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.

Risk of Type B Dissection in Marfan Syndrome: The Cornell Aortic Aneurysm Registry.

BACKGROUND: With preventive aortic grafting decreasing the incidence of type A dissections in Marfan syndrome (MFS), most dissections are now type B, for which risk factors remain largely uncertain. OBJECTIVES: We explored the determinants of type B dissection risk in a large, single-center MFS registry. METHODS: Demographic and anthropometric features, cardiovascular disease, and surgical history were compared in patients with MFS with and without type B dissection. RESULTS: Of 336 patients with MFS, 47 (14%) experienced a type B dissection (vs type A in 9%). Patients with type B dissection were more likely to have undergone elective aortic root replacement (ARR) (79 vs 46%; P < 0.001). Of the patients, 55% had type B dissection a mean of 13.3 years after ARR, whereas 45% experienced type B dissection before or in the absence of ARR; 41 patients (87%) were aware of their MFS diagnosis before type B dissection. Among those with predissection imaging, the descending aorta was normal or minimally dilated (<4.0 cm) in 88%. In multivariable analyses, patients with type B dissection were more likely to have undergone ARR and independent mitral valve surgery, to have had a type II dissection, and to have lived longer. CONCLUSIONS: In our contemporary cohort, type B dissections are more common than type A dissections and occur at traditional nonsurgical thresholds. The associations of type B dissection with ARR, independent mitral valve surgery, and type II dissection suggest a more severe phenotype in the setting of prolonged life expectancy.

Sex Differences in Thoracic Aortic Disease and Dissection: JACC Review Topic of the Week.

Despite its higher prevalence among men, women with thoracic aortic aneurysm and dissection (TAAD) have lower rates of treatment and surgical intervention and often have worse outcomes. A growing number of women with TAAD also desire pregnancy, which can be associated with an increased risk of aortic complications. Understanding sex-specific differences in TAAD has the potential to improve care delivery, reduce disparities in treatment, and optimize outcomes for women with TAAD.

Spontaneous coronary artery dissection: an unpredictable event.

Spontaneous coronary artery dissection (SCAD) is an under-recognized cause of acute coronary syndrome that predominantly affects women in adulthood and is the leading cause of acute myocardial infarction in pregnancy. The most common clinical presentation is ST-segment elevation myocardial infarction (STEMI) or non-STEMI, followed by cardiogenic shock (∼2%), sudden cardiac death (0.8% in autopsy series), cardiac arrest, ventricular arrhythmias (∼5%), and Takotsubo syndrome. The prevalence of SCAD in the general population is largely uncertain due to underdiagnosis. Oral contraceptives, post-menopausal therapy, and infertility treatments are recognized associated factors. The pathological substrates (fibromuscular dysplasia) and triggers (especially emotional stress) are commonly present in affected women. The few cases with a precise genetic aetiology occur in the context of syndromic and non-syndromic connective tissue diseases. The only true certainty in SCAD is the overwhelming prevalence in women. The first event as well as the recurrence (up to 30%, which varies depending on the definition) is largely unpredictable. The treatment strategy is highly individualized and requires extensive additional study in order to optimize outcomes and prevent major adverse cardiovascular events in affected individuals. We have known about SCAD for nearly a century, but we still do not know how best to prevent, diagnose, and treat it, making SCAD a highly important and unmet clinical need.

Prevalence and Complications of Aberrant Subclavian Artery in Patients With Heritable and Nonheritable Arteriopathies.

