Natural History Of Hypertrophic Cardiomyopathy Research Articles

Myocardial Scarring and Sudden Cardiac Death in Young Patients With Hypertrophic Cardiomyopathy

The ability to predict sudden cardiac death (SCD) in children and adolescents with hypertrophic cardiomyopathy (HCM) is currently inadequate. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) imaging is associated with SCD events in adults with HCM. To examine the prognostic significance of LGE in patients with HCM who are younger than 21 years. This multicenter, retrospective cohort study was conducted from April 8, 2015, to September 12, 2022, in patients with HCM who were younger than 21 years and had undergone CMR imaging across multiple sites in the US, Europe, and South America. Observers of CMR studies were masked toward outcomes and demographic characteristics. Natural history of HCM. The primary outcome was SCD and surrogate events, including resuscitated cardiac arrest and appropriate discharges from an implantable defibrillator. Continuous and categorical data are expressed as mean (SD), median (IQR), or number (percentage), respectively. Survivor curves comparing patients with and without LGE were constructed by the Kaplan-Meier method, and likelihood of subsequent clinical events was further evaluated using univariate and multivariable Cox proportional hazards models. Among 700 patients from 37 international centers, median (IQR) age was 14.8 (11.9-17.4) years, and 518 participants (74.0%) were male. During a median (IQR) [range] follow-up period of 1.9 (0.5-4.1) [0.1-14.8] years, 35 patients (5.0%) experienced SCD or equivalent events. LGE was present in 230 patients (32.9%), which constituted an mean (SD) burden of 5.9% (7.3%) of left ventricular myocardium. The LGE amount was higher in older patients and those with greater left ventricular mass and maximal wall thickness; patients with LGE had lower left ventricular ejection fractions and larger left atrial diameters. The presence and burden of LGE was associated with SCD, even after correcting for existing risk stratification tools. Patients with 10% or more LGE, relative to total myocardium, had a higher risk of SCD (unadjusted hazard ratio [HR], 2.19; 95% CI, 1.59-3.02; P < .001). Furthermore, the addition of LGE burden improved the performance of the HCM Risk-Kids score (before LGE addition: 0.66; 95% CI, 0.58-0.75; after LGE addition: 0.73; 95% CI, 0.66-0.81) and Precision Medicine in Cardiomyopathy score (before LGE addition: 0.68; 95% CI, 0.49-0.77; after LGE addition: 0.73; 95% CI, 0.64-0.82) SCD predictive models. In this retrospective cohort study, quantitative LGE was a risk factor for SCD in patients younger than 21 years with HCM and improved risk stratification.

Re-evaluating the Incidence and Prevalence of Clinical Hypertrophic Cardiomyopathy: An Epidemiological Study of Olmsted County, Minnesota

ObjectiveTo contemporaneously reappraise the incidence-rate, prevalence, and natural history of hypertrophic cardiomyopathy (HCM) in Olmsted County, Minnesota, from 1984 to 2015. Patients and MethodsA validated medical-record linkage system collecting information for residents of Olmsted County was used to identify all cases of HCM between January 1, 1984, and December 31, 2015. After adjudication of records from Mayo Clinic and Olmsted Medical Center, data relating to diagnoses and outcomes were abstracted. The calculated incidence rate and prevalence were standardized to the US 1980 White population (age- and sex-adjusted) and compared with a prior study examining the years 1975-1984. ResultsTwo hundred seventy subjects with HCM were identified. The age- and sex-adjusted incidence rate was 6.6 per 100,000 person-years, and the point prevalence of HCM on January 1, 2016, was 89 per 100,000 population. The incidence rate and point prevalence of HCM on January 1, 2016, standardized to the US 1980 White population (age- and sex-adjusted), were 6.7 (95% CI, 7.1 to 8.8) per 100,000 person-years and 81.5 per 100,000 population, respectively. The incidence rate of HCM increased each decade since the index study. Individuals with HCM had a higher overall standardized mortality rate than the general population with an observed to expected HR of 1.44 (95% CI, 1.21 to 1.71; P<.001) which improved by each decade. ConclusionThe incidence and prevalence of HCM are higher than rates reported from a prior study in the same community examining the years 1975-1984, but lower than other study cohorts. The risk of mortality in HCM remains higher than expected, albeit with improvement in rates of mortality observed each decade during the study period.

