Had Hypertrophic Cardiomyopathy Research Articles

Coronary microvascular dysfunction: prevalence and aetiology in patients with suspected myocardial ischaemia

To evaluate the prevalence, aetiology, and corresponding morbidity of coronary microvascular dysfunction (CMD) in patients with suspected myocardial ischaemia. The present study included 115 patients with suspected myocardial ischaemia who underwent stress perfusion cardiac magnetic resonance imaging. CMD was assessed visually based on the myocardial perfusion results. The CMR-derived myocardial perfusion reserve index (MPRI) and left ventricular (LV) strain parameters obtained using the post-processing software CVI42 were employed to evaluate LV myocardial perfusion and deformation. LV strain parameters included global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS), global systolic/diastolic longitudinal, circumferential, and radial strain rates (SLSR, SCSR, SRSR, DLSR, DCSR, and DRSR). Of the 115 patients, 12 patients were excluded and 103 patients were finally included in the study. CMD was observed in 79 % (81 patients, aged 53±12 years) of patients. Regarding aetiology, 91 (88 %) patients had non-obstructive coronary artery disease (CAD), eight (8 %) had obstructive CAD, and four (4 %) had hypertrophic cardiomyopathy (HCM). The incidence of CMD was highest (100 %) in patients with HCM, followed by those with non-obstructive CAD (up to 79 %). There were no statistical differences between CMD and non-CMD groups in GCS, GRS, GLS, SRSR, SCSR, SLSR, DCSR, DRSR and DLSR. The incidence of CMD was higher in patients with signs and symptoms of ischaemia. CMD occurred with non-obstructive CAD, obstructive CAD, and HCM, with the highest prevalence of CMD in HCM.

PO-01-048 FACTORS INFLUENCING SUBCUTANEOUS IMPLANTABLE CARDIOVERTER DEFIBRILLATOR SCREENING SUCCESS IN PAEDIATRIC POPULATION: A TERTIARY HOSPITAL EXPERIENCE

Implantable cardioverter defibrillators (ICD), used to reduce risk from life threatening ventricular arrhythmia, are important treatments. Subcutaneous ICD (SICD) offers a lower risk of endocarditis, lead fracture and vascular complication. Screening is essential to identify the appropriate candidates and reduce inappropriate shocks, however there are limited data available in the paediatric population. To assess the incidence and associated characteristics of SICD screen failure, and the incidence of inappropriate shocks in a paediatric population. All patients screened for SICD from June 2016 to November 2022 were included. Screening failures were identified from supine, standing and exercise in both left and right sternal positions. Those who passed at least two vectors in all conditions were offered an SICD. The incidence of inappropriate shocks on follow up was assessed. From 74 screened patients (baseline characteristics Table 1), 58 (78%) passed supine and standing and 51(69%) on exercise screening. 59 (67%) had Hypertrophic Cardiomyopathy (HCM), 17 (23%) Inherited arrhythmias (IA) and 8 (11%) Other Cardiomyopathies (OC). Overall, 60(81%) had a primary prevention indication. Of the 45 (61%) who passed screening on the left supine, all passed when standing and 43 (96%) passed on exercise. Those screened on the right, 18 (55%) passed supine, 16(88%) of these passed standing and 14(87%) passed on exercise. Those that failed were younger and had HCM (passed vs failed, age 14±2.6 vs 12±3.7, p=0.009, HCM 56% vs 87%, p=0.008). IA patients were more likely to pass (pass vs failed, 35% vs 8%, p=0.02). Weight, height and BMI did not impact on the failure rate (Table 1). Overall, 40 (78%) had an SICD implanted with a mean follow up 21±15 months. Four patients had inappropriate shocks; One for air in the header and three for T wave oversensing. Those who had T wave oversensing had left sided lead implants, two had HCM and one had AI. In this population the screen failure rate for SICD was high, particularly in younger patients with HCM. The addition of exercise further excluded patients however, the number was small. There was no link between weight, height and BMI and screen failure. The incidence of inappropriate shocks was low.Tabled 1Table 1 – Characteristics of patients who passed and failed Subcutaneous Internal Cardioverter Defibrillator ScreeningCharacteristicsPassed (n=51)Failed (n=23)p-valueAge, years mean (SD)14 ± 2.612 ±3.7p=0.009Sex F(%)17 (34)6 (26)p=0.6Weight kg, mean (SD)57 ±16.953 ±(22)p=0.34Height cm mean (SD)156 ±29.6155 ±17.8p=0.88BMI kg/m2 mean (SD)23 ± 10.421 ± 5.5p=0.39HCM n (%)29 (56)20 (87)p=0.008Inherited n (%)15 (29)2 (8)p=0.02Other Cardiomyopathy n (%)7 (14)1 (4)p=0.26 Open table in a new tab

