Patent foramen ovale and atrial septal defect.

Atrial septal defects (ASD) are among the most common congenital heart diseases encountered in adulthood. Patent foramen ovale (PFO) is present in up to 25% of the population. ASD could present as isolated lesion or in association with more complex congenital heart disease form as tetralogy of Fallot, or Ebstein's anomaly of tricuspid valve. There is a wide range of clinical presentation ranging from asymptomatic subjects surviving to adulthood undiagnosed to subjects presenting with right heart failure and severe pulmonary vascular disease (Eisenmenger syndrome). This manuscript is an in depth review of the complex atrial septation, the variable clinical presentation of ASD and PFO, and its clinical and therapeutic implications.

Retrograde approach to an ostial left anterior descending chronic total occlusion through a left internal mammary artery graft.

Retrograde approach to chronic total occlusions (CTO) has been described via saphenous vein grafts, septal and epicardial collaterals. We report for the first time a successful retrograde approach to an ostial left anterior descending (LAD) artery CTO through a failed left internal mammary artery (LIMA) to LAD anastamosis. This case demonstrates the technical aspects of using a LIMA conduit as a retrograde approach to CTO. © 2015 Wiley Periodicals, Inc.

Echocardiographic evaluation of patent foramen ovale and atrial septal defect.

Patent foramen ovale (PFO) is a common variant present in up to 25% of the population. Atrial septal defect (ASD) is a direct communication between the 2 atrial chambers, of which the ostium secundum variety is the most common. This manuscript is an in depth review of the complex atrial septation, the diagnosis of PFO and ASD and its clinical and therapeutic implications.

An unusual case of undifferentiated connective tissue disease presenting as cardiac tamponade.

Cardiac tamponade as an initial manifestation of undifferentiated connective tissue diseases (UCTD) is extremely rare, with only one case reported in literature thus far. We describe here, a case of a middle-aged man who presented with symptoms of fatigue, exertional dyspnea and orthopnea. His physical exam was significant for anasarca, elevated JVP and pulsus paradoxus. Chest X-ray showed pleural effusions and cardiomegaly, electrocardiogram revealed electrical alternans and a transthoracic echocardiogram demonstrated massive pericardial effusion with hemodynamic compromise. There was clear evidence of tamponade on right heart catheterization. All common causes of pericardial effusion were assiduously excluded before working up the patient for connective tissue disorders, which revealed a high antinuclear antibody titer (1:160), grossly elevated SSA, SSB antibodies and increased C-reactive protein levels (13.04 mg/dl). Patient had no signs or symptoms suggestive of systemic sclerosis (xerophthalmia or xerostomia) and did not meet criteria for any other known connective tissue diseases. He was therefore diagnosed with UCTD, and successfully treated with colchicine after emergency pericardiocentesis. This case presents UCTD as a rare cause of cardiac tamponade and large pericardial effusions and suggests that colchicine can be used to treat UCTD-associated effusions. These patients once diagnosed, are at risk of developing known connective tissue diseases within 5 years of disease onset and should be followed up in clinic periodically.

Coronary revascularization strategy for ST elevation myocardial infarction with multivessel disease: experience and results at 1-year follow-up.

