Challenge in mitral valve intervention: Super-elongated anterior and diminutive posterior mitral valve.

Diminutive posterior mitral valve leaflet with an extremely elongated anterior leaflet is a rare phenomenon. We share such a case discovered in an 82-year-old patient with severe, symptomatic mitral regurgitation. LA, left atrium; LV, left ventricle; MR, mitral regurgitation.

Prevalence of dilated mid-ascending aorta in individuals 15 years and older: In search of optimal diagnostic criteria and their effect on the burden of disease.

BACKGROUND: Controversy regarding the definition of the upper limit of normal (ULN) for dilated mid-ascending aorta (mAA) stems from variation in criteria, based on several small-sized studies with small datasets of normal subjects (DONS). The present study was carried out to demonstrate this variation in the prevalence of mAA dilation and to identify the optimal definition by creating the largest DONS. METHODS: Echocardiographic studies of patients ≥ 15 years of age performed at a large tertiary care center over 4 years (n = 49,330) were retrospectively evaluated. The leading-edge-to-leading-edge technique was used to measure the mAA in diastole. The largest-to-date DONS (n = 2334) was created, including those who were normal on medical record review, did not have any of the 28 causes of dilated aorta, and had normal echocardiograms. Because age had the strongest correlation with mAA (multivariate adjusted R2 = 0.26), as compared with sex, height, and weight, we created a new ULN based on the DONS with narrow age stratification (10-year intervals). RESULTS: The prevalence of dilated mAA varied between 17% and 23% when absolute criteria were used with sex stratification, and it varied between 6% and 11% when relative criteria (relative to age, body surface area, and sex) were used. Based on new criteria from the DONS, it was 7.6%, with a ULN of 3.07-3.64 cm in women and 3.3-3.91 cm in men. CONCLUSIONS: These data demonstrate the undesirable variation in the prevalence of dilated mAA based on prior criteria and propose a new ULN for dilated mAA.

Refining the upper limit of normal for the ascending aorta: In search of optimal criteria -- a large database study of normal individuals.

OBJECTIVES: The cutoff for dilated mid-ascending aorta (mAA) is controversial and has several definitions. The present study was carried out to determine the prevalence of mAA dilation based on published definitions and to identify the optimal cutoff. METHODS: Echocardiographic studies of patients >15 years of age performed at a large tertiary care center over 4 years, n = 49,330, were retrospectively evaluated. Leading-edge-to-leading-edge technique was used to measure the mAA in diastole. Several cutoff criteria were included. In addition, we defined normals in our database as those who, after 28 causes of dilated aorta were excluded, were normal both clinically and echocardiographically (n = 2334). RESULTS: The mean age was 64.2 ± 17.1 years, and 31.5% were men. The prevalence of dilated mAA based on absolute criteria with sex stratification varied between 17% and 23% and based on relative criteria (to age, body surface area, and sex) varied between 6% and 11%. It further decreased to 7.6% on the addition of narrow age stratification (10 year intervals) performed on normals in our database. The multivariate adjusted R2 (for variation in mAA diameter) was 0.25 for age, decreasing to 0.12 for weight and 0.07 for sex and height. CONCLUSIONS: The lowest prevalence of 7.6% probably represents the optimal cutoff for dilated mAA because it includes age, which explains most of the variation in mAA, in narrow (10 year) intervals only performed in our normals, which represents the largest sample size to date.

Prolonged post-differentiation culture influences the expression and biophysics of Na+ and Ca2+ channels in induced pluripotent stem cell-derived ventricular-like cardiomyocytes.

