Electrocardiographic abnormalities in patients with cardiomyopathies.

Abnormalities in impulse generation and transmission are among the first signs of cardiac remodeling in cardiomyopathies. Accordingly, 12-lead electrocardiogram (ECG) of patients with cardiomyopathies may show multiple abnormalities. Some findings are suggestive of specific disorders, such as the discrepancy between QRS voltages and left ventricular (LV) mass for cardiac amyloidosis or the inverted T waves in the right precordial leads for arrhythmogenic cardiomyopathy. Other findings are less sensitive and/or specific, but may orient toward a specific diagnosis in a patient with a specific phenotype, such as an increased LV wall thickness or a dilated LV. A "cardiomyopathy-oriented" mindset to ECG reading is important to detect the possible signs of an underlying cardiomyopathy and to interpret correctly the meaning of these alterations, which differs in patients with cardiomyopathies or other conditions.

Coronary Artery Dissection and Myocardial Infarction With Nonobstructed Coronary Arteries: Insights From a UK Nationwide Autopsy-Based Registry-Brief Report.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) and myocardial infarction with nonobstructed coronary arteries (MINOCA) are increasingly recognized causes of acute coronary syndrome and potentially of sudden cardiac death (SCD). SCAD has been correlated to coronary fibromuscular dysplasia (FMD), but the prevalence of SCAD and FMD among SCD victims is unclear. Therefore, we sought to assess characteristics of decedents with SCAD found at autopsy and to compare their clinical and pathological profile with MINOCA victims. METHODS: We reviewed a database of 5325 consecutive cases of SCDs referred to our cardiac pathology center between 1994 and 2017. RESULTS: We identified 18 (0.3%) cases with SCAD and 37 (0.7%) with MINOCA. No signs of coronary FMD were found among SCAD and MINOCA victims. Compared to MINOCA, SCAD decedents were mostly females (78% versus 38%, P=0.006) and SCD occurred during peripartum more frequently in SCAD rather than MINOCA female victims (28% versus 3%, P=0.012) Infarcted myocardium was identified in all cases of MINOCA but only in 5 (28%) of SCAD decedents (P<0.001). Premortem cardiac symptoms were present in 100% of SCAD and 49% of MINOCA victims (P<0.001); substances use or abuse was reported in none of SCAD versus 43% of MINOCA decedents (P=0.001). CONCLUSIONS: SCAD and MINOCA are rare causes of SCD. At autopsy, coronary FMD is not present among SCAD victims. Compared to MINOCA, SCAD victims are more frequently females, are linked to pregnancy, and always experienced premortem cardiac symptoms. Among MINOCA victims' substance use or abuse is common.

Yield of molecular autopsy in sudden cardiac death in athletes: data from a large registry in the UK.

AIMS: Sudden cardiac death (SCD) may occur in apparently healthy individuals, including athletes. The aim was to investigate the diagnostic role of post-mortem genetic testing, molecular autopsy (MA), in elucidating the cause of SCD in athletes. METHODS AND RESULTS: We reviewed a database of 6860 consecutive cases of SCD referred to our specialist cardiac pathology centre. All cases underwent detailed cardiac autopsy, and 748 were deemed to be athletes. Of these, 42 (6%) were investigated with MA (28 using a targeted sequencing, 14 exome sequencing). Variants were classified as pathogenic, likely pathogenic, or variant of unknown significance using international guidelines. Clinical information was obtained from referring coroners who completed a detailed health questionnaire. Out of the 42 decedents (average age 35 years old, 98% males) who were investigated with MA, the autopsy was in keeping with a structurally normal heart [sudden arrhythmic death syndrome (SADS)] in n = 33 (78%) cases, followed by arrhythmogenic cardiomyopathy (ACM) in eight (19%) individuals and idiopathic left ventricular fibrosis in one (2%). Death occurred during exercise and at rest in 26 (62%) and 16 (38%) individuals, respectively. Variants that were adjudicated clinically actionable were present in seven cases (17%). There was concordance between the genetic and phenotypic findings in two cases of ACM (in FLNC and TMEM43 genes). None of the variants identified in SADS cases were previously linked to channelopathies. Clinically actionable variants in cardiomyopathy-associated genes were found in five cases of SADS. CONCLUSION: The yield of MA in athletes who died suddenly is 17%. In SADS cases, clinically actionable variants were found in cardiomyopathy-associated genes and not in channelopathy-associated genes. Arrhythmogenic cardiomyopathy is a common cause of SCD in athletes, and one in four decedents with this condition had a clinically actionable variant in FLNC and TMEM43 genes.

