Search

A 48‐year‐old man from West Africa was evaluated for dyspnea. Echocardiography showed an echolucent mass at the left ventricular apex surrounded by a dense ridge of tissue, suggesting endomyocardial fibrosis (EMF). Doppler echocardiography showed restrictive hemodynamics and intramyocardial coronary blood flow at the hypertrophied apex, suggesting apical hypertrophic cardiomyopathy (ApHCM) with calcified thrombus. Cardiac magnetic resonance imaging showed a thickened myocardium with apical cavity obliteration and endomyocardial calcification, and gadolinium contrast demonstrated marked bright subendocardial and diffuse patchy intramyocardial hyperenhancement in the hypertrophied apical wall segment, confirming coexistence of EMF and ApHCM. Workup for known disorders of calcification was negative.

Postoperative atrial fibrillation (PoAF), a common complication of cardiac surgery, contributes significantly to morbidity, mortality, and increasing healthcare costs. Despite advances in surgical and medical management, the overall incidence of PoAF has not changed significantly, partly because of the limited understanding of mechanisms underlying acute surgery-related factors, such as myocardial injury, inflammation, sympathetic activation, and oxidative stress, which play an important role in the initiation of PoAF, whereas a preexisting atrial substrate appears to be more important in the maintenance of this dysrhythmia. Thus, in a majority of patients, PoAF becomes a manifestation of an underlying arrhythmogenic substrate that is unmasked after acute surgical stress. As such, the ability to identify which patients have this proarrhythmic substrate and are, therefore, at high risk for developing AF postoperatively, is important for the improved selection for prophylactic interventions, closer monitoring for complications, and establishing the probability of AF in the long term. This review highlights the role of the underlying substrate in promoting PoAF, proposed mechanisms, and the potential role of serum biomarkers to identify patients at risk for PoAF.

Timothy E. Paterick1*, Naila Choudhary2, Krishnaswamy Chandrasekaran3, A. Jamil Tajik5, and Jim Seward4 1Professor of Medicine, Director of Noninvasive Imaging, University of Florida College of Medicine, Jacksonville, FL, USA 2Cardiology, Fellow , University of Florida , College of Medicine, Jacksonville, FL, USA 3Professor of Medicine, Mayo College of Medicine, Rochester, MN, USA 4Professor of Adult and Pediatric Cardiology, Emeritus Nasseff Professor of Cardiology, Mayo Clinic, Rochester MN, USA 5Professor of Cardiology, Pediatrics and Adult Congenital Heart Disease, Aurora St. Luke’s Medical Center, Milwaukee WI, USA Journal of Exercise, Sports & Orthopedics Open Access Review Article

As the number of individuals, particularly the elderly, using herbal products with prescription drugs continues to grow, the risk for adverse interactions increases but remains poorly recognized. The true incidence and nature of adverse herb reactions or herb-drug interactions remains unknown since no postmarketing surveillance mechanism exists. Adverse events are greatly underreported, and information regarding safety mainly comes from case reports and suboptimally conducted studies in a limited number of healthy young volunteers or patients with limited comorbidities. Therefore, convincing evidence for the safety of herbal products in the elderly is lacking, and the true magnitude of problems that herb-drug interactions pose to public health, particularly in elderly patients with cardiovascular diseases, is not known. Since cardiovascular diseases themselves are life-threatening, necessitate use of multiple medications and occur in a population with extensive comorbidities, the risk of herb-drug and herb-disease interactions is not minor and cannot be ignored. This review addresses these concerns in an effort to raise awareness about the use of herbal medicine by the elderly and its potential adverse impact on the efficacy of prescription medications that can increase predisposition to catastrophic events such as major bleeding, inadequate anticoagulation leading to undesired clotting, transplant organ rejection and life-threatening cardiac arrhythmias. (J Patient-Centered Res Rev. 2015;2:174-191.)

