Gulati, Rajiv

Background: Spontaneous coronary artery dissection (SCAD) is the principal cause of peripartum myocardial infarction (MI). Clinical features remain incompletely understood. Methods: Medical records of all women enrolled in a SCAD registry at the Mayo Clinic were reviewed to identify those who were either pregnant or ≤12 weeks postpartum at time of initial event. Diagnosis of SCAD was confirmed with coronary angiography in all cases. Obstetrical outcomes and incidence of recurrent SCAD events were assessed. Results: In total, 38 of 363 women enrolled in the registry met criteria for peripartum MI due to SCAD. Mean age at time of SCAD was 36±3 (range 27-42) years; 3 patients were pregnant at the time of initial event, and all pregnancies except 2 resulted in a live birth. Ten (26%) were diagnosed with multivessel SCAD (MV-SCAD). Most (60%) postpartum events occurred within 30 days of delivery. Antecedent co-morbidities included gestational hypertension/preeclampsia (9), fibromuscular dysplasia (7), gestational diabetes (4), and mixed connective tissue disease (1). Compared to US population birth data, women with peripartum SCAD were more likely to be ≤ 30 years at the time of first delivery (60% vs 42%) and more often multiparous (80% vs 59%). On long-term follow-up (median 3.7 years, IQR 1.1-7.1), 5 (13%) women experienced recurrent SCAD, with one episode occurring following a subsequent pregnancy. MV-SCAD was not associated with increased risk of recurrence (p=0.44). Conclusion: Women with peripartum SCAD are both older than the general obstetrical population at the time of first pregnancy and frequently multiparous at time of initial SCAD event. The highest frequency of SCAD was encountered during the first postpartum month, suggesting variations in hormonal and hemodynamic factors may contribute to SCAD events in susceptible women.

Background: Spontaneous coronary artery dissection (SCAD) typically presents as acute coronary syndrome in young women with no cardiovascular risk factors. It is associated with high morbidity and mortality, and is underdiagnosed. Despite this, risk factors and pathophysiology associated with SCAD are not completely understood. The objective of the present case series was to assess family history as a risk factor in patients with SCAD. Methods: We reviewed the medical records and questionnaires of 335 participants in the Mayo Clinic SCAD Registry for history of MI, SCAD or CAD in another family member. Coronary angiograms of all affected family members were reviewed by a senior interventional cardiologist. Results: We identified 4 familial cases of SCAD comprised of affected mother-daughter, identical twin sister, sister and aunt-niece pairs, implicating both recessive and dominant modes of inheritance. The mother-daughter pair also reported history of fatal MI in 3 maternal relatives including grandmother, great grandmother and great aunt. One of the affected twin sisters died of SCAD, which was confirmed on autopsy. None of the subjects had other potential risk factors for SCAD including extreme exercise, polycystic kidney disease, connective tissue disorder, peripartum status or diagnosed non-coronary fibromuscular dysplasia. The details of their demographics, risk factors, presentation, location of SCAD and management are presented in the table. Conclusions: This series is the first to identify a familial association in SCAD suggesting a genetic predisposition. Recognition of SCAD as a heritable disorder has implications for at-risk family members and furthers our understanding of the pathophysiology of this complex disease. Whole exome sequencing in these families provides a unique opportunity to identify the molecular underpinnings of SCAD susceptibility.

