The genetics of spontaneous coronary artery dissection: a scoping review.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a multifactorial process that involves predisposing factors and precipitating stressors. Genetic abnormality has been implicated to play a mechanistic role in the development of SCAD. This systematic review aims to summarize the current evidence concerning the link between SCAD and genetic abnormalities. METHODS: We reviewed original studies published until May 2023 that reported SCAD patients with a genetic mutation by searching PubMed, Embase Ovid, and Google Scholar. Registries, cohort studies, and case reports were included if a definitive SCAD diagnosis was reported, and the genetic analysis was performed. Exclusion criteria included editorials, reviews, letters or commentaries, animal studies, meeting papers, and studies from which we were unable to extract data. Data were extracted from published reports. RESULTS: A total of 595 studies were screened and 55 studies were identified. Among 116 SCAD patients with genetic abnormalities, 20% had mutations in the COL gene, 13.70% TLN1 gene, and 8.42% TSR1 gene. Mutations affecting the genes encoding COL and TLN1 were most frequently reported (20 and 13.7%, respectively). Interestingly, 15 genes of this collection were also reported in patients with thoracic aortic diseases as well. The genetic commonality between fibromuscular dysplasia (FMD) and SCAD was also included. CONCLUSION: In this review, the inherited conditions and reported genes of undetermined significance from case reports associated with SCAD are collected. A brief description of the encoded protein and the clinical features associated with pathologic genes is provided. Current data suggested that the diagnostic yield of genetic studies for patients with SCAD would be low and routine genetic screening of such patients with no clinical features indicative of associated disorders remains debatable. This review can be used as a guide for clinicians to recognize inherited syndromic and nonsyndromic disorders associated with SCAD.

Prevalence, treatment efficacy, and risk factors of vascular complications in acute pancreatitis: A case-control study.

OBJECTIVE: We aimed to investigate the prevalence of vascular complications in acute pancreatitis (AP), to compare patient outcomes using various treatments, and to explore the related risk factors. METHODS: Consecutive AP patients admitted from January 2010 to July 2017 were retrospectively included. Demographics, vascular complications, laboratory indices, and imaging findings were collected. Univariate and multivariate analyses were used to explore potential risk factors of vascular complications. RESULTS: Of 3048 AP patients, 808 (26.5%) had vascular complications, including visceral vein thrombosis, sinistral portal hypertension, and arterial complications. And 38 (4.7%) patients received anticoagulant therapy and had a higher rate of recanalization (P < 0.001). Bleeding occurred in 95 (11.8%) patients, who received further treatment. Multivariate analysis identified male gender (odds ratio [OR] 1.650, 95% confidence interval [CI] 1.101-2.472), hyperlipidemia (OR 1.714, 95% CI 1.356-2.165), disease recurrence (OR 3.727, 95% CI 2.713-5.118), smoking (OR 1.519, 95% CI 1.011-2.283), hemoglobin level (OR 0.987, 95% CI 0.981-0.993), white blood cell (WBC) count (OR 1.094, 95% CI 1.068-1.122), non-vascular local complications (OR 3.018, 95% CI 1.992-4.573), computed tomography severity index (CTSI) (OR 1.425, 95% CI 1.273-1.596), and acute physiology and chronic health evaluation (APACHE) II score (OR 1.057, 95% CI 1.025-1.090) were related to vascular complications. CONCLUSIONS: Vascular complications in AP is prevalent and their treatment is challenging. Further investigations are warranted to determine the optimal treatment strategy. Independent risk factors included male gender, hyperlipidemia, disease recurrence, smoking, WBC count, non-vascular local complications, CTSI, and APACHE II score.

Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans.

Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3'-5' DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause DNA damage. Here, we show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and that cells expressing RVCL mutant TREX1 are more vulnerable to DNA damage induced by chemotherapy and cytokines that up-regulate TREX1, leading to depletion of TREX1-high cells in RVCL mice. RVCL-associated TREX1 mutants inhibit homology-directed repair (HDR), causing DNA deletions and vulnerablility to PARP inhibitors. In women with RVCL, we observe early-onset breast cancer, similar to patients with BRCA1/2 variants. Our results provide a mechanistic basis linking aberrant TREX1 activity to the DNA damage theory of aging, premature senescence, and microvascular disease.

