopathy Research Articles

Differentiation of Myocardial Properties in Physiological Athletic Cardiac Remodeling and Mild Hypertrophic Cardiomyopathy.

Clinical differentiation between athletes' hearts and those with hypertrophic cardiomyopathy (HCM) can be challenging. We aimed to explore the role of speckle tracking echocardiography (STE) and cardiac magnetic resonance imaging (CMR) in the differentiation between athletes' hearts and those with mild HCM. We compared 30 competitive endurance elite athletes (7% female, age 41 ± 9 years) and 20 mild phenotypic mutation-positive HCM carriers (15% female, age 51 ± 12 years) with left ventricular wall thickness 13 ± 1 mm. Mechanical dispersion (MD) was assessed by means of STE. Native T1-time and extracellular volume (ECV) were assessed by means of CMR. MD was higher in HCM mutation carriers than in athletes (54 ± 16 ms vs. 40 ± 11 ms, p = 0.001). Athletes had a lower native T1-time (1204 (IQR 1191, 1234) ms vs. 1265 (IQR 1255, 1312) ms, p < 0.001) and lower ECV (22.7 ± 3.2% vs. 25.6 ± 4.1%, p = 0.01). MD > 44 ms optimally discriminated between athletes and HCM mutation carriers (AUC 0.78, 95% CI 0.65-0.91). Among the CMR parameters, the native T1-time had the best discriminatory ability, identifying all HCM mutation carriers (100% sensitivity) with a specificity of 75% (AUC 0.83, 95% CI 0.71-0.96) using a native T1-time > 1230 ms as the cutoff. STE and CMR tissue characterization may be tools that can differentiate athletes' hearts from those with mild HCM.

Abstract 15732: Chronic Mavacamten Treatment Has Opposing Effects on Contractility in Engineered Heart Tissue Models of Severe vs. Mild Hypertrophic Cardiomyopathy

Many hypertrophic cardiomyopathy (HCM) causing mutations result in myocardial hypercontractility by increasing the number of myosin crossbridges in the disordered relaxed (DRX) state, or by sensitizing the sarcomere to the effects of Ca 2+ . Mavacamten (Mava) recently became the first FDA-approved treatment of obstructive HCM that directly targets hypercontractility by reducing the number of DRX cross bridges. Mava improves outcomes in patients with obstructive HCM but has not been approved in children or adults without obstructive HCM. The efficacy of chronic Mava treatment at preventing phenotype development in asymptomatic HCM mutation carriers remains largely unexplored. We recently showed that ablation of cardiac myosin binding protein-C (cMyBP-C -/-) in engineered heart tissue (EHT) causes rapid phenotype development in a dish. Initial hypercontractility progresses to hypocontractility with impaired relaxation, mediated by Ca 2+ mishandling. Here we investigate whether chronic Mava administration prevents phenotype progression. cMyBP-C +/+, +/- and -/- EHT were treated with 100nM Mava starting on day 7 of EHT culture. Serial twitch force (TF) measurements were performed weekly for 5 weeks, using the Mantarray platform. At day 7, prior to Mava treatment, +/- and -/- produced significantly more TF than +/+ EHT (392 ± 9 μN vs. 390 ± 15 μN vs. 199 ± 13 μN). At day 14, Mava treatment reduced TF by 31% (p &lt; 0.001) in +/+ EHT, 30% (p &lt; 0.001) in +/- EHT and 12% (p = 0.115) in -/- EHT. After an additional 4 weeks, chronic Mava treatment reduced TF by 54% (p &lt; 0.001) in +/+ EHT, 65% (p &lt; 0.001) in +/- EHT but increased TF by 23% (p = 0.034) in -/- EHT.These data show that chronic Mava treatment prevents/slows maladaptive remodeling in -/- EHT, but depresses contractility in +/+ and +/- ECT, suggesting that chronic Mava treatment may be detrimental to patients with mild HCM. Our ongoing studies are assessing the effect of chronic Mava treatment on other EHT models of HCM and on Ca 2+ -handling.