Natural history of hypertrophic cardiomyopathy in cats from rehoming centers: The CatScan II study.

The natural history of hypertrophic cardiomyopathy (HCM) in cats has been mainly studied in cats referred for suspected heart disease, which can skew the results towards cats with clinical signs. Few data are available on factors associated with development of HCM in cats. (1) Clinical variables can predict which cats will develop HCM; (2) HCM in cats not referred for suspected heart disease is associated with a low rate of cardiovascular events. One hundred seven cats from rehoming centers without a history of clinical signs of cardiac or systemic disease at the time of adoption. Prospective longitudinal study. After rehoming, shelter cats were reexamined for serial echocardiograms. Cox regression analysis was used to identify predictors of development of HCM in cats that were normal at baseline. Adverse cardiovascular events including heart failure, thromboembolism, or sudden death were recorded. Cats were monitored for a median of 5.6 [1.2-9.2] years. At baseline, 68/107 cats were normal, 18/107 were equivocal and 21/107 had HCM. Nineteen cats developed HCM during the study period. The factors at baseline associated with increased hazard of developing HCM were lower left atrial fractional shortening, higher left ventricular fractional shortening, and higher body weight. Cardiovascular events were observed in 21% of cats with HCM. Cardiovascular events were common in cats with HCM from a rehoming center study sample. Lower left atrial systolic function appears to precede overt HCM.

Temporal Changes in Cardiac Morphology and Its Relationship with Clinical Characteristics and Outcomes in Patients with Hypertrophic Cardiomyopathy

In this study, we aimed to assess a large cohort of nonapical hypertrophic cardiomyopathy (HC) patients who have undergone 2 serial cardiac magnetic resonance studies to examine morphological dynamics and their correlation to patient characteristics and clinical outcomes. A total of 214 patients with nonapical HC were enrolled in this study, with 2 sequential cardiac magnetic resonance studies separated by a mean interval of 4.8±2.1years. Progression of indexed left ventricular mass (LVMI) was correlated with lower LVMI at baseline (p<0.00001) and older age >50 years. In terms of maximal wall thickness (MWT), progression was associated with lower baseline MWT and with the presence of LV outflow tract obstruction. No association was demonstrated between the degree of progression of LVMI or MWT and baseline LV volumes, the severity of mitral regurgitation, gender, or the presence of pathogenic HC variants. Progression of left atrial size was significantly associated with the development of atrial fibrillation (p=0.014; odds ratio 1.18, confidence interval 1.03 to 1.35) and admission for heart failure (p=0.018; odds ratio 1.18, confidence interval 1.03 to 1.36). No correlation was demonstrated between changes in LV mass or MWT and clinical outcomes of admission for heart failure, progression to New York Heart Association 2/3, progression to end-stage HC, or implantable cardioverter-defibrillator implantation. In conclusion, our study provides novel insights into the natural history of HC from a morphological perspective. It shows that HC is a dynamic disease in which LV morphology and hypertrophy extent change over time, with the presence of risk factors associated with disease progression.

Pathophysiology and Treatment of Hypertrophic Cardiomyopathy: New Perspectives.