BACKGROUND: An aberrant subclavian artery (ASA) (or lusoria) is the most common congenital anomaly of the aortic arch (0.5%-2.2%; female-to-male ratio 2:1 to 3:1). ASA can become aneurysmal and result in dissection, involving Kommerell's diverticulum when present and the aorta. Data of its significance in genetic arteriopathies are not available. OBJECTIVES: The purpose of this study was to assess the prevalence and complications of ASA in gene-positive and -negative nonatherosclerotic arteriopathies. MATERIALS: The series includes 1,418 consecutive patients with gene-positive (n = 854) and gene-negative arteriopathies (n = 564) diagnosed as part of institutional work-up for nonatherosclerotic syndromic and nonsyndromic arteriopathies. Comprehensive evaluation includes genetic counseling, next-generation sequencing multigene testing, cardiovascular and multidisciplinary assessment, and whole-body computed tomography angiography. RESULTS: ASA was found in 34 of 1,418 cases (2.4%), with a similar prevalence in gene-positive (n = 21 of 854, 2.5%) and gene-negative (n = 13 of 564, 2.3%) arteriopathies. Of the former 21 patients, 14 had Marfan syndrome, 5 had Loeys-Dietz syndrome, 1 had type-IV Ehlers-Danlos syndrome, and 1 had periventricular heterotopia type 1. ASA did not segregate with genetic defects. Dissection occurred in 5 of 21 patients with genetic arteriopathies (23.8%; 2 Marfan syndrome and 3 Loeys-Dietz syndrome), all with associated Kommerell's diverticulum. No dissections occurred in gene-negative patients. At baseline, none of the 5 patients with ASA dissection fulfilled criteria for elective repair according to guidelines. CONCLUSIONS: The risk of complications of ASA is higher in patients with genetic arteriopathies and is difficult to predict. In these diseases, imaging of the supra-aortic trunks should enter baseline investigations. Determination of precise indications for repair can prevent unexpected acute events such as those described.

Impact of acute TTE-evidenced cardiac dysfunction on in-hospital and outpatient mortality: A multicenter NYC COVID-19 registry study.

BACKGROUND: COVID-19 is associated with cardiac dysfunction. This study tested the relative prognostic role of left (LV), right and bi- (BiV) ventricular dysfunction on mortality in a large multicenter cohort of patients during and after acute COVID-19 hospitalization. METHODS/RESULTS: All hospitalized COVID-19 patients who underwent clinically indicated transthoracic echocardiography within 30 days of admission at four NYC hospitals between March 2020 and January 2021 were studied. Images were re-analyzed by a central core lab blinded to clinical data. Nine hundred patients were studied (28% Hispanic, 16% African-American), and LV, RV and BiV dysfunction were observed in 50%, 38% and 17%, respectively. Within the overall cohort, 194 patients had TTEs prior to COVID-19 diagnosis, among whom LV, RV, BiV dysfunction prevalence increased following acute infection (p<0.001). Cardiac dysfunction was linked to biomarker-evidenced myocardial injury, with higher prevalence of troponin elevation in patients with LV (14%), RV (16%) and BiV (21%) dysfunction compared to those with normal BiV function (8%, all p<0.05). During in- and out-patient follow-up, 290 patients died (32%), among whom 230 died in the hospital and 60 post-discharge. Unadjusted mortality risk was greatest among patients with BiV (41%), followed by RV (39%) and LV dysfunction (37%), compared to patients without dysfunction (27%, all p<0.01). In multivariable analysis, any RV dysfunction, but not LV dysfunction, was independently associated with increased mortality risk (p<0.01). CONCLUSIONS: LV, RV and BiV function declines during acute COVID-19 infection with each contributing to increased in- and out-patient mortality risk. RV dysfunction independently increases mortality risk.

Impediments to Heart Transplantation in Adults With MELASMT-TL1:m.3243A>G Cardiomyopathy.

