Manifestation Of Hypertrophic Cardiomyopathy Research Articles

An Update on MYBPC3 Gene Mutation in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most prevalent genetically inherited cardiomyopathy that follows an autosomal dominant inheritance pattern. The majority of HCM cases can be attributed to mutation of the MYBPC3 gene, which encodes cMyBP-C, a crucial structural protein of the cardiac muscle. The manifestation of HCM's morphological, histological, and clinical symptoms is subject to the complex interplay of various determinants, including genetic mutation and environmental factors. Approximately half of MYBPC3 mutations give rise to truncated protein products, while the remaining mutations cause insertion/deletion, frameshift, or missense mutations of single amino acids. In addition, the onset of HCM may be attributed to disturbances in the protein and transcript quality control systems, namely, the ubiquitin-proteasome system and nonsense-mediated RNA dysfunctions. The aforementioned genetic modifications, which appear to be associated with unfavorable lifelong outcomes and are largely influenced by the type of mutation, exhibit a unique array of clinical manifestations ranging from asymptomatic to arrhythmic syncope and even sudden cardiac death. Although the current understanding of the MYBPC3 mutation does not comprehensively explain the varied phenotypic manifestations witnessed in patients with HCM, patients with pathogenic MYBPC3 mutations can exhibit an array of clinical manifestations ranging from asymptomatic to advanced heart failure and sudden cardiac death, leading to a higher rate of adverse clinical outcomes. This review focuses on MYBPC3 mutation and its characteristics as a prognostic determinant for disease onset and related clinical consequences in HCM.

Sudden cardiac death during exercise in young individuals with hypertrophic cardiomyopathy

Abstract Background Sudden cardiac death (SCD) in young individuals and athletes is generally caused by hereditary cardiac conditions, including cardiomyopathies such as hypertrophic cardiomyopathy (HCM). Although historically HCM has been reported as the predominant cause of SCD in young athletes, it is unclear as to what degree exercise is a trigger for possible fatal arrhythmias. Aim We aimed to report on the circumstances of SCD in a cohort of young individuals aged ≥10 and <30 whose autopsy was consistent with HCM. Methods We reviewed 6860 consecutive cases of SCD referred to our specialist cardiac pathology centre 1994 and 2020. SCD was defined as death from a cardiovascular cause within 12 hours of apparent well-being. All cases underwent detailed autopsy evaluation of the heart, including histological analysis, by expert cardiac pathologists. A minimum of 10 blocks of tissue were taken for histological analysis. HCM was defined by the presence of increased heart weight or increased wall thickness and significant myocyte disarray at histological examination. Results Of the total cases of SCD, 264 (4%) were due to HCM. Our cohort of young decedents comprised of 66 individuals (average age 21±5 years, males 76%). For the majority (n=52, 79%) SCD was the first manifestation of HCM. The average heart weight was 507±152 grams and left ventricular (LV) fibrosis was found in 28 (42%) cases (Figure 1A). Death was more common between 16 and 20 years of age (n=24) (Figure 1B). Death occurred during exertion in 25 (38%) individuals and at rest or during daily activities in the remaining 41 (62%), including 5 individuals who died during sleep. Male sex was more represented among decedents who died during exertion (88% compared with 68% in the group that died at rest, p=0.07); LV fibrosis was more commonly observed in individuals who died during exertion (56% compared with 34% in the group who died at rest, p=0.08). Younger individuals between 10–15 years of age died mostly during exercise (80%), in other age groups death occurred mainly at rest (33% in age group 16–20 years, 30% in age group 21–25 years, 33% in age group 26–30 years) (Figure 1B). Conclusions We observed a high age-related variability in terms of circumstances of death. In the context of HCM, our findings suggest that individuals aged 10–15 years are the most vulnerable in terms of exercise-related-SCD. This exemplifies the importance of preventative cardiac screening in young individuals who might be harbouring quiescent cardiac conditions associated with young 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.

Clinical characteristics of hypertrophic cardiomyopathy in children: An 8-year single center experience.