We provide a state of the art of therapeutic options in hypertrophic cardiomyopathy (HCM), focusing on recent advances in our understanding of the pathophysiology of sarcomeric disease. A wealth of novel information regarding the molecular mechanisms associated with the clinical phenotype and natural history of HCM have been developed over the last two decades. Such advances have only recently led to a number of controlled randomized studies, often limited in size and fortune. Recently, however, the allosteric inhibitors of cardiac myosin adenosine triphosphatase, countering the main pathophysiological abnormality associated with HCM-causing mutations, i.e. hypercontractility, have opened new management perspectives. Mavacamten is the first drug specifically developed for HCM used in a successful phase 3 trial, with the promise to reach symptomatic obstructive patients in the near future. In addition, the fine characterization of cardiomyocyte electrophysiological remodelling has recently highlighted relevant therapeutic targets. Current therapies for HCM focus on late disease manifestations without addressing the intrinsic pathological mechanisms. However, novel evidence-based approaches have opened the way for agents targeting HCM molecular substrates. The impact of these targeted interventions will hopefully alter the natural history of the disease in the near future.

The natural history of hypertrophic cardiomyopathy.

In the early years of the disease recognition, hypertrophic cardiomyopathy (HCM) was viewed as an ominous disease with unfavourable prognosis and with an annual mortality between 4% and 6%. At that time, 73% of the patients reported in the literature came from only two referral centres. With the introduction of echocardiography, our understanding of HCM has improved and non-selected patient populations were assembled in several centres. A more benign prognostic profile was documented with an annual mortality rate of 1.5% or less. In the 2000s, important therapeutic interventions further improved the prognosis of patients with HCM: implantable-cardioverter defibrillator for prevention of sudden death, heart transplantation for treatment of severe refractory heart failure, and an extensive treatment with myectomy for relief of left ventricular outflow tract gradient. The natural history of HCM has changed substantially with contemporary treatment achieving an annual mortality rate less than 1% with extended longevity and a greatly improved quality of life.

Hypertrophic Cardiomyopathy 2020.

To briefly review the pathophysiology and natural history of hypertrophic cardiomyopathy (HCM) and to describe the diagnosis, assessment, and contemporary management strategies. HCM-related mortality remains low; however, symptoms due in large part to LVOT obstruction remain a clinical dilemma. Several medical therapies have been shown to reduce symptoms and improve functional capacity, including several recent phase 2 clinical trials involving the novel myosin modulator mavacamten. In patients with refractory symptoms, septal reduction therapy or advanced therapies remain viable options in many cases. HCM is a complex and heterogeneous disease with diverse presentations and variable anatomy and clinical outcomes. The majority of patients will remain asymptomatic or with minimal symptoms and long-term survival remains high. For symptomatic patients, a variety of medical therapies, along with septal reduction therapies, have been shown to reduce symptoms and improve functional capacity.

Pulmonary vein isolation implemented by second-generation cryoballoon for treating hypertrophic cardiomyopathy patients with symptomatic atrial fibrillation: a case-control study.

BackgroundAtrial fibrillation (AF) is a generally acknowledged turning-point of the natural history of hypertrophic cardiomyopathy (HCM); however, data from the cryoballoon ablation (CBA) for AF in HCM patients are relatively scarce. The study aimed to evaluate the efficacy and safety of CBA in HCM patients with AF.MethodsWe retrospectively analyzed HCM patients among 1253 patients with symptomatic AF who underwent CBA for pulmonary vein isolation in a single center. The study analyzed the AF recurrence and assessed the CBA indexes, including nadir temperature, time-to-isolation, CBA failure, pulmonary vein potentials (PVPs), and redo procedure.ResultsA total of 108 patients were included (mean age: 59.0 ± 6.9 years), 27 patients (25%) had HCM, with the median follow-up duration of 25.5 months. The one-year AF-free rates were 79.0% vs. 63.0% (non-HCM vs. HCM), while the two-year AF-free rates were 77.8% vs. 55.1% [hazard ratio (HR) = 2.758, log-rank P = 0.024]. Patients with persistent AF had poor AF-free rates compared to those with paroxysmal AF (P < 0.001). The CBA failure was the most common in the right inferior pulmonary veins, which had the lowest PVPs. Multivariate Cox regression analysis indicated that HCM and persistent AF were risk factors for AF recurrence (HR = 2.74, 95% CI: 1.29–5.79, P = 0.008; and HR = 3.97, 95% CI: 1.85–8.54, P < 0.001, respectively).ConclusionsThe CBA can be effectively and safely used to treat HCM patients with symptomatic AF. The freedom from AF for HCM patients after CBA is relatively low compared to that for non-HCM patients.