Primary percutaneous coronary intervention (PCI) of culprit lesions (CLs) is the standard of care in patients presenting with ST elevation myocardial infarction (STEMI). However, optimal revascularization strategy for significant nonculprit lesions (non-CLs) in the setting of STEMI remains controversial. The importance of defining of such a strategy lies in the fact that approximately 50% of patients with STEMI have multivessel disease (MVD). The aim of this study was to describe characteristics, therapeutic strategies, and 1-year outcomes in a cohort of patients with STEMI and MVD. We retrospectively analyzed a cohort of 63 patients with STEMI and MVD obtained from a 5-year catheterization database. MVD was defined as ≥70% stenosis of ≥2 epicardial coronary arteries. This cohort was followed for a period of 1 year for major adverse cardiac events (MACE was defined as acute coronary syndrome, new onset heart failure, or death) and all-cause mortality. PCI with stent placement was the major therapeutic procedure (87.5%) performed for CLs. Non-CLs did not undergo interventions in a majority of individuals (47.6%), while the remaining patients underwent PCI (29%) and coronary artery bypass graft surgery (22%) for non-CLs. At 1-year follow-up, prevalence of MACE events and death in the entire cohort were 30% and 15%, respectively. A trend for better outcomes (1-year cumulative MACE events but not mortality) was observed in CL-only intervention cohort compared with non-CL intervention. The PCI and Coronary artery bypass graft surgery cohorts did not show any significant difference in clinical outcomes. In this retrospective cohort of patients with MVD who presented with STEMI, no intervention of noncritical lesions was the prevalent approach, reflecting guideline recommendations. CL-only intervention strategy showed a better clinical outcome than non-CL intervention. Intervention of noncritical lesions therefore did not seem to improve MACEs or all-cause mortality at 1-year of follow-up and might in fact have had a detrimental effect on outcomes.

Acute myocarditis: can novel echocardiographic techniques assist with diagnosis?

Two-dimensional echocardiography has historically played a limited role in the diagnosis of acute myocarditis because of a lack of specific diagnostic features. The emergence of novel echocardiographic modalities such as strain and myocardial perfusion imaging have greatly augmented the scope of echocardiography, permitting the assessment of myocardial contractility, blood flow, and microvascular integrity. However, the application of these cutting-edge techniques in the diagnosis of acute myocarditis is still at a nascent stage. We present a case of acute myocarditis where echo-based strain imaging/mapping and real-time myocardial contrast echocardiography enabled the detection of regional contractile and perfusion abnormalities, not otherwise apparent with conventional echocardiography. These findings and the final diagnosis were later confirmed by cardiac magnetic resonance imaging. This case highlights the potential utility of novel echocardiographic techniques in the diagnostic workup of acute myocarditis and underscores the need for prospective studies to assess the sensitivity and specificity of these newer technologies. To our knowledge, this is the first report of a multimodality echocardiographic approach towards the diagnosis of myocarditis.

Incremental value of contrast echocardiography in the diagnosis of atrial myxoma.

Intracardiac myxomas have traditionally been divided into solid ovoid and soft papillary types based on a morphological appearance. Papillary myxomas given their friable nature are far more likely to cause embolic phenomenon and present with neurological symptoms, making it necessary to discriminate between these tumor subtypes. Papillary myxomas have also been demonstrated to be significantly less vascular than their ovoid counterparts in previous angiographic studies. We describe here for the first time, the application of transesophageal real time myocardial contrast echocardiography in a case of atrial papillary myxoma to assess tumor vascularity. (Echocardiography 2010;27:E46-E49).

Interleukin-8 as a therapeutic target for chronic low back pain: Upregulation in human cerebrospinal fluid and pre-clinical validation with chronic reparixin in the SPARC-null mouse model.

BACKGROUND: Low back pain (LBP) is the leading global cause of disability and is associated with intervertebral disc degeneration (DD) in some individuals. However, many adults have DD without LBP. Understanding why DD is painful in some and not others may unmask novel therapies for chronic LBP. The objectives of this study were to a) identify factors in human cerebrospinal fluid (CSF) associated with chronic LBP and b) examine their therapeutic utility in a proof-of-concept pre-clinical study. METHODS: Pain-free human subjects without DD, pain-free human subjects with DD, and patients with chronic LBP linked to DD were recruited and lumbar MRIs, pain and disability levels were obtained. CSF was collected and analyzed by multiplex cytokine assay. Interleukin-8 (IL-8) expression was confirmed by ELISA in CSF and in intervertebral discs. The SPARC-null mouse model of progressive, age-dependent DD and chronic LBP was used for pre-clinical validation. Male SPARC-null and control mice received systemic Reparixin, a CXCR1/2 (receptors for IL-8 and murine analogues) inhibitor, for 8 weeks. Behavioral signs of axial discomfort and radiating pain were assessed. Following completion of the study, discs were excised and cultured, and conditioned media was evaluated with a protein array. FINDINGS: IL-8 was elevated in CSF of chronic LBP patients with DD compared to pain-free subjects with or without DD. Chronic inhibition with reparixin alleviated low back pain behaviors and attenuated disc inflammation in SPARC-null mice. INTERPRETATION: These studies suggest that the IL-8 signaling pathway is a viable therapy for chronic LBP. FUND: Supported by NIH, MMF, CIHR and FRQS.