Native T1 mapping for the diagnosis of cardiac amyloidosis in patients with left ventricular hypertrophy

BackgroundCardiac magnetic resonance (CMR) with parametric mapping can improve the characterization of myocardial tissue. We studied the diagnostic value of native T1 mapping to detect cardiac amyloidosis in patients with left ventricular (LV) hypertrophy.MethodsOne hundred twenty-five patients with increased LV wall thickness (≥ 12 mm end-diastole) who received clinical CMR in a 3 T scanner between 2017 and 2020 were included. 31 subjects without structural heart disease served as controls. Native T1 was measured as global mean value from 3 LV short axis slices. The study was registered at German clinical trial registry (DRKS00022048).ResultsMean age of the patients was 66 ± 14 years, 83% were males. CA was present in 24 patients, 21 patients had hypertrophic cardiomyopathy (HCM), 80 patients suffered from hypertensive heart disease (HHD). Native T1 times were higher in patients with CA (1409 ± 59 ms, p < 0.0001) compared to healthy controls (1225 ± 21 ms), HCM (1266 ± 44 ms) and HHD (1257 ± 41 ms). HCM and HHD patients did not differ in their native T1 times but were increased compared to control (p < 0.01). ROC analysis of native T1 demonstrated an area under the curve for the detection of CA vs. HCM and HHD of 0.9938 (p < 0.0001), which was higher than that of extracellular volume (0.9876) or quantitative late gadolinium enhancement (0.9406; both p < 0.0001). The optimal cut-off value of native T1 to diagnose CA was 1341 ms (sensitivity 100%, specificity 97%).ConclusionNon-contrast CMR imaging with native T1 mapping provides high diagnostic accuracy to diagnose cardiac amyloidosis in patients with left ventricular hypertrophy.

Cardiomyopathy Management and In-Hospital Outcomes in a Tertiary Care Center: Clinical Components and Venues of Advanced Care.

BackgroundThere are few reports on the prevalence of different types of cardiomyopathy, clinical presentation, severity, short-term outcomes, and implementation of advanced heart failure treatment. This study aimed to assess the prevalence, clinical background of different types of cardiomyopathy and to identify the candidate for advanced treatment in a tertiary care cardiac center with many advantages MethodA single-center retrospective cohort study included 1069 patients admitted to our center and diagnosed with cardiomyopathy during 2019 and 2020 ResultsOut of 1069 cardiomyopathy patients admitted and diagnosed at our center between 2019 and 2020, 62% had ischemic cardiomyopathy (ICM), 36% had dilated cardiomyopathy (DCM), and 2% had hypertrophic cardiomyopathy (HOCM). ICM patients were older, showed a higher prevalence of both male gender and pilgrims, and they had more frequent cardiovascular risk factors compared to dilated cardiomyopathy group of patients. However, DCM patients with more severe heart failure symptoms (NYHA class III/IV), much worse LVEF, were subsequently considered deemed for aggressive diuretic therapy, and further advanced therapy (Sacubitril-Valsartan and device therapy) compared to ICM patients. ICM patients showed poor in-hospital outcomes compared to DCM group of patients (0.05 and <0.001) for an indication for mechanical ventilation and in-hospital mortality, respectively). Increased age, presence of renal dysfunction and lower LVEF were found the independent predictors of in-hospital mortality among our studied patients ConclusionThere are discrepancies between DCM and ICM patients. Although DCM patients were younger at age and had fewer cardiovascular risk factors, they presented with severe symptoms and dysfunction, hence more eligible candidates for advanced heart failure treatment, and finally showed a lower mortality rate. Increased age, presence of renal dysfunction and lower LVEF were found the independent predictors of in-hospital mortality.