Several studies have been reported in various domains from induction methods to utilities of somatic cell pluripotent reprogramming. However, one of the major struggles facing the research field of induced pluripotent stem cell (iPSC)-derived target cells is the lack of consistency in observations. This could be due to variety of reasons including varied culture periods post-differentiation. The cardiomyocytes (CMs) derived from iPSCs are commonly studied and proposed to be utilized in the comprehensive in vitro proarrhythmia initiative for drug safety screening. As the influence of varied culture periods on the electrophysiological properties of iPSC-CMs is not clearly known, using whole-cell patch clamp technique, we compared two groups of differentiated ventricular-like iPSC-CMs that are cultured for 10 to 15 days (D10-15) and more than 30 days (≥ D30) both under current and voltage clamps. The prolonged culture imparts increased excitability with high-frequency spontaneous action potentials, robust increase in the magnitude of peak Na+ current density, relatively shallow inactivation kinetics of Na+ channels, faster recovery from inactivation, and augmented Ca2+ current density. Quantitative real-time PCR studies of α-subunit transcripts showed enhanced mRNA expression of SCN1A, SCN5A Na+ channel subtypes, and CACNA1C, CACNA1G, and CACNA1I Ca2+ channel subtypes, in ≥ D30 group. Conclusively, the prolonged culture of differentiated iPSC-CMs affects the excitability, single-cell electrophysiological properties, and ion channel expressions. Therefore, following standard periods of culture across research studies while utilizing ventricular-like iPSC-CMs for in vitro health/disease modeling to study cellular functional mechanisms or test high-throughput drugs' efficacy and toxicity becomes crucial.

Modern Imaging Techniques in Cardiomyopathies.

Modern advanced imaging techniques have allowed increasingly more rigorous assessment of the cardiac structure and function of several types of cardiomyopathies. In contemporary cardiology practice, echocardiography and cardiac magnetic resonance imaging are widely used to provide a basic framework in the evaluation and management of cardiomyopathies. Echocardiography is the quintessential imaging technique owing to its unique ability to provide real-time images of the beating heart with good temporal resolution, combined with its noninvasive nature, cost-effectiveness, availability, and portability. Cardiac magnetic resonance imaging provides data that are both complementary and uniquely distinct, thus allowing for insights into the disease process that until recently were not possible. The new catchphrase in the evaluation of cardiomyopathies is multimodality imaging, which is purported to be the efficient integration of various methods of cardiovascular imaging to improve the ability to diagnose, guide therapy, or predict outcomes. It usually involves an integrated approach to the use of echocardiography and cardiac magnetic resonance imaging for the assessment of cardiomyopathies, and, on occasion, single-photon emission computed tomography and such specialized techniques as pyrophosphate scanning.

Aging-related increase in store-operated Ca2+ influx in human ventricular fibroblasts.

Senescence-related fibrosis contributes to cardiac dysfunction. Profibrotic processes are Ca2+ dependent. The effect of aging on the Ca2+ mobilization processes of human ventricular fibroblasts (hVFs) is unclear. Therefore, we tested whether aging altered intracellular Ca2+ release and store-operated Ca2+ entry (SOCE). Disease-free hVFs from 2- to 63-yr-old trauma victims were assessed for cytosolic Ca2+ dynamics with fluo 3/confocal imaging. Angiotensin II or thapsigargin was used to release endoplasmic reticulum Ca2+ in Ca2+-free solution; CaCl2 (2 mM) was then added to assess SOCE, which was normalized to ionomycin-induced maximal Ca2+. The angiotensin II experiments were repeated after phosphoenolpyruvate pretreatment to determine the role of energy status. The expression of genes encoding SOCE-related ion channel subunits was assessed by quantitative PCR, and protein expression was assessed by immunoblot analysis. Age groups of <50 and ≥50 yr were compared using unpaired t-test or regression analysis. Ca2+ release by angiotensin II or thapsigargin was not different between the groups, but SOCE was significantly elevated in the ≥50-yr group. Regression analysis showed an age-dependent phosphoenolpyruvate-sensitive increase in SOCE of hVFs. Aging did not alter the mRNA expression of SOCE-related genes. The profibrotic phenotype of hVFs was evident by sprouty1 downregulation with age. Thus, an age-associated increase in angiotensin II- and thapsigargin-induced SOCE occurs in hVFs, independent of receptor mechanisms or alterations of mRNA expression level of SOCE-related ion channel subunits but related to the cellular bioenergetics status. Elucidation of mechanisms underlying enhanced hVF SOCE with aging may refine SOCE targets to limit aging-related progression of Ca2+-dependent cardiac fibrosis. NEW & NOTEWORTHY Human ventricular fibroblasts exhibit an age-related increase in store-operated Ca2+ influx induced by angiotensin II, an endogenous vasoactive hormone, or thapsigargin, an inhibitor of endoplasmic reticulum Ca2+-ATPase, independent of receptor mechanisms or genes encoding store-operated Ca2+ entry-related ion channel subunits. Selective inhibition of this augmented store-operated Ca2+ entry could therapeutically limit aging-related cardiac fibrosis.