Introduction: Triple oral antithrombotic therapy (TOAT) (aspirin, clopidogrel, and warfarin) is associated with an increased risk of bleeding. Despite this, the optimal management of patients with indications for warfarin following percutaneous coronary intervention (PCI) has not been established. We sought to compare long-term clinical outcomes between patients receiving TOAT with those receiving dual antiplatelet therapy (DAPT) (aspirin and clopidogrel) after PCI. Hypothesis: Patients with clinical indications for warfarin have higher baseline risk which is largely responsible for the observed differences in outcomes between patients receiving TOAT vs. DAPT. Methods: Retrospective analysis of prospectively collected data from 9,009 patients. The primary outcome was a composite of all-cause mortality, ischemic or embolic events (myocardial infarction or stroke), or bleeding. Secondary outcomes were death plus ischemic or embolic events, death plus bleeding, death, MI, stroke, and bleeding. A 2:1 propensity matched analysis was also performed. Results: In 9,009 patients, 812 received TOAT and 8,197 received DAPT. Median follow-up was 61 months. The primary end point occurred in 2,749 patients. At 1 year, 22% of patients treated with TOAT had the primary endpoint versus 11% of DAPT patients (p<0.001). At 1 year, secondary end points of death or ischemic or embolic events (19% vs. 10%, p<0.001), and death or bleeding events (15% vs. 5%, p<0.001) also occurred with a higher frequency with TOAT. After propensity matched analysis the above differences were no longer significant with 1 year primary endpoint rates of 19% vs. 17% respectively (HR 1.95%, CI 0.88, 1.47; p = 0.33). Following propensity matching the only significant difference between TOAT and DAPT groups was minor bleeding (5% vs. 2%; HR 2.65, 95% CI 1.39, 5.03; p=0.003). Conclusions: In a large single center registry with comprehensive follow up, patients treated with TOAT had higher rates of ischemic and bleeding events. However, when baseline risks are accounted for event rates are similar, other than minor bleeding, indicating patient risk characteristics are largely responsible for the observed differences in outcomes.

Background: The presence of frailty increases the risk of long-term mortality for a myriad of reasons, but its association with cardiac-specific mortality among the elderly undergoing percutaneous coronary intervention (PCI) is unknown. We sought to determine the relationship between frailty and cause-specific (cardiac versus non-cardiac) mortality among elderly patients undergoing PCI. Methods: A prospective cohort of elderly (>65 years) patients undergoing PCI at Mayo Clinic between October 2005 and September 2008 were tested for frailty using the Fried criteria. Vital status was prospectively monitored including evaluation of death certificates, telephone interviews and review of autopsy/medical records. Results: Frailty data was obtained in 428 (84%) of 508 elderly patients (median age 74.2 years [SD 6.4, range 65-100]; 59% male). Of these, 92 (21%) patients were frail while 231 (54%) had intermediate frailty and 105(25%) were not frail. Frail patients were older than intermediate and non-frail patients (77.6 vs 74.3 vs 71.0 years; p<0.001) and had more comorbidities (mean Charlson index 4.6 vs 3.9 vs 2.8; p<0.001). There were 113 deaths (26% of cohort) during 5.1 median years of follow-up, of which 77 (68%) were classified as non-cardiac and 36 (32%) which were classified as cardiac. Frailty at baseline was associated with poor overall survival compared to non-frail patients (HR 6.1, 95% CI 3.2, 11.6; p<0.001). The estimated effect of frailty was nearly 3 times greater for cardiac mortality (HR 13.1, 95% CI 3.0, 57.0; p=0.001) than non-cardiac mortality (HR 4.6, 95% CI 2.2, 9.7; p<0.001). These findings remained significant following multivariable adjustment. Conclusions: Frailty is common among elderly patients undergoing PCI and is associated with poor overall survival and both cardiac and non-cardiac causes of death.

