Nonatherosclerotic Disease Research Articles

PREVALENCE OF ACS IN AVICENNA BALKHI TEACHING HOSPITAL IN AFGHANISTAN

One third of global deaths is caused by CVD, and the most common is IHD. Approximately 80% of IHD is caused by atherosclerosis, while the rest ones are caused by non-atherosclerotic diseases such as VHD, radiation, vasculitis, and others.To study the prevalence of ACS in Avicenna Balkhi Teaching Hospital.This is a retrospective cross sectional study. We collected data of 180 patients with ACS from 01.01.2019 to 01.06.2019 in Avicenna Balkhi Teaching Hospital; data were evaluated on the basis of clinical signs, methods of a treatment and outcome in patients with ACS.180 patients with ACS were admitted during the first six months of 2019. From the aforementioned ACS, 62.7% of (113) cases were STEMI and 37.2% of (67) cases were NSTEMI/UA, with a male to female ratio 2.64:1. 66.7% of patients had an age of 60 – 79 years. The mean time of patients’ admission in CCU was 15.5h and was higher in NSTEMI/UA than in STEMI (18.3 h vs 11.8 h) respectively. Treatment of all patients with ACS such as STEMI, NSTEMI, UA was the same in 90% and they received antiplatelet, statins, anticoagulants, anxiolytics. 30,4% of patients with STEMI received thrombolytic therapy with streptokinase (which is available in Afghanistan), just in 10% of 30.4% cases we saw the effective role of streptokinase. The most common comorbidity diseases include: Hypertension 45.6%, DM 22.2%, Smoking 27.8%, Heart failure 21.7%, COPD 5.6%. Most of patients with ACS were STEMI, that were found more in males than in females. More than 50% of patients had an age of 60-79 years old, the mean admission time in the CCU was more than 10, and the most common comorbidities were HTN, smoking, DM and heart failure. The public awareness about heart diseases is increasing, the professional capacity of medical staff is expanding, and equipping of the Cath lab and cardiac surgery department is getting well. Finally, this study will serve as a resource for future research.

Notch-Rho-cGMP interaction: common point of convergence in microvascular aging-related disease.

Vascular smooth muscle biology is increasingly exploited as an interventional target in vascular disease. Vascular smooth muscle Notch3-Rho kinase-cGMP interaction has been implicated in brain and peripheral arteriopathy in CADASIL. In the present commentary, we discuss the potential implications for other, more common non-atherosclerotic microvascular diseases: INOCA and HFpEF. The relation to mechanotransduction, to cellular senescence and to sGC activators as potential intervention agents are described.

RARE LOSS-OF-FUNCTION MUTATIONS OF PTGIR IDENTIFIED IN FIBROMUSCULAR DYSPLASIA AND SPONTANEOUS CORONARY ARTERY DISSECTION

Objective: Fibromuscular Dysplasia (FMD) and Spontaneous Coronary Artery Dissection (SCAD) are related, non-atherosclerotic arterial diseases mainly affecting middle-aged women. Little is known about their physiopathological mechanisms. We aimed to identify rare genetic causes to elucidate molecular mechanisms implicated in FMD and SCAD. Design and method: We analyzed 29 exomes that included familial and sporadic FMD. Follow-up was conducted by targeted or Sanger sequencing (1,071 FMD and 365 SCAD patients) or lookups in exome (264 FMD) or genome sequences (488 SCAD), all independent and unrelated. We used TRAPD burden test to test for enrichment in patients compared to gnomAD controls. The biological effects of variants on receptor signaling and protein expression were characterized using transient overexpression in human cells. Results: We identified one rare loss-of-function variant (LoF) (MAFgnomAD = 0.000075) shared by two FMD sisters in the prostaglandin I2 receptor (hIP) gene (PTGIR), a key player in vascular remodeling. Follow-up in >1,300 FMD patients revealed four additional LoF allele carriers and a putative enrichment in FMD (PTRAPD = 8 × 10-4), in addition to several rare missense variants. We confirmed the LoFs (Q163X and P17RfsX6) and one missense (L67P) to severely impair hIP function in vitro. Genetic analyses of PTGIR in SCAD revealed one patient who carries Q163X, one with L67P and one carrying a rare splicing mutation (c.768+1C>G), but not a significant enrichment (PTRAPD = 0.12) in SCAD. Conclusions: Our study shows that rare genetic mutations in PTGIR are enriched among FMD patients and found in SCAD patients, suggesting a role for prostacyclin signaling in non-atherosclerotic stenosis and dissection.

