Abstract Background Cardiovascular disease among hemodialysis (HD) patients is linked to poor outcomes. The Acute Dialysis Quality Initiative Workgroup proposed echocardiographic (ECHO) criteria for ...structural heart disease (SHD) in dialysis patients. The association of SHD with important patient outcomes is not well defined. Objectives This study sought to determine prevalence of ECHO-determined SHD and its association with survival among incident HD patients. Methods We analyzed patients who began chronic HD from 2001 to 2013 who underwent ECHO ≤1 month prior to or ≤3 months following initiation of HD (n = 654). Results Mean patient age was 66 ± 16 years, and 60% of patients were male. ECHO findings that met 1 or more and ≥3 of the new criteria were discovered in 87% and 54% of patients, respectively. Over a median of 2.4 years, 415 patients died: 108 (26%) died within 6 months. Five-year mortality was 62%. Age- and sex-adjusted structural heart disease variables associated with death were left ventricular ejection fraction (LVEF) ≤45% (hazard ratio HR: 1.48; confidence interval CI: 1.20 to 1.83) and right ventricular (RV) systolic dysfunction (HR: 1.68; CI: 1.35 to 2.07). An additive of higher death risk included LVEF ≤45% and RV systolic dysfunction rather than neither (HR: 2.04; CI: 1.57 to 2.67; p = 0.53 for test for interaction). Following adjustment for age, sex, race, diabetic kidney disease, and dialysis access, RV dysfunction was independently associated with death (HR: 1.66; CI 1.34 to 2.06; p < 0.001). Conclusions SHD was common in our HD study population, and RV systolic dysfunction independently predicted mortality.
Spontaneous coronary artery dissection (SCAD) is the most common cause of pregnancy-associated myocardial infarction and remains poorly characterized.
This study sought to assess presentation, ...clinical factors, and outcomes of pregnancy-associated spontaneous coronary artery dissection (P-SCAD) compared with spontaneous coronary artery dissection not associated with pregnancy (NP-SCAD).
A Mayo Clinic registry was established in 2010 to include comprehensive retrospective and prospective SCAD data. Records were reviewed to identify women who were pregnant or ≤12 weeks postpartum at time of SCAD. Complete records were available for 323 women; 54 women met criteria for P-SCAD (4 during pregnancy) and they were compared with 269 women with NP-SCAD.
Most events occurred within the first month postpartum (35 of 50). Compared with NP-SCAD, P-SCAD patients more frequently presented with ST-segment elevation myocardial infarction (57% vs. 36%; p = 0.009), left main or multivessel SCAD (24% vs. 5%; p < 0.0001; and 33% vs. 14%; p = 0.0027, respectively), and left ventricular function ≤35% (26% vs. 10%; p = 0.0071). Among women with imaging of other vascular territories, P-SCAD was less likely with a diagnosis of fibromuscular dysplasia and extracoronary vascular abnormalities (42% vs. 64%; p = 0.047; and 46% vs. 77%; p = 0.0032, respectively). Compared with U.S. birth data, women with P-SCAD were more often multiparous (p = 0.0167), had a history of infertility therapies (p = 0.0004), and had pre-eclampsia (p = 0.001). On long-term follow-up (median 2.3 years) recurrent SCAD occurred in 51 patients, with no difference in the Kaplan Meier 5-year recurrence rates (10% vs. 23%; p = 0.18).
P-SCAD patients had more acute presentations and high-risk features than women with NP-SCAD did. The highest frequency of P-SCAD occurred during the first postpartum month and P-SCAD patients less often had extracoronary vascular abnormalities. Hormonal, hemodynamic variations, and yet-undefined mechanisms might be significant contributors to P-SCAD. (The “Virtual” Multicenter Spontaneous Coronary Artery Dissection SCAD Registry SCAD; NCT01429727; Genetic Investigations in Spontaneous Coronary Artery Dissection SCAD; NCT01427179)
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Spontaneous coronary artery dissection (SCAD) is an acute coronary event of uncertain origin. Clinical features and prognosis remain insufficiently characterized.
A retrospective single-center cohort ...study identified 87 patients with angiographically confirmed SCAD. Incidence, clinical characteristics, treatment modalities, in-hospital outcomes, and long-term risk of SCAD recurrence or major adverse cardiac events were evaluated. Mean age was 42.6 years; 82% were female. Extreme exertion at SCAD onset was more frequent in men (7 of 16 versus 2 of 71; P<0.001), and postpartum status was observed in 13 of 71 women (18%). Presentation was ST-elevation myocardial infarction in 49%. Multivessel SCAD was found in 23%. Initial conservative management (31 of 87) and coronary artery bypass grafting (7 of 87) were associated with an uncomplicated in-hospital course, whereas percutaneous coronary intervention was complicated by technical failure in 15 of 43 patients (35%) and 1 death. During a median follow-up of 47 months (interquartile range, 18-106 months), SCAD recurred in 15 patients, all female. Estimated 10-year rate of major adverse cardiac events (death, heart failure, myocardial infarction, and SCAD recurrence) was 47%. Fibromuscular dysplasia of the iliac artery was identified incidentally in 8 of 16 femoral angiograms (50%) undertaken before closure device placement and in the carotid arteries of 2 others with carotid dissection.