The natural history of hypertrophic cardiomyopathy in a large Mediterranean cohort.

Hypertrophic cardiomyopathy (HCM) represents the most common inherited cardiomyopathy and it is characterized by phenotypic and genetic heterogeneity. The purpose of our study was to investigate the natural history of HCM in a large Mediterranean cohort and to identify predictors of outcomes. The clinical and echocardiographic characteristics of 690 patients with HCM were examined. The predictors of mortality and sudden cardiac events were examined during a mean follow-up of 8.5 years. Asymmetrical hypertrophy was the most common among our cohort (82.9%) followed by apical hypertrophy pattern (13.6%). Atrial fibrillation was present in 22.3%, whereas nonsustained ventricular tachycardia occurred in 10.4% of the patients. During follow-up, a total of 7.4% of patients died. Specifically, 5.5% HCM patients died from cardiovascular causes, including 2.8% from heart failure and 2% from sudden death. Obstructive phenotype did not have any effect on mortality. Atrial fibrillation, ejection fraction and right ventricular systolic pressure (RVSP) were common independent predictors for overall and cardiovascular mortality. A total of 6.1% of HCM patients suffered sudden arrhythmic events and maximal wall thickness, ejection fraction, nonsustained ventricular tachycardia, syncopal episodes and, more importantly, the presence of an apical aneurysm were all independent risk factors. HCM is a relatively benign cardiomyopathy in Greece, similarly to other countries. Apical hypertrophy pattern is more common in Greece than in the other European countries, whereas the presence of apical aneurysm is the most important risk factor for arrhythmic events on top of the established risk factors for sudden death.

Hypertrophic Cardiomyopathy in “Real-World” Community Cardiology Practice

Differences in presentation and natural history of hypertrophic cardiomyopathy (HC) between community cardiology practice and referral centers has been a source of considerable uncertainty. We report here a cross-sectional analysis of 253 consecutive HC patients from a "real-world" clinical cardiology setting. When compared with a highly selected referral center cohort, patients in clinical practice proved to be similar with regard to disease expression such as left ventricular (LV) wall thickness, outflow obstruction, and natural history, including stable and largely benign clinical course with no or mild symptoms (61% in community practice vs. 55% in referred patients, p = 0.23), occurrence of atrial fibrillation (22% vs. 24%, p = 0.75) and nonfatal sudden death (SD) events (3% vs. 4%, p = 0.8). In contrast, progressive heart failure symptoms were most common in the referral cohort (36% vs. 26%, p = 0.04). In clinical practice, SD was prevented by prophylactic implatable cardioverter defibrillators (ICD) in 5 of 44 patients (11%), although risk was overestimated in 6 patients who were implanted with ICDs in the absence of risk markers (14%). In 16 of 61 (26%) severely symptomatic drug-refractory patients with LV outflow obstruction, recommendation for surgical myectomy (or alcohol septal ablation) was delayed. In conclusion, clinical characteristics and course of HC patients in community practice were generally similar to those in HC referral centers. Community cardiologists managed HC patients predominantly in concert with guideline-based strategies, although risk for SD could be overestimated, and the significance of outflow obstruction with timely reversal of refractory heart failure by intervention was underappreciated.

Tissue-level inflammation and ventricular remodeling in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a common cardiac condition caused primarily by sarcomeric protein mutations with several distinct phenotypes, ranging from asymmetric septal hypertrophy, either with or without left ventricular outflow tract obstruction, to moderate left ventricular dilation with or without apical aneurysm formation and marked, end-stage dilation with refractory heart failure. Sudden cardiac death can occur at any stage. The phenotypic variability observed in HCM is the end-result of many factors, including pre-load, after-load, wall stress and myocardial ischemia stemming from microvascular dysfunction and thrombosis; however, tissue level inflammation to include leukocyte-derived extracellular traps consisting of chromatin and histones, apoptosis, proliferation of matrix proteins and impaired or dysfunctional regulatory pathways contribute as well. Our current understanding of the pathobiology, developmental stages, transition from hypertrophy to dilation and natural history of HCM with emphasis on the role of tissue-level inflammation in myocardial fibrosis and ventricular remodeling is summarized.

