A novel clock-face method for characterizing peridevice leaks after left atrial appendage occlusion.

OBJECTIVES: To propose a novel method for mapping leak location and frequency to a clock-face representation of the left atrial appendage (LAA) ostium. BACKGROUND: LAA occlusion with the Watchman device (WD) is an established therapy to reduce thromboembolic events in patients with atrial fibrillation (AF) and intolerance to long-term oral anticoagulation. Postimplantation leaks are known sequelae, but leak locations and characteristics are poorly described. METHODS: We retrospectively reviewed 101 consecutive WD implants from April 2015 to February 2018. Leak locations from 6-week post-implant transesophageal echocardiograms were mapped to a clock-face representation of the LAA ostium: 12:00 as cranial near the limbus, 3:00 as anterior toward the pulmonary artery, 6:00 as caudal near the mitral annulus, and 9:00 as posterior. Patient demographics, LAA dimensions, and procedural characteristics were also collected. RESULTS: Thirty-four patients had ≥1 leak totaling 45 leaks at 6-week follow-up. Baseline patient demographics showed a mean age 77, CHA2 DS2 VASc 4.69, and 64% of patients with permanent AF. No patient had a detectable leak at the time of implant. At 6 weeks, mean leak size was 2.67 ± 0.89 mm with no leak over 5 mm (largest 4.60 mm). Most leaks occurred along the posterior 6:00-12:00 segment (39/45) and the 6:00-9:00 quadrant (16/45). CONCLUSION: Six-week post-WD implant leaks localize to the posterior LAA ostium. This could result from the elliptical LAA orifice, differential LAA tissue composition, or implantation technique. This study provides a novel method for describing the location of post-implant leaks and serves as the basis for further investigations.

Usable implantation depth for watchman left atrial appendage occlusion is greater with appendage angiography than transesophageal echocardiography.

OBJECTIVES: To compare left atrial appendage (LAA) angiography to transesophageal echocardiography (TEE) for assessing usable LAA depth. BACKGROUND: TEE is typically employed for procedural measurement of LAA ostial diameter and depth. Since angiography enhances distal LAA anatomy, we sought to compare angiography to TEE for determining usable LAA depth. METHODS: Seventy five Watchman device cases were retrospectively evaluated. Two independent cardiologists measured intraoperative LAA ostial diameter and depth at standard 0°, 45°, 90°, and 135° TEE omniplane views and in the right anterior oblique (RAO) 30°, caudal (CAUD) 30° angiographic view. RESULTS: The average age and CHA2 DS2 VASc score were 74 (±7.2) years and 4.6 (±1.3), respectively. The average ostial diameter and depth (mm) by TEE were 0°: 19.6 and 26.5; 45°: 17.5 and 26.6; 90°: 18.3 and 25.1; 135°: 19.5 and 23.3. The ostial diameter and depth (mm) by RAO 30° CAUD 30° angiography were 21.1 and 29.7. This angiographic view corresponds to a TEE view between 90° and 135°. In comparison to angiography, TEE 90° underestimated the LAA ostial diameter by 2.9 ± 3.7 mm (P < 0.001) and by 1.9 ± 4.0 mm at TEE 135° (P < 0.01); Pearson's r 0.53 angiography/TEE 90° and 0.50 angiography/TEE 135°. More importantly, TEE 90° underestimated the true usable LAA depth by 5.4 ± 5.8 mm (P < 0.001) and by 7.3 ± 6.1 mm at TEE 135° (P < 0.001); Pearson's r 0.39 angiography/TEE 90° and 0.30 angiography/TEE 135°. CONCLUSIONS: Compared to TEE, LAA angiography provides additional depth information and may be particularly valuable when patients have insufficient depth for Watchman by TEE measures.

Pim-1 kinase protects mitochondrial integrity in cardiomyocytes.