SCAD affects a young, predominantly female population, frequently presenting as ST-elevation myocardial infarction. Although in-hospital mortality is low regardless of initial treatment, percutaneous coronary intervention is associated with high rates of complication. Risks of SCAD recurrence and major adverse cardiac events in the long term emphasize the need for close follow-up. Fibromuscular dysplasia is a novel association and potentially causative factor.
Background Mild and moderate chronic kidney disease (CKD) is associated with decreased survival and increased adverse events after a percutaneous coronary intervention (PCI). Therapy with clopidogrel ...decreases adverse events in large patient populations. Therefore, we sought to determine the efficacy and safety of long-term clopidogrel therapy in patients with CKD. Methods Two thousand two patients from the CREDO trial in whom an elective PCI of a single or multiple vessels was planned were analyzed. Patients were randomly assigned to a 300-mg loading dose of clopidogrel before PCI followed by clopidogrel 75 mg/d for a year versus a placebo loading dose at the time of the PCI procedure and clopidogrel 75 mg/d for 28 days and placebo for the remainder of a year. Patients were categorized by their estimated creatinine clearance (>90 normal, n = 999, 60-89 mild CKD, n = 672, <60 mL/min moderate CKD, n = 331). Results Diminished renal function was associated with worse outcomes. Patients with normal renal function who received 1 year of clopidogrel had a marked reduction in death, myocardial infarction, or stroke compared with those who received placebo (10.4% vs 4.4%, P < .001), whereas patients with mild and moderate CKD did not have a significant difference in outcomes with clopidogrel therapy versus placebo (mild: 12.8% vs 10.3%, P = .30; moderate: 13.1% vs 17.8%, P = .24). Clopidogrel use was associated with an increased relative risk of major or minor bleeding, but this increased risk was not different based on renal function (relative risk 1.2, 1.3, 1.1). Conclusions Clopidogrel in mild or moderate CKD patients may not have the same beneficial effect as it does in patients with normal renal function, but was not associated with a greater relative risk of bleeding based on renal function. Further studies are needed to define the role of clopidogrel therapy in patients with CKD.
Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic acute coronary syndrome for which optimal management remains undefined.
We performed a retrospective study of 189 patients ...presenting with a first SCAD episode. We evaluated outcomes according to initial management: (1) revascularization versus conservative therapy and (2) percutaneous coronary intervention (PCI) versus conservative therapy stratified by vessel flow at presentation. Demographics were similar in revascularization versus conservative (mean age, 44±9 years; women 92% both groups), but vessel occlusion was more frequent in revascularization (44/95 versus 18/94). There was 1 in-hospital death (revascularization) and 1 late death (conservative). Procedural failure rate was 53% in those managed with PCI. In the subgroup of patients presenting with preserved vessel flow, rates of PCI failure were similarly high (50%), and 6 (13%) required emergency coronary artery bypass grafting. In the conservative group, 85 of 94 (90%) had an uneventful in-hospital course, but 9 (10%) experienced early SCAD progression requiring revascularization. Kaplan-Meier estimated 5-year rates of target vessel revascularization and recurrent SCAD were no different in revascularization versus conservative therapy (30% versus 19%; P=0.06 and 23% versus 31%; P=0.7).
PCI for SCAD is associated with high rates of technical failure even in those presenting with preserved vessel flow and does not protect against target vessel revascularization or recurrent SCAD. A strategy of conservative management with prolonged observation may be preferable.
The co-morbidities and long-term complications of spontaneous coronary artery dissection (SCAD) are incompletely understood. This study investigated the association of atrial arrhythmias (AA), ...defined as atrial fibrillation and atrial flutter, with SCAD in a patient registry and population-based cohort. This observational study was performed in 2 parts. The first was a retrospective study reviewing patients diagnosed with AA in the Mayo Clinic SCAD Registry. The second was a population-based, case-control study to assess AA in patients with SCAD compared with age- and gender-matched controls. Of 1,214 patients in the Mayo Clinic SCAD Registry, 45 patients (3.7%) with SCAD were identified with an AA. A total of 8 of those patients (17.8%) had a pre-SCAD AA; 20 (44.4%) had a peri-SCAD AA; and 17 (37.8%) had a post-SCAD AA. The univariate analysis did not reveal significant associations with traditional cardiovascular risk factors. In the population-based cohort, 5 patients with SCAD (4%) and 4 controls (1%) developed an AA before the date of SCAD for each patient (odds ratio 4.5, 95% confidence interval CI 1.05 to 19.0, p = 0.04). A total of 5 patients with SCAD (4%) and 3 controls (1%) developed an AA in the 10 years after SCAD (hazard ratio 6.3, 95% CI 1.2 to 32.8, p = 0.03). A subgroup of patients with SCAD experienced AA before and after SCAD. Patients with a history of SCAD were more likely to develop AA in the next 10 years than were age- and gender-matched healthy controls.