From gene-discovery to gene-tailored clinical management: 25 years of research in channelopathies and cardiomyopathies.

In the early nineties, few years before the birth of Europace, the clinical and scientific world of familial arrhythmogenic conditions was revolutionized by the identification of the first disease-causing genes. The explosion of genetic studies over a 15-year period led to the discovery of major disease-causing genes in practically all channelopathies and cardiomyopathies, bringing insight into the pathophysiological mechanisms of these conditions. The birth of next generation sequencing allowed a further step forward and other significant genes, as CALM1-3 in channelopathies and FLN C and TTN in cardiomyopathies were identified. Genotype-phenotype studies allowed the implementation of the genetic results in diagnosis, risk stratification, and therapeutic management with a different level of evidence in different arrhythmogenic conditions. The influence of common genetic variants, i.e. SNPs, on disease manifestation was proved in mid-twenties, and in the last 10 years with the advent of genome-wide association studies performed in familial arrhythmogenic diseases, the concept of polygenic risk score has been consolidated. Now, we are at the start of another amazing phase, i.e. the initiation of first gene therapy clinical trials.

COVID-19 and myocarditis: a systematic review and overview of current challenges.

Myocardial inflammation in COVID-19 has been documented. Its pathogenesis is not fully elucidated, but the two main theories foresee a direct role of ACE2 receptor and a hyperimmune response, which may also lead to isolated presentation of COVID-19-mediated myocarditis. The frequency and prognostic impact of COVID-19-mediated myocarditis is unknown. This review aims to summarise current evidence on this topic. We performed a systematic review of MEDLINE and Cochrane Library (1/12/19-30/09/20). We also searched clinicaltrials.gov for unpublished studies testing therapies with potential implication for COVID-19-mediated cardiovascular complication. Eligible studies had laboratory confirmed COVID-19 and a clinical and/or histological diagnosis of myocarditis by ESC or WHO/ISFC criteria. Reports of 38 cases were included (26 male patients, 24 aged < 50 years). The first histologically proven case was a virus-negative lymphocytic myocarditis; however, biopsy evidence of myocarditis secondary to SARS-CoV-2 cardiotropism has been recently demonstrated. Histological data was found in 12 cases (8 EMB and 4 autopsies) and CMR was the main imaging modality to confirm a diagnosis of myocarditis (25 patients). There was a substantial variability in biventricular systolic function during the acute episode and in therapeutic regimen used. Five patients died in hospital. Cause-effect relationship between SARS-CoV-2 infection and myocarditis is difficult to demonstrate. However, current evidence demonstrates myocardial inflammation with or without direct cardiomyocyte damage, suggesting different pathophysiology mechanisms responsible of COVID-mediated myocarditis. Established clinical approaches should be pursued until future evidence support different actions. Large multicentre registries are advisable to elucidate further.

Sudden cardiac death in cardiomyopathies: acting upon "acceptable" risk in the personalized medicine era.