RATIONALE: Cardioprotective signaling mediates antiapoptotic actions through multiple mechanisms including maintenance of mitochondrial integrity. Pim-1 kinase is an essential downstream effector of AKT-mediated cardioprotection but the mechanistic basis for maintenance of mitochondrial integrity by Pim-1 remains unexplored. This study details antiapoptotic actions responsible for enhanced cell survival in cardiomyocytes with elevated Pim-1 activity. OBJECTIVE: The purpose of this study is to demonstrate that the cardioprotective kinase Pim-1 acts to inhibit cell death by preserving mitochondrial integrity in cardiomyocytes. METHODS AND RESULTS: A combination of biochemical, molecular, and microscopic analyses demonstrate beneficial effects of Pim-1 on mitochondrial integrity. Pim-1 protein level increases in the mitochondrial fraction with a corresponding decrease in the cytosolic fraction of myocardial lysates from hearts subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Cardiac-specific overexpression of Pim-1 results in higher levels of antiapoptotic Bcl-X(L) and Bcl-2 compared to samples from normal hearts. In response to oxidative stress challenge, Pim-1 preserves the inner mitochondrial membrane potential. Ultrastructure of the mitochondria is maintained by Pim-1 activity, which prevents swelling induced by calcium overload. Finally, mitochondria isolated from hearts created with cardiac-specific overexpression of Pim-1 show inhibition of cytochrome c release triggered by a truncated form of proapoptotic Bid. CONCLUSION: Cardioprotective action of Pim-1 kinase includes preservation of mitochondrial integrity during cardiomyopathic challenge conditions, thereby raising the potential for Pim-1 kinase activation as a therapeutic interventional approach to inhibit cell death by antagonizing proapoptotic Bcl-2 family members that regulate the intrinsic apoptotic pathway.

Mesencephalic astrocyte-derived neurotrophic factor is an ischemia-inducible secreted endoplasmic reticulum stress response protein in the heart.

The endoplasmic reticulum (ER) stress response (ERSR) is activated when folding of nascent proteins in the ER lumen is impeded. Myocardial ischemia was recently shown to activate the ERSR; however, the role of this complex signaling system in the heart is not well understood. ER stress activates the transcription factor ATF6, which induces expression of proteins targeted to the ER, where they restore protein folding, thus fostering cytoprotection. We previously developed a transgenic mouse line that expresses a conditionally activated form of ATF6 in the heart. In this mouse line, ATF6 activation decreased ischemic damage in an ex vivo model of myocardial ischemia/reperfusion and induced numerous genes, including mesencephalic astrocyte-derived neurotrophic factor (MANF). In the present study, MANF expression was shown to be induced in cardiac myocytes and in other cell types in the hearts of mice subjected to in vivo myocardial infarction. Additionally, simulated ischemia induced MANF in an ATF6-dependent manner in neonatal rat ventricular myocyte cultures. In contrast to many other ER-resident ERSR proteins, MANF lacks a canonical ER-retention sequence, consistent with our finding that MANF was readily secreted from cultured cardiac myocytes. Knockdown of endogenous MANF with micro-RNA increased cell death upon simulated ischemia/reperfusion, whereas addition of recombinant MANF to media protected cultured cardiac myocytes from simulated ischemia/reperfusion-mediated death. Thus, a possible function of the ERSR in the heart is the ischemia-mediated induction of secreted proteins, such as MANF, that can function in an autocrine/paracrine manner to modulate myocardial damage from ER stresses, including ischemia.

Relationship between depressive symptoms and cardiovascular risk factors among selected Latino patients at a community clinic.

The objective of this study was to explore the relationship between severity of depression and cardiovascular disease (CVD) risk factors among selected Latino patients within a primary care setting. We conducted a cross-sectional analysis of 164 low-income Latino patients at San Ysidro Health Center (SYHC) who had been recruited into a mental health program between January 2007 and March 2008. Patients were between the ages of 18 and 83 years, 54 were males and 109 females. Patients were screened using the 9-item patient health questionnaire (PHQ-9), a standardized instrument used to measure depression severity. We used regression models to analyze the relationship between severity of depression and CVD risk factors. Seventy-eight percent of the patients had at least mild depression based on PHQ-9 score categories. Significant age-adjusted pairwise associations were found with CVD risk factors; body mass index (BMI), diabetes status, serum cholesterol level, and serum triglyceride level were all associated with depression severity score. Regression models indicated that diabetic patients on anti-depressive medication with higher BMI scores and triglyceride levels had significantly higher depression severity scores. Clinicians should be made aware that depressive symptoms may impede efforts to modify BMI, serum triglycerides, anti-depression medication, and diabetes among Latino patients. They should, therefore, screen and treat depression among Latinos at risk to CVD.

