Spontaneous coronary artery dissection: a focus on post-dissection care for the vascular medicine clinician.

Spontaneous coronary artery dissection (SCAD) is an uncommon condition which is increasingly recognized as a cause of significant morbidity. SCAD can cause acute coronary syndrome and myocardial infarction (MI), as well as sudden cardiac death. It presents similarly to atherosclerotic MI although typically in patients with few or no atherosclerotic risk factors, and particularly in women. As more patients are recognized to have this condition, there is a great need for clinician familiarity with diagnostic criteria, as well as with contemporary treatment approaches, and with appropriate patient-centered counseling, including genetic testing, exercise recommendations, and psychological care. The standard of care for patients with SCAD is rapidly evolving. This review therefore summarizes the diagnosis of SCAD, epidemiology, modern treatment, cardiac rehabilitation and preconception counseling, and the current approach to genetic testing, exercise recommendations, and psychological care, all of which are crucial to the vascular medicine specialist.

Myocardial Infarction Simulated From Improper Telemetry (MISFIT): An Autobiographical Case Report.

An electrocardiogram, used to not only assess the rate and rhythm of the heart but also to evaluate for injury to the heart, is performed by attaching 12 leads to the patient's body. A myocardial infarction can be mimicked by the misplacement of the leads. A 58-year-old man with long-distance running-associated bradycardia developed postoperative atrial fibrillation with a rapid ventricular response. He converted to normal sinus rhythm after a single oral dose of 30 milligrams of diltiazem; however, the automated reading of the electrocardiogram performed in the hospital showed new changes suggestive of a postero-lateral myocardial infarction, including Q waves in leads I and aVL, as well as early precordial R wave progression with R waves and positive T waves in V2 and V3, and a dominant R wave (R wave to S wave ratio greater than one) in V2. A cardiac work-up was entirely normal: serial troponin levels, thyroid stimulating hormone, echocardiogram, computerized tomography of the chest, and Doppler studies of the extremities. Lead misplacement during the electrocardiogram was suspected during the subsequent evaluation by an astute cardiologist; the findings were diagnostic for a left arm to right arm limb lead reversal. All the changes in myocardial infarction were absent when the electrocardiogram was repeated in the office. Misplacement of leads during an electrocardiogram is not a rare event; therefore, the clinician needs to consider the possibility of improper placement of the leads when evaluating an electrocardiogram. Indeed, emotional distress, additional diagnostic procedures, and potentially harmful procedures may be experienced by the patient from incorrect diagnoses based on electrode misplacement during an electrocardiogram; in addition, there are often increased costs to the patient and the healthcare system. Therefore, in the setting of an incorrect diagnosis attributed to lead misplacement during the performance of an electrocardiogram, the acronym MISFIT (which uses the first letters of the words "myocardial infarction simulated from improper telemetry") has been introduced. In conclusion, it is important to emphasize that a MISFIT is characterized by an electrocardiogram 'mis'diagnosis of a myocardial infarction that does not 'fit' with the clinical scenario.

Insulin resistance is associated with subclinical myocardial dysfunction and reduced functional capacity in heart failure with preserved ejection fraction.

BACKGROUND: Obesity and insulin resistance are prevalent in heart failure with preserved ejection fraction (HFpEF) and are associated with adverse cardiovascular outcomes. Measuring insulin resistance is difficult outside of research settings, and its correlation to parameters of myocardial dysfunction and functional status is unknown. METHODS: A total of 92 HFpEF patients with New York Heart Association class II to IV symptoms underwent clinical assessment, 2D echocardiography, and 6-min walk (6 MW) test. Insulin resistance was defined by estimated glucose disposal rate (eGDR) using the formula: eGDR = 19.02 - [0.22 × body mass index (BMI), kg/m2] - (3.26 × hypertension, presence) - (0.61 × glycated hemoglobin, %). Lower eGDR indicates increased insulin resistance (unfavorable). Myocardial structure and function were assessed by left ventricular (LV) mass, average E/e' ratio, right ventricular systolic pressure, left atrial volume, LV ejection fraction, LV longitudinal strain (LVLS), and tricuspid annular plane systolic excursion. Associations between eGDR and adverse myocardial function were evaluated in unadjusted and multivariable-adjusted analyses using analysis of variance testing and multivariable linear regression. RESULTS: Mean age (SD) was 65 (11) years, 64 % were women, and 95 % had hypertension. Mean (SD) BMI was 39 (9.6) kg/m2, glycated hemoglobin 6.7 (1.6) %, and eGDR 3.3 (2.6) mg × kg-1 min-1. Increased insulin resistance was associated with worse LVLS in a graded fashion [mean (SD) -13.8 % (4.9 %), -14.4 % (5.8 %), -17.5 % (4.4 %) for first, second, and third eGDR tertiles, respectively, p = 0.047]. This association persisted after multivariable adjustment, p = 0.040. There was also a significant association between worse insulin resistance and decreased 6 MW distance on univariate analysis, but not on multivariable adjusted analysis. CONCLUSION: Our findings may inform treatment strategies focused on the use of tools to estimate insulin resistance and selection of insulin sensitizing drugs which may improve cardiac function and exercise capacity.