Natural history of mitral valve prolapse (MVP) in the community is widely heterogeneous [(1)][1]. Prognosis in MVP ranges from normal life expectancy to subsets with high morbidity/excess mortality, including sudden cardiac death [(2)][2]. Although MVP is identified in a significant number of

Primary cardiac leiomyosarcoma is a rare tumor with poor prognosis. We present a 53-year-old female patient with biatrial leiomyosarcoma with inferior vena cava and coronary sinus involvement who underwent aggressive surgical resection with reconstruction of her left and right atrium and coronary sinus with bovine pericardium followed by adjuvant radiation therapy. She is living well with no recurrence 9 years after diagnosis.

Introduction Atrial fibrillation (AF) is highly prevalent in patients with heart failure with preserved ejection fraction (HFPEF). Both conditions are associated with shared risk factors including older age, hypertension and diastolic dysfunction. Given the significant phenotypical overlap between these diseases, it is difficult to disentangle outcomes. Therefore, a clinical tool for collective risk stratification is needed. Hypothesis We hypothesized that outcomes in patients with concomitant HFPEF and AF can be reliably stratified using a scoring system. To test this hypothesis, we developed HAD-AFIB, a comprehensive risk-stratification score based on risk factors for clinical use. Methods A random sample of 1,205 cases of concomitant HFPEF and AF was selected out of which 803 cases were used for the development of the predictive score and 402 were designated for validation. Using univariate Cox proportional hazards models, risk factors with significant contribution to mortality and heart failure (HF) hospitalization were identified. Forward stepwise selection along with clinical input was then used to identify multivariable models. Independent predictors for mortality and HF hospitalization were assigned scores based on hazard ratios. The score was then calculated and tested for association and fit in the validation cohort. Results Based on multivariate analyses, Hypertension, Age, Diastolic Dysfunction, Admission for HF, Filtration rate, Ischemic Heart Disease and BMI were selected as outcome predictors. The study cohort characteristics were: mean age at baseline of 74 ± 13 years, 601 (50%) males, 664 (55%) of patients were on two or fewer hypertension medications, 861 (71%) were not on an ACE-I, 439 (36%) had coronary artery disease (CAD), 184 (15%) had GFR less than 40 ml/min, 51 (4%) had BMI less than 20, and 271 (22%) had a prior hospitalization for HF. The median follow-up time was 41 months. Age, hypertension, GFR less than 40 ml/min, BMI less than 20 and prior hospitalization were found to be independent predictors for mortality and HF hospitalization. Diastolic dysfunction and CAD were independent predictors for HF hospitalization only. Based on these variables and tested in the validation cohort, the HAD-AFIB score had a C-statistic of 0.72 (0.67-0.78) for mortality (HR=1.28 (1.20-1.36), p Conclusions Patients with HFPEF and AF can be risk stratified for mortality and heart failure hospitalization using the HAD-AFIB score.

Importance Malignant arrhythmic mitral valve prolapse (MVP) phenotype poses a substantial risk of sudden cardiac death (SCD), and an estimated 26 000 individuals in the United States are at risk of SCD per year. Thus, identifying risk-stratification strategies for SCD is imperative. Observations Patients with MVP have a heterogenous clinical spectrum, ranging from a benign course to a devastating complication such as SCD. Some of the high-risk markers of MVP, which are identified electrocardiographically, include inverted or biphasic T waves, QT dispersion, QT prolongation, and premature ventricular contractions originating from the left ventricular outflow tract and papillary muscles. Morphofunctional characteristics of SCD are leaflet thickness of 5 mm or greater, mitral annulus disjunction, paradoxical systolic increase of the mitral annulus diameter, increased tissue Doppler velocity of the mitral annulus, and higher mechanical dispersion on echocardiography and fibrosis identified by late gadolinium enhancement on cardiac magnetic resonance imaging. Conclusions and Relevance Findings from this review suggest that SCD can occur earlier in the course of MVP from complex arrhythmias that are triggered by the repeated tugging and traction of the chordopapillary muscle unit and basal mid-myocardium, even before macrofibrosis can be identified in these regions by late gadolinium enhancement on cardiac magnetic resonance imaging. Some of the newer markers identified by speckle-tracking Doppler, such as mechanical dispersion, myocardial work index, and postsystolic shortening, need further validation in a larger population.