Anesthetic management during endocardial radiofrequency ablation of septal hypertrophy – a case report

Background: Hypertrophic cardiomyopathy (HCM) is a genetic disorder present in up to 1/500 individuals, about 20–30% of them presenting with hypertrophic obstructive cardiomyopathy (HOCM) due to left ventricle outflow tract obstruction. This is an important cause of sudden cardiac death. Endocardial radiofrequency ablation of septal hypertrophy (ERASH) might be an attractive treatment for HOCM, particularly in patients who do not respond to transcoronary alcohol septal ablation (TASA).Aim: To describe technical aspects related to the procedure and anesthetic management of an ERASH case.Case report: A 64-year-old woman with HOCM was scheduled for ERASH. She had worsening of dyspnea on exertion and generalized fatigue for the previous weeks after previous surgical myomectomy about 6 months ago. The anatomy was unfavorable for TASA and the patient was not willing to undergo another surgery. Preoperative transthoracic echocardiography (TTE) showed asymmetric mid-septal hypertrophy, systolic anterior motion with septal contact and left ventricular outflow tract maximum gradient of 68 mmHg at rest and 105 mmHg after the Valsalva maneuver. General anesthesia was performed. Pulse pressure variation, echocardiography parameters and passive leg raising test where used to guide fluid therapy. At the end of the procedure, analgesia was provided together with prophylaxis of nausea and vomiting. Extubation was uneventful and the patient was transported to the intensive care unit eupneic and hemodynamically stable. On the fourth postoperative day, TTE showed septal hypocontractility and maximum gradient reduction of 33% at rest (68 mmHg to 45 mmHg) and 31% after the Valsalva maneuver (105 mmHg to 73 mmHg). The patient was discharged from hospital at the sixth postoperative day. One month later, she reported progressive improvement of symptoms and expressed satisfaction with the results.Conclusion: Better understanding of the pathophysiology and natural history of HCM has enabled earlier diagnosis, as well as a more adequate therapeutic approach. Anesthesiologists should be aware of the pathophysiology of HOCM and must be prepared to anticipate the hemodynamic changes and cardiovascular instability that such patients may show perioperatively. ERASH is a promising therapeutic modality increasingly used for HOCM and anesthesiologists should become more familiar with it.

Abstract 16: A Minipig Genetic Model of Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is a heritable disease of heart muscle associated with increased risk of heart failure and sudden death. Mutations in genes encoding sarcomere proteins are commonly associated with HCM. However, the mechanisms by which these mutations lead to molecular, cellular and organ-level pathophysiology are uncertain, partly because of the lack of model systems amenable to integrated translational studies. Methods: Using homologous recombination and somatic cell nuclear transfer, we generated Yucatan minipigs with a heterozygous knock-in of the R403Q mutation in MYH7 , a well-characterized human HCM mutation. We conducted deep phenotyping with biomechanical studies of myocardial tissue samples, circulating biomarker analysis, cardiac imaging and histologic and multi-omic analysis of LV biopsy samples. Results: We followed a cohort of 22 R403Q pigs and 6 WT herdmates. Juvenile animals (3 months) showed early signs of HCM with elevated serum troponin I, increased myocardial contractility in muscle fibers and hearts and interstitial fibrosis and myocyte disarray. At late adolescence (9 months), disarray and fibrosis had progressed, but contractility had normalized with some pigs progressing to systolic dysfunction. Across the cohort, end-diastolic pressure was increased with evidence of diastolic dysfunction and elevation in B-type natriuretic peptide. Transcriptomic analysis at both 3 and 9 months showed dysregulation of metabolic modules and an upregulation of pro-fibrotic pathways. By one year of age, 11 of 22 R403Q pigs had suffered sudden cardiac death, whereas all wildtype pigs survived. Conclusions: We have developed the first large-animal genetic model of HCM. Young pigs with the MYH7 R403Q mutation show functional and histologic features of the preclinical human phenotype, and late adolescent animals have signs of advanced disease with an increased rate of sudden cardiac death. These data suggest that our minipig model may yield insights throughout the natural history of HCM from preclinical to end-stage disease. This model will thus be invaluable for advancing understanding of HCM and for the development of novel therapeutics.