Patients with cardiomyopathies are confronted with the risk of sudden cardiac death (SCD) throughout their lifetime. Despite the fact that SCD is relatively rare, prognostic stratification is an integral part of physician-patient discussion, with the goal of risk modification and prevention. The current approach is based on a concept of "acceptable risk." However, there are intrinsic problems with an algorithm-based approach to risk management, magnified by the absence of robust evidence underlying clinical decision support tools, which can make high- versus low-risk classifications arbitrary. Strategies aimed at risk reduction range from selecting patients for an implantable cardioverter defibrillator (ICD) to disqualification from competitive sports. These clinical options, especially when implying the use of finite financial resources, are often delivered from the physician's perspective citing decision-making algorithms. When the burden of intervention-related risks or financial costs is deemed higher than an "acceptable risk" of SCD, the patient's perspective may not be appropriately considered. Designating a numeric threshold of "acceptable risk" has ethical implications. One could reasonably ask "acceptable to whom?" In an era when individual choice and autonomy are pillars of the physician-patient relationship, the subjective aspects of perceived risk should be acknowledged and be part of shared decision-making. This is particularly true when the lack of a strong scientific evidence base makes a dichotomous algorithm-driven approach suboptimal for unmitigated translation to clinical practice.

Role of the electrocardiogram in differentiating genetically determined dilated cardiomyopathy from athlete's heart.

BACKGROUND: Physiological cardiac remodelling in highly trained athletes may overlap with dilated cardiomyopathy (DCM). OBJECTIVES: The aim of this study was to investigate the role of the electrocardiogram (ECG) in differentiating between physiological and pathological remodelling. METHODS: The study population consisted of 30 patients with DCM who revealed a pathogenic variant at genetic testing and 30 elite athletes with significant cardiac remodelling defined by a left ventricular (LV) end-diastolic diameter >62 mm and/or LV ejection fraction between 45% and 50%. RESULTS: The ECG was abnormal in 22 (73%) patients with DCM. The most common abnormalities were low voltages (n = 14, 47%), lateral T-wave inversion (TWI) (n = 6, 20%), ventricular ectopic beats (n = 5, 17%) and anterior TWI (n = 4, 13). Two athletes revealed an abnormal ECG: complete left bundle branch block (LBBB) in one case and atrial flutter in the other. The sensitivity, specificity and accuracy of the ECG in differentiating DCM from physiological adaptation to exercise in athletes was 73% (confidence interval [CI]: 54%-88%), 93% (CI: 78%-99%) and 0.83 (CI: 0.71-0.92) respectively. CONCLUSIONS: While the ECG is usually normal in athletes exhibiting significant LV dilatation and/or systolic dysfunction, this test is often abnormal in patients with DCM harbouring a pathogenic variant. Low voltages in the limb leads and lateral TWI are the most common abnormalities.

The Electrocardiogram in the Diagnosis and Management of Patients With Left Ventricular Non-Compaction.

PURPOSE OF THE REVIEW: Left ventricular non-compaction (LVNC) is characterised by prominent left ventricular trabeculae and deep inter-trabecular recesses. Although considered a distinct cardiomyopathy, prominent trabeculations may also be found in other cardiomyopathies, in athletes or during pregnancy. Clinical presentation includes heart failure symptoms, systemic embolic events, arrhythmias and sudden cardiac death. Currently, LVNC diagnosis relies on imaging criteria, and clinicians face several challenges in the assessment of patients with prominent trabeculations. In this review, we summarise the available information on the role of the ECG in the diagnosis and management of LVNC. RECENT FINDINGS: ECG abnormalities have been reported in 75-94% of adults and children with LVNC. The lack of specificity of these ECG abnormalities does not allow (in isolation) to diagnose the condition. However, when considered in a set of diagnostic criteria including family history, clinical information, and imaging features, the ECG may differentiate between physiological and pathological findings or may provide clues raising the possibility of specific underlying conditions. Finally, some ECG features in LVNC constitute ominous signs that require a stricter patient surveillance or specific therapeutic measures. The ECG remains a cornerstone in the diagnosis and management of patients with cardiomyopathies, including LVNC.

Outcomes of Cardiac Screening in Adolescent Soccer Players.