BACKGROUND: The heart is commonly involved in maternally inherited mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome caused by the MT-TL1 m.3243A>G mutation of the mitochondrial DNA. Heart transplantation (HTx) is controversial and has rarely been performed with conflicting results. OBJECTIVES: We analyzed factors preventing HTx in consecutive adult patients with MELASMT-TL1:m.3243A>G cardiomyopathy diagnosed and followed during the last 23 years in our HTx referral center. METHODS: The series consists of 14 unrelated adult probands who were referred for evaluation of cardiomyopathy from 1998 to 2021. None had a suspected diagnosis of MELAS before referral. All patients underwent clinical and genetic visit and counseling, mitochondrial DNA sequencing, cardiovascular investigation (including right heart catheterization and endomyocardial biopsy in 10), multidisciplinary assessment, and biochemical tests. Family screening identified 2 affected relatives. RESULTS: The cardiac phenotype was characterized by hypertrophic, concentric, nonobstructive cardiomyopathy that often evolved into a dilated cardiomyopathy-like phenotype. Of the 14 probands, 7 were potential candidates for HTx, 2 for heart and kidney Tx, and 1 was on the active HTx list for 3 years. None of the 10 probands underwent HTx. One is currently being evaluated for HTx. All had diabetes, hearing loss, and myopathy, and 10 had chronic kidney disease and progressive encephalomyopathy. During follow-up, 10 died from heart failure associated with multiorgan failure within 5 years of the genetic diagnosis. CONCLUSIONS: High risk of stroke-like episodes, chronic kidney disease, and wasting myopathy in MELASMT-TL1:m.3243A>G patients prevents activation of plans for HTx. As a result, the management of their cardiomyopathy in this syndromic context remains an unmet clinical need.

Pregnancy-Related Aortic Complications in Women With Marfan Syndrome.

BACKGROUND: The risk of pregnancy-associated vascular complications in Marfan syndrome (MFS) is uncertain because of ascertainment bias, prepartum lack of knowledge of diagnosis, and insufficient peripartum imaging data. Furthermore, U.S. and European guidelines differ in pregnancy recommendations in MFS. OBJECTIVES: This study describes a single-center experience of 169 MFS women to address these gaps. METHODS: Clinical, imaging, and pregnancy history were compared in never vs ever-pregnant MFS women, and pregnancy-associated vascular complications were described. RESULTS: A total of 74 ever-pregnant women had 112 live births. Elective aortic root replacement occurred at a younger age in never-pregnant women (33 years vs 42 years; P = 0.0026). Although aortic dissection prevalence did not differ between never-pregnant vs ever-pregnant women (23% vs 31%; P = 0.25), it tended to occur at an earlier age in the former group (38 years vs 45 years; P = 0.07). Of observed "sanctioned" pregnancies with prepartum diameters ≤4.5 cm, mean pregnancy-related aortic diameters remained stable. In total, 5 dissections were associated with pregnancy: 2 type A in women unaware of their diagnosis; and 2 type B and 1 isolated coronary artery dissection in women aware of their diagnosis. Dissection rates were 5-fold higher in the pregnancy vs nonpregnancy period. CONCLUSIONS: Pregnancy-related type A dissection only occurred in patients unaware of their diagnosis. Type B dissection remains an unpredictable complication. Although there were baseline differences between the never- and ever-pregnant groups, no difference in dissection risk was observed outside the peripartum period. Those with prepartum aortic diameters between 4.0 and 4.5 cm demonstrated stable aortic dimensions throughout pregnancy. These findings provide a rationale to update existing U.S. guidelines for the management of pregnancy in MFS.

Sex-Based Disparities in Outcomes With Abdominal Aortic Aneurysms.