Abstract 402: Mutation-Specific Activation of CaMK-II in Hypertrophic Cardiomyopathy

Approximately 5-10% of all Hypertrophic Cardiomyopathy (HCM) mutations reside within cardiac troponin T (cTnT). Residue Arg92 of cTnT represents a mutational hotspot, including Arg92Leu (R92L) and Arg92Trp (R92W). Interestingly, patients expressing these substitutions that differ by only a single amino acid present with distinct phenotypes and disease severity. Studying the differential effects of the R92 mutations on Ca 2+ homeostasis revealed an age-dependent increase in phospholamban (PLB) phosphorylation at Thr17 (targeted by CaMKII) only in R92W mice. Thus, we hypothesized a mutation-specific role of CaMKII in cTnT-linked HCM progression and tested this hypothesis via genetic partial inhibition of CaMKII (AC3I peptide) in both R92W and R92L transgenic mice. A progressive increase in PKA-mediated PLB-Ser16 phosphorylation was observed in the AC3I/RW mice, leading to an increase in SERCA2 activity. This improved Ca 2+ re-uptake activity was coupled with a decrease in atrial mass, indicative of a decrease in diastolic filling pressure. Thus, the R92W mutation initiates downstream pathophysiologic activation of CaMKII, leading to progressive cardiomyopathic remodeling. Partial inhibition of CaMKII in R92W mice resulted in the alteration of the natural history of HCM, indicating a potential therapeutic target for patients expressing the mutation. In contrast, AC3I/RL mice showed no change in SERCA2 activity or atrial morphology, suggesting a CaMKII-independent progression to disease for R92L-linked HCM. Finally, R92L and R92W mice were treated with diltiazem hydrochloride, an L-type Ca 2+ channel blocker, and diastolic function monitored over time. R92W mice showed improvement in diastolic function with treatment while R92L mice showed a progressive decrease in diastolic function. These findings suggest that closely related mutations, even at the same residue, can have discrete molecular effects that result in mutation-specific ventricular remodeling and these observations can be incorporated in targeted disease management.

What Do Patients With Hypertrophic Cardiomyopathy Die from?

Hypertrophic cardiomyopathy (HC) has become a contemporary and treatable genetic heart disease, now with disease-related mortality reduced to as low as 0.5% per year, based largely on more effective risk stratification and the use of the implantable cardioverter-defibrillator for primary prevention of sudden death. This paradigm change in the natural history of HC has caused us to reconsider the overall mortality risk in this disease. We interrogated the databases of 2 HC referral centers, Minneapolis Heart Institute and Tufts Medical Center. Of 1,902 consecutive patients evaluated between 1992 and 2013, 1,653 patients (87%) have survived to the end of follow-up and 249 patients (13%) have died. Most deaths (178 of 249; 72%) were unrelated to HC, commonly because of cancer and predominantly in older patients. Non-HC mortality was significantly more common in adults presenting ≥ 60 years and least common in the youngest patients aged <30 years (p <0.001). Notably, deaths from non-HC causes substantially exceeded HC-related causes by 2.6-fold (p <0.001). In conclusion, only about 25% of patients with HC ultimately died of their disease, including predominantly those who were <30 years of age. These data allow patients with HC to develop a more realistic and reassured perception of their disease.

Clinical and Pathological Impact of Tissue Fibrosis on Lethal Arrhythmic Events in Hypertrophic Cardiomyopathy Patients With Impaired Systolic Function.