Electrocardiography-documented sudden cardiac death due to ventricular fibrillation in a young cat without echocardiographic evidence of severe structural heart disease

An asymptomatic three-year-old male European Domestic Shorthair cat was referred for an irregular heart auscultation. Apart from localized concentric left ventricular septal hypertrophy, echocardiography was normal. However, ventricular ectopy was observed on electrocardiography (ECG) during echocardiography. The cat died suddenly 55 minutes after the start of the subsequent Holter ECG. Analysis showed sinus rhythm interrupted by 192 single ventricular premature complexes, a ventricular couplet, two incidents of ventricular bigeminy and two runs of ventricular tachycardia (VT). The last run of VT deteriorated into ventricular fibrillation (VF) and ultimately cardiac arrest. Structural heart disease including mild feline hypertrophic cardiomyopathy or myocarditis, primary arrhythmia (channelopathy) or extra-cardiac disease were maintained as differential diagnosis. Unfortunately, a necropsy was declined leaving no definitive diagnosis available. In this case report, it is shown that VF due to ventricular ectopy is a possible cause of SCD even in asymptomatic cats with only mild echocardiographic signs of structural heart disease.

Circulating Acylcarnitines Associated with Hypertrophic Cardiomyopathy Severity: an Exploratory Cross-Sectional Study in MYBPC3 Founder Variant Carriers

Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease characterised by myocardial hypertrophy. HCM can cause outflow tract obstruction, sudden cardiac death and heart failure, but severity is highly variable. In this exploratory cross-sectional study, circulating acylcarnitines were assessed as potential biomarkers in 124 MYBPC3 founder variant carriers (59 with severe HCM, 26 with mild HCM and 39 phenotype-negative [G + P-]). Elastic net logistic regression identified eight acylcarnitines associated with HCM severity. C3, C4, C6-DC, C8:1, C16, C18 and C18:2 were significantly increased in severe HCM compared to G + P-, and C3, C6-DC, C8:1 and C18 in mild HCM compared to G + P-. In multivariable linear regression, C6-DC and C8:1 correlated to log-transformed maximum wall thickness (coefficient 5.01, p = 0.005 and coefficient 0.803, p = 0.007, respectively), and C6-DC to log-transformed ejection fraction (coefficient -2.50, p = 0.004). Acylcarnitines seem promising biomarkers for HCM severity, however prospective studies are required to determine their prognostic value.Graphical abstract

Management of severe hypothermia and pulsus alternans in an anaesthetised cat

AbstractAn 8‐year‐old, domestic, shorthair cat was presented for management of a significant degloving injury. After initial wound management, the cat was scheduled for anaesthesia to allow a free skin and pad graft to the affected foot. During anaesthesia, temperature rapidly dropped to a nidus of 28.0°C. Associated with this, the cat developed bradycardia and a marked pulsus alternans. The presumed ventricular myocardial dysfunction was treated with pimobendan (0.15 mg/kg intravenously). Within 5 minutes, the pulses equalised in amplitude. Additional active rewarming measures were initiated, which raised the temperature to 36.4°C before recovery in an incubator. A urinary catheter was placed to monitor for cold diuresis, and fluid therapy was altered to match urine output for 12 hours. A post‐anaesthetic echocardiogram revealed mild left ventricular concentric hypertrophy and dynamic right ventricular outflow tract obstruction indicating mild hypertrophic cardiomyopathy. The cat was discharged following 3 weeks of successful intensive wound and graft management.

S2653 Recurrent Bleeding Gastrointestinal Angioectasias and Acquired Von Willebrand Deficiency (Heyde’s Syndrome) Developing in the Setting of Mild Hypertrophic Obstructive Cardiomyopathy