Inappropriate Shock from Subcutaneous Implantable Cardioverter-Defibrillator Caused by Electrical Remodeling After Wolff-Parkinson-White Ablation.

Hypertrophic cardiomyopathy (HCM) and Wolff-Parkinson-White syndrome have been associated with sudden cardiac death. A subcutaneous implantable cardioverter-defibrillator (S-ICD) is an effective device used to reduce the risk of sudden cardiac death in these patients. The most common cause of inappropriate shocks with S-ICD is T-wave oversensing. We present the case of a 19-year-old man with repeated shocks from his S-ICD. This case highlights some of the sensing issues related to the S-ICD that can result in inappropriate shocks. A vector change may have occurred after T-wave remodeling, post accessory pathway ablation, and loss of R-waves due to HCM scar progression, leading to this consequence.

Watchman Occlusion in Long-Standing Persistent Atrial Fibrillation: Larger Left Atrial Appendages With Greater Residual Leak.

OBJECTIVES: This study sought to compare patients with and without long-standing persistent atrial fibrillation (LSPAF) undergoing Watchman left atrial appendage (LAA) occlusion. BACKGROUND: An increased burden of atrial fibrillation is associated with progressive left atrial remodeling and enlargement. METHODS: Transesophageal echocardiography (TEE) measures of LAA ostial diameter and depth, device compression, and residual leak were evaluated in 101 consecutive Watchman cases. The patients were categorized into LSPAF (n = 48) or non-LSPAF (n = 53) groups and compared. RESULTS: The average LAA ostial diameter for LSPAF versus non-LSPAF by TEE omniplane at 0° was 21.1 ± 4.1 mm versus 18.2 ± 3.6 mm (p = 0.0002); at 45° was 18.7 ± 3.4 mm versus 16.3 ± 3.1 mm (p = 0.0004); at 90° was 19.6 ± 3.8 mm versus 16.2 ± 3.4 mm (p = 0.00001); and at 135° was 21.0 ± 4.1 mm versus 18.0 ± 4.1 mm (p = 0.0005). The average LAA depth for LSPAF versus non-LSPAF by TEE at 0° was 28.1 ± 6.4 mm versus 25.2 ± 4.9 mm (p = 0.02); at 45° was 27.9 ± 5.8 mm versus 25.1 ± 4.3 mm (p = 0.007); at 90° was 27.2 ± 5.2 mm versus 22.8 ± 3.7 mm (p = 0.0001); and at 135° was 25.6 ± 5.4 mm versus 21.5 ± 3.8 mm (p = 0.0001). In successfully treated patients, 77% of the LSPAF group received larger device (27, 30, or 33 mm) implants versus only 46% in the non-LSPAF group (p = 0.003). While both groups had similar rates of moderate (3 to 5 mm) leaks at implant (2% vs. 0%; p = 0.14), 27% of the LSPAF vs. 4% of the non-LSPAF group had moderate leaks (p = 0.04) on 6-week follow-up TEE. CONCLUSIONS: Patients with LSPAF have significantly larger LAA sizes, require larger devices, and have more residual leak on follow-up TEE. LSPAF may represent a higher risk group that warrants more stringent long-term follow-up.

Resolution of AV block after ablation for atrial fibrillation.

We report a case with complete atrioventricular block (AVB) present both during sinus rhythm and with atrial fibrillation (AF). He had declined pacemaker placement and opted for ablation for the symptomatic AF. He underwent staged hybrid approach with video-assisted thoracoscopic surgical maze (VATS) followed by endocardial ablation. VATS included ganglionic plexi cauterization. One month after the endocardial procedure, he had complete resolution of AF and AVB and remains so at 18 months follow up. We discuss possible abolition of vagal input for this improvement in AV conduction.

Analysis of the quantitative improvements in resting echocardiographic image sharpness through the use of contrast enhanced echocardiography.