A Prospective, Longitudinal Magnetic Resonance Imaging Evaluation of Cerebrovascular Reactivity and Infarct Development in Patients With Intracranial Stenosis.

Patients with symptomatic atherosclerotic and non-atherosclerotic (i.e., moyamoya) intracranial steno-occlusive disease experience high 2-year infarct rates. To investigate whether cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) measures may provide biomarkers of 1-to-2-year infarct risk. Prospective, longitudinal study. Adult participants (age=18-85 years) with symptomatic intracranial atherosclerotic disease (N=26) or non-atherosclerotic (i.e., moyamoya; N=43) and stenosis ≥50% of a major intracranial artery were initially scanned within 45 days of stroke. Follow-up imaging (target =1.5 years) was acquired for new infarct assessment. 3.0 Tesla with normocapnic arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) imaging acquired during an interleaved hypercapnic (3 minutes) and normocapnic (3 minutes) respiratory stimulus. CBF, maximum CVR, and time-to-maximum CVR (i.e., CVRDELAY ) were calculated. Laterality indices (difference between infarcted and contralesional hemispheres divided by sum of absolute values) of metrics at enrollment were contrasted between participants with vs. without new infarcts on follow-up. Laterality indices were compared using non-parametric Wilcoxon tests (significance: two-sided P < 0.05) and effect sizes as Cohen's d. Continuous variables are presented as mean ± SD. New infarcts were observed on follow-up in 15.0% of participants. The laterality index of the CVRDELAY was elevated (P=0.01) in participants with atherosclerosis with new infarcts (index=0.13) compared to participants without new infarcts (index=0.05). Elevated CVRDELAY may indicate brain parenchyma at increased risk for new infarcts in patients with symptomatic intracranial atherosclerotic disease treated with standard-of-care medical management. 2 TECHNICAL EFFICACY STAGE: 3.

Fibromuscular dysplasia of mesenteric arteries: a rare cause of multiple bowel resections\u2014a case report and literature review

BackgroundFibromuscular dysplasia (FMD) is a type of unexplained nonatherosclerotic vascular disease that usually involves the renal and internal carotid arteries and rarely involves the mesenteric artery. Mesenteric artery FMD is difficult to distinguish from Crohn’s disease (CD) and Behcet’s disease (BD) solely based on symptoms. Patients with mesenteric artery FMD can present with an acute abdomen, but case reports of patients who have a long medical history and undergo multiple bowel resections are extremely rare.Case presentationThe patient was a 45-year-old woman with an 11-year history of intermittent lower abdominal pain and fever. At the age of 34 years, she underwent right hemicolectomy and appendectomy due to an acute abdomen. She suffered from oral ulcers between 34 and 36 years old. A clinical diagnosis of presumed CD was made by the age of 41, and she was treated with mesalazine; however, the effect was poor. At the age of 42, she came to our centre, and based on her atypical symptoms and examination results, we thought she had CD. Hence, she was treated with glucocorticoids for 3 years. However, when she was 45, due to steroid dependence, thalidomide tablets were added. Unfortunately, she suffered from another episode of intestinal obstruction. Therefore, she underwent enterectomy. The postoperative histopathological diagnosis was mesenteric artery FMD. She no longer underwent pharmacotherapy after the surgery. Although she did not have any of her previous symptoms and postoperative colonoscopy showed no signs of recurrence, splenomegaly and abnormal routine blood results were still present.ConclusionsPatients with mesenteric artery FMD can present with an acute abdomen. In addition, the symptoms and endoscopic manifestations of mesenteric artery FMD may appear similar to CD and BD. Hence, it is difficult to make a clear clinical diagnosis and proceed with treatment. Mesenteric artery FMD often requires surgical pathology to confirm its diagnosis. For patients who suffer from this disorder, surgery may be the best choice to improve the patient’s quality of life.

Current progress in clinical, molecular, and genetic aspects of adult fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string-of-beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research has led to improve our understanding of the disease's clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD.

