Systolic blood pressure ≤110 mm Hg is associated with severe coronary microvascular ischemia and higher risk for ventricular arrhythmias in hypertrophic cardiomyopathy.

Background: Coronary microvascular dysfunction (CMD) and hypertension (HTN) occur frequently in hypertrophic cardiomyopathy (HCM), but whether blood pressure (BP) influences CMD and outcomes is unknown. Objective: The purpose of this study was to test the hypothesis that HTN is associated with worse CMD and outcomes. Methods: This retrospective study included 690 HCM patients. All patients underwent cardiac magnetic resonance imaging, echocardiography, and rhythm monitoring; 127 patients also underwent rest/vasodilator stress 13NH3 positron emission tomography myocardial perfusion imaging. Patients were divided into 3 groups based on their rest systolic blood pressure (SBP) (group 1 ≤110 mm Hg; group 2 111-140; group 3 >140 mm Hg) and were followed for development of ventricular tachycardia (VT)/ventricular fibrillation (VF), heart failure (HF), death, and composite outcome. Results: Group 1 patients had the lowest age and left ventricular (LV) mass but the highest prevalence of nonobstructive hemodynamics and restrictive diastolic filling. LV scar was similar in the 3 groups. Group 1 had the lowest rest and stress myocardial blood flow (MBF) and highest SDS (summed difference score). Rest SBP was positively correlated with stress MBF and negatively correlated with SDS. Group 1 had the highest incidence of VT/VF, whereas the incidences of HF, death, and composite outcome were similar among the 3 groups. In multivariate analysis, rest SBP ≤110 mm Hg was independently associated with VT/VF (hazard ratio 2.6; 95% confidence interval 1.0-6.7; P = .04). Conclusion: SBP ≤110 mm Hg is associated with greater severity of CMD and coronary microvascular ischemia and higher incidence of ventricular arrhythmias in HCM.

Prevalence and prognostic implications of hypertensive response to exercise in patients with hypertrophic cardiomyopathy.

Objective: Hypertensive response to exercise (HRE) is observed in patients with hypertrophic cardiomyopathy (HCM) with normal resting blood pressure (BP). However, the prevalence or prognostic implications of HRE in HCM remain unclear. Methods: In this study, normotensive HCM subjects were enrolled. HRE was defined as systolic BP > 210 mmHg in men or >190 mmHg in women, or diastolic BP > 90 mmHg, or an increase in diastolic BP > 10 mmHg during treadmill exercise. All participants were followed for subsequent development of hypertension, atrial fibrillation (AF), heart failure (HF), sustained ventricular tachycardia/fibrillation (VT/VF), and all-cause death. Six hundred and eighty HCM patients were screened. Results: 347 patients had baseline hypertension, and 333 patients were baseline normotensive. 132 (40%) of the 333 patients had HRE. HRE was associated with female sex, lower body mass index and milder left ventricular outflow tract obstruction. Exercise duration and metabolic equivalents were similar between patients with or without HRE, but the HRE group had higher peak heart rate (HR), better chronotropic response and more rapid HR recovery. Conversely, non-HRE patients were more likely to exhibit chronotropic incompetence and hypotensive response to exercise. After a mean follow-up of 3.4 years, patients with and without HRE had similar risks of progression to hypertension, AF, HF, sustained VT/VF or death. Conclusion: HRE is common in normotensive HCM patients during exercise. HRE did not carry higher risks of future hypertension or cardiovascular adverse outcomes. Conversely, the absence of HRE was associated with chronotropic incompetence and hypotensive response to exercise.

Association of Systemic Vascular Resistance Analog and Cardiovascular Outcomes: The Heart and Soul Study.

Background Systemic vascular resistance (SVR) is an integral component of the hemodynamic profile. Previous studies have demonstrated a close correlation between an estimated SVR analog (eSVR) based on echocardiographic methods and SVR by direct hemodynamic measurement. However, the prognostic impact of eSVR remains unestablished. Methods and Results Study participants with established coronary artery disease from the Heart and Soul Study formed this study cohort. We defined Doppler-derived eSVR as the ratio of systolic blood pressure to left ventricular outflow tract velocity time integral. Study participants were separated based on baseline eSVR tertile: <5.6, 5.6 to <6.9, and ≧6.9. An elevated eSVR was defined as an eSVR in the third tertile (≧6.9). Follow-up eSVR was calculated at the fifth year of checkup. Cardiovascular outcomes included heart failure, major cardiovascular events, and all-cause death. Among the 984 participants (67±11 years old, 82% men), subjects with the highest baseline eSVR tertile were the oldest, with the highest systolic blood pressure and lowest left ventricular outflow tract velocity time integral. A higher eSVR was associated with increased risk of heart failure, major cardiovascular events, and death. The hazard ratio for major cardiovascular events was 1.38 (95% CI, 1.02-1.86, P=0.03) for subjects with the highest eSVR tertile compared with the lowest. In addition, those with a persistently elevated eSVR during follow-up had the most adverse outcomes. Conclusions An elevated eSVR, derived by the ratio of systolic blood pressure and left ventricular outflow tract velocity time integral, was more closely correlated with cardiovascular events than systolic blood pressure alone. Repeatedly elevated eSVR was associated with more adverse outcomes.