The natural history of hypertrophic cardiomyopathy (HCM) varies from an asymptomatic benign course to a poor prognosis. Myocardial fibrosis may play a critical role in ventricular tachyarrhythmias (VT/VF); however, the clinical significance of tissue fibrosis by right ventricular (RV) biopsy in the long-term prognosis of HCM patients remains unclear. We enrolled 185 HCM patients (mean age, 57±14 years). The amount of fibrosis (%area) was quantified using a digital microscope. Hemodynamic, echocardiographic, and electrophysiologic parameters were also evaluated. Patients with severe fibrosis had longer QRS duration and positive late potential (LP) on signal-averaged ECG, resulting in a higher incidence of VT/VF. At the 5±4 year follow-up, VT/VF occurred in 31 (17%) patients. Multivariate Cox regression analysis revealed that tissue fibrosis (hazard ratio (HR): 1.65; P=0.003 per 10% increase), lower left ventricular ejection fraction (HR: 0.64; P=0.001 per 10% increase), and positive SAECG (HR: 3.14; P=0.04) led to a greater risk of VT/VF. The combination of tissue fibrosis severity and lower left ventricular ejection fraction could be used to stratify the risk of lethal arrhythmic events in HCM patients. Myocardial fibrosis in RV biopsy samples may contribute to abnormal conduction delay and spontaneous VT/VF, leading to a poor prognosis in HCM patients.

Cardiac events in Costello syndrome: One case and a review of the literature

Costello syndrome is a rare syndrome associated with de novo mutations in the HRAS gene. It is mostly revealed during in the first months of life by growth retardation, facial dysmorphic features, skin and cardiac abnormalities and subsequent cognitive deficit of varying severity. We report a case of Costello syndrome in a 3-month-old infant. The initial cardiac investigations were normal except frequent premature atrial complexes. After few months, worsening arrhythmia with bursts of ventricular tachycardia were noted as well as the secondary progressive obstructive left ventricular hypertrophic cardiomyopathy (HCM).Cardiac involvement is determinant for the prognosis of Costello syndrome. It frequently consists of hypertrophic cardiomyopathy (one third of patients), with involvement of the left ventricle in half of the cases. It is often asymmetrical and associated with obstruction of the outflow recalling family hypertrophic cardiomyopathy. The natural history of HCM in Costello syndrome and its management remains poorly known because of paucity of reported cases. Progression of the HCM can be very rapid like the reported case. On the other hand, the spontaneous regression of the HCM in some patients has been reported. In addition, cardiac threatening arrhythmias may be noted. So that, cardiac assessment and monitoring with regular echocardiography and electrocardiogram follow up is mandatory.

Hypertrophic cardiomyopathy in the Saudi Arabian population: Clinical and echocardiographic characteristics and outcome analysis

BackgroundCurrent published literature on hypertrophic cardiomyopathy (HCM) comes primarily from Western populations. There is no published data on clinical and echocardiographic characteristics and long-term outcome of HCM in an Arab population. MethodsWe conducted a retrospective analysis of all patients 16years or older diagnosed with HCM at our institution. Detailed clinical and echocardiographic data were collected and outcome was analyzed. ResultsA total of 69 patients were identified as having HCM. The mean age was 42±16years with 71% male patients. All patients were Saudi citizens with Arab ancestry. Details about family history and presenting symptoms were available for 44 and 48 patients consecutively. Nine (18%) patients were asymptomatic and were diagnosed based on abnormal cardiac auscultation. The commonest presenting symptoms were dyspnea with or without chest pain and palpitations occurring in 40 (81%) patients. Only four (9%) of 44 patients had a family history of HCM and /or sudden cardiac death (SCD). The most common ECG abnormality was left ventricular hypertrophy (LVH) present in 60 (86%) patients. The commonest septal hypertrophy morphology was mid-septal (catenoid) in 30 (43%) followed by neutral in 23 (33%), basal septal (sigmoid) in 3 (4%) and apical in 6 (8%) patients. Twenty (28%) patients had evidence of resting left ventricular cavity gradient of ⩾30mmHg. Eleven (16%) patients had evidence of biventricular hypertrophy. Left ventricular ejection fraction was normal in 65 (94%) patients. Over a median (25–75 percentile) follow-up of 7years (4.5–10), only three patients died, all of non-cardiac causes. There were no cases of SCD during the follow-up period. Six patients required an implantable cardioverter-defibrillator (ICD); five for primary prevention and one for secondary prevention. Only one patient progressed to end stage dilated cardiomyopathy. ConclusionThe natural history of hypertrophic cardiomyopathy in the Saudi population appears to be benign with catenoid morphology being the most common septal hypertrophy pattern. Risk of SCD appears to be quite low in this population.