Although abdominal aortic aneurysms (AAA) are more common in men, women with AAA have increased morbidity and mortality. Additionally, there are discrepancies among professional society guidelines for AAA screening in women. In this retrospective study from the Nationwide Inpatient Sample (NIS) database from 2003 to 2014, we compared rates of AAA repair (rupture and elective) and AAA-related mortality in men vs. women to identify predictors of death among men and women with AAA. We divided the population into 1) AAA rupture 2) elective AAA repair. The main outcomes included temporal trends in AAA rupture, rupture-related death, AAA repair, in-hospital death, and predictors of AAA-related death. There were 570,253 discharge records for AAA admissions between 2003 and 2014, including 22.8% women and 77.2% men. Women had a higher proportion of rupture (18.4% vs 12.6%, p <0.01). A smaller proportion of women underwent endovascular aortic repair (EVAR) compared with men in the ruptured AAA (13.9% vs. 20.3%, p <0.01) and elective repair (55.7% vs. 67.4%, p <0.01) cohorts. Within the ruptured cohort, a higher proportion of women did not receive repair (46.4% vs. 26.1%, p <0.01). On multivariable analysis, female gender was a significant predictor of death with rupture (OR 1.39, 95% CI 1.16 to 1.66) and elective repair (OR 1.74, 95% CI 1.36 to 2.22), with both elective EVAR (OR 2.52, 95% CI 2.06 to 3.09) and elective open aortic repair (OAR; OR 1.50, 95% CI 1.33 to 1.68). Propensity score matching confirmed a higher risk of death in women in both the rupture (OR 1.19, 95% CI 1.09 to 1.30) and elective repair (OR 1.50, 95% CI 1.35 to 1.67) cohorts. In conclusion, AAA poses significant morbidity and mortality, especially in women. Women were more likely to die before repair with AAA rupture and female gender was an independent predictor of mortality in both the rupture and elective repair groups.

Prognostic Utility of Right Ventricular Remodeling Over Conventional Risk Stratification in Patients With COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a growing pandemic that confers augmented risk for right ventricular (RV) dysfunction and dilation; the prognostic utility of adverse RV remodeling in COVID-19 patients is uncertain. OBJECTIVES: The purpose of this study was to test whether adverse RV remodeling (dysfunction/dilation) predicts COVID-19 prognosis independent of clinical and biomarker risk stratification. METHODS: Consecutive COVID-19 inpatients undergoing clinical transthoracic echocardiography at 3 New York City hospitals were studied; images were analyzed by a central core laboratory blinded to clinical and biomarker data. RESULTS: In total, 510 patients (age 64 ± 14 years, 66% men) were studied; RV dilation and dysfunction were present in 35% and 15%, respectively. RV dysfunction increased stepwise in relation to RV chamber size (p = 0.007). During inpatient follow-up (median 20 days), 77% of patients had a study-related endpoint (death 32%, discharge 45%). RV dysfunction (hazard ratio [HR]: 2.57; 95% confidence interval [CI]: 1.49 to 4.43; p = 0.001) and dilation (HR: 1.43; 95% CI: 1.05 to 1.96; p = 0.02) each independently conferred mortality risk. Patients without adverse RV remodeling were more likely to survive to hospital discharge (HR: 1.39; 95% CI: 1.01 to 1.90; p = 0.041). RV indices provided additional risk stratification beyond biomarker strata; risk for death was greatest among patients with adverse RV remodeling and positive biomarkers and was lesser among patients with isolated biomarker elevations (p ≤ 0.001). In multivariate analysis, adverse RV remodeling conferred a >2-fold increase in mortality risk, which remained significant (p < 0.01) when controlling for age and biomarker elevations; the predictive value of adverse RV remodeling was similar irrespective of whether analyses were performed using troponin, D-dimer, or ferritin. CONCLUSIONS: Adverse RV remodeling predicts mortality in COVID-19 independent of standard clinical and biomarker-based assessment.

Pathologic Disparities Between Peripheral Artery Disease and Coronary Artery Disease.

Atherosclerosis is a systemic disease that involves multiple vascular beds. The pathological characteristics and clinical presentation, however, vary among the different vascular territories. Acute coronary syndrome is a relatively common manifestation of coronary atherosclerotic disease, wherein the thrombosis occurs secondary to disruption (65%-75%) and erosion (25%-35%) of the fibrous caps of atheromatous plaques. The plaques associated with plaque rupture have large necrotic cores and thin and inflamed fibrous caps. However, the pathological manifestations of peripheral artery disease result from thrombosis regardless of the extent of atherosclerosis. Approximately 75% of peripheral arteries with significant stenosis demonstrate presence of thrombi, of which two-thirds have thrombi associated with insignificant atherosclerosis. The presence of obliterative thrombi in peripheral arteries of patients with critical limb ischemia in the absence of coronary artery-like lesions suggests a locally thrombogenic or remotely embolic basis of disease. Extensive calcification of the medial vascular layer is commonly observed. In this review, we have described and compared the pathological basis of coronary and peripheral artery disease in patients with acute coronary syndrome and critical limb ischemia. It is expected that pathogenetic characterization would allow for definition of strategic targets for superior management of peripheral artery disease.