Hypertrophic cardiomyopathy (HCM) is the second most common pediatric cardiomyopathy. Although there is a large body of literature about HCM in adults, there is limited information on HCM in childhood. We evaluated various aspects of pediatric HCM patients treated at our center. We identified 152 pediatric patients with HCM between October 2011 and October 2019. Clinical history, invasive (ICD, pacemaker, electrophysiologic study, catheter ablation therapy) and non-invasive (ECG, holter moniterization, echocardiography, cardiac MR, genetic study, medicam treatment) data were collected and evaluated. The mean ± standard deviation age of patients was 8.9±5.7years (1month-18years) and 67.8% were male. The most frequent clinical symptoms were murmur and palpitations. Three cases (2%) had aborted sudden death as the first manifestation of HCM. Of these patients, 120 (78.9%) had non-syndromic HCM and 32 (27.2%) had syndromic HCM. Asymmetric septal hypertrophy was common (48.3%) in the non-syndromic group, whereas concentric hypertrophy was common (56.2%) in syndromic group. Left ventricular outflow tract obstruction (LVOTO) occurred in 39 (25.6%) patients. Nine (5.9%) patients underwent electrophysiologic study and/or ablation and 16 patients underwent surgical intervention. Implantable cardioverter defibrillator (ICD) insertion was performed in 38 patients (26 transvenous, 12 epicardial). ICDs were inserted in three (7.9%) patients for secondary prevention; in the remaining patients (92.1%) the devices were placed for primary prevention. Mean SD follow-up time was 27.1±22 months. Five (3.3%) patients died during the follow-up. No patient had heart transplantation or a long-term assistive device. The etiology of HCM is heterogeneous and present at any age. It is important to determine the timing of surgery and potential risks for sudden cardiac arrest. As most cases of HCM are familial, evaluation of family members at risk should be a routine component of clinical management.

Heat shock proteins and small nucleolar RNAs are dysregulated in a Drosophila model for feline hypertrophic cardiomyopathy.

In cats, mutations in myosin binding protein C (encoded by the MYBPC3 gene) have been associated with hypertrophic cardiomyopathy (HCM). However, the molecular mechanisms linking these mutations to HCM remain unknown. Here, we establish Drosophila melanogaster as a model to understand this connection by generating flies harboring MYBPC3 missense mutations (A31P and R820W) associated with feline HCM. The A31P and R820W flies displayed cardiovascular defects in their heart rates and exercise endurance. We used RNA-seq to determine which processes are misregulated in the presence of mutant MYBPC3 alleles. Transcriptome analysis revealed significant downregulation of genes encoding small nucleolar RNA (snoRNAs) in exercised female flies harboring the mutant alleles compared to flies that harbor the wild-type allele. Other processes that were affected included the unfolded protein response and immune/defense responses. These data show that mutant MYBPC3 proteins have widespread effects on the transcriptome of co-regulated genes. Transcriptionally differentially expressed genes are also candidate genes for future evaluation as genetic modifiers of HCM as well as candidate genes for genotype by exercise environment interaction effects on the manifestation of HCM; in cats as well as humans.

Myocardial morphology in hypertrophic cardiomyopathy: the current state of the problem

The objective. Based on the modern sources of scientific data to analyze the morphological features of the myocardium in hypertrophic cardiomyopathy. The paper presents a literature review on current views on the features of structural remodeling of the left ventricular myocardium in patients with hypertrophic cardiomyopathy, as well as the most common classifications of this pathology. The emphasis is made on the problem of the interrelation of myocardial disarray and fibrosis. The “small vessel disease” is an important pathogenetic link in the development of heart failure, which enhances the relation between disorder of myocardial histoarchitectonics and progressive cardiac ischemia in hypertrophic cardiomyopathy. Conclusions. Notwithstanding the numerous research data on hypertrophic cardiomyopathy, no consensus among the authors regarding the etiology and pathogenesis of hypertrophic cardiomyopathy exists to date. Controversial data on the interrelation and sequence of disarray, myocardial hypertrophy, interstitial fibrosis, changes in the microvasculature and structural changes of the mitral valve in patients with hypertrophic cardiomyopathy hamper the search for adequate etiotropic treatment. Polymorphism of clinical and morphological manifestations of hypertrophic cardiomyopathy requires collaborative efforts to study the disease by cardiologists and pathologists.

Echocardiographic evaluation of pre-diagnostic development in young relatives genetically predisposed to hypertrophic cardiomyopathy.