Left ventricular end-systolic volume response post-stress echocardiography: Dilation as a marker of multi-vessel coronary artery disease.

BACKGROUND: Transient ischemic dilation of the left ventricle (LV) during stress echocardiography indicates extensive myocardial ischemia. It remains unclear whether the change of LV end-systolic volume (ESV) or end-diastolic volume (EDV) better correlated with significant coronary artery disease (CAD). Meanwhile, the clinical significance of the extent of the volumetric change post-stress has not been investigated. METHODS: One hundred and five individuals (62 ± 12 years and 75% men) who underwent coronary angiography following exercise treadmill echocardiography were enrolled retrospectively. An additional 30 age- and sex-matched healthy subjects were included for comparison. LV dilation was defined as any increase in LV volume from rest to peak exercise. Patients who had at least two coronary arteries with significant stenosis were considered as having multi-vessel CAD. RESULTS: Thirty-four patients had ESV dilation during exercise echocardiography. On the contrary, ESV decreased at peak exercise in all healthy subjects. Forty-one patients had multi-vessel CAD, and its prevalence was higher in patients with ESV dilation (65% vs 27%, p = 0.001). The extent of ESV increase correlated with CAD severity. ESV dilation is associated with multi-vessel CAD (Odds ratio [OR] 5.02, 95% confidence interval [CI] 2.09 - 12.07, p < 0.001). After adjustment for EDV increase, clinical, electrocardiographic, and echocardiographic variables, the association remained significant (adjusted OR 5.57, 95% CI 1.37-22.64; p = 0.02). CONCLUSIONS: ESV dilation independently correlated with multi-vessel CAD, whereas EDV dilation did not. The amount of ESV increase correlated with the severity of CAD. Our findings provide a rationale for incorporating volume measurements into stress echocardiography practice.

Personalized computational heart models with T1-mapped fibrotic remodeling predict sudden death risk in patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is associated with risk of sudden cardiac death (SCD) due to ventricular arrhythmias (VAs) arising from the proliferation of fibrosis in the heart. Current clinical risk stratification criteria inadequately identify at-risk patients in need of primary prevention of VA. Here, we use mechanistic computational modeling of the heart to analyze how HCM-specific remodeling promotes arrhythmogenesis and to develop a personalized strategy to forecast risk of VAs in these patients. We combine contrast-enhanced cardiac magnetic resonance imaging and T1 mapping data to construct digital replicas of HCM patient hearts that represent the patient-specific distribution of focal and diffuse fibrosis and evaluate the substrate propensity to VA. Our analysis indicates that the presence of diffuse fibrosis, which is rarely assessed in these patients, increases arrhythmogenic propensity. In forecasting future VA events in HCM patients, the imaging-based computational heart approach achieved 84.6%, 76.9%, and 80.1% sensitivity, specificity, and accuracy, respectively, and significantly outperformed current clinical risk predictors. This novel VA risk assessment may have the potential to prevent SCD and help deploy primary prevention appropriately in HCM patients.

Reduced global longitudinal strain as a marker for early detection of Fabry cardiomyopathy.

AIMS: Fabry cardiomyopathy (FC) is characterized by progressive left ventricular hypertrophy (LVH). Conventional echocardiography is not sensitive in detecting preclinical FC before the development of LVH. We aim to investigate whether myocardial deformation analysis is useful to detect preclinical FC before LVH. METHODS AND RESULTS: One hundred and sixty patients carrying mutated gene were prospectively enrolled, including 86 patients without LVH and 74 patients with LVH. Another 33 healthy individuals were also included for comparison. Standard transthoracic two-dimensional, Doppler, tissue Doppler echocardiography and deformation analysis were performed. The mean age of the overall 193 subjects was 48 ± 15 years, with 51% men. Fabry patients with LVH were older, more often to be men. They also had the worst diastolic function as evidenced by the largest left atrium, lowest E/A, and highest E/e' ratio. The global longitudinal strain (GLS) deteriorated with the development of LVH (control vs. LVH- patients vs. LVH+ patients = -21.2 ± 2.7 vs. -19.0 ± 2.9 vs. -16.5 ± 4.2%, P < 0.001). Despite similar LV systolic, diastolic function, and LV mass, LVH- Fabry patients still had a reduced GLS as well as regional longitudinal strains at mid-to-apical, anterior, and inferolateral wall when compared to healthy subjects. The basal longitudinal strain was consistently worse in male patients than in female patients, irrespective of LVH. CONCLUSION: Reduced GLS could be a marker of early FC before the development of LVH.