Assessment and Prediction of Cardiovascular Contributions to Severe Maternal Morbidity.

Severe maternal morbidity (SMM) refers to any unexpected outcome directly related to pregnancy and childbirth that results in both short-term delivery complications and long-term consequences to a women's health. This affects about 60,000 women annually in the United States. Cardiovascular contributions to SMM including cardiac arrest, arrhythmia, and acute myocardial infarction are on the rise, probably driven by changing demographics of the pregnant population including more women of extreme maternal age and an increased prevalence of cardiometabolic and structural heart disease. The utilization of SMM prediction tools and risk scores specific to cardiovascular disease in pregnancy has helped with risk stratification. Furthermore, health system data monitoring and reporting to identify and assess etiologies of cardiovascular complications has led to improvement in outcomes and greater standardization of care for mothers with cardiovascular disease. Improving cardiovascular disease-related SMM relies on a multipronged approach comprised of patient-level identification of risk factors, individualized review of SMM cases, and validation of risk stratification tools and system-wide improvements in quality of care. In this article, we review the epidemiology and cardiac causes of SMM, we provide a framework of risk prediction clinical tools, and we highlight need for organization of care to improve outcomes.

Case Report: Steroid-Responsive Takotsubo Cardiomyopathy Associated With Cytokine Storm and Obstructive Shock.

A growing body of evidence suggests that inflammation may play a key role in the development of Takotsubo stress cardiomyopathy. Here, we report the case of a 63-year-old woman who presented with chest pain and was diagnosed with this cardiomyopathy. After an initial improvement, the patient experienced a systemic inflammatory response of unclear origin and deteriorated rapidly into obstructive shock. Her presentation was considered consistent with cytokine storm. She was, therefore, treated with steroids with rapid improvement in her clinical picture. She relapsed after the taper. Endomyocardial biopsy soon after initiation of pulse dose steroids showed macrophage and lymphocytic infiltration. This case highlights the potential intimate connection between systemic inflammatory response and Takotsubo stress cardiomyopathy and contributes to the evolving understanding of inflammation in the pathogenesis of this disease.

Adalimumab-Induced Lupus Nephritis: Case Report and Review of the Literature.

Tumor necrosis factor-alpha inhibitors are known causative agents of systemic lupus erythemato- sus but have rarely been implicated in lupus nephritis. A patient with Crohn's disease on long-term adalimumab treatment presented with new-onset Raynaud's phenomenon and was found to have hematuria and proteinuria. Elevated antinuclear, anti-dsDNA, and MPO antibodies were found. A renal biopsy confirmed the diagnosis of lupus nephritis. Adalimumab was discontinued ensuing improvement in urine studies and resolution of dsDNA and MPO antibodies. Adalimumab can induce systemic lupus erythematosus and lupus nephritis.

Role of Multimodality Imaging in the Assessment of Myocardial Infarction With Nonobstructive Coronary Arteries: Beyond Conventional Coronary Angiography.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous clinical entity, encompassing multiple different causes, and a cause of substantial morbidity and mortality. Current guidelines suggest a multimodality imaging approach in establishing the underlying cause for MINOCA, which is considered a working diagnosis. Recent studies have suggested that an initial workup consisting of cardiac magnetic resonance and invasive coronary imaging can yield the diagnosis in most patients. Cardiac magnetic resonance is particularly helpful in excluding nonischemic causes that can mimic MINOCA including myocarditis and Takotsubo cardiomyopathy, as well as for long-term prognostication. Additionally, intracoronary imaging with intravascular ultrasound or optical coherence tomography may be warranted to evaluate plaque composition, or evaluate for plaque disruption or spontaneous coronary dissection. The role of noninvasive imaging modalities such as coronary computed tomography angiography is currently being investigated in the diagnostic approach and follow-up of MINOCA and may be appropriate in lieu of invasive coronary angiography in select patients. In recent years, many strides have been made in the workup of MINOCA; however, significant knowledge gaps remain in the field, particularly in terms of treatment strategies. In this review, we summarize recent society guideline recommendations and consensus statements on the initial evaluation of MINOCA, review contemporary multimodality imaging approaches, and discuss treatment strategies including an ongoing clinical trial.