Objective To compare the prevalence and patterns of anomalous coronary artery origin from the opposite sinus (ACAOS) in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). Methods Retrospective review of consecutive patients with surgically excised BAV and TAV was performed from 1994 to 2015. Clinical notes, echocardiograms, coronary angiograms, CT angiographies, and pathology reports were reviewed. ACAOS included right coronary artery from the left cusp, left circumflex artery from the right cusp and left main or left anterior descending artery from the right cusp. Results 2371 (years 1994–2015) and 1679 (years 2009–2015) consecutive patients with pathology-confirmed BAV and TAV, respectively, and defined preoperative coronary anatomy were identified. A left dominant coronary circulation was present in 386 (18%) patients with BAV and 179 (11%) patients with TAV (p<0.001). ACAOS was identified in 43 (1.8%) patients with BAV and 15 (0.9%) patients with TAV, p=0.02. Among patients with BAV and ACAOS, the most common phenotype was right-left fusion (n=34, 79%) with present raphe (n=36, 84%), with no association between BAV phenotype and ACAOS type. On multivariate analysis, BAV status and size of the mid-ascending aorta were independently associated with ACAOS (OR 3.29; CI 1.26 to 8.6; p=0.02; OR 0.93; CI 0.87 to 0.98; p=0.01; respectively). Only two patients with ACAOS, one with BAV and one with TAV, had a perioperative coronary ischaemic event. Conclusions The prevalence of the potentially malignant ACAOS is significantly higher (threefold higher odds) in patients with BAV as compared with TAV, yet remains uncommon in absolute terms. Most patients with BAV and ACAOS had right-left cusp fusion and present raphe. Perioperative coronary events are rare in patients with ACAOS.

Introduction: Spontaneous coronary artery dissection (SCAD) is an uncommon but increasingly recognized cause of acute coronary syndrome and sudden cardiac death. We aim to review the occurrence of atrial fibrillation and atrial flutter in the Mayo Clinic SCAD Registry (MCSR) to gain insight into the association of SCAD and atrial arrhythmias. Methods: Atrial arrhythmias were queried amongst patients in the MCSR using diagnostic codes and text contained in both a large data repository known as the Advanced Cohort Explorer as well as a clinical database maintained by nurse abstractors for patients in the MCSR. All positive were manually verified using available medical records. Univariable logistic regression analysis was performed using JMP to investigate associations with classic cardiovascular risk factors. Results: A total of 1,215 patients from the Mayo SCAD registry were included. Six patients had a pre SCAD atrial arrhythmia, 19 had an atrial arrhythmia during a SCAD event, and 11 had a post SCAD atrial arrhythmia. Univariable analysis did not reveal significant associations with diabetes, hypertension, hyperlipidemia, or smoking. Conclusion: Atrial arrhythmias were not uncommonly seen in patients at the time of or after SCAD, especially after cardiac arrest or coronary artery bypass grafting. No significant associations with traditional cardiovascular risk factors were observed. Further investigation into the mechanism of atrial arrhythmia development as well as its management in the setting of SCAD is warranted.

Introduction: Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction in otherwise healthy and most times presumably fit young women. In the absence of evidence for benefit or harm, exercise prescription (EXP) after SCAD remains arbitrary. We assessed EXP patterns among participants in a large multinational SCAD registry. Methods: Participants with SCAD as confirmed by coronary angiography completed surveys detailing exercise (EX) habits prior to SCAD (initial survey), and EXP from their provider on initial and subsequent visits after SCAD (follow-up survey). Demographic and clinical characteristics were collected by electronic health record review by trained nurse abstractors. EXP was categorized according to EX components that include: type, intensity, frequency, time/session, and external conditions. Results: Among 950 participants, mean ± age was 46.8 ± 9.5 years, 96% were women and 77% reported attending ≥1 Cardiopulmonary Rehabilitation session. Prior to SCAD, 49% were aerobically exercising ≥ 3times per week, and only 32% performed strength-building EX regularly. Initial and subsequent post-SCAD visit details in 299/950 participants showed that most (93%) patients received some form of EX (Figure 1-A) counseling, namely: EXP, unspecific advice or were discouraged from any EX (Figure 1-B) . Limits regarding EX type and intensity were the most common advice received among EXP group (Figure 1-C) . Conclusions: Insights from our study show that only 40% of patients were achieving current exercise recommendations for adults prior to SCAD (vs 53% adult U.S population; CDC, 2018) which suggests that SCAD patients may not be as active as previously described. Most patients receive some form of EX counseling after SCAD; however, a structured EXP is needed to avoid overly cautious approaches that could lead to uncertainty, deconditioning, impaired quality of life, or increase risks associated with a sedentary lifestyle.