A single-center retrospective analysis of patency rates of intraluminal versus subintimal endovascular revascularization of long femoropopliteal occlusions.

OBJECTIVE: The evaluation of patency rates of intraluminal versus subintimal endovascular revascularization of long femoropopliteal (FP) lesions. BACKGROUND: Chronic total occlusions (CTO) of the FP artery in peripheral interventions are crossed either with a support catheter-guidewire based technique or subintimal dissection and re-entry device assisted approach. Both techniques have a high procedural success rate, but their long term patency is not well studied. There is also lack of comparative data addressing the patency of long non-CTO vs. CTO occlusions. METHODS: We performed a single center retrospective analysis, studying the patency rates in 215 patients (254 limbs) with TASC C and D FP lesions treated with stents. There were 3 patient groups: without CTO (non-CTO); CTO crossed using support catheter and guide-wire (CTO-SW) and CTO crossed with a re-entry device (CTO-RE). RESULTS: There were 155 limbs in CTO-SW group; 50 in CTO-RE group and 49 in non-CTO. Lesion length (mean±SD) was 251.81±7.48mm in CTO-SW group; 280±13.18mm in CTO-RE group and 248.77±13.31 in non-CTO group (p=non-significant). In-stent restenosis (ISR) at a mean follow-up of 19.26±16.14months did not differ between groups occurring in 23 (47%) limbs in non-CTO; 66 (42%) in CTO-SW; and 24 (48%) in CTO-RE. Smoking and stent fracture were predictors of ISR by multivariate analysis. CONCLUSION: In patients with long FP lesions, ISR rates were similar between patients with and without CTO. In the CTO group mid-term vessel patency was not affected by the crossing technique utilized.

Evidence for a Role of Nerve Injury in Painful Intervertebral Disc Degeneration: A Cross-Sectional Proteomic Analysis of Human Cerebrospinal Fluid.

Intervertebral disc degeneration (DD) is a cause of low back pain (LBP) in some individuals. However, although >30% of adults have DD, LBP only develops in a subset of individuals. To gain insight into the mechanisms underlying nonpainful versus painful DD, human cerebrospinal fluid (CSF) was examined using differential expression shotgun proteomic techniques comparing healthy control participants, subjects with nonpainful DD, and patients with painful DD scheduled for spinal fusion surgery. Eighty-eight proteins were detected, 27 of which were differentially expressed. Proteins associated with DD tended to be related to inflammation (eg, cystatin C) regardless of pain status. In contrast, most differentially expressed proteins in DD-associated chronic LBP patients were linked to nerve injury (eg, hemopexin). Cystatin C and hemopexin were selected for further examination using enzyme-linked immunosorbent assay in a larger cohort. While cystatin C correlated with DD severity but not pain or disability, hemopexin correlated with pain intensity, physical disability, and DD severity. This study shows that CSF can be used to study mechanisms underlying painful DD in humans, and suggests that while painful DD is associated with nerve injury, inflammation itself is not sufficient to develop LBP. PERSPECTIVE: CSF was examined for differential protein expression in healthy control participants, pain-free adults with asymptomatic intervertebral DD, and LBP patients with painful intervertebral DD. While DD was related to inflammation regardless of pain status, painful degeneration was associated with markers linked to nerve injury.

A gender-stratified comparative analysis of various definitions of metabolic syndrome and cardiovascular risk in a multiethnic U.S. population.