P4654Clinical and electrocardiographic features of restrictive cardiomyopathy in children

Abstract Introduction Restrictive cardiomyopathy (RCM) is a rare myocardial disease with an impaired diastolic function and poor prognosis. The mean survival duration after a diagnosis of RCM is reported to be around 2 years in children and most need heart transplantations. Purpose This study aimed to determine the 12-lead electrocardiogram (ECG) diagnostic criteria of RCM based on the initial diagnostic electrocardiogram. Methods ECGs in pediatric cardiomyopathy patients were collected from 15 institutes in Japan between 1979 and 2013. We compared the ECG findings, especially of the P wave, in RCM patients between the cardiomyopathy group and healthy children group separately for each gender and the age. The ECGs in the healthy group were obtained from school heart screening in Japan of first-graders, and seventh-graders. Statistical significance was determined as p&lt;0.001. Results Among 376 registered cardiomyopathy patients, 63 had hypertrophic cardiomyopathy (HCM) (36%), 91 (24%) dilated cardiomyopathy (DCM), 106 (28%) a left ventricular myocardial noncompaction (LVNCs), 25 (7%) restrictive cardiomyopathy (RCM), 14 (4%) arrhythmogenic right ventricular cardiomyopathy (ARVC), and 5 (1%) other cardiomyopathies. Of the 25 RCM patients (9.9±3.4 years old, F:M=11:14), 36% were discovered during school heart screening. The first onset was an abnormal ECG in 9, symptoms of heart failure in 6, respiratory tract infections in 3, syncope in 1, and 6 with other. Of those patients, 2 (8%) had a family history of RCM, 24 (92%) no family history. A genetic diagnosis was performed in 5 of the 25 cases, and 3 had genetic abnormalities related to RCM. The mean follow-up period was 65±95 months (mean±standard deviation). During follow up, 19 patients (76%) survived, 6 (24%) died, 7 (28%) had heart transplantations, and 3 (12%) were waiting for heart transplantations with a left ventricular assist device. The P wave was bimodal in lead I or biphasic in lead V1 in 15 patients (93%), and 13 (81%) patients had both variations. We evaluated the duration and amplitude of the first and second component of the P wave as P1 and P2. The number of control and RCM patients (control/RCM), duration of P1+P2, and sum total absolute value of the amplitude of P1+P2 in lead V1 were 8350/5, 90±9/116±10ms, and 72±28/528±278μV in first grade boys, 8423/3, 91±10/120±22ms, and 66±28/326±229μV in first grade girls, 8943/1, 97±1/100ms, and 71±31/328μV in seventh grade boys, and 9183/5, 98±11/112±10ms, and 55±27/315±56μV in seventh grade girls. Although the number of patients in the RCM group was small, sum total absolute value of the amplitude of P1+P2 in lead V1 showed a significant difference in any group. Conclusion The ECG in children with RCM exhibits P wave abnormalities in almost all patients. In particular, not the P wave interval but P wave shape in I and V1 and the sum total absolute value of the amplitude of P1+P2 in lead V1 were observed differences.

Assessment of premature ventricular beats in athletes

IntroductionPremature ventricular complexes (PVC) are generally considered as a benign electrocardiographic abnormality in the athletic population. However it may be indicative of underlying heart disease which may increase the risk of sudden death. This implies the need for cardiological evaluation before indicating the ability to practice competitive sports. AimThe aim of this study was to evaluate an athlete population with PVC and establish underlying etiologies in order to take a decision regarding practicing sports. MethodsThis is a prospective study which included athletes examined in the Tunisian National Centre of Sports Medicine and Sports Science (TNCSM) from January 2013 to June 2015 who presented PVC on an electrocardiogram. ResultsFive thousand seven hundred and ninety eight athletes were referred to the TNCSM. We identified 42 athletes having PVC with a prevalence of 1.8%. The average age of the study population was 21.6±5.99 years. 83% were men. 88% were asymptomatic. The electrocardiogram was considered normal in 62% of the athletes according to the Seattle criteria. At the Holter monitoring, the average number of PVC was 920 PVC/24hours. Thirteen athletes had doublets and 11 had triplets. One patient had polymorphic PVC and an R/T phenomenon. The transthoracic echocardiography (TTE) was normal in 71% of cases. Three athletes had hypertrophic cardiomyopathy (HCM). All patients underwent a stress test. The PVC disappeared in 12% of athletes MRI was performed in 10 athletes confirming the three cases of HCM and revealing a case of arrhythmogenic right ventricular dysplasia and a case of compression of the right ventricle by pectus exacavatum. ConclusionAfter this assessment, five athletes were not allowed to practice sport. This study shows the necessity of a thorough cardiological assessment of athletes with ventricular arrhythmia in order to detect underlying heart disease and prevent sudden death in this young apparently healthy population.