Lactobacilli spp.: real-time evaluation of biofilm growth.

BACKGROUND: Biofilm is a fundamental bacterial survival mode which proceeds through three main generalized phases: adhesion, maturation, and dispersion. Lactobacilli spp. (LB) are critical components of gut and reproductive health and are widely used probiotics. Evaluation of time-dependent mechanisms of biofilm formation is important for understanding of host-microbial interaction and development of therapeutic interventions. Time-dependent LB biofilm growth was studied in two systems: large biofilm output in continuous flow system (microfermenter (M), Institute Pasteur, France) and electrical impedance-based real time label-free cell analyzer (C) (xCELLigence, ACEA Bioscience Inc., San Diego, CA). L. plantarum biofilm growth in M system was video-recorded, followed by analyses using IMARIS software (Bitplane, Oxford Instrument Company, Concord, MA, USA). Additionally, whole genome expression and analyses of attached (A) and dispersed (D) biofilm phases at 24 and 48 h were performed. RESULTS: The dynamic of biofilm growth of L. plantarum was similar in both systems except for D phases. Comparison of the transcriptome of A and D phases revealed, that 121 transcripts differ between two phases at 24 h. and 35 transcripts - at 48 h. of M growth. The main pathways, down-regulated in A compared to D phases after 24 h. were transcriptional regulation, purine nucleotide biosynthesis, and L-aspartate biosynthesis, and the upregulated pathways were fatty acid and phospholipid metabolism as well as ABC transporters and purine nucleotide biosynthesis. Four LB species differed in the duration and amplitude of attachment phases, while growth phases were similar. CONCLUSION: LB spp. biofilm growth and propagation area dynamic, time-dependent processes with species-specific and time specific characteristics. The dynamic of LB biofilm growth agrees with published pathophysiological data and points out that real time evaluation is an important tool in understanding growth of microbial communities.

Effects of powdered rifampin and vancomycin solutions on biofilm production of staphylococcus aureus on orthopedic implants.

PURPOSE: Hardware infections in orthopedic surgery, specifically those involving biofilm producing bacteria, are troublesome and are highly resistant to systemic antibiotics. The purpose of this study was to demonstrate the power of rifampin and vancomycin solutions in inhibiting as well as eliminating in vitro on staphylococcus aureus (S. aureus) biofilm in vitro on stainless-steel implants. METHODS: A suspension of either S. aureus or a S. aureus containing a plasmid that cods for the green fluorescence protein containing fluorescent protein plasmid was applied to 1 × 1cm sterile stainless steel orthopedic plating material (coupon). Biofilm development was confirmed by; the quantitative assay (colony forming unit [CFU/coupon]) and visualized using confocal laser scanning microscopy. With this established method of biofilm development, we determined the minimum biofilm inhibitory concentration (MBIC) and the minimum biofilm eradication concertation (MBEC) of Rifampicin and Vancomycin. To determine the MBIC, stainless steel plates were subjected to different concentrations of antibiotic solution and inoculated with overnight cultures of S. aureus. After 24 h of incubation at 37 °C, the biofilms on the untreated and antibiotic-treated coupons were quantified. To determine the MBEC, partial S. aureus biofilms were developed on the coupons and then treated with the different concentrations of each antibiotic for 24 h. The number of bacteria within the control untreated as well as treated coupons was determined. RESULTS: Both rifampin and vancomycin solutions inhibited biofilm production of S. aureus on stainless steel mediums; the MBIC for rifampin and vancomycin were 80 ng/mL and 1 µg/mL respectively. The MBEC for Rifampicin was similar to the MBIC. However, the MBEC for Vancomycin was 6 mg/ml. CONCLUSIONS: When applied to orthopedic stainless steel hardware in vitro, solutions of rifampin and vancomycin powder separately or in combination can completely prevent and eliminate biofilm produced by S. aureus. LEVEL OF EVIDENCE: II.

The Antifibrotic Effect of A2B Adenosine Receptor Antagonism in a Mouse Model of Dermal Fibrosis.