Inferior vena cava (IVC) syndrome is commonly due to obstruction from deep vein thrombosis or a mass effect. We present an unusual cause of IVC syndrome diagnosed by transthoracic echocardiography (TTE). A 74-year-old female with history of paraplegia and hypertrophic cardiomyopathy presented to

Contrast echocardiography aids in endocardial definition in stress testing, and we evaluated its use in apical hypertrophic cardiomyopathy (AHCM). AHCM is characterized by severe apical hypertrophy, and complications include apical pouch development that is associated with high rate of

Physicians encounter new medical liability risks in a medical milieu subjugated to electronic health information exchange. The budding electronic medical record systems have revolutionized how health care is dispensed. They alter the doctor-patient relationship in many uncertain and evolving ways. The shifting landscape of electronic information and medical liability risk is important for every practicing physician to understand. We review the historical changes of the electronic medical record, the emerging changes of the maturing electronic medical record, and the medical liability risk for physicians using the emerging electronic medical record systems. Because the electronic medical record appears to be here to stay, it is imperative that physicians adapt to efficient and effective use of the electronic information highway.

Background: Circulating microRNAs have recently been identified as biomarkers predicting A-Fib and heart failure. Yet, their role in identifying those at risk for postoperative atrial fibrillation (PoAF) in a gender-specific manner has not been studied. Methods: Preoperative blood from patients undergoing cardiac surgery with no prior history of AF, supraventricular/ventricular tachycardia was used for RNA isolation. Differences in the relative levels of miRNA between those who did/did not develop PoAF were assessed using qPCR. Principal component analysis and receiver operative characteristics were performed to predict miRNA associated with PoAF. Results: Out of 56 patients, 29 developed PoAF (52%, mean age 70.4± 9y, 51% males), while 27 (mean age 63y ± 10) remained free of AF. Patients who developed PoAF were older (P Conclusion: This indicates the existence of different substrate/precipitating factors reflected in miRNAs profile in male and female patients who developed PoAF. Gender differences exist in circulatory miRNA levels can help in predicting the development of new-onset AF after cardiac surgery.

Background: Cardiomyocytes (CM), derived from human induced-pluripotent stem cells (iPSC-CM), are promising tools for in vitro proarrhythmia screening for drug safety. However, among various challenges with interpretation of iPSC-CM experimental results, the influence of varied culture periods post-differentiation on the electrophysiological properties of iPSC-CMs is unclear. Objective: To test the hypothesis that prolonged post-differentiation culture of iPSC-CMs will influence the biophysical characteristics of Na + - and Ca 2+ -channels. Methods: Using whole-cell patch clamp, we compared the electrophysiological properties of differentiated ventricular-like iPSC-CMs (APD 30-40 /APD 70-80 >1.5) cultured for 10 to 15 days (D10-15) to those cultured for more than 30 days (≥ D30) both under current- and voltage- clamp configurations. Quantitative real-time PCR was used to quantify the mRNA expression of voltage-gated Na channel subunits SCN1A, SCN5A and Ca channel subunits CACNA1C, CACNA1G and CACNA1I. Fold change was calculated by 2 -ΔΔCt method. Data were analyzed by Student’s t test, and P value Results: Post-differentiation prolonged culture imparts increased cellular excitability with high frequency spontaneous action potentials, robust increase in the magnitude of peak Na + -current level, relatively shallow inactivation kinetics of Na + channels, faster recovery from inactivation, and augmented Ca 2+ current density compared to early cultured iPSC-CM. This was associated with a greatly enhanced mRNA expression of α-subunit transcripts of SCN1A (7.5 fold) and SCN5A (38 fold) Na channel subtypes while less robust elevation in the mRNA expression of CACNA1C (0.5 fold), CACNA1G (2 fold) and CACNA1I (2 fold) subunits in prolonged culture compared to early cultured iPSC-CM. Conclusion: Prolonged culture of ventricular-like iPSC-CMs affects the excitability, single-cell electrophysiological properties and differential ion channels subunit expression. Standardization of post-differentiation period for ventricular-like iPSC-CMs culture is crucial for in vitro proarrhythmia screening, health/disease modelling to study cellular mechanisms or test high-throughput drugs’ efficacy and toxicity.