Long-term outcomes of kidney donors with fibromuscular dysplasia

Fibromuscular dysplasia (FMD) is a non-atherosclerotic systemic arterial disease that is not infrequently discovered during kidney donor evaluation. Current guidelines do not provide recommendations regarding the use of kidneys from donors with FMD and there is a paucity of data on the outcomes of these donors. The Renal and Lung Living Donor Evaluation (RELIVE) Study addressed long-term outcomes of 8922 kidney donors who donated 1963 - 2007. We compared the development of hypertension, cardiovascular disease, proteinuria and reduced eGFR in 113 kidney donors with FMD discovered during donor evaluation to 452 propensity score matched donors without FMD. Outcomes modeling with logistic and Cox regression analysis and Kaplan Meier statistics were performed. Donors with FMD were older (51 vs. 39 years), were more likely to be women (80% vs. 56%) and had a higher systolic blood pressure at donation (124.7 vs. 121.3 mmHg), p < 0.05 for all. After a mean follow-up of 15.5 ± 8.9 years, a similar proportion of donors with and without FMD were alive, developed hypertension (22.2% vs 19.8%), proteinuria (20.6% vs 13.7%) and CVD (13.3% vs 13.5%). No donor with FMD developed an eGFR <30 ml/min/1.73 m2 or ESKD. The multivariable risk of mortality, cardiovascular disease and renal outcomes in donors with FMD were not elevated. Kidney donors with FMD appear to do well, do not appear to incur increased risks of hypertension, proteinuria, CVD or reduced eGFR and perhaps carefully selected candidates with FMD can safely donate as long as involvement of other vascular beds is ruled out.

MiR-100 alleviates the inflammatory damage and apoptosis of H2O2-induced human umbilical vein endothelial cells via inactivation of Notch signaling by targeting MMP9.

Thromboangiitis obliterans is a nonatherosclerotic segmental inflammatory disease, and miR-100 plays an anti-inflammatory role in chronic inflammation. Therefore, we hypothesized that miR-100 might alleviate the inflammatory damage and apoptosis of H2O2-induced ECV304 cells and aimed to investigate the relationship between miR-100 and thromboangiitis obliterans and the related molecular mechanism. Cell counting kit-8 was used to detect cell viability, and the expression of inflammatory factors and oxidative stress was measured by ELISA. TUNEL assay was used to detect the apoptosis of human umbilical vein endothelial cells after induction by H2O2. Furthermore, the interaction between miR-100 and matrix metalloproteinase-9 was verified by dual-luciferase assay. Quantitative reverse transcription polymerase chain reaction and western blot were used to detect the expression of the adhesion factors, apoptosis-related proteins and Notch pathway-related protein. The results revealed that miR-100 was decreased in H2O2-induced human umbilical vein endothelial cells. Overexpression of miR-100 attenuated inflammatory response and cell apoptosis in H2O2-induced human umbilical vein endothelial cells. The overexpression of miR-100 inhibited matrix metalloproteinase-9 expression in H2O2-induced human umbilical vein endothelial cells. miR-100 inhibited H2O2-induced human umbilical vein endothelial cell inflammation, oxidative stress, and cell apoptosis via inactivation of Notch signaling by targeting matrix metalloproteinase. Our study demonstrated that miR-100 reduced the inflammatory damage and apoptosis of H2O2-induced human umbilical vein endothelial cells via inactivation of Notch signaling by targeting matrix metalloproteinase. These findings suggested that miR-100 might be a novel therapeutic target for the prevention of thromboangiitis obliterans.

Cardiac involvement in eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome): Prospective evaluation at a tertiary referral centre

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis. Cardiac specific involvement (CSI) is caused by coronary artery vasculitis, but also by myocardial eosinophilic infiltration. To date, the prevalence of CSI associated with EGPA is unresolved. Aim of this study was to systematically assess the prevalence and clinical impact of CSI in a consecutive outpatient EGPA population. MethodsBetween October 2018 and July 2019, we prospectively enrolled 52 consecutive EGPA patients. All underwent comprehensive evaluation including a standardized questionnaire, physical examination, 12-lead-ECG, echocardiography. Cardiac magnetic resonance and 24 h-Holter were performed as deemed clinically appropriate. Cardiac abnormalities were defined as CSI based on the likelihood of their relation to EGPA vasculitis, after exclusion of alternative diagnoses. Results52 enrolled patients, mean age 59±1 years. Thirteen of the 52 patients (25%) were classified as CSI+. CSI was characterized by myocarditis in four patients, non-scar-related regional wall motions abnormalities (RWMA) in three, apical thrombosis in two (one also had RWMA), pericarditis in three and non-atherosclerotic coronary disease (Prinzmetal angina and coronaritis) in 2. Five (38%) of the 13 CSI+ patients, presented an apical aneurysm. Peak eosinophil count at diagnosis was higher in CSI+: 8000 /μl vs CSI-: 3000 /μl, p = 0.017. Overall, 2 patients had severe LV dysfunction, 5 required urgent hospitalization and 8 required long-term cardioactive therapy. ConclusionsCSI was present in one-quarter of patients, often associated with high peak eosinophils. Myocarditis, RWMA and apical aneurysms were the most common manifestations. Although rarely severe and life-threatening, CSI often required long-term cardioactive treatment.