Physical Activity and Other Health Behaviors in Adults With Hypertrophic Cardiomyopathy

The clinical expression of hypertrophic cardiomyopathy (HC) is undoubtedly influenced by modifying genetic and environmental factors. Lifestyle practices such as tobacco and alcohol use, poor nutritional intake, and physical inactivity are strongly associated with adverse cardiovascular outcomes and increased mortality in the general population. Before addressing the direct effect of such modifiable factors on the natural history of HC, it is critical to define their prevalence in this population. A voluntary survey, drawing questions in part from the 2007 to 2008 National Health and Nutrition Examination Survey (NHANES), was posted on the HC Association website and administered to patients with HC at the University of Michigan. Propensity score matching to NHANES participants was used. Dichotomous and continuous health behaviors were analyzed using logistic and linear regression, respectively, and adjusted for body mass index and propensity score quintile. Compared to the matched NHANES participants, the patients with HC reported significantly less alcohol and tobacco use but also less time engaged in physical activity at work and for leisure. Time spent participating in vigorous or moderate activity was a strong predictor of self-reported exercise capacity. The body mass index was greater in the HC cohort than in the NHANES cohort. Exercise restrictions negatively affected emotional well-being in most surveyed subjects. In conclusion, patients with HC are less active than the general United States population. The well-established relation of inactivity, obesity, and cardiovascular mortality might be exaggerated in patients with HC. More data are needed on exercise in those with HC to strike a balance between acute risks and the long-term health benefits of exercise.

Hypertrophic Cardiomyopathy With Longevity to 90 Years or Older

Hypertrophic cardiomyopathy (HC) is the most common cause of sudden death in the young, but survival to particularly advanced age is less well appreciated. The investigators report the prevalence, clinical features, and demographics of patients with HC surviving to ≥90 years of age. Of 1,297 patients with HC in the Hypertrophic Cardiomyopathy Center database (Minneapolis Heart Institute Foundation), 26 (2.0%) were identified who had achieved the age of ≥90 years; 18 (69%) were women. HC diagnosis came late in life, at 61 to 92 years (mean 80 ± 8; ≥75 years in 21 patients), recognized fortuitously by the detection of a heart murmur or during family screening (n = 6) or after onset of new symptoms (n = 20). At most recent evaluation (or death) patients were aged 90 to 96.7 years (mean 92.2 ± 2), with 6 presently alive at 91 to 96 years of age; HC did not appear to be the primary cause of death in any patient. Left ventricular wall thicknesses were 15 to 31 mm (mean 20 ± 3); 8 patients (31%) had obstruction to left ventricular outflow at rest (peak instantaneous gradients, 38 to 135 mm Hg). Significant HC-related complications occurred in 13 patients (50%), including progressive heart failure symptoms, atrial fibrillation, and nonfatal embolic stroke. Although no patient died suddenly, 13 (50%) nevertheless carried conventional HC risk markers. A greater proportion of cohort patients reached ≥90 years of age (2.0%) than expected in the general population (0.8%) (p <0.001). In conclusion, HC may be unrecognized until late in life and is consistent with survival to particularly advanced age into the 10th decade of life without the need for major HC-related treatment interventions, and with demise ultimately largely unrelated to this disease. This principle regarding the natural history of HC can afford a measure of reassurance to many patients.