Introduction: Heyde’s Syndrome is classically described as a triad of gastrointestinal arteriovenous malformations, aortic stenosis (AS), and acquired von Willebrand syndrome (aVWS). Acknowledged as under-diagnosed, the syndrome is frequently missed even in the presence of classically associated moderate-to-severe AS. Perhaps compounding diagnostic difficulty are more recent reports of alternative forms of structural heart disease, including hypertrophic obstructive cardiomyopathy (HOCM), that, although rarer, are capable of producing the syndrome as well. Case Description/Methods: 68-year-old woman with mild hypertrophic obstructive cardiomyopathy that resulted in 5 years of gastrointestinal bleeding episodes before the discovery of bleeding duodenal angioectasias. Initially diagnosed with “HOCM morphology” without evidence of dynamic obstruction on stress echocardiogram, bleeding episodes began to develop shortly after routine annual surveillance echo demonstrated a progression to mildly increased left ventricular outflow tract (LVOT) gradient. Cardiac magnetic resonance imaging (MRI) not only confirmed mild primary HOCM without secondary cause of hypertrophy, but also demonstrated mild flow acceleration across the LVOT, consistent with the hypothesized hemodynamic turbulence and sheer-stress believed to be the mechanism behind acquired von Willebrand deficiency. Within a year, gastrointestinal bleeding would ensue, beginning a prolonged clinical course with multiple hospitalizations for symptomatic anemia requiring transfusions. The eventual discovery of angioectasias prompted von Willebrand Factor analysis which found evidence of acquired deficiency and confirmed the diagnosis of Heyde Syndrome. The patient was subsequently referred for evaluation and definitive treatment of her HOCM with septal ablation, an intervention with which case series have demonstrated the potential for reversal of von Willebrand Factor deficiency and bleeding episodes. Discussion: Often a delayed diagnosis owing to the seemingly disparate constellation of findings in Heyde’s, this particular case additionally highlights that even more mild states of structural heart disease can provoke the syndrome outside of previously reported severe structural disease. Diagnostic suspicion must remain high and von Willebrand factor analysis considered in the combined presence of GI bleed and mild cardiomyopathy and valvulopathy.

Assessment of mitral valve function in children and young adults with hypertrophic cardiomyopathy using three-dimensional echocardiography

ObjectiveThe objective of this study was to assess papillary muscle (PM) and mitral valve (MV) structure and function in children and young adults with mild and moderate hypertrophic cardiomyopathy (HCM) using real-time three-dimensional echocardiography (3DE) and to correlate them with HCM related adverse outcomes. MethodsTransthoracic research 3DE was performed in HCM patients and controls matched for age and gender. Anterolateral and posteromedial PM mass, apical displacement of anterolateral PM, and left ventricular (LV) mass were measured and indexed to body surface area. The MV annulus and leaflet structure and function were analyzed. Individual PMs were manually planimetered by tracing the endocardial borders on each mid systole frame, taking care to distinguish PMs as distinct from the LV wall. Apical PM displacement was expressed as ratio of the distance between the apex and the base of the anterolateral PM to the entire length of the LV lateral wall (APL index). All 3DE measurements were correlated to adverse outcomes. ResultsForty subjects were studied, including 20 HCM patients (age 18.1 ± 9.6 years, 16 male and 4 female), and 20 controls (18.2 ± 9.6 years, 16 male and 4 female). The indexed LV mass in HCM was 74.8 ± 25.8 g/m2 compared to 50.8 ± 12.4 g/m2 in controls (p = 0.001). The anterolateral, posteromedial and combined PM mass were 3.1 ± 2.2 g/m2, 1.7 ± 1.2 g/m2 and 4.9 ± 2.7 g/m2 in HCM, in contrast to respective measurements of 1.1 ± 0.6 g/m2, 1.2 ± 0.6 g/m2 and 2.3 ± 0.8 g/m2 in controls (p < 0.001, p = 0.062, and p < 0.001, respectively). The mitral valve annular parameters (annulus circumference, height and area) in HCM were not significantly different from controls. The APL index in HCM was less than in controls (0.44 ± 0.07 vs. 0.55 ± 0.04, p < 0.001). The LV lateral wall length and LV mass correlated with adverse HCM outcomes, while the APL index and PM total mass were not associated with adverse events. ConclusionIt is feasible to evaluate PM muscles and MV annulus geometry in children and young adults with HCM using 3DE. The morphologic and functional changes of anterolateral PM may occur in the absence of MV annulus changes. Prospective validation will be required to determine if LV lateral wall length and LV mass may be used as predictors of adverse events.