Identification of the first echocardiographic manifestations of hypertrophic cardiomyopathy may be important for clinical management and our understanding of the pathogenesis. We studied the development of pre-diagnostic echocardiographic changes in young relatives to HCM patients during long-term years follow-up. HCM-relatives not fulfilling the diagnostic criteria for HCM and age of <18 years were included in this study. We performed echocardiographic evaluations at inclusion and after 12 ± 1 years follow-up. Based on family screening of 11 sarcomere genes, CRYAB, α-GAL, and titin, we evaluated: (1) non-carriers (known family mutation ruled out-controls), (2) carriers (phenotype negative gene mutation carriers) and (3) phenotype negative relatives with unknown genetic status (relatives from families without identified mutations). At inclusion (age 11 ± 5 years), there were no differences in echocardiographic chamber dimensions, systolic or diastolic function between the three groups. During follow-up (age 23 ± 5 years), carriers (n = 8) developed lower left ventricular end-diastolic dimension (LVEDd) compared to non-carriers (n = 23) (41 ± 4 vs. 46 ± 4 mm; p = 0.04) and a higher ratio of early left ventricular filling velocity and early diastolic velocity of lateral mitral annulus (E/e' 6 ± 1 vs. 5 ± 1; p = 0.003). No significant differences in LVEDd or E/e' were found between relatives with unknown genetic status (n = 24) and non-carriers though Z-scores for these parameters were >2 in a subset of relatives with unknown genetic status. Children carrying pathogenic sarcomere gene mutations develop reduced LVEDd and increased E/e' as first pre-diagnostic echocardiographic manifestations during follow-up into adulthood.

Association between non-coding polymorphisms of HOPX gene and syncope in hypertrophic cardiomyopathy.

Homeodomain Only Protein X (HOPX) is an unusual homeodomain protein which regulates Serum Response Factor (SRF) dependent gene expression. Due to the regulatory role of HOPX on SRF activity and the regulatory role of SRF on cardiac hypertrophy, we aimed to investigate the relationship between HOPX gene variations and hypertrophic cardiomyopathy (HCM). In this study, designed as a case-control study, we analyzed coding and flanking non-coding regions of the HOPX gene through 67 patients with HCM and 31 healty subjects. Certain regions of the gene were investigated by Single Stranded Conformation Polymorphism (SSCP) and Restriction Fragment Length Polymorphism (RFLP). Statistical analyses of genotypes and their relationship with clinical parameters were performed by chi-square, Kruskal-Wallis and the Fisher's exact test. In 5' Untranslated Region (UTR) and intronic region of the HOPX gene, we found a C>T substitution and an 8-bp insertion/deletion (In/Del) polymorphism, respectively. These two polymorphisms seemed to constitute an haplotype. While the frequency of homozygous genotypes of In/Del and C/T polymorphisms were found significantly lower in the patients with syncope (p=0.014 and p=0.017, respectively), frequency of their heterozygous genotypes were found significantly higher in the patients with syncope (p=0.048 and p=0.030, respectively). CONCLUSİON: Though there was not found any mutation in coding sequence of HOPX gene, two non-coding polymorphisms were found related to syncope in HCM patients. While homozygous status of these polymorphisms was found to be protective against the syncope, their heterozygous status seemed to be a risk factor for syncope in HCM patients. Our results suggest that HOPX may contribute to pathogenesis or manifestation of HCM as a modifier gene.

Magnetic Resonance Imaging for Hypertrophic Cardiomyopathy Update

Hypertrophic cardiomyopathy (HCM) is a genetic disease of the myocardium. Although many patients remain asymptomatic, sudden cardiac death could be the first manifestation of HCM. Magnetic resonance imaging (MRI) plays an important role in the diagnosis and management of this disease. The epidemiology, pathophysiology, and diagnosis of HCM will be briefly reviewed. This is followed by a discussion on the role of cardiac MRI, recommended protocol, typical imaging findings of HCM, and advanced MRI techniques. Although MRI is not intended to be a first-line tool for the assessment of HCM, MRI does provide valuable information to aid the management of patients either at risk of or diagnosed with HCM.

The nurse's role in diagnosing hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder and the most common cause of sudden cardiac death (SCD) in people under 30 years. Although the causes are generally well known, SCD is often the first clinical manifestation of HCM. If those at risk of SCD and other complications are identified and treated appropriately, HCM is relatively benign. Priority should lie with identifying family and first-degree relatives of SCD victims, as HCM is predominantly a familial disorder. Patients with symptoms of HCM should be thoroughly assessed by health-care professionals. Knowledge of symptoms of HCM can lead to further investigations that can aid diagnosis. Symptoms include angina, dyspnoea, syncope/presyncope, palpitations and dizziness. The nurse plays an important role in assessing the patient for signs and symptoms of HCM through competent knowledge and skills in history taking, physical examination and electrocardiogram interpretation, which may provide the basis for a referral for an echocardiogram that can lead to the diagnosis of HCM. Treatment can then be commenced, thus reducing the risk of SCD. Implantable cardiac defibrillators are a common surgical intervention in HCM that have proven to be life saving.