To evaluate outcomes by sex in older adults with cardiogenic shock complicating acute myocardial infarction (AMI-CS).
A retrospective cohort of older (≥75 years) AMI-CS admissions during January 1, ...2000, to December 31, 2014, was identified using the National Inpatient Sample. Interhospital transfers were excluded. Use of angiography, percutaneous coronary intervention (PCI), mechanical circulatory support (MCS), and noncardiac interventions was identified. The primary outcome was in-hospital mortality stratified by sex, and secondary outcomes included temporal trends of prevalence, in-hospital mortality, use of cardiac and noncardiac interventions, hospitalization costs, and length of stay.
In this 15-year period, there were 134,501 AMI-CS admissions 75 years or older, of whom 51.5% (n=69,220) were women. Women were on average older, were more often Hispanic or nonwhite race, and had lower comorbidity, acute organ failure, and concomitant cardiac arrest. Compared with older men (n=65,281), older women (n=69,220) had lower use of coronary angiography (55.4% n=35,905 vs 49.2% n=33,918), PCI (36.3% n=23,501 vs 34.4% n=23,535), MCS (34.3% n=22,391 vs 27.2% n=18,689), mechanical ventilation, and hemodialysis (all P<.001). Female sex was an independent predictor of higher in-hospital mortality (adjusted odds ratio, 1.05; 95% CI, 1.02-1.08; P<.001) and more frequent discharges to a skilled nursing facility. In subgroup analyses of ethnicity, presence of cardiac arrest, and those receiving PCI and MCS, female sex remained an independent predictor of increased mortality.
Female sex is an independent predictor of worse in-hospital outcomes in older adults with AMI-CS in the United States.
Background Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome predominantly in women without usual cardiovascular risk factors. Many have a history of migraine ...headaches, but this association is poorly understood. This study aimed to determine migraine prevalence among SCAD patients and assess differences in clinical factors based on migraine history. Methods and Results A cohort study was conducted using the Mayo Clinic SCAD "Virtual" Multi-Center Registry composed of patients with SCAD as confirmed on coronary angiography. Participant-provided data and records were reviewed for migraine history, risk factors, SCAD details, therapies, and outcomes. Among 585 patients (96% women), 236 had migraine history; the lifetime and 1-year prevalence of migraine were 40% and 26%, respectively. Migraine was more common in SCAD women than comparable literature-reported female populations (42% versus 24%, P<0.0001; 42% versus 33%, P<0.0001). Among all SCAD patients, those with migraine history were more likely to be female (99.6% versus 94%; P=0.0002); have SCAD at a younger age (45.2±9.0 years versus 47.6±9.9 years; P=0.0027); have depression (27% versus 17%; P=0.025); have recurrent post-SCAD chest pain at 1 month (50% versus 39%; P=0.035); and, among those assessed, have aneurysms, pseudoaneurysms, or dissections (28% versus 18%; P=0.018). There was no difference in recurrent SCAD at 5 years for those with versus without migraine (15% versus 19%; P=0.39). Conclusions Many SCAD patients have a history of migraine. SCAD patients with migraine are younger at the time of SCAD; have more aneurysms, pseudoaneurysms, and dissections among those imaged; and more often report a history of depression and post-SCAD chest pain. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01429727, NCT01427179.