Diagnostic accuracy of bicuspid aortic valve by echocardiography.

BACKGROUND: Echocardiography is regarded as the gold standard for diagnosis of bicuspid aortic valve (BAV), yet diagnostic accuracy has been evaluated previously only in single-center studies. We systematically evaluated the accuracy of BAV diagnosis in a large healthcare system of multiple echocardiography laboratories. METHODS AND RESULTS: Aurora Health Care is a multihospital, multi-clinic system across the state of Wisconsin encompassing 33 inpatient and outpatient echocardiography laboratories with 39 cardiologist readers and 72 sonographers. As all laboratories store echocardiograms in one database, we queried all patients with "bicuspid aortic valve" diagnosis on echocardiography. Echocardiograms were classified as "BAV" or "possible BAV" based on initial reader confidence. An expert review panel categorized each as BAV, no BAV, or Indeterminate. Of the 745 cases identified, 589 (79.1%, initial reader interpretation: n = 494 "BAV," n = 95 "possible") were BAV. A high level of agreement (84%) was present in BAV diagnosis. There were 156 (20.9%) echocardiograms that were no BAV (8.4%) or Indeterminate (12.4%). We identified three common reasons for misdiagnosis: poor image quality (n = 70, 44.9%), leaflet calcium (n = 44, 28.2%), and oblique axis imaging (n = 33, 21.1%). A clear reason for misclassification was not elucidated in nine cases (n = 9, 5.7%). CONCLUSIONS: This is the first study to evaluate BAV accuracy across a community health system with multiple echocardiography laboratories and a heterogeneous group of readers and sonographers. We establish a high degree of accuracy of echocardiography in BAV diagnosis and draw attention to common echocardiographic pitfalls that lead to BAV misclassification, highlighting opportunities for education and quality improvement.

Syncope in Young Women: Broadening the Differential Diagnosis.

Syncope is defined as a sudden transient loss of consciousness (TLOC) with concomitant loss of postural tone followed by spontaneous recovery. It is a subset of a broader class of medical conditions, including postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension, and neurally mediated syncope (NMS), that may result in TLOC. The overlap of these clinical conditions leads to confusion regarding syncope classification that can hinder evaluation strategies, and pose challenges for diagnosis and treatment, particularly in young women. In this article, we review POTS, orthostatic hypotension, and NMS with an emphasis on NMS. These diverse orthostatic clinical entities may be associated with syncope and are frequently observed in young, healthy women. The importance of considering NMS as a diagnosis of exclusion cannot be overstated. We report a series of three young, otherwise healthy women, initially diagnosed with NMS, whose clinical course evolved over time into more sinister diagnoses that were overlooked and associated with devastating clinical outcomes. These cases highlight the importance of maintaining a broad differential diagnosis when considering the diagnosis of NMS. Each case synopsis provides key clinical features that must be considered to avoid overlooking more serious clinical conditions.

Relationship of cardiac troponin to systolic global longitudinal strain in hypertrophic cardiomyopathy.

BACKGROUND: A high proportion of stable hypertrophic cardiomyopathy (HCM) patients have elevated serum cardiac troponin I (cTnI), but its clinical and echocardiographic determinants are unknown. Our objective was to determine the prevalence and clinical predictors of positive troponin (cTnI+) in a well-defined population of HCM patients using a highly sensitive assay. METHODS: We retrospectively interrogated medical records of 167 stable HCM patients from 1/2011 to 3/2014. cTnI >0.04 ng/mL was considered positive. RESULTS: Thirty-four percent were troponin-positive (median cTnI was 0.1 [0.07, 0.2] ng/dL). cTnI as a continuous variable correlated positively with maximal left ventricular wall thickness (LVT), maximal interventricular septal thickness, and global longitudinal strain (GLS) (P<.001). Unadjusted OR (95% CI) for positive troponin was 0.5 (0.3-0.9, P=.05) for obstructive HCM, 3.2 (1.7-5.9, P<.0001) for increased LVT, 0.3 (0.2-0.6, P<.0001) for -5% increase in GLS, 0.2 (0.04-0.9, P=.04) for moderate-to-severe mitral regurgitation, and 1.9 (0.9-3.9, P=.06) for implantable cardioverter defibrillator history. After adjusting for these variables, only maximum LVT (OR 2.5 [95% CI: 1.1-5.7, P=.02]) and GLS (OR 0.3 [95% CI: 0.2-0.6, P=.001]) were independent predictors. The percentage of patients with a positive cTnI increased from 19% to 24% and 57% across tertiles of LVT (P=.003) and decreased from 54% to 33% and 14% across tertiles of GLS (P<.0001). CONCLUSION: In this cohort of HCM patients, the association of reduced GLS and positive troponin was independent of LVT. Further studies are warranted to evaluate whether their combination adds prognostic value in identifying high-risk patients to define effective and early intervention strategies.