INTRODUCTION: We sought to evaluate the ability of various metabolic syndrome definitions in predicting primary cardiovascular disease (CVD) outcomes in a vast multiethnic U.S. cohort. METHODS: This study included 6,814 self-identified men and women aged 45-84 years enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) study. Gender-stratified analyses were performed to calculate hazard ratios of CVD, stroke, and mortality associated with various metabolic syndrome definitions and their individual constructs. RESULTS: The hazard ratios [95% confidence interval (CI)] for all-cause CVD in men were 2.90 (2.18-3.85), 2.64 (1.98-3.51), 2.16 (1.62-2.88), 2.56 (1.91-3.44), 1.82 (1.35-2.46), and 2.92 (2.15-3.95) for the National Cholesterol Education Program (NCEP), American Heart Association (AHA), World Health Organization (WHO), International Diabetes Federation (IDF), European Group for the Study of Insulin Resistance (EGIR), and the newly defined consensus criteria. Hazard ratios in women were 2.11 (1.41-3.15), 2.17 (1.45-3.27), 2.04 (1.37-3.06), 1.91 (1.27-2.88), 1.85 (1.23-2.79), and 2.08 (1.37-3.14), respectively. Metabolic syndrome was strongly associated with stroke risk only in males. In men, all constitutive metabolic syndrome components were continuously and strongly associated with CVD. In women, high-density lipoprotein and triglycerides did not appear to be associated with short term CVD risk. CONCLUSION: We found the newly defined consensus criteria for metabolic syndrome to be similarly predictive of cardiovascular events when compared to existing definitions. Significant gender differences exist in the association between metabolic syndrome, its individual components, and CVD.

Two-dimensional strain profiles in patients with physiological and pathological hypertrophy and preserved left ventricular systolic function: a comparative analyses.

OBJECTIVE: This study was designed to examine the utility of two-dimensional strain (2DS) or speckle tracking imaging to typify functional adaptations of the left ventricle in variant forms of left ventricular hypertrophy (LVH). DESIGN: Cross-sectional study. SETTING: Urban tertiary care academic medical centres. PARTICIPANTS: A total of 129 subjects, 56 with hypertrophic cardiomyopathy (HCM), 34 with hypertensive left ventricular hypertrophy (H-LVH), 27 professional athletes with LVH (AT-LVH) and 12 healthy controls in sinus rhythm with preserved left ventricular systolic function. METHODS: Conventional echocardiographic and tissue Doppler examinations were performed in all study subjects. Bi-dimensional acquisitions were analysed to map longitudinal systolic strain (automated function imaging, AFI, GE Healthcare, Waukesha, Wisconsin, USA) from apical views. RESULTS: Subjects with HCM had significantly lower regional and average global peak longitudinal systolic strain (GLS-avg) compared with controls and other forms of LVH. Strain dispersion index, a measure of regional contractile heterogeneity, was higher in HCM compared with the rest of the groups. On receiver operator characteristics analysis, GLS-avg had excellent discriminatory ability to distinguish HCM from H-LVH area under curve (AUC) (0.893, p<0.001) or AT-LVH AUC (0.920, p<0.001). Tissue Doppler and LV morphological parameters were better suited to differentiate the athlete heart from HCM. CONCLUSIONS: 2DS (AFI) allows rapid characterisation of regional and global systolic function and may have the potential to differentiate HCM from variant forms of LVH.

Comparative prognostic utility of conventional and novel lipid parameters for cardiovascular disease risk prediction: do novel lipid parameters offer an advantage?