Findings suggestive of coronary microvascular dysfunction in cats with myocardial ischemia.

Background:Myocardial infarction (MI) is an important cause of death and disability among humans worldwide. Few studies have reported the occurrence of MI in small animals as well. Reports in human medicine indicate that up to 30% of patients with clinical signs compatible with myocardial ischemia suggestive of coronary disease exhibit normal epicardial arteries at angiography. These symptoms have been associated with a syndrome characterized by alterations in cardiac microvasculature, known as coronary microvascular dysfunction (CMD). Aim:This study aimed to describe the necropsy findings and clinical-pathological characterization (when available) of cats with histopathological findings suggesting CMD. Methods:Necropsy records of cats presenting histopathological diagnosis compatible with acute and/or chronic MI, with normal epicardial arteries and microvascular disorders were evaluated.Results:Twenty animals met the inclusion criteria. Eight cats (40%) exhibited findings compatible with mild hypertrophic cardiomyopathy (HCM) without left atrial enlargement, one (5%) presented restrictive cardiomyopathy, and another one (5%) had lesions consistent with histiocytoid cardiomyopathy. The remaining cats (50%) showed alterations compatible with severe HCM with left atrial enlargement. In all cases, epicardial arteries were normal (without obstruction). All the evaluated hearts exhibited myocardial multifocal fibrosis along with replacement of cardiomyocytes by adipose tissue and blood vessels with hyperplasia and hypertrophy of the muscular layer with protrusion of the nuclei of the endothelial cells.Conclusion:These findings suggest the presence of microvascular dysplasia of the coronary arteries. Further studies are necessary to confirm and clinically characterize these results.

Abstract 15889: The Role of Physical Deconditioning in Distinguishing Hypertrophic Cardiomyopathy From Athlete's Heart

Background: Vigorous systematic physical training can result in increased left ventricular wall thickness (LVWT) (i.e., “athlete’s heart”) which can be challenging to differentiate diagnostically from mild non-obstructive hypertrophic cardiomyopathy (HCM). The efficacy of a deconditioning strategy to observe changes in LVWT using cardiovascular magnetic resonance (CMR) that would support a diagnosis of athlete’s heart vs. HCM is not well established. Methods: We identified 9 highly trained patients involved in various organized sports who were referred to the Tufts Medical Center HCM center with a maximal LVWT in a diagnostic “gray area” of 13-15 mm. Maximal LVWT and other clinical and imaging variables were compared at baseline and following &gt; 3 months of deconditioning from athletic training. A clinically relevant change in maximal LVWT at the end of athletic deconditioning was defined as a decrease of ≥2 mm, consistent with “athlete’s heart”. Imaging studies were interpreted blinded to study time period. Results: Among the 9 patients (23.1 ± 12.3 years old; 100% male), 4 demonstrated a ≥ 2 mm decrease in maximal LVWT (range: 2 mm to 3 mm) to ≤ 12 mm in 3 patients and 13 mm in one patient, with an average decrease of 2.3 mm. Among these 4 patients, LV and LA size also decreased (217.3 ± 31.5 ml to 208.9 ± 16.8 ml; and 55.4 ± 10.0 mm to 51.7 ± 9.1 mm, respectively), and there was no late gadolinium enhancement, pathogenic sarcomere mutation, or family history of HCM. Parameters of diastolic function were normal prior to deconditioning. After deconditioning evaluation and significant change in LVWT, these 4 patients were judged to not have a clinical diagnosis of HCM. The remaining 5 patients had a non-significant change in maximal LVWT after deconditioning of 0.2 mm, with maximal LVWT remaining ≥ 13 mm, and no change in LV or LA cavity size (p&gt;0.2 for each). After deconditioning, these 5 patients were judged to have a clinical diagnosis of HCM. In the 9 patients that underwent a period of deconditioning, there was an average heart rate increase of 6.33. Conclusion: In athletes with maximal LVWT within the “gray zone” (13-15 mm) of overlap with HCM, athletic deconditioning using CMR to detect changes in maximal LVWT can aid in the differential diagnosis and inform management decisions.