Isolated papillary muscle hypertrophy: a variant of hypertrophic cardiomyopathy, but further evidences are still needed: reply

We are grateful to Dr de Gregorio for his interest in our article1 and for his insights into this matter. We also agree on the need of further studies regarding this particular issue. The discussion of isolated papillary muscle (PM) hypertrophy as a possible manifestation of hypertrophic cardiomyopathy (HCM) is not new but, unfortunately, remains uncertain. Regarding the possible prognostic impact of HCM, systematic studies are urgent to better elucidate the clinical meaning of this morphological abnormality. This is particularly important when we are dealing with athletes, like the cases reported by de Gregorio et al .2 since the most feared manifestation of …

Hypertrophe Kardiomyopathie

Hypertrophic cardiomyopathy (HCM) is associated with hypertrophy of the left and/or right ventricle. Development of the disease may be based on genetic predispositions. An increased frequency in families can be seen in 50% of cases. Up to 0.2% of the general population are affected. But there is probably a high number of unknown cases because sudden cardiac death is often the first manifestation of HCM. HCM is also the most frequent cause of sudden deaths among adolescents and athletes. Symptoms can be very different. Most patients have no or mild clinical signs, but symptoms of diastolic heart failure are possible. Diagnosis is based on ECG, 24 hour ECG, echocardiography, cardiac catheter, and other methods. For treatment drugs like beta blockers or calcium antagonists can be helpful. Other therapeutic options are a percutaneous septal myocardial ablation. In case of left ventricular dilatation prognosis is relatively poor. Overall mortality per year is estimated up to 2% for adults and up to 4 to 6% for children.

Gender-specific differences in the clinical features of hypertrophic cardiomyopathy in a community-based Japanese population: Results from Kochi RYOMA study

Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with a broad spectrum of clinical features. Although gender may be one of the important modifying factors in HCM, there has been little information on gender differences. We investigated gender-specific differences in the clinical features of HCM in a community-based Japanese population. We established cardiomyopathy registration in Kochi Prefecture named Kochi RYOMA study consisting of 9 hospitals as an unselected regional Japanese population. 261 patients with diagnosis of HCM were registered. At registration, 88 patients (34%) were women. Female patients were more frequently diagnosed as having HCM at ≥65 years (41% versus 27%) and had a higher ratio of familial HCM (35% versus 19%). More female patients had diagnosis of HCM due to cardiac symptoms (64% versus 40%) and were symptomatic both at diagnosis and at registration. Although the prevalence of atrial fibrillation was not different between males and females, embolic events occurred less frequently in female patients at registration than in male patients (2% versus 10%). In female patients, there were more obstructive HCM patients and fewer patients with apical HCM. Left ventricular and left atrial diameters were smaller and fractional shortening was higher in females than in males. The manifestations of HCM in unselected Japanese patients differed in men and women, which suggest that hormonal, social, and genetic factors may influence the clinical presentation of HCM.

Abstract 4366: Relation of Functional and Morphological Changes in Mitochondria to Myocardial Contractile and Relaxation Reserves in Asymptomatic to Mildly Symptomatic Patients with Hypertrophic Cardiomyopathy

Impairment of myocardial relaxation reserve and subsequent impairment of contractile reserve constitute a primary manifestation of hypertrophic cardiomyopathy (HCM). Although these reserves reflect energy-consuming processes, the relation between their impairment and mitochondrial function in HCM has remained unclear. Thirty HCM patients underwent biventricular cardiac catheterization analysis both at rest and during atrial pacing as well as myocardial 99m Tc-sestamibi (MIBI) scintigraphy at rest. MIBI washout rate (WR) was calculated from initial and delayed left ventricular (LV) planar images. Endomyocardial biopsy specimens were obtained for quantitative mRNA analysis and electron microscopic observation. The HCM patients were divided into two groups: Group A consisted of 15 patients showing a normal force-frequency relation (FFR) and pressure half-time ( T 1/2 ) of &lt;30 ms, whereas group B consisted of 15 patients showing an abnormal FFR or T 1/2 of ≥30 ms. The MIBI WR was significantly correlated with T 1/2 at the peak pacing rate for all patients ( r = 0.74, P &lt;0.01). It was also significantly greater in group B (29.2 ± 6.3%) than in group A (19.3 ± 3.1%). The abundance of mRNAs for mitochondrial electron transport-related enzymes was significantly higher in group A than in group B. Mitochondria showed a greater variation in size and were more disorganized in group B than in group A. Mitochondria showed functional impairment and morphological disorganization in the left ventricle of HCM patients without baseline systolic dysfunction. These mitochondrial changes were associated with impaired myocardial contractile and relaxation reserves.