BACKGROUND: Reports on the incidence and causes of sudden cardiac death among young athletes have relied largely on estimated rates of participation and varied methods of reporting. We sought to investigate the incidence and causes of sudden cardiac death among adolescent soccer players in the United Kingdom. METHODS: From 1996 through 2016, we screened 11,168 adolescent athletes with a mean (±SD) age of 16.4±1.2 years (95% of whom were male) in the English Football Association (FA) cardiac screening program, which consisted of a health questionnaire, physical examination, electrocardiography, and echocardiography. The FA registry was interrogated to identify sudden cardiac deaths, which were confirmed with autopsy reports. RESULTS: During screening, 42 athletes (0.38%) were found to have cardiac disorders that are associated with sudden cardiac death. A further 225 athletes (2%) with congenital or valvular abnormalities were identified. After screening, there were 23 deaths from any cause, of which 8 (35%) were sudden deaths attributed to cardiac disease. Cardiomyopathy accounted for 7 of 8 sudden cardiac deaths (88%). Six athletes (75%) with sudden cardiac death had had normal cardiac screening results. The mean time between screening and sudden cardiac death was 6.8 years. On the basis of a total of 118,351 person-years, the incidence of sudden cardiac death among previously screened adolescent soccer players was 1 per 14,794 person-years (6.8 per 100,000 athletes). CONCLUSIONS: Diseases that are associated with sudden cardiac death were identified in 0.38% of adolescent soccer players in a cohort that underwent cardiovascular screening. The incidence of sudden cardiac death was 1 per 14,794 person-years, or 6.8 per 100,000 athletes; most of these deaths were due to cardiomyopathies that had not been detected on screening. (Funded by the English Football Association and others.).

Arrhythmogenic potential of myocardial disarray in hypertrophic cardiomyopathy: genetic basis, functional consequences and relation to sudden cardiac death.

Myocardial disarray is defined as disorganized cardiomyocyte spatial distribution, with loss of physiological fibre alignment and orientation. Since the first pathological descriptions of hypertrophic cardiomyopathy (HCM), disarray appeared as a typical feature of this condition and sparked vivid debate regarding its specificity to the disease and clinical significance as a diagnostic marker and a risk factor for sudden death. Although much of the controversy surrounding its diagnostic value in HCM persists, it is increasingly recognized that myocardial disarray may be found in physiological contexts and in cardiac conditions different from HCM, raising the possibility that central focus should be placed on its quantity and distribution, rather than a mere presence. While further studies are needed to establish what amount of disarray should be considered as a hallmark of the disease, novel experimental approaches and emerging imaging techniques for the first time allow ex vivo and in vivo characterization of the myocardium to a molecular level. Such advances hold the promise of filling major gaps in our understanding of the functional consequences of myocardial disarray in HCM and specifically on arrhythmogenic propensity and as a risk factor for sudden death. Ultimately, these studies will clarify whether disarray represents a major determinant of the HCM clinical profile, and a potential therapeutic target, as opposed to an intriguing but largely innocent bystander.

Diagnostic yield and financial implications of a nationwide electrocardiographic screening programme to detect cardiac disease in the young.

AIMS: There is limited information on the role of screening with electrocardiography (ECG) for identifying cardiovascular diseases associated with sudden cardiac death (SCD) in a non-select group of adolescents and young adults in the general population. METHODS AND RESULTS: Between 2012 and 2014, 26 900 young individuals (aged 14-35 years) were prospectively evaluated with a health questionnaire and ECG. Individuals with abnormal results underwent secondary investigations, the costs of which were being based on the UK National Health Service tariffs. Six hundred and seventy-five (2.5%) individuals required further investigation for an abnormal health questionnaire, 2175 (8.1%) for an abnormal ECG, and 114 (0.5%) for both. Diseases associated with young SCD were identified in 88 (0.3%) individuals of which 15 (17%) were detected with the health questionnaire, 72 (81%) with ECG and 2 (2%) with both. Forty-nine (56%) of these individuals received medical intervention beyond lifestyle modification advice in the follow-up period of 24 months. The overall cost of the evaluation process was €97 per person screened, €17 834 per cardiovascular disease detected, and €29 588 per cardiovascular disease associated with SCD detected. Inclusion of ECG was associated with a 36% cost reduction per diagnosis of diseases associated with SCD compared with the health questionnaire alone. CONCLUSION: The inclusion of an ECG to a health questionnaire is associated with a five-fold increase in the ability to detect disease associated with SCD in young individuals and is more cost effective for detecting serious disease compared with screening with a health questionnaire alone.