Physicians practicing medicine face many challenges in today's healthcare arena. The stress of practicing medicine is increasing exponentially as new medical information is exploding on a daily basis and new stresses to practicing are occurring in a burgeoning telecommunication world. The impact of rapidly increasing medical information and the era of electronic medical records allowing physicians to communicate with patients and physicians electronically, without the benefit of observing body language or clarifying misunderstandings, has had a huge impact on practicing physician-patient risk for misinterpretation of the electronically transmitted medical information. The risk of malpractice allegations is real even under the best circumstances. The potential risk to physicians alleged to be negligent has resulted in a clinical entity called medical malpractice stress syndrome; it is a "forme fruste" of posttraumatic stress disorder.

Physicians practicing medicine in today's ever-shifting and advancing medical world are at risk for malpractice liability. The introduction of a vast array of telecommunication media into the physician world is creating a growing area of malpractice risk for physicians. This article explores the new malpractice considerations facing physicians in our constantly evolving digital world. Although they are novel and just on the horizon, these risks are real, and it is prudent for every practicing physician to consider them carefully.

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.

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.

Diabetes mellitus is a major risk factor for arrhythmogenesis and is associated with a two-fold increase in all-cause mortality and a four-fold increase in cardiovascular mortality including sudden cardiac death when compared with nondiabetics. Implantable cardioverter defibrillators (ICD) have been shown to effectively reduce arrhythmic death and all-cause mortality in patients with severe myocardial dysfunction. With a high competing risk of nonarrhythmic cardiac and noncardiac death, survival benefit of ICD in patients with diabetes mellitus could be reduced, but the subanalysis of diabetic patients in randomized clinical trials provides reassurance regarding a similar beneficial survival effect of ICD and cardiac resynchronization therapy in diabetics, as observed in the overall population with advanced heart disease. In this article, the authors highlight some of the clinical issues related to diabetes, summarize the data on the efficacy of ICD in diabetics when compared with nondiabetics and discuss concerns related to ICD implantation in patients with diabetes.

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.

BACKGROUND Mechanisms of decreased exercise capacity in patients with hypertrophic cardiomyopathy (HCM) are not well understood. Sleep-disordered breathing (SDB) is a highly prevalent but treatable disorder in patients with HCM. The role of comorbid SDB in the attenuated exercise capacity in HCM has not been studied previously. METHODS Overnight oximetry, cardiopulmonary exercise testing, and echocardiographic studies were performed in consecutive patients with HCM seen at the Mayo Clinic. SDB was considered present if the oxygen desaturation index (number of ≥ 4' desaturations/h) was ≥ 10. Peak oxygen consumption ( V . o 2 peak) (the most reproducible and prognostic measure of cardiovascular fitness) was then correlated with the presence and severity of SDB. RESULTS A total of 198 patients with HCM were studied (age, 53 ± 16 years; 122 men), of whom 32' met the criteria for the SDB diagnosis. Patients with SDB had decreased V . o 2 peak compared with those without SDB (16 mL O 2 /kg/min vs 21 mL O 2 /kg/min, P < .001). SDB remained significantly associated with V . o 2 peak after accounting for confounding clinical variables ( P CONCLUSIONS In patients with HCM, the presence of SDB is associated with decreased V . o 2 peak. SDB may represent an important and potentially modifiable contributor to impaired exercise tolerance in this unique population.

The physical examination skills of young physicians in training need careful examination as advancing technology seems to have replaced those skills compared to prior generations of physicians. A question to ponder is how should medical education address the convincing evidence that physician trainees of today are less astute at the physical examination than those that came before them? This inquiry must address whether the decline in physical examination skills hinders accurate, cost effective, and timely diagnoses. Additionally, it must consider whether the absence of a comprehensive physical examination impairs the patient–physician relationship. This type of inquiry leads to the conclusion that the physical examination and technology must be merged as the clinical situation dictates to provide accurate, cost effective and accurate diagnoses. The carefully performed physical examination in conjunction with a detailed history should dictate the use of our ever-advancing technologic advances in medicine.