Early clinical exposure improves medical students' recognition of the need for professionalism and interprofessional collaboration.

BACKGROUND: Medical students in Taiwan start their clerkship in their fifth year. A lack of early clinical exposure can mean they have a lack of medical professionalism and collaborative practice. This study investigates whether early engagement in hospital-based clinical practice could improve their understanding of these requirements. METHODS: From 2017 to 2019, a total of 59 medical students at the end of their third year joined a 2-week summer camp at the hospital. Every participant was assigned to work with one patient and they accompanied this patient throughout their hospital course. The students were also asked to interview other medical professionals within the hospital and to write up interview reports. In addition, they had to complete pre- and postcamp questionnaires which included 10 questions to evaluate their recognition of professionalism, doctor-patient relationships, and interprofessional collaboration. Answers to the questions were all rated using a 5-score Likert scale. RESULTS: The total postcamp Likert scores were significantly increased after the 2-week training camp compared with the precourse scores (pre- vs postcourse: 44.08 ± 0.45 vs 46.66 ± 0.33, p < 0.001). In addition, the students' recognition of medical professionalism, the importance of communication with patients, and their respect for other medical professionals were significantly improved after the 2-week training. CONCLUSION: Our data showed that early clinical exposure through a preclerkship summer camp can help medical students improve their recognition of medical professionalism and interprofessional collaboration.

Machine Learning Methods for Identifying Atrial Fibrillation Cases and Their Predictors in Patients With Hypertrophic Cardiomyopathy: The HCM-AF-Risk Model.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) patients have a high incidence of atrial fibrillation (AF) and increased stroke risk, even with low CHA2DS2-VASc (congestive heart failure, hypertension, age diabetes, previous stroke/transient ischemic attack) scores. Hence, there is a need to understand the pathophysiology of AF/stroke in HCM. In this retrospective study, we develop and apply a data-driven, machine learning-based method to identify AF cases, and clinical/imaging features associated with AF, using electronic health record data. METHODS: HCM patients with documented paroxysmal/persistent/permanent AF (n = 191) were considered AF cases, and the remaining patients in sinus rhythm (n = 640) were tagged as No-AF. We evaluated 93 clinical variables; the most informative variables useful for distinguishing AF from No-AF cases were selected based on the 2-sample t test and the information gain criterion. RESULTS: We identified 18 highly informative variables that are positively (n = 11) and negatively (n = 7) correlated with AF in HCM. Next, patient records were represented via these 18 variables. Data imbalance resulting from the relatively low number of AF cases was addressed via a combination of oversampling and undersampling strategies. We trained and tested multiple classifiers under this sampling approach, showing effective classification. Specifically, an ensemble of logistic regression and naïve Bayes classifiers, trained based on the 18 variables and corrected for data imbalance, proved most effective for separating AF from No-AF cases (sensitivity = 0.74, specificity = 0.70, C-index = 0.80). CONCLUSIONS: Our model (HCM-AF-Risk Model) is the first machine learning-based method for identification of AF cases in HCM. This model demonstrates good performance, addresses data imbalance, and suggests that AF is associated with a more severe cardiac HCM phenotype.

INTRODUCTION: Les patients atteints d'une cardiomyopathie hypertrophique (CMH) présentent une forte incidence de fibrillation auriculaire (FA) et un risque accru d'accident vasculaire cérébral (AVC), malgré des scores CHA2DS2-VASc (congestive heart failure, hypertension, age diabetes, previous stroke/transient ischemic attack, c'est-à-dire : insuffisance cardiaque congestive, hypertension, âge, diabète, AVC ou accident ischémique transitoire antérieur) faibles. Par conséquent, il est nécessaire de comprendre la physiopathologie de la FA et de l'AVC en présence d'une CMH. Dans la présente étude rétrospective, nous avons élaboré et appliqué une méthode d'apprentissage automatique dirigée sur les données pour déterminer les cas de FA, et les caractéristiques cliniques/d'imagerie associées à la FA, à l'aide des données des dossiers de santé électroniques. MÉTHODES: Nous avons considéré les patients atteints d'une CMH qui ont une FA paroxystique/persistante/permanente documentée (n = 191) comme des cas de FA, et avons étiqueté les autres patients en rythme sinusal (n = 640) comme des cas sans FA. Nous avons évalué 93 variables cliniques; nous avons sélectionné les variables les plus informatives qui sont utiles pour distinguer les cas de FA des cas sans FA en fonction du test t pour deux échantillons et du critère de gain d'information. RÉSULTATS: Nous avons relevé 18 variables hautement informatives qui ont une corrélation positive (n = 11) et une corrélation négative (n = 7) avec la FA en présence d'une CMH. Ensuite, nous avons représenté les dossiers des patients au moyen de ces 18 variables. Nous avons remédié au déséquilibre des données, qui résulte du nombre relativement faible de cas de FA, grâce à une combinaison de stratégies de suréchantillonnage et de sous-échantillonnage. Nous avons formé et testé de nombreux classificateurs selon cette approche d'échantillonnage, qui montre une classification efficace. Particulièrement, un ensemble de régression logistique et de classificateurs bayésiens naïfs formés en fonction des 18 variables et corrigés en fonction du déséquilibre des données s'est révélé le plus efficace pour séparer les cas de FA des cas sans FA (sensibilité = 0,74, spécificité = 0,70, indice C = 0,80). CONCLUSIONS: Notre modèle (modèle de risque de CMH-FA) est la première méthode d'apprentissage automatique qui sert à déterminer les cas de FA en présence de CMH. Ce modèle permet de démontrer une bonne performance, de remédier au déséquilibre des données, et de croire que la FA est associée à un phénotype grave de CMH.