Sudden Death and Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by myocardial fibrofatty replacement and an increased risk of sudden cardiac death (SCD). Originally described as a right ventricular disease, ACM is increasingly recognized as a biventricular entity. We evaluated pathological, genetic, and clinical associations in a large SCD cohort. METHODS: We investigated 5205 consecutive cases of SCD referred to a national cardiac pathology center between 1994 and 2018. Hearts and tissue blocks were examined by expert cardiac pathologists. After comprehensive histological evaluation, 202 cases (4%) were diagnosed with ACM. Of these, 15 (7%) were diagnosed antemortem with dilated cardiomyopathy (n=8) or ACM (n=7). Previous symptoms, medical history, circumstances of death, and participation in competitive sport were recorded. Postmortem genetic testing was undertaken in 24 of 202 (12%). Rare genetic variants were classified according to American College of Medical Genetics and Genomics criteria. RESULTS: Of 202 ACM decedents (35.4±13.2 years; 82% male), no previous cardiac symptoms were reported in 157 (78%). Forty-one decedents (41/202; 20%) had been participants in competitive sport. The adjusted odds of dying during physical exertion were higher in men than in women (odds ratio, 4.58; 95% CI, 1.54-13.68; P=0.006) and in competitive athletes in comparison with nonathletes (odds ratio, 16.62; 95% CI, 5.39-51.24; P<0.001). None of the decedents with an antemortem diagnosis of dilated cardiomyopathy fulfilled definite 2010 Task Force criteria. The macroscopic appearance of the heart was normal in 40 of 202 (20%) cases. There was left ventricular histopathologic involvement in 176 of 202 (87%). Isolated right ventricular disease was seen in 13%, isolated left ventricular disease in 17%, and biventricular involvement in 70%. Among whole hearts, the most common areas of fibrofatty infiltration were the left ventricular posterobasal (68%) and anterolateral walls (58%). Postmortem genetic testing yielded pathogenic variants in ACM-related genes in 6 of 24 (25%) decedents. CONCLUSIONS: SCD attributable to ACM affects men predominantly, most commonly occurring during exertion in athletic individuals in the absence of previous reported cardiac symptoms. Left ventricular involvement is observed in the vast majority of SCD cases diagnosed with ACM at autopsy. Current Task Force criteria may fail to diagnose biventricular ACM before death.

Diagnostic yield of hypertrophic cardiomyopathy in first-degree relatives of decedents with idiopathic left ventricular hypertrophy.

AIMS: Idiopathic left ventricular hypertrophy (LVH) is defined as LVH in the absence of myocyte disarray or secondary causes. It is unclear whether idiopathic LVH represents the phenotypic spectrum of hypertrophic cardiomyopathy (HCM) or whether it is a unique disease entity. We aimed to ascertain the prevalence of HCM in first-degree relatives of decedents from sudden death with idiopathic LVH at autopsy. Decedents also underwent molecular autopsy to identify the presence of pathogenic variants in genes implicated in HCM. METHODS AND RESULTS: Families of 46 decedents with idiopathic LVH (125 first-degree relatives) were investigated with electrocardiogram, echocardiogram exercise tolerance test, cardiovascular magnetic resonance imaging, 24-h Holter, and ajmaline provocation test. Next-generation sequencing molecular autopsy was performed in 14 (30%) cases. Decedents with idiopathic LVH were aged 33 ± 14 years and 40 (87%) were male. Fourteen families (30%) comprising 16 individuals were diagnosed with cardiac disease, including Brugada syndrome (n = 8), long QT syndrome (n = 3), cardiomyopathy (n = 2), and Wolff-Parkinson-White syndrome (n = 1). None of the family members were diagnosed with HCM. Molecular autopsy did not identify any pathogenic or likely pathogenic variants in genes encoding sarcomeric proteins. Two decedents had pathogenic variants associated with long QT syndrome, which were confirmed in relatives with the clinical phenotype. One decedent had a pathogenic variant associated with Danon disease in the absence of any histopathological findings of the condition or clinical phenotype in the family. CONCLUSION: Idiopathic LVH appears to be a distinct disease entity from HCM and is associated with fatal arrhythmias in individuals with primary arrhythmia syndromes. Family screening in relatives of decedents with idiopathic LVH should be comprehensive and encompass the broader spectrum of inherited cardiac conditions, including channelopathies.