There is growing evidence of a differential etiological basis for thoracic aortic aneurysms (TAA), with ascending (As) TAAs being genetically mediated and descending (Des) TAAs more strongly related to acquired pathologies. A comprehensive literature review of this hypothesis has not been carried out. We carried out a systematic literature review based on the latest guidelines on TAA endorsed by the American Heart Association. The etiologies were classified as genetic and inherited, the studies were tabulated accordingly, and Hill's epidemiological criteria of causality were applied. We found 38 studies addressing the etiology of TAAs. Out of these, 17 were about genetic causes, 9 about acquired causes, and 4 had information regarding both etiologies. Multiple genetic studies showed a strong association of As TAA with different genetic mutations. Contrary to commonly held beliefs, acquired causes, that is, dyslipidemia, diabetes, and atherosclerosis, were negatively associated with As TAA and positively associated with Des TAA. Hypertension was only associated with Des TAA and dissections (TAAD), not with As TAA. Multiple studies fulfilled the criteria of strength of association (n = 4), consistency (n = 9), specificity (n = 5), temporality (24), biological gradient (n = 3), plausibility (n = 38), biological coherence (n = 25), experiment (n = 4), and analogy (n = 6). Our literature review supports the hypothesis that As TAA is genetically mediated and Des TAA is predominantly an acquired pathology, and supports the argument for genetic testing in all cases of As TAA.

Anderson-Fabry’s disease, an X-linked inherited deficiency of alpha-galactosidase A ( GLA gene) with a birth frequency of 1 in 100,000, results in systemic sphingolipid accumulation with characteristic clinical findings. The predominant causes of significant morbidity and mortality are renal

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.

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

Cardiologists performing preoperative cardiac evaluations for non-cardiac surgery have a unique opportunity to assess and optimize the patient's baseline and general health; determine the patient's inherent surgical risk based upon a comprehensive history, physical examination and pertinent laboratory data; ensure the patient has made an informed choice regarding surgery, and identify post-operative risks that must be considered to reduce the potential for major adverse cardiovascular events. There is always a small but inherent risk in surgical procedures. When an adverse outcome occurs there is potential for an allegation of negligence resulting in a detailed autopsy of the medical record. The best defense to an allegation of negligence is comprehensive documentation and a detailed rational for the cardiologist's management decisions.

Introduction: Although generations of reactive oxygen species and mitochondrial dysfunction have been implicated in pathogenesis of alcoholic cardiomyopathy (ACM), molecular target(s) responsible for myocardial dysfunction in ACM are not well known. Objective: To determine the impact of chronic alcohol exposure on mitochondrial oxidative phosphorylation system (OXPHOS), permeability transition pore (mPTP) opening, and oxidative stress using a rat model of ACM. Methods: Sprague Dawley male rats (1 mo old) were exposed to alcohol (7.5% ethanol) for 3 months to develop ACM. Activity of OXPHOS was assessed enzymatically and by measuring mitochondrial oxygen consumption rate (OCR). The mPTP opening was determined by monitoring abrupt release of Ca 2+ after exposure of mitochondria to Ca 2+ . Western blot and RT-PCR were used to assess the expression of OXPHOS and mPTP protein components and corresponding genes. Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were determined in heart tissue homogenates. Results: There was no significant change in OCR or activity of OXPHOS complexes I-V, despite a decrease in complex V protein and Atp6v1e2 gene expression (-1.7-fold, p2+ -induced mPTP opening. This was associated with increase in protein expression level of adenine nucleotide translocase 1/2 and voltage dependent anion channel 1. There was no difference in MDA or 4-HNE levels. Conclusion: Increased sensitivity of mitochondria to mPTP opening during long-term alcohol consumption may compromise cardiac energetic reserves and contractility, leading to ACM development and progression.