Tortuosity in non-atherosclerotic vascular diseases is associated with age, arterial aneurysms, and hypertension.

BACKGROUND: Increased arterial tortuosity has been associated with various cardiovascular complications. However, the extent and role of arterial tortuosity in non-atherosclerotic vascular diseases remain to be fully elucidated. This study aimed to assess arterial tortuosity index (ATI) in patients with non-atherosclerotic vascular diseases and the associated factors. METHODS: This is a retrospective analysis of patients with non-atherosclerotic vascular diseases referred to the Malformation and Rare Vascular Disease Center at the University Hospital in Lausanne (Switzerland). Computed tomography angiography (CTA) images performed between October 2010 and April 2022 were retrieved and the aortic tortuosity index (ATI) was calculated. Patients were classified based on diagnosis into the following groups: arterial dissection & aneurysm, arteritis & autoimmune disease, hereditary connective tissue diseases, and fibromuscular dysplasia (FMD). Univariate and multivariate logistic regression analysis was used to determine potentially relevant predictors of aortic tortuosity. RESULTS: The mean age upon computed tomography angiography (CTA) was 46.8 (standard deviation [SD] 14.6) years and 59.1% of the patients were female. Mean ATI was higher in patients over 60 years old (1.27), in those with arterial aneurysms (mean: 1.11), and in those diagnosed with hypertension (mean: 1.13). When only patients over 60 years old were considered, those diagnosed with connective tissue diseases had the highest ATI. At multivariate regression analysis, increasing age (p < 0.05), presence of arterial aneurysms (p < 0.05), and hypertension (p < 0.05) were independently associated with ATI. CONCLUSIONS: The ATI may be a promising tool in diagnostic evaluation, cardiovascular risk stratification, medical or surgical management, and prognostic assessment in several non-atherosclerotic vascular conditions. Further studies with longitudinal design and larger cohorts are needed to validate the role of ATI in the full spectrum of vascular diseases.

Migraine headache in patients with spontaneous coronary artery dissection: A report of the iSCAD Registry.

INTRODUCTION: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction. Migraine headache has been reported to be common among patients with SCAD, but the degree of migraine-related disability has not been quantified. METHODS: Clinical data and headache variables were obtained from the baseline assessment of the prospective, multicenter iSCAD Registry. Migraine-related disability was quantified using the self-reported Migraine Disability Assessment (MIDAS). Demographic, clinical, psychosocial, and medical characteristics from data entry forms were compared between patients with and without migraine. RESULTS: Of the 773 patients with available data, 46% reported previous or current migraines. Those with migraines were more likely to be women (96.9% vs 90.3%, p = 0.0003). The presence of underlying carotid fibromuscular dysplasia was associated with migraine (35% vs 27%, p = 0.0175). There was not a significant association with carotid artery dissection and migraine. Current migraine frequency was less than monthly (58%), monthly (24%), weekly (16%), and daily (3%). Triptan use was reported in 32.5% of patients, and 17.5% used daily migraine prophylactic medications. Using the MIDAS to quantify disability related to migraine, 60.2% reported little or no disability, 14.4% mild, 12.7% moderate, and 12.7% severe. The mean MIDAS score was 9.9 (mild to moderate disability). Patients with SCAD had higher rates of depression and anxiety (28.2% vs 17.7% [p = 0.0004] and 35.3% vs 26.7% [p = 0.0099], respectively). CONCLUSIONS: Migraines are common, frequent, and a source of disability in patients with SCAD. The association between female sex, anxiety, and depression may provide some insight for potential treatment modalities.

Congenital Vascular and Lymphatic Diseases.

Over the past several centuries, the integration of contemporary medical techniques and innovative technologies, like genetic sequencing, have played a pivotal role in enhancing our comprehension of congenital vascular and lymphatic disorders. Nonetheless, the uncommon and complex characteristics of these disorders, especially considering their formation during the intrauterine stage, present significant obstacles in diagnosis and treatment. Here, we review the intricacies of these congenital abnormalities, offering an in-depth examination of key diagnostic approaches, genetic factors, and therapeutic methods.