Pathologic substrate of gastropathy in Anderson-Fabry disease.

In both classic and late-onset AFD, mutations of the GLA gene cause deficient activity of the alpha-galactosidase enzyme resulting in intracellular accumulation of the undigested substrate. Gastrointestinal symptoms (GI) are common but non-specific and imputed to the AFD, irrespective of the demonstration of substrate accumulation in GI cells. We demonstrate substrate accumulation in gastric epithelial, vascular, and nerve cells of patients with classic AFD and, vice versa, absence of accumulation in late-onset AFD and controls.

A Challenging Case of Extensive Spontaneous Coronary Artery Dissection.

The detection of spontaneous coronary artery dissection (SCAD) causing myocardial infarction is integral in pursuing the appropriate management. Our case posed a diagnostic challenge, with Takotsubo cardiomyopathy and coronary embolism among the potential differential diagnoses upon the initial presentation. Extensive propagation of spontaneous coronary artery dissection subsequently resulted in a significant challenge to management requiring surgical revascularization. (Level of Difficulty: Intermediate.).

Circulating Osteogenic Progenitor Cells in Mild, Moderate, and Severe Aortic Valve Stenosis.

The aim of this study was to characterize endothelial progenitor cells with osteoblastic phenotype (EPC-OCNs) and their role in individuals with varying degrees of aortic stenosis (AS). Peripheral blood mononuclear cells retrieved from blood samples of individuals with mild (n=40), moderate (n=35), or severe (n=103) AS from September 16, 2008, through March 30, 2015, were analyzed by flow cytometry for the EPC surface markers CD34, CD133, and kinase insert domain receptor (KDR) and the osteoblastic cell surface marker OCN. Levels of EPC-OCNs were correlated with AS severity and calcifications. Patients with severe AS had significantly elevated numbers of total circulating EPC-OCNs, including the EPC-OCN subtypes CD133+/OCN+, CD34+/CD133+/OCN+, and CD133+/KDR+/OCN+, compared with those with mild AS. Individuals with moderate AS also had significantly increased numbers of the circulating progenitor cell CD133+/OCN+ compared with patients with mild AS. There was a significant association between total circulating EPC-OCN levels and aortic valve (AV) calcification, AV mean gradient, and AV area measured by echocardiography. In summary, this study found the presence of circulating EPC-OCNs in patients with progressive AV stenosis. These findings might support the potential role for EPC-OCNs in the progression of AV stenosis and calcification.

Is Cardiac Diastolic Dysfunction a Part of Post-Menopausal Syndrome?

Post-menopausal women exhibit an exponential increase in the incidence of heart failure with preserved ejection fraction compared with men of the same age, which indicates a potential role of hormonal changes in subclinical and clinical diastolic dysfunction. This paper reviews the preclinical evidence that demonstrates the involvement of estrogen in many regulatory molecular pathways of cardiac diastolic function and the clinical data that investigates the effect of estrogen on diastolic function in post-menopausal women. Published reports show that estrogen deficiency influences both early diastolic relaxation via calcium homeostasis and the late diastolic compliance associated with cardiac hypertrophy and fibrosis. Because of the high risk of diastolic dysfunction and heart failure with preserved ejection fraction in post-menopausal women and the positive effects of estrogen on preserving cardiac function, further clinical studies are needed to clarify the role of endogenous estrogen or hormone replacement in mitigating the onset and progression of heart failure with preserved ejection fraction in women.