Childhood Cardiomyopathies: A Study in Tertiary Care Hospital in Upper Egypt.

IntroductionCardiomyopathy (CMP) is defined by the World Health Organization (WHO) as a disease of the myocardium associated with cardiac dysfunction. An understanding of CMP is very important, as it is a common cause of heart failure in children, and the most common indication for heart transplantation in children older than one year, but data on CMP in Egypt are scarce. The aim of this study was to determine the number, risk factors, clinical presentation, complications and outcome of different types of childhood cardiomyopathies in Sohag University Hospital.MethodsThis cross-sectional hospital based study enrolled fifty children with Cardiomyopathy in Pediatric Departments, Neonatal Care Units, and Cardiac Outpatient Clinics in Sohag University Hospital from March 01, 2014 to February 28, 2015.ResultsCases with Dilated Cardiomyopathy (DCMP) were 38 (76%), and those who had Hypertrophic Cardiomyopathy (HCMP) were 12 (24%). Dyspnea was the most common presenting complaint in 71% of cases. In cases with DCMP, the mean EF was 33.8, and FS was 17.11, while in cases with HCMP, the mean EF was 70.75, FS was 37. Fifty percent of cases were found to have moderate to severe PHT. Serum CK-MB was elevated in 3 (6%) cases, while serum Troponin I was elevated in 2 (4.2%) cases who diagnosed as having myocarditis. Viral myocarditis was the most common identified etiological agent responsible for 14 (37%) cases with DCMP.ConclusionsCMP represents a considerable percentage of children with cardiac disorders. DCMP is the most common type, usually presented with congestive heart failure, and the most common cause is myocarditis. L-Carnitine profile was normal in all cases, despite its routine use. Pediatricians need to raise their clinical suspicion to CMPs, as atypical presentations are not uncommon. To do screening for other family members, cardiac enzymes (CK-MB, Troponin I) have to be done in all newly diagnosed CMP cases, along with a revision of the routine prescription of L-Carnitine.

Hearing Profile in Patients with Dilated and Hypertrophic Cardiomyopathies.

IntroductionCardiomyopathy may cause disruptions in the micro-vascular system of the stria vascularis in the cochlea, and, subsequently, may result in cochlear degeneration. Degeneration in the stria vascularis affects the physical and chemical processes in the organ of Corti, thereby causing a possible hearing impairment. The objective of this study was to assess the hearing profiles of patients with dilated and hypertrophic cardiomyopathies to determine the relationship between the degree of hearing loss and the degree and duration of the disease and to compare the dilated and hypertrophic cardiomyopathies as regards hearing profile.MethodsIn this case control study, we studied 21 patients (cases/study group/group 1) and 15 healthy individuals (controls/group 2). Six patients (group 1a) had hypertrophic cardiomyopathy (HCM), and 15 patients (group 1b) had dilated cardiomyopathy (DCM). The data were analyzed using the t-test, chi-squared test, Kruskal-Wallis test, and the Multiple Mann-Whitney test.ResultsThe results of this study showed that 80% of those patients with DCM (group 1b) had bilateral sensorineural hearing loss (SNHL), and 100% of the patients with HCM (group 1a) had mild to severe bilateral sloping SNHL. Distortion Product Otoacoustic Emissions (DPOAEs) were present in 14% of the study group and in 100 % of the control group. The results of the measurements of auditory brainstem response (ABR) showed that 50% of the study group had abnormal latencies compared to the control group, and there was no correlation between the duration of the disease and the degree of hearing loss or DPOAE. Fifty percent of the patients with HCM and 35% of the patients with DCM had positive family histories of similar conditions, and 35% of those with HCM had a positive family history of sudden death.ConclusionThe results of this study suggested that the link between heart disease and hearing loss and early identification of hearing loss in patients with cardiomyopathy may reduce morbidity since hearing deficits sometimes precede heart disease.