Role-play of real patients improves the clinical performance of medical students.

BACKGROUND: This study aimed to evaluate whether the role-play (RP) of real patients by medical students as part of interactive clinical reasoning training can improve medical students' clinical performance. METHODS: A total of 26 medical students volunteered to portray real patients within this program and were treated as the RP group while the other 72 students as the non-RP group. In the interactive morning meeting, the medical students practiced how to approach the RP student as if they were encountering a real patient. All students were evaluated by mini-clinical evaluation exercises (mini-CEX) before and after this training program. RESULTS: We found that all students had an increased total mini-CEX score after 4-week training, especially for interviewing skills. Notably, after training, the RP students had significantly elevated total mini-CEX scores (51.23 ± 1.06 vs 53.12 ± 1.11, p = 0.028), and for counselling (7.15 ± 0.14 vs 7.54 ± 0.18, p = 0.015) and overall clinical competence (7.27 ± 0.15 vs 7.65 ± 0.16, p = 0.030). In contrast, the non-RP students had lower scores compared with the RP group, as revealed by both the pre- and post-training tests. Moreover, their mini-CEX scores were not improved after training. CONCLUSION: Medical students who were motivated to RP real patients had better performance scores than those who did not. In addition, RP can enhance their counselling skills and clinical competences.

Exercise physiology of the left atrium: quantity and timing of contribution to cardiac output.

Although the phases of left atrial (LA) function at rest have been studied, the physiological response of the LA to exercise is undefined. This study defines the exercise behavior of the normal left atrium by quantitating its volumetric response to graded effort. Healthy subjects (n = 131) were enrolled from the Health eHeart cohort. Echocardiograms were obtained at baseline and during ramped supine bicycle exercise. Left ventricular volume index, stroke volume index (LVSVI), left atrial end-systolic volume index (LAESVI), left atrial end-diastolic volume index (LAEDVI), and left atrial emptying fraction (LAEF), reservoir fraction, and conduit fraction were analyzed. The LVSVI increased with low exercise but did not increase further with peak exercise; cardiac output increased through the agency of heart rate. The LAESVI and LAEDVI decreased and the LAEF increased with exercise. As a result, the LA reservoir volume index was static throughout exercise. The reservoir fraction decreased from 46% at rest to 40% with low exercise (P < 0.001) in association with increased LVSVI and remained similar at peak exercise. The conduit volume index increased from 20 mL/m2 at rest to 24 mL/m2 at low exercise and stayed the same at peak exercise. Similarly, the conduit fraction increased from 54% at rest to 60% at low exercise (P < 0.001) and did not change further with peak exercise. Although atrial function increased with exercise, the major contribution to the augmentation of LV stroke volume is LA conduit fraction, a marker of active ventricular relaxation. Furthermore, the major determinant of raising cardiac output during high-level exercise is heart rate.NEW & NOTEWORTHY Diseases of the left atrium (LA) are major sources of disability (e.g., strokes and fatigue), but its exercise physiology has been unstudied. Such knowledge may allow early recognition of disease and suggest therapies. We show that in normal subjects, low-level exercise decreases LA volume and increases its ejection fraction. However, these changes offset each other volumetrically, and the contribution to LV filling from a full to an empty LA (reservoir function) is static. Higher levels of exercise do not change LA reservoir contribution. Blood flowing directly from the pulmonary vein to LV (conduit flow) impelled by augmented LV active relaxation (suction) is the major source of a modest increase in LV stroke volume. The major source of increased cardiac output with exercise is heart rate. During all stages of exercise, the LA works hard but only to keep up. We believe that our findings provide an additional set of benchmarks through which to quantitate LA pathology and gauge its progression.