Novel NDUFA13 Mutations Associated with OXPHOS Deficiency and Leigh Syndrome: A Second Family Report

Leigh syndrome (LS) usually presents as an early onset mitochondrial encephalopathy characterized by bilateral symmetric lesions in the basal ganglia and cerebral stem. More than 75 genes have been associated with this condition, including genes involved in the biogenesis of mitochondrial complex I (CI). In this study, we used a next-generation sequencing (NGS) panel to identify two novel biallelic variants in the NADH:ubiquinone oxidoreductase subunit A13 (NDUFA13) gene in a patient with isolated CI deficiency in skeletal muscle. Our patient, who represents the second family report with mutations in the CI NDUFA13 subunit, presented with LS lesions in brain magnetic resonance imaging, mild hypertrophic cardiomyopathy, and progressive spastic tetraparesis. This phenotype manifestation is different from that previously described in the first NDUFA13 family, which was predominantly characterized by neurosensorial symptoms. Both in silico pathogenicity predictions and oxidative phosphorylation (OXPHOS) functional findings in patient’s skin fibroblasts (delayed cell growth, isolated CI enzyme defect, decreased basal and maximal oxygen consumption and as well as ATP production, together with markedly diminished levels of the NDUFA13 protein, CI, and respirasomes) suggest that these novel variants in the NDUFA13 gene are the underlying cause of the CI defect, expanding the genetic heterogeneity of LS.

Baseline Characteristics of the VANISH Cohort.

The VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) targeted young sarcomeric gene mutation carriers with early-stage hypertrophic cardiomyopathy (HCM) to test whether valsartan can modify disease progression. We describe the baseline characteristics of the VANISH cohort and compare to previous trials evaluating angiotensin receptor blockers. Applying a randomized, double-blinded, placebo-controlled design, 178 participants with nonobstructive HCM (age, 23.3±10.1 years; 61% men) were randomized in the primary cohort and 34 (age, 16.5±4.9 years; 50% men) in the exploratory cohort of sarcomeric mutation carriers without left ventricular hypertrophy. In the primary cohort, maximal left ventricular wall thickness was 17±4 mm for adults and Z score 7.0±4.5 for children. Nineteen percent had late gadolinium enhancement on cardiac magnetic resonance. Mean peak oxygen consumption was 33 mL/kg per minute, and 92% of participants were New York Heart Association functional class I. New York Heart Association class II was associated with older age, MYH7 variants, and more prominent imaging abnormalities. Six previous trials of angiotensin receptor blockers in HCM enrolled a median of 24 patients (range, 19-133) with mean age of 51.2 years; 42% of patients were in New York Heart Association class ≥II, and sarcomeric mutations were not required. The VANISH cohort is much larger, younger, less heterogeneous, and has less advanced disease than prior angiotensin receptor blocker trials in HCM. Participants had relatively normal functional capacity and mild HCM features. New York Heart Association functional class II symptoms were associated with older age, more prominent imaging abnormalities, and MYH7 variants, suggesting both phenotype and genotype contribute to disease manifestations. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01912534.

LEFT VENTRICULAR HYPERTROPHY IN A COLLEGE ATHLETE: PHYSIOLOGICAL OR PATHOLOGICAL?

The differentiation of ‘athlete's heart’ from morphologically mild hypertrophic cardiomyopathy (HCM) is important as an erroneous diagnosis can lead to the catastrophic event of sudden cardiac death. Conversely, an athlete with physiological adaptation may be unnecessarily restricted. A 20-year

Sudden death in mild hypertrophic cardiomyopathy with compound DSG2/DSC2/MYH6 mutations: Revisiting phenotype after genetic assessment in a master runner athlete

Cardiomyopathies represent a well-known cause of heart failure and sudden death. Although cardiomyopathies are generally categorized in distinct nosographic entities, characterized by single gene-to-disease causal relationships, recently, oligogenic mutations have also been associated to relevant cardiac clinical features. We report the case of a master athlete carrying trigenic mutations in desmoglein-2 (DSG2), desmocollin-2 (DSC2) and heavy chain myosin 6 (MYH6), which determine a mild hypertrophic phenotype associated both to ventricular tachyarrhythmias and atrio-ventricular block. We discuss the differential diagnosis and prognostic approach in patient affected by complex cardiomyopathy phenotype, along with the importance of sport restriction and sudden death prevention.