Clinical and echocardiogram profile of Cardiomyopathy at tertiary care centre

Background: Cardiomyopathies represent a heterogeneous group of diseases that often lead to progressive heart failure with significant morbidity and mortality. The improved recognition or of other factor, the incidence and prevalence of heart failure due to cardiomyopathy appears to be increasing. Aims & Objectives: To study the prevalence, clinical profile and outcome of patients with cardiomyopathies and to study the echocardiographic profile. Material & methods: It is retrospective observational study of 65 patients, with age >15 years and admitted in medical ICU and ward of KIMSU, karad. This study was conducted over period of one year. All eligible subjects underwent relevant investigations including echocardiogram, Doppler study, electrocardiogram, chest radiogram and coronary angiogram. Proforma included age gender presenting complaints, past history, history of medications, clinical examination and laboratory investigations. Trans-thoracic 2-dimensional echocardiogram and Doppler study was done according to the standard protocol. Statistical analysis: Results were given as mean ± SD. Means are compared by unpaired Students t-test. Chi-square was used as appropriate. The observations and data were analyzed in the statistical package social sciences (SPSS) trial version 11. The level of significance was set at P<0.05. Results: A total of 65 patients were admitted from Jan 2010 to Dec 2012 who were diagnosed with cardiomyopathy with mean age of 58.76 years (SD±15.98). Out of the total 65 cardiomyopathy patients admitted 27 (41.53%) had Dilated cardiomyopathy (idiopathic), 15 (23.07%) patients were diagnosed with Ischemic cardiomyopathy. Total 42 (64.61%) patients had Dilated cardiomyopathy (i.e. idiopathic and ischemic dilated cardiomyopathy). A total 11 (16.92%) had Hypertrophic cardiomyopathy (HCM), 2 (3.07%) patients had Hypertrophic obstructive cardiomyopathy (HOCM) with LVOT significant gradient, 5 (7.69%) patients had Restrictive cardiomyopathy (RCMP), 4 (6.15%) had Peripartum cardiomyopathy (PPCM) and 1 (1.53%) patient had miscellaneous (alcohol induced) Cardiomyopathy. Out of 27 patients diagnosed with Dilated Cardiomyopathy (DCM), 15 (55.55%) were male patients and 12 (44.45%) were females. Out of 15 patients diagnosed with Ischemic cardiomyopathy, 7(46.66%) were males and 8(53.33%) were females. Out of 11 patients diagnosed with HCM, 9(81.81%) were males and 2(18.18%) were females. Out of 2 patients diagnosed with HOCM 1(50%) was a male patient and 1(50%) was a female patient. There were 4 female patients who were diagnosed with PPCM. A total of 5 patients were diagnosed with RCMP, out of which 1(20%) was a male patient 4(80%) patients were females. There was 1 male patient diagnosed with cardiomyopathy secondary to chronic alcohol consumption. In present study breathlessness 89.23% was most common presenting symptom and palpitations (81.53%) and cough (58.46%) were next to it with ‘p’ <0.001. Overall VPC’s (36%) were the most common ECG abnormality in patients with cardiomyopathy in present study with ‘p’ value <0.01. The LBBB (35.71%) was more frequently seen in patients with dilated cardiomyopathy with ‘p’ <0.02. The atrial flutter/ fibrillation found more commonly in patients with restrictive cardiomyopathy (80%) with ‘p’ value < 0.02. Total 74.07% of DCM, 86.67% of ischemic cardiomyopathy, 50% of PPCM, 81.82% of HCM, 100% of HOCM, RCMP and alcoholic cardiomyopathy patients had diastolic dysfunction. Idiopathic Dilated cardiomyopathy had 22% (±7.7) of lowest left ventricular ejection fraction (LVEF). Out of total 65 patients two patients with dilated cardiomyopathy succumbed with overall mortality 3.08% and case fatality rate for DCM was 4.76%. Total 96.92% patient were discharged after treatment from the hospital. Conclusion: Present study highlights significant burden of Idiopathic dilated cardiomyopathy and next to it was ischemic cardiomyopathy. A total 6 (9.23%) patients had potentially reversible cardiomyopathy like peripartum, alcoholic and myocarditis. The cardiomyopathy is asymptomatic in the early stages hence early diagnosis and management is of vital importance in the form of judicious use of anticoagulant, digoxin, diuretics, ACE inhibitors and betablocker is mandatory to reduce complications, morbidity and mortality associated cardiomyopathies. Trans-thoracic echocardiogram is an important, simple and noninvasive modality of investigation which can be reproducible for the diagnosis and fallow upof most of the cardiomyopathies. Key words: Echocardiogram, Dilated cardiomyopathy, Hypertrophic obstructivecardiomyopathy, Peripartum cardiomyopathy, Restrictive cardiomypathy.