Spontaneous coronary artery dissection (SCAD): A contemporary review.

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction that most frequently affects younger women, making it an important cause of morbidity and mortality within these demographics. The evolution of intracoronary imaging, improved diagnosis with coronary angiography, and ongoing research efforts and attention via social media, has led to increasing recognition of this previously underdiagnosed condition. In this review, we provide a summary of the current body of knowledge, as well as focused updates on the pathogenesis of SCAD, insights on genetic susceptibility, contemporary diagnostic tools, and immediate, short- and long-term management.

From Atherosclerosis to Spontaneous Coronary Artery Dissection: Defining a Clinical and Genetic Risk Spectrum for Myocardial Infarction.

PURPOSE OF REVIEW: Spontaneous coronary artery dissection (SCAD) has been increasingly recognized as a significant cause of acute myocardial infarction (AMI) in young and middle-aged women and arises through mechanisms independent of atherosclerosis. SCAD has a multifactorial etiology that includes environmental, individual, and genetic factors distinct from those typically associated with coronary artery disease. Here, we summarize the current understanding of the genetic factors contributing to the development of SCAD and highlight those factors which differentiate SCAD from atherosclerotic coronary artery disease. RECENT FINDINGS: Recent studies have revealed several associated variants with varying effect sizes for SCAD, giving rise to a complex genetic architecture. Associated genes highlight an important role for arterial cells and their extracellular matrix in the pathogenesis of SCAD, as well as notable genetic overlap between SCAD and other systemic arteriopathies such as fibromuscular dysplasia and vascular connective tissue diseases. Further investigation of individual variants (including in the associated gene PHACTR1) along with polygenic score analysis have demonstrated an inverse genetic relationship between SCAD and atherosclerosis as distinct causes of AMI. SCAD represents an increasingly recognized cause of AMI with opposing clinical and genetic risk factors from that of AMI due to atherosclerosis, and it is often associated with complex underlying genetic conditions. Genetic study of SCAD on a larger scale and with more diverse cohorts will not only further our evolving understanding of a newly defined genetic spectrum for AMI, but it will also inform the clinical utility of integrating genetic testing in AMI prevention and management moving forward.

Orai1/STIMs modulators in pulmonary vascular diseases.

Calcium (Ca2+) is a secondary messenger that regulates various cellular processes. However, Ca2+ mishandling could lead to pathological conditions. Orai1 is a Ca2+channel contributing to the store-operated calcium entry (SOCE) and plays a critical role in Ca2+ homeostasis in several cell types. Dysregulation of Orai1 contributed to severe combined immune deficiency syndrome, some cancers, pulmonary arterial hypertension (PAH), and other cardiorespiratory diseases. During its activation process, Orai1 is mainly regulated by stromal interacting molecule (STIM) proteins, especially STIM1; however, many other regulatory partners have also been recently described. Increasing knowledge about these regulatory partners provides a better view of the downstream signalling pathways of SOCE and offers an excellent opportunity to decipher Orai1 dysregulation in these diseases. These proteins participate in other cellular functions, making them attractive therapeutic targets. This review mainly focuses on Orai1 regulatory partners in the physiological and pathological conditions of the pulmonary circulation and inflammation.

Retrospective analysis of 1,203 cases of referral to a quaternary vascular surgery outpatient clinic within the Unified Health System, São Paulo, Brazil.

OBJECTIVE: Through a retrospective analysis of 1,203 cases of referral from primary healthcare units to a specialized quaternary vascular surgical service, the findings of this study revealed a high proportion of inappropriate referrals, which may represent a substantial subutilization of this highly complex service. Consequently, in this study, we aimed to evaluate 1,203 cases of referral to a quaternary vascular surgical service, in São Paulo, Brazil, over a 6-year period, to assess the appropriate need for referral; in addition to the prevalence of surgical indications. METHODS: In this retrospective analysis, we reviewed the institutional records of participants referred from Basic Healthcare Units to a vascular surgical service inside the Brazilian Unified Health System, between May 2015 and December 2020. Demographic and clinical data were collected. The participants were stratified, as per the reason for referral to the vascular surgical service, previous imaging studies, and surgical treatment indications. Referral appropriateness and complementary examinations were evaluated for each disease cohort. Finally, the prevalence of cases requiring surgical treatment was defined as the outcome measure. RESULTS: Of the 1,203 referrals evaluated, venous disease was the main reason for referral (53%), followed by peripheral arterial disease (19.4%). A considerable proportion of participants had been referred without complementary imaging or after a long duration of undergoing an examination. Referrals were regarded as inappropriate in 517 (43%) cases. Of these, 32 cases (6.2%) had been referred to the vascular surgical service, as the incorrect specialty. The percentage of referred participants who ultimately underwent surgical treatment was 39.92%. Carotid (18%) and peripheral arterial diseases (18.4%) were correlated with a lower prevalence of surgical treatments. CONCLUSION: The rate of referral appropriateness to specialized vascular care from primary care settings was low. This may represent a subutilization of quaternary surgical services, with low rates of surgical treatment.