Introduction: Spontaneous coronary artery dissection (SCAD) is a rare but life threatening cause of acute coronary syndrome and a common etiology of pregnancy-associated myocardial infarction (PAMI). Hypothesis: We aimed to examine the clinical presentation, treatment, and outcomes of the largest pregnancy associated-SCAD (P-SCAD) patient cohort to date. Methods: A total of 128 women enrolled in the Mayo Clinic SCAD Registry between 2010-2020 who were pregnant or up to 1 year postpartum at time of P-SCAD were identified. We subdivided P-SCAD in an “early” group with <12 weeks of delivery and a “late” group presenting between >12 weeks -12 months following delivery. Results: Among the 128 women with P-SCAD, 7(5%) occurred during pregnancy (2/7 first trimester, 5/7 third trimester). Of the 121 women with postpartum P-SCAD, 88/121(72%) occurred <12 weeks of delivery and 33/121(27%) at 12 weeks to 1 year postpartum. The mean age of P-SCAD was 35.3 +/- 4 years (26-48). The most common symptom on presentation was chest pain 118/128(92%); 62/128(48%) presented with ST elevation MI and 58/128(45%) presented with non-ST elevation MI. Multivessel involvement occurred in 40/128(31%), left anterior descending artery (LAD) in 88/128(69%), and left main (LM) in 28/128(22%) of all P-SCAD. Percutaneous coronary intervention (PCI) was performed in 52/128(41%) with a success rate of 81%. Coronary artery bypass grafting was performed in 24/128(19%) of which 6/24 patients had an unsuccessful PCI, 14/24 had proximal or multivessel SCAD, and 4/24 had persistent or extension of initial SCAD. Of those treated conservatively 52/128(40%), 11/52(21%) had LM and LAD. Among all the P-SCAD patients, 84/128 (66%) were screened for an underlying arteriopathy, of whom 44 (52 %) were diagnosed with fibromuscular dysplasia. At a median follow up of 3 years (IQR 1 to 6), 12/128 (9%) of all P-SCAD survivors had a recurrent SCAD event and 7/12 (58%) were within 1 year postpartum. There were no deaths. Conclusions: P-SCAD most commonly presents with ST-elevation MI and multivessel involvement within the initial 12 weeks postpartum. Clinicians need to be familiar with this etiology of PAMI to avoid delay in diagnosis and appropriate management.

Background The temporal incidence of high‐grade atrioventricular block (HAVB) after transcatheter aortic valve replacement (TAVR) is uncertain. As a result, periprocedural monitoring and pacing strategies remain controversial. This study aimed to describe the temporal incidence of initial episode of HAVB stratified by pre‐ and post‐TAVR conduction and identify predictors of delayed events. Methods and Results Consecutive patients undergoing TAVR at a single center between February 2012 and June 2019 were retrospectively assessed for HAVB within 30 days. Patients with prior aortic valve replacement, permanent pacemaker (PPM), or conversion to surgical replacement were excluded. Multivariable logistic regression was performed to assess predictors of delayed HAVB (initial event >24 hours post‐TAVR). A total of 953 patients were included in this study. HAVB occurred in 153 (16.1%). After exclusion of those with prophylactic PPM placed post‐TAVR, the incidence of delayed HAVB was 33/882 (3.7%). Variables independently associated with delayed HAVB included baseline first‐degree atrioventricular block or right bundle‐branch block, self‐expanding valve, and new left bundle‐branch block. Forty patients had intraprocedural transient HAVB, including 16 who developed HAVB recurrence and 6 who had PPM implantation without recurrence. PPM was placed for HAVB in 130 (13.6%) (self‐expanding valve, 23.7% versus balloon‐expandable valve, 11.9%; P <0.001). Eight (0.8%) patients died by 30 days, including 1 unexplained without PPM present. Conclusions Delayed HAVB occurs with higher frequency in patients with baseline first‐degree atrioventricular block or right bundle‐branch block, new left bundle‐branch block, and self‐expanding valve. These findings provide insight into optimal monitoring and pacing strategies based on periprocedural ECG findings.