Relationship between left ventricular ejection fraction and mitral annular displacement derived by speckle tracking echocardiography in patients with different heart diseases

Speckle tracking echocardiography (STE)-derived mitral annular displacement (MAD) utilizes the speckle tracking technique to measure strain vectors, which provides accurate estimates of left ventricular ejection fraction (LVEF). Here, we investigated a link between STE-derived MAD and LVEF in patients with different heart diseases and evaluated its clinical usefulness. This study included 266 outpatients and 84 controls. Of the study patients, 52 patients had ischemic heart disease (IHD), 37 patients had dilated cardiomyopathy (DCM), 34 patients had hypertrophic cardiomyopathy (HCM), 74 patients had valvular heart disease (VHD), and 69 patients had hypertensive heart disease (HHD). STE continuously tracked annular motion throughout the cardiac cycle in the apical 4- and 2-chamber views. In all participants, the curvilinear relationship was found between STE-derived MAD and LVEF (R(2)=0.642). The strong correlation between STE-derived MAD and LVEF was also found in the patients with IHD (R(2)=0.733, p=0.001) and in those with DCM (R(2)=0.614, p=0.008). However, such a correlation was not found in the patients with HCM, VHD, or HHD. The specificity in the correlation between STE-derived MAD and LVEF was found in patients with each heart disease, which should be taken into account when assessing these parameters.

Infants of diabetic mothers: echocardiographic measurements and cord blood IGF-I and IGFBP-1

Cardiac malformations in infants of diabetic mothers (IDMs) are five times higher than in normal pregnancies. Insulin-like growth factor-I (IGF-I) is the most important growth factor in utero and is predominantly bound by IGF binding protein-1 (IGFBP-1). To examine the echocardiographic findings of neonates of diabetic mothers and the relationship with cord blood IGF-I and IGBP-1. This study was conducted on 69 neonates born to diabetic mothers who were admitted to the neonatal intensive care unit, Ain Shams University Hospitals between August 2007 and February 2008. They were classified into three groups: 20 small for gestational age, 25 appropriate for gestational age, and 24 large for gestational age. Neonates were subjected to thorough clinical examination and echocardiographic evaluation. Maternal hemoglobin A1c (HbA1c) and cord blood IGF-I and IGBP-1 were assessed. Thirty neonates (43.5%) had hypertrophic cardiomyopathy (HCM); all of them were infants of suboptimally controlled diabetic mothers (HbA1c ≥ 7) with positive correlation between HbA1c and interventricular septal (IVS) thickness. Impaired left ventricular contractility was recorded in 52 IDMs (75.4%). The echocardiographic and laboratory measurements showed significant difference between the three studied groups. Cardiac morphological data were negatively correlated to IGFBP-1 and positively correlated to IGF-I and birth weight. The opposing relationships between cord blood IGF-I and IGFBP-1 on the cardiac morphological measurements supporting their putative opposing roles in HCM seen in IDMs. Birth weight is the best predictor of hypertrophied IVS especially in infants born to suboptimally controlled diabetic mothers.

Response to Letter to the Editor on Article: Stellpflug SJ, Fritzlar SJ, Cole JB, Engebretsen KM, Holger JS. Cardiotoxic Overdose Treated with Intravenous Fat Emulsion and High-dose Insulin in the Setting of Hypertrophic Cardiomyopathy. J Med Toxicol 2011; 7(2):151–3