Abstract 4839: Colocalization of Regional MEF2 Activity With Myocardial Scarring in Hypertrophic Cardiomyopathy

Background- The molecular triggers activated by a sarcomere gene mutation that remodel the heart and produce histopathologic manifestations of hypertrophic cardiomyopathy (HCM) are incompletely known. Myocyte enhancer factor 2 (MEF2) has emerged as a critical regulator of gene expression in the heart. Objective- To examine whether MEF2 is essential for HCM pathogenesis, we assessed in vivo MEF2 expression versus myocyte hypertrophy, disarray and interstitial fibrosis, the prototypic histopathology of HCM. Methods and Results- Wild-type or heterozygous mice harboring an Arg403Gln missense mutation in the alpha-myosin heavy chain gene (MHC403/+ mice) were crossed with transgenic mice harboring a MEF2-dependent reporter gene. Mouse hearts at 30 weeks of the age were evaluated by beta-galactosidase staining to detect transcriptional activity of MEF2 in vivo. Activity of MEF2 was heterogeneously increased in the left ventricle of MHC403/+ mouse hearts compared with wild-type mouse hearts. Gomori’s trichrome staining for collagen revealed that regional activation of MEF2 uniquely colocalized with myocardial scarring in MHC403/+ mouse hearts whereas only baseline activity of MEF2 was detected in the area without myocardial scarring. von Kossa staining revealed myocardial necrosis near to MEF2 staining. To further explore whether MEF2 activity is involved in the pathogenesis of myocardial necrosis, mice carrying a homozygous Arg403Gln mutation (MHC403/403) and the MEF2-dependent reporter gene were analyzed. MEF2 was regionally activated in 3-days old MHC403/403 mouse hearts, in advance of the myocardial necrosis that occurs in homozygous mutant hearts. At 6-days, greater MEF2 activity was observed compared with 3-days old MHC403/403 hearts, and massive necrosis was present where MEF2 was activated. Conclusions- These findings provide the first evidence for regional activation of the MEF2-pathway is involved in evolution of myocardial fibrosis and necrosis in HCM. Because myocyte loss and myocardial scarring is implicated in the progression of ventricular dysfunction, these data indicate that strategies to prevent MEF2 activation may attenuate remodeling and heart failure development.

Risk stratification and prevention of sudden death in hypertrophic cardiomyopathy

Sudden cardiac death is the most devastating manifestation of hypertrophic cardiomyopathy (HCM) and often occurs in young and previously asymptomatic patients. Therefore, risk stratification for sudden death has a major role in the management of HCM and has acquired even greater relevance since the implantable cardioverter-defibrillator (ICD) has proved to be highly effective in preventing sudden death in this disease. The ICD is definitely indicated for secondary prevention of sudden death in patients with HCM who have survived a cardiac arrest with documented ventricular fibrillation, or experienced one or more episodes of sustained ventricular tachycardia. However, uncertainties persist regarding the precise selection of patients for primary prophylactic ICD implantation. A number of risk markers are used to assess the magnitude of risk, including family history of premature sudden death; extreme left ventricular (LV) hypertrophy (> 30 mm) in young patients; nonsustained ventricular tachycardia on Holter electrocardiographic recording; unexplained (not neurally mediated) syncope, particularly in young patients; and blood pressure decrease or inadequate increase during upright exercise. Multiple risk factors convey a definite increase in risk. However, a single risk factor such as family history of multiple sudden deaths, massive LV hypertrophy in a young patient, or frequent and/or prolonged runs of nonsustained ventricular tachycardia on Holter, may also justify consideration of a prophylactic ICD.

'End-stage' hypertrophic cardiomyopathy: from mystery to model

'End-stage' hypertrophic cardiomyopathy (HCM) is one of the most serious manifestations of HCM, yet its etiology remains poorly understood. Here, Yacoub et al. discuss recent advances in our knowledge of end-stage HCM, explore avenues for future research, and propose that elucidating this 'mysterious' condition might provide a model for other myocardial diseases.