Accuracy of the 2017 international recommendations for clinicians who interpret adolescent athletes' ECGs: a cohort study of 11 168 British white and black soccer players.

AIM: To investigate the accuracy of the recently published international recommendations for ECG interpretation in young athletes in a large cohort of white and black adolescent soccer players. METHODS: 11 168 soccer players (mean age 16.4±1.2 years) were evaluated with a health questionnaire, ECG and echocardiogram; 10 581 (95%) of the players were male and 10 163 (91%) were white. ECGs were retrospectively analysed according to (1) the 2010 European Society of Cardiology (ESC) recommendations, (2) Seattle criteria, (3) refined criteria and (4) the international recommendations for ECG interpretation in young athletes. RESULTS: The ESC recommendations resulted in a higher number of abnormal ECGs compared with the Seattle, refined and international criteria (13.2%, 4.3%, 2.9% and 1.8%, respectively). All four criteria were associated with a higher prevalence of abnormal ECGs in black athletes compared with white athletes (ESC: 16.2% vs 12.9%; Seattle: 5.9% vs 4.2%; refined: 3.8% vs 2.8%; international 3.6% vs 1.6%; p<0.001 each). Compared with ESC recommendations, the Seattle, refined and international criteria identified a lower number of abnormal ECGs-by 67%, 78% and 86%, respectively. All four criteria identified 36 (86%) of 42 athletes with serious cardiac pathology. Compared with ESC recommendations, the Seattle criteria improved specificity from 87% to 96% in white athletes and 84% to 94% in black athletes. The international recommendations demonstrated the highest specificity for white (99%) and black (97%) athletes and a sensitivity of 86%. CONCLUSIONS: The 2017 international recommendations for ECG interpretation in young athletes can be applied to adolescent athletes to detect serious cardiac disease. These recommendations perform more effectively than previous ECG criteria in both white and black adolescent soccer players.

Electrocardiographic differentiation between 'benign T-wave inversion' and arrhythmogenic right ventricular cardiomyopathy.

AIMS: To characterize the most common electrocardiographic (ECG) abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), including anterior T-wave inversion (TWI) and to compare the characteristics of TWI in patients with ARVC and in a cohort of young healthy athletes and sedentary individuals. METHODS AND RESULTS: The study population consisted of 162 patients with a definite diagnosis of ARVC and 129 young controls with anterior TWI. Cardiac disease was excluded in all controls after a comprehensive diagnostic work-up. The ECG was abnormal in 131 patients with ARVC (81%). Abnormalities included anterior TWI (n = 82, 51%), QRS duration ratio V2:V5 >1.2 (n = 51, 31%), prolonged terminal S wave activation duration in V2 >55 ms (n = 42, 26%), inferior TWI (n = 30, 18%), and lateral TWI (n = 26, 16%). The J-point preceding anterior TWI was <0.1 mV in 80/82 (98%) patients with ARVC and in 98 (76%) controls. Among the ARVC patients with anterior TWI, 62 (77%) showed at least one additional abnormal feature, most commonly QRS duration ratio V2:V5 > 1.2 (52%) and inferior or lateral TWI (47%). CONCLUSION: The ECG is frequently abnormal in patients with ARVC and anterior TWI is the most common feature. Anterior TWI is usually accompanied by other abnormalities in ARVC, which are uncommon in healthy individuals. J point <0.1 mV preceding anterior TWI is not specific to ARVC and is observed in the majority of healthy individuals, including athletes, indicating a limited role for differentiating physiology or normal variants from ARVC.