Thank you for reading our case report and discussion with interest, and for the constructive comments. We agree that in this patient, the lack of clinical improvement during the high-dose insulin (HDI) therapy and the improvement following the intravenous fat emulsion (IFE) therapy makes it likely that this was indeed another case of a patient improving primarily because of the IFE. The conclusion was stated in an intentionally nonspecific way with “The treatment combination…was successful for this patient…” because there were several treatments used simultaneously. This wording was used in an effort to comply with the slight uncertainty of the cause for clinical improvement and also the reviewers' comments during the editing. Although the conclusion is technically correct, we understand that the nonspecific nature of it likely underestimates the effect of the IFE treatment for the reader. The comments elsewhere in the manuscript certainly do not contradict the conclusion; they are just more specific. It is true that many, if not all, IFE case reports demonstrate the effect only following conventional treatments. IFE has historically (in its brief history) been used following conventional treatments, so this is not a surprise. Conventional therapies for beta blocker and calcium channel blocker overdoses may currently include pressors for some providers, as indicated in your letter to the editor, but we need to clarify that point. Casually mentioning pressors as “conventional” may be interpreted by readers as “correct,” and they should not necessarily be so interpreted. Peripheral vasopressors should likely only be used in the treatment of calcium channel blocker and beta blocker overdoses if other primary therapies (intravenous fluid boluses, calcium, and appropriately dosed high-dose insulin) are unsuccessful. Even at that point, pressors should only be used if there is concern about less than optimal perfusion, especially to the brain, at that point in clinical decision making. The best animal studies available on this topic all indicate that pressors are less effective than high-dose insulin and may actually increase mortality (Kline et al. J Pharmacol Exp Ther, 1993; Kerns et al. Ann Emerg Med, 1997; Holger et al. Clin Toxicol, 2007). A head-to-head HDI vs. IFE study would be interesting to see, but there are a couple of notable items from your comments on this topic. The first note is that although it would be an interesting study to read, I am not sure that it would be very clinically applicable right now because of how these two treatments are used. HDI is typically used early on in patients such as the one in our case report in an effort to avoid further decline in the clinical status. IFE, on the other hand, is typically used in the setting of cardiac arrest or at a stage of severe clinical decline (this pre-arrest usage is supported by the recent ACMT position statement and a few case reports such as ours). The head-to-head comparison would thus be of two different modalities typically used at different points in the treatment course. The second note is that even if a potential head-to-head HDI/IFE study would be clinically useful, this case does not make an argument to complete such a study. As stated in the case discussion, this patient was highly unique in that she had hypertrophic cardiomyopathy (HCM). Based on the clinical status and the real-time echocardiography, the HDI (or the combination of treatments) likely induced obstructive cardiac pathophysiology. The ineffectiveness of the HDI likely had as much to do with the HCM as anything else in this case. An argument for a head-to-head study should be made based on a patient with normal baseline cardiac function, not a patient such as the one in our report.

Nemaline myopathy and non-fatal hypertrophic cardiomyopathy caused by a novel ACTA1 E239K mutation

A twenty-year old male presented with diffuse limb muscle weakness and exertional dyspnea since childhood. The diagnosis of nemaline myopathy was given based on the muscle pathology findings that revealed nemaline rods on light and electron microscopy and discovery of a novel mutation, E239K, in ACTA1. Incidentally, the patient had hypertrophic cardiomyopathy (HCM) as shown by echocardiography. In nemaline myopathy, a few cases of HCM have been reported, albeit rarely and always fatal, but only one patient had ACTA1 mutation. This present report describes an infantile onset of nemaline myopathy with a milder clinical course and non-fatal HCM as compared with previous cases, showing clinical diversity in skeletal and cardiac manifestations of conditions associated with ACTA1 mutations.

Germline gain-of-function mutations in RAF1 cause Noonan syndrome

Noonan syndrome is characterized by short stature, facial dysmorphia and a wide spectrum of congenital heart defects. Mutations of PTPN11, KRAS and SOS1 in the RAS-MAPK pathway cause approximately 60% of cases of Noonan syndrome. However, the gene(s) responsible for the remainder are unknown. We have identified five different mutations in RAF1 in ten individuals with Noonan syndrome; those with any of four mutations causing changes in the CR2 domain of RAF1 had hypertrophic cardiomyopathy (HCM), whereas affected individuals with mutations leading to changes in the CR3 domain did not. Cells transfected with constructs containing Noonan syndrome-associated RAF1 mutations showed increased in vitro kinase and ERK activation, and zebrafish embryos with morpholino knockdown of raf1 demonstrated the need for raf1 for the development of normal myocardial structure and function. Thus, our findings implicate RAF1 gain-of-function mutations as a causative agent of a human developmental disorder, representing a new genetic mechanism for the activation of the MAPK pathway.