RNF213-Related Vasculopathy: Various Systemic Vascular Diseases Involving RNF213 Gene Mutations: Review.

Moyamoya disease (MMD) is a cerebrovascular disorder that is predominantly observed in women of East Asian descent, and is characterized by progressive stenosis of the internal carotid artery, beginning in early childhood, and a distinctive network of collateral vessels known as "moyamoya vessels" in the basal ganglia. Additionally, a prevalent genetic variant found in most MMD cases is the p.R4810K polymorphism of RNF213 on chromosome 17q25.3. Recent studies have revealed that RNF213 mutations are associated not only with MMD, but also with other systemic vascular disorders, including intracranial atherosclerosis and systemic vascular abnormalities such as pulmonary artery stenosis and coronary artery diseases. Therefore, the concept of "RNF213-related vasculopathy" has been proposed. This review focuses on polymorphisms in the RNF213 gene and describes a wide range of clinical and genetic phenotypes associated with RNF213-related vasculopathy. The RNF213 gene has been suggested to play an important role in the pathogenesis of vascular diseases and developing new therapies. Therefore, further research and knowledge sharing through collaboration between clinicians and researchers are required.

Spontaneous Coronary Artery Dissection in a Male Patient With Fibromuscular Dysplasia.

A male patient presented with cardiac arrest attributed to anterior ST-segment elevation myocardial infarction from type 1 spontaneous coronary artery dissection. Subsequent imaging confirmed fibromuscular dysplasia in noncoronary arterial segments. The patient was started on guideline-directed medical therapy and referred to cardiac rehabilitation, showing substantial improvements in clinical status. With greater awareness and advancements in imaging, spontaneous coronary artery dissection has been more frequently recognized, and although as many as 81% to 92% of all cases occur in female patients, it can be seen among men, as well. Adjunctive imaging for arteriopathies may help establish the diagnosis for equivocal causes of acute coronary syndrome in women and men.

Spontaneous coronary artery dissection in patients with prior psychophysical stress: a systematic review of case reports and case series.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an underdiagnosed cause of acute coronary syndrome, particularly in younger women. Due to limited information about SCAD, case reports and case series can provide valuable insights into its features and management. This study aimed to comprehensively evaluate the features of SCAD patients who experienced psychophysical stress before the SCAD event. METHODS: We conducted an electronic search of PubMed, Scopus, and Web of Science from inception until January 7, 2023. We included case reports or series that described patients with SCAD who had experienced psychophysical stress before SCAD. Patients with pregnancy-associated SCAD were excluded from our analysis. RESULTS: In total, we included 93 case reports or series describing 105 patients with SCAD. The average patient age was 44.29 ± 13.05 years and a total of 44 (41.9%) of patients were male. Among the included SCAD patients the most prevalent comorbidities were fibromuscular dysplasia (FMD) and hypertension with the prevalence of 36.4 and 21.9%, respectively. Preceding physical stress was more frequently reported in men than in women; 38 out of 44 (86.4%) men reported physical stress, while 36 out of 61 (59.1%) females reported physical stress (p value = 0.009). On the other hand, the opposite was true for emotional stress (men: 6 (13.6%)), women: 29 (47.6%), p value < 0.001). Coronary angiography was the main diagnostic tool. The most frequently involved artery was the left anterior descending (LAD) (62.9%). In our study, recurrence of SCAD due to either the progression of a previous lesion or new SCAD in another coronary location occurred more frequently in those treated conservatively, however the observed difference was not statistically significant (p value = 0.138). CONCLUSION: While physical stress seems to precede SCAD in most cases, emotional stress is implicated in females more than males.