Stem Cell Therapy for Thromboangiitis Obliterans (Buerger’s Disease)

Buerger’s disease or Thromboangiitis Obliterans (TAO) is a nonatherosclerotic segmental vascular disease which affects small and medium arteries and veins in the upper and lower extremities. Based on pathological findings, TAO can be considered as a distinct form of vasculitis that is most prevalent in young male smokers. There is no definitive cure for this disease as therapeutic modalities are limited in number and efficacy. Surgical bypass has limited utility and 24% of patients will ultimately require amputation. Recently, studies have shown that therapeutic angiogenesis and immunomodulatory approaches through the delivery of stem cells to target tissues are potential options for ischemic lesion treatment. In this review, we summarize the current knowledge of TAO treatment and provide an overview of stem cell-based treatment modalities.

Aortic invovement in fibromuscular dysplasia. 3-dimensional CT, case-control study. THE ARCADIA-POL BIS study

Abstract Background Fibromuscular dysplasia (FMD) is a non-atherosclerotic arterial disease that manifests as the presence of beaded or focal lesions in medium or small-sized arteries and may also include arterial dissection, aneurysm, and tortuosity. FMD could be revealed in various manifestations, however limited data on the involvement of the thoracic aorta is reported. Purpose To measure and evaluate involvement of thoracic aorta in patients with FMD. Methods We analysed aortas of 144 consecutive patients (mean age 50.2±14.0, 116 women) with confirmed FMD in at least one vascular bed. The control group consisted of 144 (mean age 50.5±14.0, 116 women) age and sex matched individuals. All patients underwent detailed clinical evaluation including angio-CT scan including aortic valve, thoracic aorta and coronary arteries. We measured the aortic valve annulus, sinus of valsalva, sinotubular junction, the diameters of ascending and descending aorta, aortic unfolding, the height of ostium of RCA and LCA and diameter of right and left coronary artery ostia in patients with fibromuscular dysplasia and compared them to matched controls. Results The FMD group had significantly smaller dimensions of aortic valve annulus and sinus of Valsalva than control group (2.3 [2.1–2.6] vs 2.9 [2.7–3.1] p&amp;lt;0,0001; 2.9 [2.7–3.2] vs 3.1 [2.8–3.3] p=0,0011 respectively). In addition the FMD group had a significantly greater mean diameter of the ascending and the descending aorta than the control group (3.1 [2.7–3.3] vs 3 [2.9–3] p=0,0436; 2.4 [2.2–2.7] vs 2.3 [1.8–2.5] p&amp;lt;0,0001 respectively). The height of the ostium of the left and of the right coronary artery was smaller in FMD than in the control group (1.2 [1.1–1.4] vs 1.3 [1.2–1.4] p=0,0001; 1.1 [1–1.3] vs 1.3 [1.1–1.4] p&amp;lt;0,0001 respectively). There was no difference in the diameter of sinotubular junction and the right and the left coronary artery ostias between the FMD and control groups (2.7 [2.5–2.9] vs 2.7 [2.5–2.9]; 0.3 [0.2–0.3] vs 0.3 [0.2–0.3]; 0.3 [0.3–0.3] vs 0.3 [0.3–0.4] respectively). Conclusions Patients with fibromuscular dysplasia display smaller dimensions of aortic valve and larger diameter of ascending and descending aorta as compared to control subjects. Despite the predominant clinical significance of focal pathologies in FMD patients, the disease may display a specific, pan-vascular phenotype. Funding Acknowledgement Type of funding source: None