OBJECTIVE: Systemic sclerosis (SSc; scleroderma) is a chronic disease that affects the skin and various internal organs. Dermal fibrosis is a major component of this disease. The mechanisms that promote dermal fibrosis remain elusive. Elevations in tissue adenosine levels and the subsequent engagement of the profibrotic A2B adenosine receptor (ADORA2B) have been shown to regulate fibrosis in multiple organs including the lung, kidney, and penis; however, the role of ADORA2B in dermal fibrosis has not been investigated. We undertook this study to test our hypothesis that elevated expression of ADORA2B in the skin drives the development of dermal fibrosis. METHODS: We assessed the involvement of ADORA2B in the regulation of dermal fibrosis using a well-established mouse model of dermal fibrosis. Using an orally active ADORA2B antagonist, we demonstrated how inhibition of ADORA2B results in reduced dermal fibrosis in 2 distinct experimental models. Finally, using human dermal fibroblasts, we characterized the expression of adenosine receptors. RESULTS: We demonstrated that levels of ADORA2B were significantly elevated in dermal fibrosis and that the therapeutic blockade of this receptor in vivo using an ADORA2B antagonist could reduce the production of profibrotic mediators in the skin and attenuate dermal fibrosis. Antagonism of ADORA2B resulted in reduced numbers of arginase-expressing macrophages and myofibroblasts and in reduced levels of the extracellular matrix proteins fibronectin, collagen, and hyaluronan. CONCLUSION: These findings identify ADORA2B as a potential profibrotic regulator in dermal fibrosis and suggest that ADORA2B antagonism may be a useful approach for the treatment of SSc.

Metatranscriptomic Analysis of Pycnopodia helianthoides (Asteroidea) Affected by Sea Star Wasting Disease.

Sea star wasting disease (SSWD) describes a suite of symptoms reported in asteroids of the North American Pacific Coast. We performed a metatranscriptomic survey of asymptomatic and symptomatic sunflower star (Pycnopodia helianthoides) body wall tissues to understand holobiont gene expression in tissues affected by SSWD. Metatranscriptomes were highly variable between replicate libraries, and most differentially expressed genes represented either transcripts of associated microorganisms (particularly Pseudomonas and Vibrio relatives) or low-level echinoderm transcripts of unknown function. However, the pattern of annotated host functional genes reflects enhanced apoptotic and tissue degradation processes and decreased energy metabolism, while signalling of death-related proteins was greater in asymptomatic and symptomatic tissues. Our results suggest that the body wall tissues of SSWD-affected asteroids may undergo structural changes during disease progression, and that they are stimulated to undergo autocatalytic cell death processes.

Densovirus associated with sea-star wasting disease and mass mortality.

Populations of at least 20 asteroid species on the Northeast Pacific Coast have recently experienced an extensive outbreak of sea-star (asteroid) wasting disease (SSWD). The disease leads to behavioral changes, lesions, loss of turgor, limb autotomy, and death characterized by rapid degradation ("melting"). Here, we present evidence from experimental challenge studies and field observations that link the mass mortalities to a densovirus (Parvoviridae). Virus-sized material (i.e., <0.2 µm) from symptomatic tissues that was inoculated into asymptomatic asteroids consistently resulted in SSWD signs whereas animals receiving heat-killed (i.e., control) virus-sized inoculum remained asymptomatic. Viral metagenomic investigations revealed the sea star-associated densovirus (SSaDV) as the most likely candidate virus associated with tissues from symptomatic asteroids. Quantification of SSaDV during transmission trials indicated that progression of SSWD paralleled increased SSaDV load. In field surveys, SSaDV loads were more abundant in symptomatic than in asymptomatic asteroids. SSaDV could be detected in plankton, sediments and in nonasteroid echinoderms, providing a possible mechanism for viral spread. SSaDV was detected in museum specimens of asteroids from 1942, suggesting that it has been present on the North American Pacific Coast for at least 72 y. SSaDV is therefore the most promising candidate disease agent responsible for asteroid mass mortality.

Discovery of urchin-associated densoviruses (family Parvoviridae) in coastal waters of the Big Island, Hawaii.

Echinoderms are important constituents of marine ecosystems, where they may influence the recruitment success of benthic flora and fauna, and are important consumers of detritus and plant materials. There are currently no described viruses of echinoderms. We used a viral metagenomic approach to examine viral consortia within three urchins - Colobocentrotus atratus, Tripneustes gratilla and Echinometra mathaei - which are common constituents of reef communities in the Hawaiian archipelago. Metagenomic libraries revealed the presence of bacteriophages and densoviruses (family Parvoviridae) in tissues of all three urchins. Densoviruses are known typically to infect terrestrial and aquatic arthropods. Urchin-associated densoviruses were detected by quantitative PCR in all tissues tested, and were also detected in filtered suspended matter (>0.2 µm) from plankton and in sediments at several locations near to where the urchins were collected for metagenomic analysis. To the best of our knowledge, this is the first report of echinoderm-associated viruses, which extends the known host range of parvoviruses.