Athletic Remodeling in Female College Athletes: The "Morganroth Hypothesis" Revisited.

BACKGROUND: There is limited data regarding ventricular remodeling in college female athletes, especially when appropriate scaling of cardiac dimensions to lean body mass (LBM) is considered. Moreover, it is not well established whether cardiac remodeling in female athletes is a balanced process with proportional increase in left ventricular (LV) mass and volume or the right and LV size. METHODS: During the preparticipation competitive screening, 72 female college athletes volunteered to undergo dual energy x-ray absorptiometry scan for quantification of LBM and comprehensive 2D echocardiography including assessment of longitudinal myocardial strain. The athletes were divided in 2 groups according to the intensity of the dynamic and static components of their sport categories, ie, a higher intensity dynamic and resistive group (n = 37 participating in rowing, water polo and lacrosse) and a lower intensity group (n = 35, participating in short distance running, sailing, synchronized swimming, and softball). In addition, we recruited a group of 31 age-matched nonathlete controls. RESULTS: The mean age of the study population was 18.7 ± 1.0 years. When scaled to body surface area, the higher intensity group had 17.1 ± 3.6% (P < 0.001) greater LV mass when compared with the lower intensity group and 21.7 ± 4.0% (P < 0.001) greater LV mass than the control group. The differences persisted after scaling to LBM with 14.2 ± 3.2% (P < 0.001) greater LV mass in the higher intensity group. By contrast, there was no difference in any of the relative remodeling indices including the LV mass to volume ratio, right to LV area ratio, or left atrial to LV volume ratio (P > 0.50 for all). In addition, no significant difference was noted among the 3 groups in LV ejection fraction (P = 0.22), LV global longitudinal strain (P = 0.55), LV systolic strain rate (P = 0.62), or right ventricular global longitudinal strain (P = 0.61). CONCLUSION: Female collegiate athletes participating in higher intensity dynamic and resistive sports have higher indexed LV mass even when scaled to LBM. The remodeling process does however appear to be a balanced process not only at the intraventricular level but also at the interventricular and atrioventricular levels.

Left atrial function and phenotypes in asymmetric hypertrophic cardiomyopathy.

BACKGROUND: Few studies have analyzed changes in left atrial (LA) function associated with different phenotypes of asymmetric hypertrophic cardiomyopathy (HCM). We sought to demonstrate the association of impairments in LA function with disease phenotype in patients with obstructive and nonobstructive HCM. METHODS: From Stanford Cardiomyopathy Registry, we randomly selected 50 age-/sex-matched healthy controls, 35 patients with nonobstructive HCM (HCM 1), 35 patients with obstructive HCM (HCM 2), and 35 patients with obstructive HCM requiring septal reduction therapy (HCM 3). Echocardiography was performed to evaluate left ventricular (LV) strain as well as LA function including LA emptying fraction and LA strain. RESULTS: The mean age was 51±14 years and 57% were male. LA volume index differed among all four predefined groups (25.6±6.7 mL/m2 in controls, 32.2±13.3 mL/m2 in HCM 1, 42.0±12.9 mL/m2 in HCM 2, 52.4±15.2 mL/m2 for HCM 3, and P<.05 all between groups). All measurement of LA function was impaired in patients with HCM than controls. Total and passive LA function was further impaired in HCM 2 or 3 compared with HCM 1, while active LA function was not different among the three groups. Among LV strains, only septal longitudinal strain differed among all groups (-18.5±1.9% in controls, -14.5±1.9% in HCM 1, -13.3±1.8% in HCM 2, -11.6±2.3% in HCM 3, and P<.05 all between groups). CONCLUSIONS: LA function was impaired in patients with HCM even in minimally symptomatic nonobstructive phenotype. Total and passive LA function was further impaired in patients with obstructive HCM.