Coronary arteries in fibromuscular dysplasia. 3-Dimensional coronary CT, case-control study. The ARCARDIA-POL BIS study

Abstract Background Fibromuscular dysplasia (FMD) is a non-atherosclerotic arterial disease characterized by the presence of string-of-beads or focal stenosis. Other FMD-related lesions include arterial dissections, aneurysms, and tortuosity. However, limited data are available on the involvement of coronary arteries in pts diagnosed with “extra-coronary” FMD. Purpose To examine FMD-related coronary artery involvement, coronary artery lesions and coronary tortuosity in patients with a diagnosis of “extra-coronary” FMD. Methods In a case control study we enrolled 103 (age 45.7±13.2, 82 women) consecutive patients with a diagnosis of FMD, in whom atherosclerotic coronary artery disease was excluded on the basis of coronary CTA, and 96 (age 47.3±12.2, 75 women) sex- and age-matched controls without coronary atherosclerosis based on CTA imaging (Siemens Force 2x192 scanner). Detailed analysis of coronary arteries was assessed, with detailed analysis of arterial tortuosity, defined as curves &amp;gt;30 OR &amp;gt;45 OR &amp;gt;90 degrees. Tortuosity Index (TI) was defined as number of curves x artery length (centerline) / vector artery start-end. Each arterial tortuosity evaluation was performed per coronary segment AND per artery. Size (area, length) of coronary arteries was also measured. Results Intravessel symmetry sign and cork-screw sign were more common in arteries of FMD patients than in controls (5.4% vs 1.3%, p&amp;lt;0.001; 1.2% vs 0%, p=0.03, respectively). Number of arterial curves and TI of LAD, LCx and RCA were higher in FMD patients than in controls (arterial curves: p&amp;lt;0.01 for all arteries – TI: 14.9 vs 8.5 for LAD, 9.8 vs 6.6 for LCX, and 11.2 vs 6.6 for RCA; p&amp;lt;0.001 for all arteries). According to the segmental analysis, AUC under the ROC curve indicated the highest value for prediction of FMD for the number of curves (&amp;gt;30 degrees) (0.777; 95% CI:0.713 to 0.833) or TI (0.794; 95% CI: 0.731 to 0.848), both in distal LAD. For the distal LAD indices, the best sensitivity and specificity values were for ≥4 curves (sens. 74%, spec. 72%) or for a TI &amp;gt;5.6 (sens. 55%, spec. 94%), respectively. These predictive values were confirmed after correction for potential confounders. Interestingly, neither proximal LAD or proximal LCx number of curves or TI were related to FMD. No difference was found in terms of areas of coronary arteries between FMD patients and controls, with the only exception of LM (20.8±6.6 vs 17.9±5.8, p=0.002). Mean coronary artery lenght was significantly different between controls and patients with FMD (respectively LM 8.4±4.2 vs 9.8±4.5, p=0.022; LAD 117.8±28.6 vs 109.1±30.2, p=0.042; LCx 85.2±43.9 vs 62.9±31.4, p&amp;lt;0.001; RCA 104.2±24.4 vs 115.7±25.8, p=0.002). No coronary aneurysms, ectasias or dissections were found in the examined cohort. Conclusions Distal and not proximal coronary arterial tortuosity is related to FMD. Coronary tortuosity defined as 4 distal LAD curves or a TI &amp;gt;5.6 are highly specific for FMD. Funding Acknowledgement Type of funding source: None

Prevalence and manifestations of diagnosed fibromuscular dysplasia by sex and race: Analysis of >4500 FMD cases in the United States