Background: AF, a common sustained arrhythmia that predisposes heart failure and stroke, is associated with cardiac fibrosis and oxidative stress. Peroxisome proliferator-activated receptor (PPAR)-α, important for ROS and lipid degradation, is reported to negatively correlate with kidney, liver, and lung fibrosis, but its role in cardiac fibrosis is less clear. We hypothesize that reduced expression of PPARα in AF contributes to oxidative stress and interferes with TGFβ signaling, a cytokine implicated in cardiac fibrosis. Methods: Myocardial fibrosis was detected (Masson trichrome) in right atrial appendages of AF and non-AF patients. Levels of 4-hydroxynonenal (4-HNE) (ELISA) and superoxide production (MitoSOX) were assayed in patients’ atrial tissue homogenates and cardiac myofibers respectively. Using atrial fibroblasts (hAF) from AF and non-AF patients, α-SMA, COL1A1 and c-Jun/c-Fos expressions were determined (RT-PCR and/or Western Blot) in the absence and presence of TGF-β (5 ng) with or without ciprofibrate (200 μM), a PPARα agonist. Results: Increased atrial fibrosis, levels of 4-HNE (101.7 vs 7.4 ng/mg protein; p=0.02(n=6)) and oxidative stress (8.7 fold; p=0.04) correlated with reduced PPAR-α mRNA (2.1 fold; p Conclusion: Reduced expression of PPARα is associated with impaired cardiac mitochondrial metabolism and promotes TGFβ-induced profibrotic pathway. Preliminary data suggest PPARα agonist might confer therapeutic benefits for patients with cardiac fibrosis and oxidative stress in AF.

Introduction: The mechanical and electrical dysfunction in heart failure (HF) is associated with excessive cardiac fibrosis (CF). Activation of human ventricular fibroblasts (hVF) and transdifferentiation to myofibroblasts underlies the increased CF. We recently reported that statin therapy reduced differentiation of hVF in HF patients. However, the underlying mechanism is not known. Therefore, we studied the effect of statin therapy on the transcriptome of hVF from HF patients. Hypothesis: We tested the hypothesis that statin therapy alters the expression of differentiation-associated transcription factors (TF) in hVFs from HF patients. Methods: Primary cultures of hVF obtained from HF patients undergoing left ventricular assist device implantation either under statin therapy for at least 1 year (n=3) or not (n=3). The extent of transcriptomic changes induced by statin therapy in hVFs was studied from total RNA using RT 2 Profiler TM PCR array - human transcription factors (Qiagen, Catalog No: PAHS-075Z ) run on Roche LightCycler 96-well block. Fold change was calculated by 2 -ΔΔCt method. Data were analyzed by Student’s t test, and P value Results: Out of the 84 related genes profiled, statin therapy upregulated significantly (P Conclusion: Statin therapy mitigates differentiation of hVFs from human failing heart patients by associated changes in the transcriptome. Selective targeting of hVF transcription factor may be a potential therapeutic strategy to de-differentiate myofibroblasts and mitigate the progression of CF and HF.

Weight loss after bariatric surgery is associated with reduction in adverse cardiovascular outcomes; however, the impact of obstructive sleep apnea (OSA) on reduction of cardiovascular outcomes after bariatric surgery in morbidly obese patients is not known. We retrospectively assessed differences in cardiovascular events after laparoscopic adjustable gastric banding (LAGB)-induced weight loss in patients with and without OSA before and after propensity score matching for age, sex, body mass index (BMI), and major comorbidities between the two groups and determined predictors of poor outcomes. OSA was present in 222 out of 830 patients (27 per cent) who underwent LAGB between 2001 and 2011. Despite a similar reduction in BMI (20.0 and 20.8 per cent), a significantly higher percentage of cardiovascular events were observed in patients with than without OSA (35.6 vs 6.9 per cent; p < 0.001) at 3 years (mean follow-up 6.0 ± 3.2; range: 0.5 to 13 years). The differences in the cumulative endpoint of new onset stroke, heart failure, myocardial infarction, venous thrombosis, and pulmonary embolism between the OSA and non-OSA groups were maintained after propensity matching. Patients with OSA treated with continuous positive airway pressure (CPAP) during sleep [n = 66] had lower cardiovascular event rates at 30 months compared with those not treated (p < 0.041). OSA (hazard ratio: 6.92, 95% CI: 3.39-14.13, p < 0.001) remained an independent predictor of cardiovascular events after multivariate analysis. Thus, patients with OSA, despite a similar initial weight loss after LAGB, had a higher incidence of cardiovascular events compared with a propensity-matched group without OSA. Treatment with CPAP appears to reduce such events.