Cardiovascular pre-participation screening of young competitive athletes for prevention of sudden death in China

The cardiovascular pre-participation screening proposal for young competitive athletes has the potential to save young lives. This study aimed to identify individuals at risk for potentially lethal cardiovascular diseases in athletes before competition. Between June 2005 and July 2005, 351 (170 male and 181 female) elite Chinese athletes from 21 sports were profiled. The 12-lead electrocardiogram and echocardiography were employed to evaluate cardiovascular diseases. The vast majority had no definitive evidence of cardiovascular disease. However, abnormal ECGs were identified in 16 athletes (4.5%), including 4 with distinctly abnormal and 12 with mildly abnormal patterns. Only 13 athletes (3.7%) had echocardiographic evidence of relatively mild valve regurgitation that had not been previously suspected. In three athletes with relatively mild ventricular septal hypertrophy (13-14 mm), it was not possible to discern with absolute certainty whether the wall thickening was a manifestation of hypertrophic cardiomyopathy or secondary to athletic conditioning ("athlete heart"). This screening protocol identified no athletes with definite evidence of hypertrophic cardiomyopathy, Marfan's syndrome or other cardiovascular diseases that convey a significant potential risk for sudden death or disease progression during athletic activity. This is largely due to the relative low prevalence of conditions resulting in sudden cardiac death in young athletes and high false positive/negative rates in the tests used as part of the screening process (due to a large overlap between cardiovascular changes due to pathology and those due to intense training).

Echocardiographic Findings and Clinical Manifestations of Hypertrophic Cardiomyopathy: Including 3 Cases of Anomalous Insertion of Papillary Muscle

Echocardiographic Findings and Clinical Manifestations of Hypertrophic Cardiomyopathy: Including 3 Cases of Anomalous Insertion of Papillary Muscle

The molecular genetics of hypertrophic cardiomyopathy: prognostic implications.

Hypertrophic cardiomyopathy (HCM) is an inheritable cardiac disorder with heterogeneous clinical features. Sudden cardiac death is a frequent complication, occurring at an annual incidence of 2–3% in young, otherwise healthy individuals with HCM and accounting for nearly 35% of all sudden deaths within this age group. Often, sudden cardiac death is the initial manifestation of HCM, underscoring the need for the precise elucidation of the mechanisms that lead to its occurrence. Over the past decade, modern molecular techniques have greatly increased the understanding of the pathophysiology underlying HCM. Through collaborative efforts, over 100 mutations in eight genes have been found to be responsible for the disease. All presently known aberrations affect the encoding of sarcomeric proteins, whose modification predisposes the heart to myocyte disarray, fibrosis, hypertrophy, and small vessel disease as well as haemodynamic alterations in diastolic and systolic function. Importantly, the natural history of the disease appears to be influenced by the particular protein affected, as well as by the specific changes within the protein encoded by the mutation. This knowledge has provided greater insight into the vulnerability of the myocardial substrate to mechanisms of sudden death. Knowledge of the genetic abnormalities of HCM and their implications will help the clinician to identify HCM patients at high-risk for sudden death, and to make appropriate recommendations in clinical management and prognosis. This article reviews the current understanding of the genetic mutations in HCM with emphasis on prognosis for sudden and disease-related death.

Results of screening a large group of intercollegiate competitive athletes for cardiovascular disease

To determine the feasibility of detecting cardiovascular disease in a large group of young competitive athletes, a prospective screening evaluation of intercollegiate student athletes was undertaken at the University of Maryland. Initial clinical screening (including personal and family history, physical examination and 12 lead electrocardiogram) was performed in 501 athletes. Ninety of these subjects had positive findings on one or more of the three studies and agreed to further cardiologic evaluation. The vast majority (75 [84%] of 90) had no definitive evidence of cardiovascular disease, although 1 athlete had mild systemic hypertension and 14 (15%) had echocardiographic evidence of relatively mild mitral valve prolapse that had not been previously suspected. In three athletes with relatively mild ventricular septal hypertrophy (14 to 15 mm), it was not possible to discern with absolute certainty whether the wall thickening was a manifestation of hypertrophic cardiomyopathy or secondary to athletic conditioning ("athlete heart"). Therefore, this screening protocol identified no athletes with definite evidence of hypertrophic cardiomyopathy, Marfan's syndrome or other cardiovascular diseases that convey a significant potential risk for sudden death or disease progression during athletic activity. This failure to identify such diseases could have been due to a lack of sensitivity of the screening tests or to the low frequency with which these diseases occur in youthful healthy athletes. A systematic preparticipation screening program (such as the present one) does not appear to be an efficient means of detecting clinically important cardiovascular disease in young athletes.