BACKGROUND: Comparative data on the prognostic utility of novel lipid parameters vs. conventional lipid parameters in predicting coronary events are scant. OBJECTIVE: We sought to compare the predictive value of various lipid measures for coronary events and to further examine the incremental value of novel lipid parameters over traditional cardiovascular risk factors in estimating cardiac risk. METHODS: We performed a post-hoc analysis of the National Heart Lung and Blood Institute limited access dataset of Multi-Ethnic Study of Atherosclerosis subjects (n = 6693). The lipid measures considered in the estimation of coronary risk were conventional and novel lipid parameters, the latter included total low-density lipoprotein (LDL), high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL)-particle concentrations (LDL-p, HDL-p and VLDL-p), LDL-p/HDL-p ratio, and LDL-p subfractions. The outcome measured was occurrence of any coronary event (CE) that included myocardial infarction, resuscitated cardiac arrest, cardiac death, and angina. RESULTS: During an average follow up of 4.5 years, 228 patients developed coronary events. In the multivariate Cox proportional hazards model, TC/HDL-c (HR: 3.27; 95% CI: 1.95 to 5.47, P < .0001) was a stronger predictor of CE. Among the novel lipid parameters, LDL-p/HDL-p (hazard ratio 2.84; 95% confidence interval 1.89 to 4.26; P < .0001) was a powerful independent predictor of CE. The c-statistics were similar for both LDL-p/HDL-p and TC/HDL-c ratios (0.60). The addition of LDL-p/HDL-p ratio to the Framingham risk score components resulted in a very small increase in the overall C statistic. CONCLUSION: In our large study cohort, a predictive model for future coronary events incorporating the best-available novel lipid parameter (LDL-p/HDL-p ratio) was comparable with the same model that incorporated conventional lipid ratios such as the TC/HDL-c ratio . The use of LDL-p/HDL-p ratio did not appear to offer incremental value over more traditional risk prediction models.

Usefulness of microalbuminuria in patients with the metabolic syndrome to predict subclinical atherosclerosis and cardiovascular disease outcomes.

The clinical implications of microalbuminuria (MA) in nondiabetic persons with the metabolic syndrome (MS) are largely unknown. The present post hoc analysis of the Multiethnic Study of Atherosclerosis (MESA) included 5,809 nondiabetic persons with no history of cardiovascular disease aged 45 to 84 years. The study population was divided according to the presence or absence of MS and MA into 4 study groups: no MS and no MA, MA only, MS only, and MS plus MA. The measurements included markers of systemic inflammation, subclinical atherosclerosis, left ventricular mass index, composite and individual cardiovascular end points, and all-cause mortality. Prospective and cross-sectional analyses were performed to ascertain the association of study groups with these covariates. The MS plus MA group showed a consistently stronger association with the markers of systemic inflammation, subclinical atherosclerosis, and most clinical end points compared to the other study groups. In conclusion, stratification by MA can help identify a high-risk subset of nondiabetic patients with the MS.

Usefulness of intravenously administered fluid replenishment for detection of patent foramen ovale by transesophageal echocardiography.

Patent foramen ovale (PFO) is associated with cryptogenic stroke, migraine headache, decompression sickness, and platypnea-orthodeoxia syndrome. Patients undergoing transesophageal echocardiography are often hypovolemic from preprocedural fasting and might not demonstrate right to left shunting owing to insufficient right atrial pressure generation, despite provocative maneuvers. We hypothesized that volume replenishment with saline loading could potentially unmask a PFO by favorably modulating the interatrial pressure gradient. Our study sought to examine the role of pre- or intraprocedural intravenous fluid replenishment on PFO detection during transesophageal echocardiography. A total of 103 patients were enrolled. An initial series of bubble injections was performed unprovoked and then with provocative maneuvers such as the Valsalva maneuver and coughing. The patients were then given a rapid 500 ml saline bolus, and the same sequence of bubble injections was repeated. The presence, type, and magnitude of the right to left shunts were noted before and after the saline bolus. The detection rate of PFO increased from 10.6% to 26.2% after saline loading without any provocative maneuvers. When combined with provocative maneuvers (Valsalva or cough), saline loading improved the detection rate from 17.4% to 32.0%. Overall, from amongst the 103 enrolled patients, saline bolusing resulted in a de novo diagnosis of PFO in 15 patients, atrial septal aneurysm in 15, PFO coexisting with an atrial septal aneurysm in 10, and pulmonary arteriovenous fistula in 5 patients. In conclusion, saline infusion in appropriately selected patients during transesophageal echocardiography significantly enhances the detection of PFOs and pulmonary arteriovenous fistulas.