Chamber-specific differences in human cardiac fibroblast proliferation and responsiveness toward simvastatin.

Fibroblasts, the most abundant cells in the heart, contribute to cardiac fibrosis, the substrate for the development of arrythmogenesis, and therefore are potential targets for preventing arrhythmic cardiac remodeling. A chamber-specific difference in the responsiveness of fibroblasts from the atria and ventricles toward cytokine and growth factors has been described in animal models, but it is unclear whether similar differences exist in human cardiac fibroblasts (HCFs) and whether drugs affect their proliferation differentially. Using cardiac fibroblasts from humans, differences between atrial and ventricular fibroblasts in serum-induced proliferation, DNA synthesis, cell cycle progression, cyclin gene expression, and their inhibition by simvastatin were determined. The serum-induced proliferation rate of human atrial fibroblasts was more than threefold greater than ventricular fibroblasts with faster DNA synthesis and higher mRNA levels of cyclin genes. Simvastatin predominantly decreased the rate of proliferation of atrial fibroblasts, with inhibition of cell cycle progression and an increase in the G0/G1 phase in atrial fibroblasts with a higher sensitivity toward inhibition compared with ventricular fibroblasts. The DNA synthesis and mRNA levels of cyclin A, D, and E were significantly reduced by simvastatin in atrial but not in ventricular fibroblasts. The inhibitory effect of simvastatin on atrial fibroblasts was abrogated by mevalonic acid (500 µM) that bypasses 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition. Chamber-specific differences exist in the human heart because atrial fibroblasts have a higher proliferative capacity and are more sensitive to simvastatin-mediated inhibition through HMG-CoA reductase pathway. This mechanism may be useful in selectively preventing excessive atrial fibrosis without inhibiting adaptive ventricular remodeling during cardiac injury.

Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation.

Mitochondria are critical for maintaining normal cardiac function, and a deficit in mitochondrial energetics can lead to the development of the substrate that promotes atrial fibrillation (AF) and its progression. However, the link between mitochondrial dysfunction and AF in humans is still not fully defined. The aim of this study was to elucidate differences in the functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes and oxidative stress in right atrial tissue from patients without (non-AF) and with AF (AF) who were undergoing open-heart surgery and were not significantly different for age, sex, major comorbidities, and medications. The overall functional activity of the electron transport chain (ETC), NADH:O2 oxidoreductase activity, was reduced by 30% in atrial tissue from AF compared with non-AF patients. This was predominantly due to a selective reduction in complex I (0.06 ± 0.007 vs. 0.09 ± 0.006 nmol·min(-1)·citrate synthase activity(-1), P = 0.02) and II (0.11 ± 0.012 vs. 0.16 ± 0.012 nmol·min(-1)·citrate synthase activity(-1), P = 0.003) functional activity in AF patients. Conversely, complex V activity was significantly increased in AF patients (0.21 ± 0.027 vs. 0.12 ± 0.01 nmol·min(-1)·citrate synthase activity(-1), P = 0.005). In addition, AF patients exhibited a higher oxidative stress with increased production of mitochondrial superoxide (73 ± 17 vs. 11 ± 2 arbitrary units, P = 0.03) and 4-hydroxynonenal level (77.64 ± 30.2 vs. 9.83 ± 2.83 ng·mg(-1) protein, P = 0.048). Our findings suggest that AF is associated with selective downregulation of ETC activity and increased oxidative stress that can contribute to the progression of the substrate for AF.