Introduction Danon disease is an X-linked lysosomal condition that causes a deficiency of lysosome-associated membrane protein 2 (LAMP2) gene. It is characterized clinically by a triad of skeletal myopathy, cardiomyopathy, and intellectual disability. Methods We examined clinical, echocardiographic, and genetic data on 5 patients with Danon disease, highlighting their clinical course and outcomes. Results All patients presented phenotypically with hypertrophic cardiomyopathy and later developed systolic dysfunction. The mean age at diagnosis was 19years (11–31years). All patients had diastolic dysfunction (mean e' of 5cm/s [3.5–6cm/s], mean E/e′ of 17 [15–21]). Three patients required cardiac transplantation (ages 15, 27, and 42). Of the two deaths in this group, both were in women. Conclusion We highlight the aggressive cardiac phenotype of Danon disease in our clinical experience with rapid progression to end-stage cardiomyopathy; this progression occurred in both men and women. A timely diagnosis and an early referral for cardiac transplantation is crucial for improved outcomes.

(2017). Improving Health Outcomes Through Patient Education and Partnerships with Patients. Baylor University Medical Center Proceedings: Vol. 30, No. 1, pp. 112-113.

Over 1,500 gene mutations are known to cause hypertrophic cardiomyopathy (HCM). Previous studies suggest that cardiac β-myosin heavy chain (MYH7) gene mutations are commonly associated with a more severe phenotype, compared to cardiac myosin binding protein-C (MYBPC3) gene mutations with milder phenotype, incomplete penetrance and later age of onset. Compound mutations can worsen the phenotype. This study aimed to validate these comparative differences in a large cohort of individuals and families with HCM. We performed genome-phenome correlation among 80 symptomatic HCM patients, 35 asymptomatic carriers and 35 non-carriers, using an 18-gene clinical diagnostic HCM panel. A total of 125 mutations were identified in 14 genes. MYBPC3 and MYH7 mutations contributed to 50.0% and 24.4% of the HCM patients, respectively, suggesting that MYBPC3 mutations were the most frequent cause of HCM in our cohort. Double mutations were found in only nine HCM patients (7.8%) who were phenotypically indistinguishable from single-mutation carriers. Comparisons of clinical parameters of MYBPC3 and MYH7 mutants were not statistically significant, but asymptomatic carriers had high left ventricular ejection fraction and diastolic dysfunction when compared to non-carriers. The presence of double mutations increases the risk for symptomatic HCM with no change in severity, as determined in this study subset. The pathologic effects of MYBPC3 and MYH7 were found to be independent of gene mutation location. Furthermore, HCM pathology is independent of protein domain disruption in both MYBPC3 and MYH7. These data provide evidence that MYBPC3 mutations constitute the preeminent cause of HCM and that they are phenotypically indistinguishable from HCM caused by MYH7 mutations.

Excessive cardiac fibrosis, characterized by increased collagen-rich extracellular matrix (ECM) deposition, is a major predisposing factor for mechanical and electrical dysfunction in heart failure (HF). The human ventricular fibroblast (hVF) remodeling mechanisms that cause excessive collagen deposition in HF are unclear, although reports suggest a role for [Ca2+]i in fibrosis. Therefore, we determined the association of differences in cellular Ca2+ dynamics and collagen secretion/deposition between hVFs from failing and normal (control) hearts. Histology of left ventricle sections (Masson trichrome) confirmed excessive fibrosis in HF vs normal. In vitro, hVFs from HF showed increased secretion/deposition of soluble collagen in 48 hours of culture compared with control [85.9±7.4 μg/106 vs 58.5±8.8 μg/106 cells, P