ST-segment elevation myocardial infarction (STEMI) caused by spontaneous coronary artery dissection (SCAD) in a patient with von Willebrand disease.

A postpartum woman in her early 40s, with a history of pre-eclampsia and von Willebrand disease (VWD), presented to the emergency room with chest pain suggestive of an acute coronary syndrome. Initial workup revealed an evolving anterior wall ST-segment elevation myocardial infarction on ECG and elevated cardiac biomarkers, confirming myocardial damage. Point-of-care ultrasound showed apical hypokinesis and coronary angiography revealed a distal dissection of the left anterior descending coronary artery. There was TIMI 3 flow and no evidence of plaque rupture. No percutaneous coronary intervention was performed and the patient was managed conservatively.Fibromuscular dysplasia was ruled out on screening CT angiography. Dual antiplatelet therapy was initiated for an amended course of 3 months given the history of VWD. Our patient had an uncomplicated course in the hospital with a downward trend in their cardiac biomarkers, resolving anterior ST elevation on serial ECGs, and no bleeding complications.

Increased mortality in acromegaly is due to vascular and respiratory disease and is normalised by control of GH levels-A retrospective analysis from the UK Acromegaly Register 1970-2016.

CONTEXT: Epidemiological studies involving patients with acromegaly have yielded conflicting results regarding cancer incidence and causes of mortality in relation to control of growth hormone (GH) excess. OBJECTIVE: The objective of this retrospective cohort study is to clarify these questions and identify goals for treatment and monitoring patients. METHODS: We studied 1845 subjects from the UK Acromegaly Register (1970-2016), obtaining cancer standardised incidence rates (SIR) and all causes standardised mortality rates (SMR) from UK Office for National Statistics, to determine the relationship between causes of mortality-age at diagnosis, duration of disease, post-treatment and mean GH levels. RESULTS: We found an increased incidence of all cancers (SIR, 1.38; 95% CI: 1.06-1.33, p < .001), but no increase in incidence of female breast, thyroid, colon cancer or any measure of cancer mortality. All-cause mortality rates were increased (SMR, 1.35; 95% CI: 1.24-1.46, p < .001), as were those due to vascular and respiratory diseases. All-cause, all cancer and cardiovascular deaths were highest in the first 5 years following diagnosis. We found a positive association between post-treatment and mean treatment GH levels and all-cause mortality (p < .001 and p < .001), which normalised with posttreatment GH levels of <1.0 µg/L or meantreatment GH levels of <2.5 µg/L. CONCLUSION: Acromegaly is associated with increased incidence of all cancers but not thyroid or colon cancer and no increase in cancer mortality. Excess mortality is due to vascular and respiratory disease. The risk is highest in the first 5 years following diagnosis and is mitigated by normalising GH levels.

Portal vein gas is a sign of intestinal necrosis after pesticide poisoning: a case report.

Portal vein gas accumulation and intestinal pneumatosis are uncommon signs indicating a high mortality risk in cases of intestinal ischemic necrosis. However, the widespread use of computed tomography has led to an increase in detection of benign lesions. We report a case of portal vein gas accumulation resulting from organophosphorus pesticide poisoning. A male patient was brought to the hospital in a comatose state with bilateral pupils that measured 1.0 mm, and he showed shortness of breath and wet rattles in the lungs. A cholinesterase concentration of 214 U/L was detected on an auxiliary examination. The patient was diagnosed with organophosphorus pesticide poisoning and underwent mechanical ventilation, hemoperfusion, and continuous renal replacement therapy according to the poisoning guidelines. On the fifth day, considerable abdominal distension was observed. An abdominal computed tomography scan revealed dilation of the small bowel and ascending colon with fluid and gas accumulation, as well as gas within the intestinal wall and hepatic veins. Although portal vein gas and intestinal pneumatosis are a sign of mortality requiring immediate surgical intervention, an increasing number of benign cases suggests potential benefits of conservative treatment approaches.