ObjectiveFibromuscular Dysplasia (FMD) is a rare non-atherosclerotic non-inflammatory vascular disease associated with arterial aneurysms and dissections. The epidemiology of FMD is not well understood. We sought to characterize the epidemiology of FMD utilizing a large aggregated electronic medical record database. MethodsWe used a commercial database (Explorys, IBM Watson), which aggregates data from electronic health records from 26 major integrated healthcare systems in the United States. Fibromuscular dysplasia cases were identified using a unique systemized nomenclature of medical terminology (SNOMED CT) term. We calculated the overall and age-, race-, and sex-based prevalence of FMD, and evaluated sex and race-specific differences in manifestations. ResultsA total of 40,566,670 individuals were active in the database from January 2015 to January 2020. Of these, 4860 had a diagnosis of FMD with an overall prevalence of 12.0 cases per 100,000 individuals. The majority of patients with FMD were female (n=4130, 85.0%), Caucasian (n=3960, 80.5%) and adults aged 18 to 65 years (n=2610, 53.7%). FMD was more common in women (prevalence 18.4 per 100,000) than men (4.0 per 100,000) and among Caucasians (15.8 per 100,000) than African Americans (11.2 per 100,000). Men and African Americans with FMD were more likely to have traditional atherosclerotic risk factors (hypertension, diabetes mellitus type 2, smoking, obesity, hyperlipidemia, chronic kidney disease), and vascular manifestations (stroke, renal infarction, claudication), compared with women and Caucasians. Men with FMD were more likely to have dissection of aorta and renal artery as well as aneurysm of vertebral artery, coronary artery, aorta and iliac artery. African-Americans were more likely to have ruptured aortic aneurysms than Caucasians. ConclusionsThe overall prevalence of FMD in this large aggregated electronic medical record study is estimated at 12.0 per 100,000 persons. FMD is more common in women and Caucasians, with variable characteristics and manifestations.

SPONTANEOUS CORONARY ARTERY DISSECTION MASQUERADING AS TAKOTSUBO CARDIOMYOPATHY

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Spontaneous coronary artery dissection (SCAD) is a phenomenon that disproportionately affects young peripartum women. The pathophysiology is not well understood. The proposed mechanism of injury describes intimal tear of the vasa vasorum with intramedial hemorrhage and progression to an intramural hematoma and creation of a false lumen. Coronary artery flow is occluded which ultimately results in myocardial ischemia and infarction. In peripartum women, it is theorized that hormones and hemodynamic stress weaken the coronary artery wall. Risk increases with multiparity. Diagnostically, the finding of apical akinesis via echocardiogram is a sensitive, however non-specific finding of left anterior descending artery spontaneous coronary dissection. Apical akinesis can also be found in Takotsubo cardiomyopathy and other important differential diagnoses in the postpartum female. The following case emphasizes the importance of maintaining a broad differential and holding a high suspicion for SCAD in the peripartum patient with chest pain. CASE PRESENTATION: A 33-year old female, G7P3043, on postpartum day nine presented to the emergency department with severe substernal chest pain with radiation to the back, associated with nausea and vomiting. Medical history was significant for gestational hypertension. She was noted to be hypertensive to 190 mmHg systolic. Electrocardiogram demonstrated ST elevations in leads II, III, and aVF. Bedside echocardiogram revealed apical akinesis with basal- and mid-sparing of the anterior and inferior segments. Initial troponin was negative however a serial troponin after four hours was greater than 25 ng/mL. She was started on intravenous heparin and monitored in the cardiac intensive care unit overnight due to high suspicion for Takotsubo. The following morning she was taken for cardiac catheterization, which found coronary artery dissection in the proximal portion of the left anterior descending artery with intramural hematoma and extension into the apical segments. No significant atherosclerotic disease was noted. Interventions were withheld. She had an uncomplicated hospital course and her chest pain subsided. She was discharged on Aspirin 81mg daily, Atorvastatin 80mg daily and Carvedilol 12.5 mg twice daily. DISCUSSION: Our patient was initially evaluated for a pulmonary embolism and cardiomyopathy before SCAD was considered, causing percutaneous coronary intervention to be initially deferred. Only when the patient continued to have a worsening troponin elevation and ongoing angina was she taken to cardiac catheterization. CONCLUSIONS: When young, postpartum women with minimal risk factors present with chest pain, clinicians should maintain a high suspicion for spontaneous coronary artery dissection.SCAD is the cause of acute coronary syndromes in only 4 % of all patients, but is present in nearly a quarter of the cases in women younger than 50 years old. Reference #1: Alfonso, Fernando. “Spontaneous Coronary Artery Dissection.” Circulation, vol. 126, no. 6, July 2012, pp. 667–670., doi:10.1161/circulationaha.112.122093. Reference #2: Mortensen, K.h., et al. “Spontaneous Coronary Artery Dissection: A Western Denmark Heart Registry Study.” Catheterization and Cardiovascular Interventions, vol. 74, no. 5, Jan. 2009, pp. 710–717., doi:10.1002/ccd.22115. Reference #3: Saw, Jacqueline, et al. “Nonatherosclerotic Coronary Artery Disease in Young Women.” Canadian Journal of Cardiology, vol. 30, no. 7, 2014, pp. 814–819., doi:10.1016/j.cjca.2014.01.011. DISCLOSURES: No relevant relationships by Lucie Henry, source=Web Response No relevant relationships by Philip Krupka, source=Web Response No relevant relationships by Meghan Snuckel, source=Web Response No relevant relationships by Bryan Stringer, source=Web Response