Feasibility of the transcatheter mitral valve repair for patients with severe mitral regurgitation and endangered heart failure.

BACKGROUND: The transcatheter edge-to-edge mitral valve repair using MitraClip has been a safe and effective treatment for severe mitral regurgitation (MR). In patients with severe MR and cardiogenic shock under hemodynamic supporting devices, emergent surgical mitral valve interventions carry extremely high risk for peri-operative morbidities and mortalities. The feasibility and efficacy of emergent MitraClip to rescue patients in critical conditions remains elucidate. METHODS: Patients with severe MR and high or prohibitive surgical risks were referred for MitraClip procedures. Emergent MitraClip were conducted in patients with unstable hemodynamics and under mechanical or inotropic support. The hemodynamic measures, transthoracic echocardiography, transesophageal echocardiography, and blood tests were performed before MitraClip procedures. Procedural success was defined as having mild mitral regurgitation immediately after MitraClip, and patients were free from in-hospital mortality. Clinical and echocardiographic outcomes were followed by telephones and clinics. RESULTS: Among 50 consecutive patients (74.7 ± 11.2 years, 74% male), 8 emergent MitraClip procedures were conducted to rescue patients with cardiogenic shock. Extracorporeal membrane oxygenations were used in 2 patients and intra-aortic balloon pump were applied in 4 patients (50%). Compare to those who underwent elective procedures, patients underwent emergent MitraClip had higher surgical risk profile (EuroSCORE II 34.8% vs 5.1% and STS score 19.7% vs 5.1%), poorer renal function and higher right atrial pressure. There was no peri-procedural death, myocardial infarction, stroke or any adverse events requiring emergent cardiac surgery in both groups. Mild mitral regurgitation was achieved in 87.5% patients from the emergent group and 95.2% patients in the elective group (P = 0.514). The Kaplan-Meier analysis showed patients who underwent emergent procedures have poorer long-term survival rate as compare to those who received elective procedures. (P value = 0.008). CONCLUSION: When open-heart surgery is not feasible, trans-catheter mitral valve repair is an alternative way to rescue patients in cardiogenic shock status.

Sustained effects of faculty leadership development modules for clinical instructors of core competences education in Taiwan: a four-year explanatory case study.

BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) core competencies (CC) in general medicine-based primary care are essential for junior medical trainees. In this country, a regular faculty development (FD) program aimed at training faculty in instructing (teaching and assessing) these CC had operated. However, leadership was not emphasized. In a new intervention module, the roles and associated responsibilities of clinical instructors to conduct, design, and lead CC-based education were emphasis. AIMS: This follow-up explanatory case study compares the effectiveness of intervention module with that of the previous regular module. METHODS: The regular group (n = 28) comprised clinical instructors who participated in the FD module during the 2013-2014 year while the intervention group (n = 28) was composed of 2015-2016 participants. Prior to the formal (hands-on) training, participants in the intervention group were asked to study the online materials of the regular module. These participants then received a 30-h hands-on training in conducting, designing, and leading skills. Finally, they prepared a 10-h reflective end-of-module presentation of their real-world practices. RESULTS: Following the training, a higher degree improvement in participants self-reported familiarity with CC education, self-confidence in their ability to deliver CC education and sustained involve CC education were noted among the intervention FD group, compared with the regular FD group. In the intervention group, senior academicians (associate and full professor) are more substantially involved in designing and leading CC-based courses than junior academicians (lecturers and assistant professors). Among non-teaching award winners of in the intervention FD group, the follow-up degree of sustained involvement in delivering, designing and leading CC-based courses was significantly higher than that of the regular group. CONCLUSIONS: Our study demonstrated that leadership training in the intervention FD modules substantially motivated clinical instructors to become leaders in CC education.

Higher incidence of vasodilator-induced left ventricular cavity dilation by PET when compared to treadmill exercise-ECHO in hypertrophic cardiomyopathy.