Two women (18%) had coronary artery obstruction on coronary angiography (CA) (1 with persistent dissection and another with in-stent stenosis); these patients’ catamenial chest pain persisted despite ...revascularization and negative subsequent stress studies. Table 1 Patient Details Specific to History of SCAD and Subsequent Chest Pain Symptoms CA = coronary angiography; CABG = coronary artery bypass grafting; CCB = calcium-channel blocker; CCTA = coronary computed tomography angiography; CP = chest pain; EDS = Ehlers-Danlos syndrome; FMD = fibromuscular dysplasia; PCI = percutaneous coronary intervention; PP = postpartum; prn = pro re nata (when necessary); SCAD = spontaneous coronary artery dissection. Patient # Age∗, yrs SCAD Risk Factors Initial SCAD Management Timing of Symptoms % of Cycles Affected Evaluation of Recurrent CP Treatment 1 35 5 days PP PCI 5 days pre-menstrual 100 PCI to residual dissection; persistent pain without ischemia on subsequent stress test Short-acting nitrate prn 2 42 Prior SCAD Unsuccessful PCI; CABG 1-2 days pre-menstrual 5-10 No ischemia on stress test Short-acting nitrate prn, CCB 3 39 13 days PP, FMD Unsuccessful conservative;† PCI 1-2 days pre-menstrual 90 Patent coronary arteries on CA Short-acting nitrate prn, CCB, beta-blocker 4 46 None Conservative 1-2 days pre-menstrual 100 Improved coronary artery caliber on CA Long-acting nitrate, ranolazine, endometrial ablation 5 44 None Conservative 1-2 days pre-menstrual through menses 100 for 2 yrs, now 5-10 No ischemia on stress test; stable CCTA Short-acting nitrate prn 6 34 FMD Unsuccessful conservative; PCI 1-2 days pre-menstrual through menses 50 Complex PCI for in-stent stenosis; intracoronary thrombus requiring emergent CABG; persistent pain without ischemia on stress test; patent stents/grafts on repeat CA Ranolazine, CCB, beta-blockers, long-acting nitrate 7 45 EDS type IV Unsuccessful conservative; unsuccessful PCI; interval CABG 1-2 days pre-menstrual during first 2 days of menses 100 Patent coronary arteries on CCTA Short-acting nitrate prn, CCB, long-acting nitrate 8 43 Emotional stress Conservative 3 days pre-menstrual during first 2 days of menses 100 No ischemia on stress test; patent coronaries on CA Short-acting nitrate prn 9 37 10 weeks PP PCI 1-2 days pre-menstrual Only heavy cycles No ischemia on stress test Short-acting nitrate prn 10 37 15 days PP CABG 1-2 days pre-menstrual 50 No ischemia on stress test Short-acting nitrate prn, long-acting nitrate, ranolazine 11 41 None Conservative 1-2 days pre-menstrual 20 No ischemia on stress test Short-acting nitrates prn, CCB 1 M.S. Tweet, S.N. Hayes, E. Codsi, Spontaneous coronary artery dissection associated with pregnancy, J Am Coll Cardiol, Vol. 70, 2017, 426-435 2 H. Kawano, T. Motoyama, M. Ohgushi, Menstrual cyclic variation of myocardial ischemia in premenopausal women with variant angina, Ann Intern Med, Vol. 135, 2001, 977-981 3 E.A. MacGregor, A. Hackshaw, Prevalence of migraine on each day of the natural menstrual cycle, Neurology, Vol. 63, 2004, 351-353 4 H. Kawano, T. Motoyama, K. Kugiyama, Gender difference in improvement of endothelium-dependent vasodilation after estrogen supplementation, J Am Coll Cardiol, Vol. 30, 1997, 914-919
The development of new cancer drugs is slow and costly. HIV protease inhibitors are Food and Drug Administration approved for HIV patients. Because these drugs cause toxicities that can be associated ...with inhibition of Akt, an emerging target in cancer, we assessed the potential of HIV protease inhibitors as anticancer agents.
HIV protease inhibitors were screened in vitro using assays that measure cellular proliferation, apoptotic and nonapoptotic cell death, endoplasmic reticulum (ER) stress, autophagy, and activation of Akt. Nelfinavir was tested in non-small cell lung carcinoma (NSCLC) xenografts with biomarker assessment.
Three of six HIV protease inhibitors, nelfinavir, ritonavir, and saquinavir, inhibited proliferation of NSCLC cells, as well as every cell line in the NCI60 cell line panel. Nelfinavir was most potent with a mean 50% growth inhibition of 5.2 micromol/L, a concentration achievable in HIV patients. Nelfinavir caused two types of cell death, caspase-dependent apoptosis and caspase-independent death that was characterized by induction of ER stress and autophagy. Autophagy was protective because an inhibitor of autophagy increased nelfinavir-induced death. Akt was variably inhibited by HIV protease inhibitors, but nelfinavir caused the greatest inhibition of endogenous and growth factor-induced Akt activation. Nelfinavir decreased the viability of a panel of drug-resistant breast cancer cell lines and inhibited the growth of NSCLC xenografts that was associated with induction of ER stress, autophagy, and apoptosis.
Nelfinavir is a lead HIV protease inhibitor with pleiotropic effects in cancer cells. Given its wide spectrum of activity, oral availability, and familiarity of administration, nelfinavir is a Food and Drug Administration-approved drug that could be repositioned as a cancer therapeutic.
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