Rare loss-of-function mutations of PTGIR identified in fibromuscular dysplasia and spontaneous coronary artery dissection

Fibromuscular Dysplasia (FMD) and Spontaneous Coronary Artery Dissection (SCAD) are related, non-atherosclerotic arterial diseases mainly affecting middle-aged women. Little is known about their physiopathological mechanisms. We aimed to identify rare genetic causes to elucidate molecular mechanisms implicated in FMD and SCAD. We analyzed 29 exomes that included familial and sporadic FMD. Follow-up was conducted by targeted or Sanger sequencing (1,071 FMD and 365 SCAD patients) or lookups in exome (264 FMD) or genome sequences (488 SCAD), all independent and unrelated. We used TRAPD burden test to test for enrichment in patients compared to gnomAD controls. The biological effects of variants on receptor signaling and protein expression were characterized using transient overexpression in human cells. We identified one rare loss-of-function variant (LoF) (MAFgnomAD = 0.000075) shared by two FMD sisters in the prostaglandin I2 receptor (hIP) gene (PTGIR), a key player in vascular remodeling. Follow-up in > 1,300 FMD patients revealed four additional LoF allele carriers and a putative enrichment in FMD (PTRAPD = 8 × 10-4), in addition to several rare missense variants. We confirmed the LoFs (Q163X and P17RfsX6) and one missense (L67P) to severely impair hIP function in vitro. Genetic analyses of PTGIR in SCAD revealed one patient who carries Q163X, one with L67P and one carrying a rare splicing mutation (c.768 + 1C > G), but not a significant enrichment (PTRAPD = 0.12) in SCAD. Our study shows that rare genetic mutations in PTGIR are enriched among FMD patients and found in SCAD patients, suggesting a role for prostacyclin signaling in non-atherosclerotic stenosis and dissection.

Effectiveness of Surgical Treatment with Complete Cyst Excision for Cystic Adventitial Disease of the Popliteal Artery

Cystic adventitial disease is a rare, nonatherosclerotic disease that affects various arteries and veins, involving the formation of a mucinous cyst within the adventitia. The etiology of the cystic adventitial disease is currently unclear, with several hypotheses having been suggested. The purpose of this retrospective observational study was to evaluate the etiology of popliteal cystic adventitial disease based on imaging and surgical findings and to evaluate the efficacy of surgical treatment. From April 2013 to January 2020, nine patients were diagnosed with the popliteal cystic adventitial disease and underwent surgical treatment. We performed complete resection of the cyst and the affected segment of the popliteal artery, followed by interposition with autologous reversed small saphenous vein or great saphenous vein. The resected adventitial cyst tissue was multilobular, filled with high-viscosity mucus. Pathologic examination of the surgical specimen revealed intramural cysts filled with gelatinous material located between the media and the adventitia, consistent with the clinical diagnosis of cystic adventitial disease. The median follow-up period was 27.5months (range: 2-91months). All patients underwent cyst excision with graft interposition, and the overall graft patency was 80.9months (95% CI: 62.2-99.6months). Computed tomography, magnetic resonance imaging, and surgical findings confirmed communication between the synovial cyst and arterial adventitia. It is recommended that priority be given to surgical resection and graft interposition because this can eliminate the disease's cause and reduce its recurrence.