BACKGROUND: Vasodilator-induced transient left ventricular cavity dilation (LVCD) by positron emission tomography (PET) is associated with microvascular dysfunction in hypertrophic cardiomyopathy (HCM). Here we assessed whether HCM patients who develop LVCD by PET during vasodilator stress also develop LV cavity dilation by echocardiography (ECHO-LVCD) following exercise stress. METHODS: A retrospective analysis of cardiac function and myocardial blood flow (MBF) was conducted in 108 HCM patients who underwent perfusion-PET and exercise-ECHO as part of their clinical evaluation. We performed a head-to-head comparison of LV volumes and ejection fraction (LVEF) at rest and stress (during vasodilator stress, post-exercise), in 108 HCM patients. A ratio > 1.13 of stress to rest LV volumes was used to define PET-LVCD, and a ratio > 1.17 of stress to rest LVESV was used to define ECHO-LVCD. Patients were divided into 2 groups based on the presence/absence of PET-LVCD. MBF and myocardial flow reserve were quantified by PET, and global longitudinal strain (GLS) was assessed by ECHO at rest/stress in the two groups. RESULTS: PET-LVCD was observed in 51% (n = 55) of HCM patients, but only one patient had evidence of ECHO-LVCD (ratio = 1.36)-this patient also had evidence of PET-LVCD (ratio = 1.20). The PET-LVCD group had lower PET-LVEF during vasodilator stress, but ECHO-LVEF increased in both groups post-exercise. The PET-LVCD group demonstrated higher LV mass, worse GLS at rest/stress, and lower myocardial flow reserve. Incidence of ischemic ST-T changes was higher in the PET-LVCD group during vasodilator stress (42 vs 17%), but similar (30%) in the two groups during exercise. CONCLUSION: PET-LVCD reflects greater degree of myopathy and microvascular dysfunction in HCM. Differences in the cardiac effects of exercise and vasodilators and timing of stress-image acquisition could underlie discordance in ischemic EKG changes and LVCD by ECHO and PET, in HCM.

Sex-specific cardiac phenotype and clinical outcomes in patients with hypertrophic cardiomyopathy.

BACKGROUND: It is unknown whether sex-specific differences in mortality observed in HCM are due to older age of women at presentation, or whether women have greater degree of LV myopathy than men. METHODS: We retrospectively compared clinical/imaging characteristics and outcomes between women and men in our overall cohort composed of 728 HCM patients, and in an age-matched subgroup comprised of 400 age-matched patients. We examined sex-specific differences in LV myopathy, and dissected the influence of age and sex on outcomes. LV myopathy was assessed by measuring LV mass, LVEF, global peak longitudinal systolic strain (LV-GLS), diastolic function (E/A, E/e'), late gadolinium enhancement (LV-LGE) and myocardial blood flow (MBF) at rest/stress. The primary endpoint was a composite outcome, comprising heart failure (HF), atrial fibrillation (AFib), ventricular tachycardia/fibrillation (VT/VF) and death; individual outcomes were defined as the secondary endpoint. RESULTS: Women in the overall cohort were older by 6 years. Women were more symptomatic and more likely to have obstructive HCM. Women had smaller LV cavity size, stroke volume and LV mass, higher indexed maximum wall thickness (IMWT), more hyperdynamic LVEF and higher/similar LV-GLS. Women had similar LV-LGE and E/A, but higher E/e' and rest/stress MBF. Female sex was independently associated with the composite outcome in the overall cohort, and with HF in the overall cohort and age-matched subgroup after adjusting for obstructive HCM, LA diameter, LV-GLS. CONCLUSIONS: Our results suggest that sex-specific differences in LV geometry, hyper-contractility and diastolic function, not greater degree of LV myopathy, contribute to a higher, age-independent risk of diastolic HF in women with HCM.

Perturbations of pulsatile hemodynamics and clinical outcomes in patients with acute heart failure and reduced, mid-range or preserved ejection fraction.

BACKGROUND: Heart failure with mid-range ejection fraction (HFmrEF) has been proposed as a new phenotype of heart failure. We therefore investigated the pulsatile hemodynamic characteristics and outcomes in patients with HFmrEF, in comparison with those with reduced (HFrEF) or preserved (HFpEF) ejection fraction. METHODS: The study was composed of two cohorts of patients hospitalized due to acute heart failure. Pulsatile hemodynamic measures, including carotid-femoral pulse wave velocity (cf-PWV), carotid pulse pressure (cPP), amplitude of the backward pressure wave (Pb) and carotid augmentation index (cAIx), were recorded on admission and before discharge in Cohort A (n = 230, mean age 69.9 ±15.4 years), and long-term follow-up was performed in Cohort B (n = 2677, mean age 76.3 ± 33.4 years). RESULTS: In Cohort A, patients with HFmrEF had persistently greater cf-PWV, cPP, Pb, and cAI than those with HFrEF, both on admission and before discharge. In contrast, patients with HFmrEF and HFpEF had similar pulsatile hemodynamic characteristics. In cohort B, patients with HFmrEF and HFrEF had similar three-year mortality rates and both were significantly higher than that in patients with HFpEF (both P values < 0.05). CONCLUSIONS: Patients with HFmrEF were characterized by a worse left ventricular systolic function than patients with HFpEF and excessive wave reflections than patients with HFrEF. Future studies are required to confirm that the unfavorable ventriculo-arterial coupling in HFmrEF might play a role in the pathogenesis of high long-term mortality in these patients.

Electrophysiological and clinical characteristics of catheter ablation for isolated left side atrial tachycardia over a 10-year period.