ST-segment Elevation: Myocardial Infarction or Simulacrum?

A rapid diagnosis of ST-segment elevation myocardial infarction (STEMI) is mandatory for optimal treatment of an acute coronary syndrome. However, a small number of patients with suspected STEMI are afflicted with other medical conditions. These medical conditions are rare, but important clinical entities that should be considered when evaluating a STEMI alert. These conditions include coronary vasospasm, Takotsubo cardiomyopathy, coronary arteritis/aneurysm, myopericarditis, Brugada syndrome, left bundle branch block, early repolarization, aortic dissection, infective endocarditis with root abscess, subarachnoid hemorrhage, ventricular aneurysm after transmural myocardial infarction, and hemodynamically significant pulmonary embolism with right ventricular strain. Herein, we present several STEMI mimickers.

The Importance of the Medical Record: A Critical Professional Responsibility.

Comprehensive, detailed documentation in the medical record is critical to patient care and to a physician when allegations of negligence arise. Physicians, therefore, would be prudent to have a clear understanding of this documentation. It is important to understand who is responsible for documentation, what is important to document, when to document, and how to document. Additionally, it should be understood who owns the medical record, the significance of the transition to the electronic medical record, problems and pitfalls when using the electronic medical record, and how the Health Information Technology for Economic and Clinical Health Act affects healthcare providers and health information technology.

Why Patients Sue Physicians: Risk Management Strategies.

Physicians may head off allegations of negligence by developing a comprehensive understanding of why patients sue physicians and by appreciating what activities commonly lead to patient injury. With this knowledge, physicians can develop risk management strategies to reduce the likelihood of being named in a negligence lawsuit. We outline the common reasons why patients sue physicians, and what activities frequently lead to patient harm. The case examples emphasize the factors that can lead to allegations of negligence and patient harm.

Professional Liability Pertinent to Graduate Medical Education: The Intersection of Medical Education, Patient Care, and Law.

Physicians in training, nurse practitioners, physician assistants, attending physicians, and institutions that sponsor medical education are all at risk for potential professional liability issues. The unique relationship between healthcare providers and their sponsoring institution generates complex and evolving legal issues for all participants in medical education training. The law has played a great role integrating quality care and patient safety with excellent medical education for training physicians, while providing an avenue for relief when a medical error occurs. The intersection of law and medicine, while allowing for optimal medical education and patient care, exposes participating medical providers and the sponsoring institutions to specific professional liability issues. This article addresses these medical education settings and their potential professional liability issues.

Transient Apical Thickening Following Apical Ballooning Syndrome: A Case Series.

The authors describe transient apical thickening mimicking apical hypertrophic cardiomyopathy following apical ballooning syndrome. These findings are observed on multimodality cardiac imaging and appear to constitute a novel entity. Possible pathophysiologic mechanisms are explored.

Guiding the management of ventricular arrhythmias in patients with left ventricular noncompaction cardiomyopathy: a knowledge gap.

Left ventricular noncompaction (LVNC) is a cardiomyopathy that occurs due to an arrest of myocardial maturation during embryogenesis. The diagnostic echocardiographic features in individuals with LVNC include a thick, bilayered myocardium, prominent ventricular trabeculations, and deep intertrabecular recesses. Clinical features associated with LVNC vary in asymptomatic and symptomatic patients, and include the potential for heart failure, conduction defects (eg, left bundle branch block), supraventricular and ventricular arrhythmias, thromboembolic events, and sudden cardiac death. The authors report five cases that emphasize asymptomatic and apparently benign symptoms in patients with LVNC; despite normal physical examination and 12-lead electrocardiogram results, all of these cases unveiled potentially serious clinical consequences. These cases highlight the concern that LVNC patients with mild to moderate left ventricular systolic dysfunction, particularly in the presence of ventricular arrhythmias or a family history of sudden cardiac death, may need consideration for an implantable cardioverter defibrillator (ICD). All potential benefits of an ICD need to be balanced by the risk of device infection, lead and device malfunction, and potential for inappropriate shocks.