Contrast enhanced echocardiography (CEE) is a technique for the improvement of suboptimal echocardiographic studies. While commonly performed at selected institutions, its value has only been shown qualitatively, and to this point no study has been directed at establishing a quantitative improvement in image quality compared with non-contrast enhanced echocardiography (non-CEE). The purpose of this study was to quantitatively measure the effect of contrast on the quality of images obtained during non-CEE versus CEE. Thirty consecutive patients underwent CEE. In all subjects a non-CEE was obtained prior to administering any contrast, allowing for a direct comparison and an internal control group. Sharpness of the septal, apical and lateral myocardial walls in the apical 4-chamber view was calculated with and without contrast. Three signal intensity levels were obtained for each wall then averaged to compare the images with and without contrast for a statistically significant difference in sharpness. Quantitative analysis showed a significant difference in sharpness between CEE and non-CEE in the left ventricular septal myocardial wall, p < 0.01. A more drastic significant increase in image sharpness was observed between non-CEE and CEE in the apical and lateral left ventricular myocardial walls, both p < 0.000001. CEE significantly increases the sharpness at all left ventricular myocardial walls thus allowing higher quality images with presumably more accurate diagnosis of regional wall motion abnormalities, left ventricular endocardial border detection, left ventricular dimensions, ejection fraction and apical pathology.

Relationship between self-reported high-heeled shoe use and bone mineral density using quantitative ultrasound at a community health fair.

This is the first known study to examine the relationship between high-heel use and bone mineral density (BMD). Because women are disproportionately affected by osteoporosis, it is important to identify possible modifiable behaviors of women that may adversely affect bone health. Many studies have shown changes in body mechanics when wearing high-heeled shoes in comparison to normal gait. Because the composition of bone changes according to mechanical load and muscle activity, this study investigates whether wearing high heels may alter BMD. Two hundred and twenty-one participants at a community health fair in Lansing, Michigan, were surveyed on high-heel use and bone health risk (gender, thin/small frame, fair skin, family history of fracture, smoking history, walking, dairy consumption, and early menopause or oopherectomy at <45 years old). Quantitative ultrasound (QUS) of the heel by Hologic's Sahara Sonometer was used to measure BMD. The mean age was 45.2 (SD 13.7) years, and the majority of participants were female (208, 94 %). A significant difference between mean BMD and high-heel use was not found. Independent correlations existed between fair skinned/sunburn easily and BMD, r(212) = -0.14, p = 0.038, as well as history of smoking and BMD, r(212) = -0.14, p = 0.042. Bone health risk score was strongly correlated with heel use binary variable "yes/no," r(210) = 0.21, p = 0.003. Our study suggests that wearing high-heeled shoes does not lead to appreciable differences in BMD among community health fair participants as assessed by QUS.

Tattooing: medical uses and problems.

Decorative tattooing is a custom thousands of years old and is growing in popularity today. Medical professionals may be less familiar with its medical applications-medical alert tattooing, reconstructive and cosmetic applications, endoscopic tattooing, corneal tattooing, tattooing in radiation oncology, and uses in forensic medicine. We review current medically related tattooing applications and discuss their potential risks and benefits.

Asymptomatic severe hypocalcemia secondary to vitamin d deficiency in an elderly patient.

Objective. To describe an asymptomatic presentation of severe hypocalcemia secondary to vitamin D deficiency in an elderly patient. Methods. We describe the presentation and clinical course of an elderly woman with asymptomatic severe hypocalcemia referred to an endocrinology clinic for hyperparathyroidism. Results. The patient is an 83-year-old Caucasian woman who presented to an endocrinology clinic for evaluation of hyperparathyroidism, with an intact PTH of 462 pg/mL (normal range 14-72 pg/mL). The same lab report included a serum calcium of 5.2 mg/dL (normal range 8-10.5 mg/dL). She displayed no signs or symptoms of hypocalcemia. Given the extreme severity of hypocalcemia and her age, she was hospitalized. Vitamin D deficiency was suspected and was subsequently confirmed with undetectable serum levels. The patient remained asymptomatic throughout her hospital stay. Total and ionized calcium levels at discharge were 7.2 mg/dL and 1.03 mmol/L (normal range 1.1-1.4 mmol/L), respectively. Conclusion. Physicians should exercise prudent management with respect to the vitamin D status of the elderly patient, as certain patients may exhibit severe hypovitaminosis D and hypocalcemia without apparent clinical symptoms.