AIMS: Most left atrial tachycardia (LAT) is associated with atrial fibrillation (AF). The clinical and electrophysiological characteristics and outcomes of LAT without AF have not been investigated. This study sought to determine the long-term ablation outcomes and predictors of recurrence of isolated LAT. METHODS: This is a single-center study of consecutive patients with isolated LAT. Atrial arrhythmia recurrence was determined from follow-up records of patients who underwent LAT ablation from 2008 to 2017. Clinical and electrophysiologic characteristics associated with atrial arrhythmia recurrence were identified. RESULTS: A total of 50 patients (53 ± 19 years, 46% male) with 59 LAT (1.16 ± 0.47 per patient) were enrolled. Over a mean follow-up of 37 ± 33 months, atrial arrhythmia recurrence occurred in 22 (44%) patients, 11 with atrial tachycardia (AT) only, five with AF only, and six with concurrent AT and AF. The incidence of pulmonary vein (PV) origins increased significantly in the repeat procedure (P = 0.036). Multivariate analysis identified left ventricular ejection fraction (LVEF) as the only predictor of any atrial arrhythmia recurrence and LAT recurrence, while smoking and identified macroreentrant LAT in the index procedure predicted AF recurrence. CONCLUSION: This study demonstrated a higher rate of atrial arrhythmia recurrence, including AF, among patients with initially isolated LAT. A lower LVEF predicted any atrial arrhythmia and LAT recurrence, whereas smoking and index macroreentrant AT mechanism predicted long-term AF. PV ATs were frequently observed in recurrent patients irrespective of index procedure origin.

Identifying Ventricular Arrhythmias and Their Predictors by Applying Machine Learning Methods to Electronic Health Records in Patients With Hypertrophic Cardiomyopathy (HCM-VAr-Risk Model).

Clinical risk stratification for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HC) employs rules derived from American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines or the HCM Risk-SCD model (C-index ∼0.69), which utilize a few clinical variables. We assessed whether data-driven machine learning methods that consider a wider range of variables can effectively identify HC patients with ventricular arrhythmias (VAr) that lead to SCD. We scanned the electronic health records of 711 HC patients for sustained ventricular tachycardia or ventricular fibrillation. Patients with ventricular tachycardia or ventricular fibrillation (n = 61) were tagged as VAr cases and the remaining (n = 650) as non-VAr. The 2-sample ttest and information gain criterion were used to identify the most informative clinical variables that distinguish VAr from non-VAr; patient records were reduced to include only these variables. Data imbalance stemming from low number of VAr cases was addressed by applying a combination of over- and undersampling strategies. We trained and tested multiple classifiers under this sampling approach, showing effective classification. We evaluated 93 clinical variables, of which 22 proved predictive of VAr. The ensemble of logistic regression and naïve Bayes classifiers, trained based on these 22 variables and corrected for data imbalance, was most effective in separating VAr from non-VAr cases (sensitivity = 0.73, specificity = 0.76, C-index = 0.83). Our method (HCM-VAr-Risk Model) identified 12 new predictors of VAr, in addition to 10 established SCD predictors. In conclusion, this is the first application of machine learning for identifying HC patients with VAr, using clinical attributes. Our model demonstrates good performance (C-index) compared with currently employed SCD prediction algorithms, while addressing imbalance inherent in clinical data.

Hypertrophic Cardiomyopathy Patients With Paroxysmal Atrial Fibrillation Have a High Burden of Left Atrial Fibrosis by Cardiac Magnetic Resonance Imaging.

OBJECTIVES: This study hypothesized that paroxysmal atrial fibrillation (PAF) reflects the presence of a more severe cardiac hypertrophic cardiomyopathy (HCM) phenotype. BACKGROUND: HCM is characterized by myocyte hypertrophy, fibrosis, and a high prevalence of PAF. It is currently unresolved whether atrial fibrillation (AF) is a marker or a mediator of adverse outcomes in HCM. METHODS: This study retrospectively examined 45 HCM patients who underwent cardiovascular magnetic resonance (CMR) imaging in sinus rhythm. The function of all 4 cardiac chambers was assessed, as well as late gadolinium enhancement (LGE) in the left atrium (LA) and left ventricle (LV), as indicators of fibrosis. A fat-saturated, 3-dimensional inversion recovery-prepared, fast-spoiled, gradient-recalled echo sequence, and the image intensity ratio method were used to measure LA-LGE; LGE in the LV was quantified using a semi-automated threshold technique. RESULTS: HCM patients (n = 45) were divided into 2 groups (PAF, no AF) based on history of PAF. All HCM patients had LGE in the LA posterior wall. The PAF group (n = 18) had higher LA volume, a lower LA ejection fraction, a lower global peak longitudinal LA strain (PLAS), and a higher amount of LA-LGE compared with the no AF group (n = 27). A modest inverse association was noted between the LA ejection fraction, PLAS, and LA-LGE; a positive association was present between LV-LGE and LA-LGE. The PAF group had lower ejection fractions in the LV, right atrium, and right ventricle compared with those in the no AF group. CONCLUSIONS: PAF is associated with a greater degree of structural LA remodeling and global myopathy, which suggests a more severe cardiac HCM phenotype.