10 Vortex formation time: a novel differentiator between physiological and pathological cardiac adaptation

Introduction Elite athletes undertake endurance training that can lead to increased left ventricular wall thickness thus creating uncertainty regarding the differential diagnosis of athlete’s heart from hypertrophic cardiomyopathy (HCM). The distinction of physiological from pathological LV wall hypertrophy is crucial because of the risk of sudden cardiac death associated with HCM. Vortex formation time (VFT) is a novel index of biological fluid transport efficiency. It is a dimensionless index of the left ventricular filling that integrates all phases of diastole (T≈ 4 (3.3–5.5)). It has been shown to reliably differentiate between healthy control subjects and heart failure patients. We hypothesised that VFT can be used to differentiate between physiological and pathological cardiac adaptation, especially in this challenging population of “athletes heart” versus mild hypertrophic cardiomyopathy. Methods We compared echocardiographic indices between 41 elite male strength endurance athletes with mild symmetrical LVH, 11 male patients with a mild phenotype of hypertrophic cardiomyopathy against 20 sedentary volunteers (age, weight and sex-matched). VFT was obtained using the validated formula: 4 × (1 − β )/ π × α ³ × LVEF, wheris the fraction of total transmitral diastolic stroke volume contributed by atrial contraction and α is the biplane end-diastolic volume (EDV) 1/3 divided by mitral annular diameter during early diastole. Multiple regression analysis was used to adjust for heart rate and age. Results There was no difference in gender and body surface area between the controls, athletes and hypertrophic cardiomyopathic patients. Septal wall thickness was 1.4 cm ± 0.1 in the HCM group compared to 1.3 cm ± 0.1 in the athletes and 0.89 cm ± 0.2 in the controls. The heart rate was 63 ± 10 bpm in the athletes vs. 74 ± 7 bpm in sedentary controls and 81 ± 4 bpm in HCM group (p = 0.001). The VFT was highest in the athletic group, lower in the sedentary group and lowest in the HCM group (4.01 ± 0. 80 vs. 3.12 ± 0.38 vs. 2.5 ± 0.8) (p Conclusion The VFT was normal in endurance Rowers and controls but significantly reduced below the optimal value in the hypertrophic cardiomyopathy patients. We conclude that pathological left ventricular hypertrophy (LVH) can be differentiated from physiological LVH by the presence of decreased Vortex formation time. Vortex formation time is a new useful differentiator between pathological and physiological LVH to guide physicians decision making in this challenging population.

G.P.315 - Coexisting TIA1 and MYH7 distal myopathy

Distal myopathies are genetically heterogeneous. TIA1 mutations cause Welander distal myopathy. MYH7 mutations result in various clinical phenotypes, including Laing distal myopathy, myosin storage myopathy and hypertrophic/dilated cardiomyopathy. We describe a family affected by distal myopathy and variable presence of cardiomyopathy due to coexisting TIA1 and MYH7 mutations. The propositus is a 67-year-old woman of Swedish and Greek descent with history of easy tripping since childhood who has experienced a stepwise progression of asymmetric distal limb weakness in the past 20 years. Neurological examination revealed mild to severe asymmetric distal lower >upper limb weakness. CK value was normal. EMG study showed myopathic changes with minimal fibrillation potentials and myotonic discharges. Biopsy of the extensor carpi radialis muscle showed: rare rimmed vacuoles, minicore-like structures and congophilic inclusions; few necrotic and regenerating fibers; fiber splitting; increased internal nuclei; and fiber type grouping. There was no cardiac involvement by ECG and echocardiogram. Her 66-year-old sister has 8 years of mild distal limb weakness, supraventricular tachycardia and hypertrophic cardiomyopathy documented by echocardiogram and MRI. Another sibling has distal weakness while parents were asymptomatic. Both sisters carry a known pathogenic heterozygous TIA1 mutation (p.Glu384Lys) and a rare heterozygous MYH7 variant (c.5459G > A; p.Arg1820Gln), which involves a highly conserved residue and is predicted to be pathogenic. Because a homozygous MYH7 mutation (p.Arg1820Trp) was reported in recessive myosin storage myopathy, aCGH deletion/duplication analysis of MYH7 was performed in the proband and it was normal. The clinical phenotype is dictated by the coexistent TIA1 and MYH7 mutations, which can result in similar pathological findings. The proband's early onset of distal leg weakness and the sister's cardiomyopathy support the pathogenicity of the MYH7.