Familial Hypertrophic Cardiomyopathy With Triphasic Transmitral Flow Velocity

We describe a family in which five members had hypertrophic cardiomyopathy (HCM) with a similar distribution of left ventricular (LV) hypertrophy and LV filling pattern. All five family members had myocardial hypertrophy localized between the anterior LV wall and ventricular septum, in addition to having a triphasic transmitral flow (TMF) velocity pattern with a mid-diastolic wave. The HCM patients with this TMF velocity pattern exhibit decreased LV compliance and delayed LV relaxation, suggesting that the features of diastolic failure may be specific. Thus, these findings may provide an important clue to elucidating the relationship between the pathophysiology and mode of inheritance in patients with HCM.

Hemodynamic effects of isometric exercise in hypertrophic cardiomyopathy: Comparison with normal subjects

Background. We assessed the hemodynamic effects of isometric exercise by an ambulatory radionuclide monitoring device (VEST) that measured left ventricular function in patients who had hypertrophic cardiomyopathy (HCM), with and without significant left ventricular outflow-tract obstruction at rest, compared with control subjects. Methods and Results. We studied 10 patients with obstructive HCM, 25 patients with nonobstructive HCM, and 11 control subjects. During VEST monitoring, all patients gripped a dynamometer at 75% of maximal strength for up to 5 minutes. End-diastolic, end-systolic, and stroke volumes; cardiac output; and systemic vascular resistance were expressed as a percentage of baseline. The mean exercise duration was similar among the 3 groups. During handgrip, heart rate, systolic blood pressure, and cardiac output increased significantly and similarly in the 3 groups. There was a significant difference in the lung activity between obstructive and nonobstructive HCM patients and control subjects ( P < .001), with a fall in control subjects and no change in HCM patients, irrespective of obstruction. Control subjects showed a decrease in end-systolic volume ( P = .02) and an increase in ejection fraction ( P = .003) and stroke volume ( P = .009), whereas these parameters did not change in HCM patients, irrespective of obstruction. Systemic vascular resistance increased in obstructive ( P = .02) and nonobstructive ( P < .01) HCM patients but did not change in control subjects. Conclusions. Isometric exercise causes an abnormal and similar adaptation to load changes in obstructive and nonobstructive HCM patients, as compared with control subjects. (J Nucl Cardiol 2003;10:154-60)

Left Ventricular Function During Physiological Cardiac Pacing: Relation to Rate, Pacing Mode, and Underlying Myocardial Disease

The hemodynamic effects of cardiac pacing at different rates and in different modes were studied in 21 patients who were candidates for permanent pacemaker implantation. Nine of these had primary conduction disturbances (PCD), ten had ischemic heart disease (IHD), seven with additional cardiac failure (CHF), and two had hypertrophic cardiomyopathy (HCM). In patients with PCD, atrial (AOO) and AV sequential (DVI) pacing did not change systolic blood pressure and pulse pressure but ventricular (VVI) pacing caused a progressive fall in these measurements, especially as heart rate increased. Ventricular volume and stroke volume (counts) derived from radionuclide ventriculography (RVG) decreased progressively with higher pacing rates, especially during VVI pacing. Cardiac output was maintained during VVI pacing by the increase in heart rate; during AOO and DVI pacing, cardiac output increased. Similar but more marked differences were observed in patients with IHD and CHF and the changes were even greater in the patients with HCM. Left ventricular (LV) ejection fraction changed little with increasing heart rate in PCD but decreased progressively with the onset of ischemia in IHD and CHF. There was no difference in ejection fraction in the different pacing modes. Graphs related to LV contractility (end-systolic pressure-volume relations) showed that AOO pacing produced the highest and VVI pacing produced the lowest curves of myocardial contractility in all patient groups, except that at higher rates the AOO curve shifted down again in patients with IHD and CHF, presumably with the onset of myocardial ischemia. This study showed that physiological pacing produced the best hemodynamic results in all patient groups. Higher pacing rates should be avoided in patients with ischemic heart disease while VVI pacing should not be used in patients with HCM. Blood pressure and RVG studies during temporary pacing are useful in selecting the optimal pacing system in an individual patient when the clinical choice is not clear.