Low Left Atrial Strain Is Associated With Adverse Outcomes in Hypertrophic Cardiomyopathy Patients.

BACKGROUND: Paroxysmal atrial fibrillation (PAF) and left atrial (LA) structural remodeling are common in hypertrophic cardiomyopathy (HCM) patients, who are also at risk for adverse cardiovascular outcomes. OBJECTIVE: We assessed whether PAF and/or LA remodeling was associated with adverse outcomes in HCM. METHODS: We retrospectively studied 45 HCM patients with PAF (PAF group) and 59 HCM patients without atrial fibrillation (AF; no-AF group). LA/left ventricular (LV) function and mechanics were assessed by echocardiography. Patients were followed for development of the composite endpoint comprising heart failure, stroke, and death. RESULTS: Clinical/demographic characteristics, degree of LV hypertrophy, and E/e' were similar in the two groups The PAF group had significantly higher LA volume, but lower LA ejection fraction (LAEF), LA contractile, and reservoir strain/strain rate than the no-AF group. During follow-up, 27 patients developed the composite endpoint. Incidence of the composite endpoint was similar in the two groups. Absolute values of 23.8% for reservoir strain and 10.2% for conduit strain were the best cutoffs for the composite endpoint, using receiver operating characteristic analysis. Kaplan-Meier survival analysis showed lower event-free survival in patients with reservoir strain ≤23.8% or conduit strain ≤10.2%. Univariate Cox analysis revealed an association between female sex, LAEF, LA reservoir/conduit strain, and LV global longitudinal strain with the composite endpoint. The association between LA reservoir/conduit strain and the composite endpoint persisted after controlling for age, sex, LAEF, and LV global longitudinal strain. CONCLUSIONS: In this pilot HCM patient study, PAF was associated with a greater degree of LA myopathy, and low LA reservoir and conduit strain were associated with higher risk for adverse cardiovascular outcomes.

Comparison of two software systems for quantification of myocardial blood flow in patients with hypertrophic cardiomyopathy.

BACKGORUND: Quantification of myocardial blood flow (MBF) by positron emission tomography (PET) is important for investigation of angina in hypertrophic cardiomyopathy (HCM). Several software programs exist for MBF quantification, but they have been mostly evaluated in patients (with normal cardiac geometry), referred for evaluation of coronary artery disease (CAD). Software performance has not been evaluated in HCM patients who frequently have hyperdynamic LV function, LV outflow tract (LVOT) obstruction, small LV cavity size, and variation in the degree/location of LV hypertrophy. AIM: We compared results of MBF obtained using PMod, which permits manual segmentation, to those obtained by FDA-approved QPET software which has an automated segmentation algorithm. METHODS: 13N-ammonia PET perfusion data were acquired in list mode at rest and during pharmacologic vasodilation, in 76 HCM patients and 10 non-HCM patients referred for evaluation of CAD (CAD group.) Data were resampled to create static, ECG-gated and 36-frame-dynamic images. Myocardial flow reserve (MFR) and MBF (in ml/min/g) were calculated using QPET and PMod softwares. RESULTS: All HCM patients had asymmetric septal hypertrophy, and 50% had evidence of LVOT obstruction, whereas non-HCM patients (CAD group) had normal wall thickness and ejection fraction. PMod yielded significantly higher values for global and regional stress-MBF and MFR than for QPET in HCM. Reasonably fair correlation was observed for global rest-MBF, stress-MBF, and MFR using these two softwares (rest-MBF: r = 0.78; stress-MBF: r = 0.66.; MFR: r = 0.7) in HCM patients. Agreement between global MBF and MFR values improved when HCM patients with high spillover fractions (> 0.65) were excluded from the analysis (rest-MBF: r = 0.84; stress-MBF: r = 0.72; MFR: r = 0.8.) Regionally, the highest agreement between PMod and QPET was observed in the LAD territory (rest-MBF: r = 0.82, Stress-MBF: r = 0.68) where spillover fraction was the lowest. Unlike HCM patients, the non-HCM patients (CAD group) demonstrated excellent agreement in MBF/MFR values, obtained by the two softwares, when patients with high spillover fractions were excluded (rest-MBF: r = 0.95; stress-MBF: r = 0.92; MFR: r = 0.95). CONCLUSIONS: Anatomic characteristics specific to HCM hearts contribute to lower correlations between MBF/MFR values obtained by PMod and QPET, compared with non-HCM patients. These differences indicate that PMod and QPET cannot be used interchangeably for MBF/MFR analyses in HCM patients.