A review of metabolic syndrome parameters: Key players in aging pathogenesis

Metabolic syndrome represents a cluster of metabolic abnormalities (e.g., central obesity, hypertension, dyslipidemia, atherogenic, and insulin resistance), and is strongly linked to an enhanced risk for developing atherosclerotic, diabetes and nonatherosclerotic cardiovascular disease. To determine to what extent metabolic syndrome parameters are involved in the pathogenesis, and progression of aging. The scientific literature (Scopus, Google scholar, and PubMed) was searched from 1980 and 2020. The relationship among metabolic syndrome profiles and the aging is emerging as a public health question of importance to primary care practitioners. A number of studies have suggested a link between metabolic syndrome parameters with aging. Therefore, further investigations on the parameters of metabolic syndrome may be involved in the pathogenesis of aging. This review emphasizes the studies investigating the roles of metabolic syndrome, oxidative stress, inflammation, dyslipidemia, insulin resistance, overweight, high blood pressure, cardiovascular, type 2 diabetes in aging. © 2020, Advanced Scientific Research. All rights reserved.

The shearing stress of baseball–spontaneous coronary artery dissection in a male athlete

The following is a case report of an atypical presentation of spontaneous coronary artery disease. In this case, a male with risk factors, precipitated by an emotional stress, presented to the emergency room with atypical chest pain. Cardiac catheterization revealed tapering of the mid-left anterior descending artery, consistent with non-atherosclerotic spontaneous coronary artery disease. However due to repeat chest pain, a repeat cardiac catheterization was performed, revealing 100% occlusion of the mid-LAD. This case represents an atypical presentation of a pathology that is frequently missed, and underreported. This is important to discuss in order to increase awareness, as the management and follow up are actually conservative.

Targeting multiple domains of residual cardiovascular disease risk in patients with diabetes.

There has been a recent resurgence of diabetes-related cardiovascular complications after years of steady improvement. This review highlights established and emerging contemporary secondary prevention approaches that lower the risk of atherosclerotic and nonatherosclerotic cardiovascular disease events among patients with diabetes. Secondary prevention therapies modify residual risk targets, including cardiometabolic pathways, lipoproteins, thrombosis, and inflammation. Large-scale clinical trials of sodium-glucose cotransporter-2 inhibitors have demonstrated significant reductions in hospitalization for heart failure. Glucagon-like peptide-1 receptor agonists have reduced the risk of major adverse cardiovascular events. Recent clinical trials provide evidence supporting the use of nonstatin lipid-lowering therapies, novel antiplatelet and anticoagulant strategies, and antiinflammatory strategies in select cases. Therapeutic approaches targeting multiple distinct pathways have been shown to improve cardiometabolic risk in diabetes. Individual patient characteristics and consideration of residual risk targets may help guide selection of comprehensive secondary prevention approaches.

ASSOCIATION BETWEEN ERECTILE DYSFUNCTION AND SEVERITY OF CORONARY ARTERY DISEASE

Background: Erectile dysfunction (ED) is the most common sexual problem in men and defined as inability to attain or maintain a penile erection sufficient for successful vaginal intercourse. Erectile dysfunction is considered a primarily vascular disease in the majority of the cases. Numerous risk factors that contribute to the development and onset of ED are principal for the development of coronary artery disease (CAD). Objective: Documentation of the relation between erectile dysfunction and severity of coronary artery disease in patients presented with acute coronary syndrome focusing on the relation between onset of erectile dysfunction and onset of acute coronary ischemia. Patients and methods: This study included Egyptian patients admitted with acute coronary syndrome (ACS) with history of erectile dysfunction (ED), and underwent coronary angiography. They were subdivided into 3 groups: Group1 (control group G1, n= 30) which have a normal coronary angiography or non-atherosclerotic coronary artery disease, group 2 (G2, n= 36) which have a single coronary artery disease, group 3 (G3, n= 34) which have more than one coronary artery disease. Comparative study was done between three groups according to risk factors, comorbidities and severity of atherosclerotic coronary artery lesions according Gensini score, degree of erectile dysfunction which was assessed by international index of erectile function (IIEF) and penile artery duplex. Results: The total number of patients admitted with acute coronary syndrome (ACS) and diagnosed as erectile dysfunction patients according international index of erectile function (IIEF) was 36. The total number was 6 (20.0%) in the control group, 10 (27.8%) in the second group, 20 (58.8%) in the third group with a significant difference between groups. Comparison between results of penile artery duplex in our study groups was classified according to response to papaverine injection into either no erection, tumescence and rigidity not sufficient for intercourse, tumescence and rigidity sufficient for intercourse or full erection. There was no significant difference between groups. Conclusion: The recognition of ED was a warning sign of silent vascular disease. It has led to the concept that a man with ED and no cardiac symptoms is a cardiac (or vascular) patient until proven otherwise.