91 Differentiating Physiological Left Ventricular Hypertrophy from Hypertrophic Cardiomyopathy in Athletes: Proposed Echocardiographic Protocol

PurposeHypertrophic cardiomyopathy (HCM) is the commonest cause of SCD in young athletes. The differentiation between physiological left ventricular hypertrophy (LVH) and morphologically mild hypertrophic cardiomyopathy (HCM) is crucial and an...

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Complex I and IV deficiency in an athletic adolescent with mild global retardation, exertional dyspnea, hypertrophic cardiomyopathy, and slight dysdiadochokinesia

Complex I and IV deficiency in an athletic adolescent with mild global retardation, exertional dyspnea, hypertrophic cardiomyopathy, and slight dysdiadochokinesia

Efficacy of Various “Classic” Echocardiographic and Laboratory Indices in Distinguishing the “Gray Zone” between Athlete's Heart and Hypertrophic Cardiomyopathy: A Pilot Study

Left ventricular hypertrophy (LVH) with intraventricular septum thickness (IVST) between 1.2 and 1.5cm in athletes represents a "gray zone" between physiologic adaptation and mild hypertrophic cardiomyopathy (HCM). Various echo and laboratory parameters have been reported till now in the literature to discriminate the "gray zone" entities. Aim of this study was to assess the efficacy of these "classic" parameters in differentiating physiologic LVH in athletes from mild HCM in a highly selected population. Nine highly trained athletes with IVST (1.28±0.07cm), 9 patients with mild HCM (1.38±0.11cm), and 26 athletes without LVH (1.06±0.09cm; P<0.0005) underwent echocardiographic study, cardiopulmonary treadmill exercise stress test, and brain natriuretic peptide (BNP) measurement before and after exercise. Among all parameters tested, 7 were found to significantly differ between "gray zone" groups. After bootstrapping analysis, it was found that athletes with left ventricular end-diastolic diameter <4.74cm, mitral deceleration time >200ms, isovolumic relaxation time >94ms, tricuspid E/A<1.63, septum Em<9.5cm/sec, relative wall thickness >0.445, and a BNP value at rest >9.84pg/mL had a greater possibility for having underlying cardiomyopathy. A 10-point score based on these parameters showed accuracy (area under the curve=0.958 [95%CI: 0.738-1.0; P=0.00005, standard error=0.0342]) for revealing HCM in a gray zone athletic population. Differentiation of adaptive LVH versus HCM in a gray zone population could be facilitated by recognition of certain features referring to LV dimensions, diastolic function, and BNP.

Clinical features and new molecular findings in muscle phosphofructokinase deficiency (GSD type VII)

Muscle phosphofructokinase (PFKM) deficiency, a rare disorder of glycogen metabolism also known as glycogen storage disease type VII (GSDVII), is characterized by exercise intolerance, myalgias, cramps and episodic myoglobinuria associated with compensated hemolytic anaemia and hyperuricemia. We studied five patients with PFKM deficiency coming from different Italian regions. All probands showed exercise intolerance, hyperCKemia, cramps and myoglobinuria. One patient had a mild hypertrophic cardiomyopathy. Biochemical studies revealed residual PFK activity ranging from 1 to 5%. Molecular genetic analysis identified four novel mutations in the PFKM gene. In our series of patients, clinical and laboratory features were similar in all but one patient, who had an unusual phenotype characterized by 25years disease history, high CK levels, hypertrophic cardiomyopathy with paroxysmal atrial fibrillation without fixed muscle weakness.