Cardiovascular Fellowship Training in Cardio-Obstetrics: JACC Review Topic of the Week.

The United States has the highest maternal mortality in the developed world with cardiovascular disease as the leading cause of pregnancy-related deaths. In response to this, the emerging subspecialty of cardio-obstetrics has been growing over the past decade. Cardiologists with training and expertise in caring for patients with cardiovascular disease in pregnancy are essential to provide effective, comprehensive, multidisciplinary, and high-quality care for this vulnerable population. This document provides a blueprint on incorporation of cardio-obstetrics training into cardiovascular disease fellowship programs to improve knowledge, skill, and expertise among cardiologists caring for these patients, with the goal of improving maternal and fetal outcomes.

Contemporary Management Before Chronic Total Occlusion Percutaneous Coronary Interventions: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

BACKGROUND: Guidelines recommend maximal antianginal medical therapy before attempted coronary artery chronic total occlusion (CTO) percutaneous coronary intervention (PCI). The degree to which this occurs in contemporary practice is unknown. We aimed to characterize the frequency and variability of preprocedural use of antianginal therapy and stress testing within 3 months before PCI of CTO (CTO PCI) across a nationally integrated health care system. METHODS: We identified patients who underwent attempted CTO PCI from January 2012 to September 2018 within the Veterans Affairs Healthcare System. Patients were categorized by management before CTO PCI: presence of ≥2 antianginals, stress testing, and ≥2 antianginals and stress testing within 3 months of PCI attempt. Multivariable logistic regression and inverse propensity weighting were used for adjustment before trimming, with median odds ratios calculated for variability estimates. RESULTS: Among 4250 patients undergoing attempted CTO PCI, 40% received ≥2 antianginal medications and 24% underwent preprocedural stress testing. The odds of antianginal therapy with more than one medication before CTO PCI did not change over the years of the study (odds ratio [OR], 1.0 [95% CI, 0.97-1.04]), whereas the odds of undergoing preprocedural stress testing decreased (OR, 0.97 [95% CI, 0.93-0.99]), and the odds of antianginal therapy with ≥2 antianginals and stress testing did not change (OR, 0.98 [95% CI, 0.93-1.04]). Median odds ratios (MOR) showed substantial variability in antianginal therapy across hospital sites (MOR, 1.3 [95% CI, 1.26-1.42]) and operators (MOR, 1.35 [95% CI, 1.26-1.63]). Similarly, preprocedural stress testing varied significantly by site (MOR, 1.68 [95% CI, 1.58-1.81]) and operator (MOR, 1.80 [95% CI, 1.56-2.38]). CONCLUSIONS: Just under half of patients received guideline-recommended management before CTO PCI, with significant site and operator variability. These findings suggest an opportunity to reduce variability in management before CTO PCI.

Temporal Trends in Pregnancy-Associated Stroke and Its Outcomes Among Women With Hypertensive Disorders of Pregnancy.

Background Stroke is a serious complication of hypertensive disorders of pregnancy (HDP), with potentially severe and long-term sequelae. However, the temporal trends, predictors, and outcomes of stroke in women with HDP at delivery remain unknown. Methods and Results All HDP delivery hospitalizations with or without stroke event (ischemic, hemorrhagic, or unspecified) between 2004 and 2014 in the United States National Inpatient Sample were analyzed to examine incidence, predictors, and prognostic impact of stroke. Of 4 240 284 HDP delivery hospitalizations, 3391 (0.08%) women had stroke. While the prevalence of HDP increased over time, incident stroke rates decreased from 10 to 6 per 10 000 HDP delivery hospitalizations between 2004 and 2014. Women with stroke were increasingly multimorbid, with some risk factors being more strongly associated with ischemic strokes, including congenital heart disease, peripheral vascular disease, dyslipidemia, and sickle cell disease. Delivery complications were also associated with stroke, including cesarean section (odds ratio [OR], 1.58; 95% CI, 1.33-1.86), postpartum hemorrhage (OR, 1.91; 95% CI, 1.33-1.86), and maternal mortality (OR, 99.78; 95% CI, 59.15-168.31), independently of potential confounders. Women with stroke had longer hospital stays (median, 6 versus 3 days), higher hospital charges (median, $14 655 versus $4762), and a higher proportion of nonroutine discharge locations (38% versus 4%). Conclusions The incidence of stroke in women with HDP has declined over time. While a relatively rare event, identification of women at highest risk of ischemic or hemorrhagic stroke on admission for delivery is important to reduce long-term sequelae.

Home-Based Cardiac Rehabilitation (HBCR) In Post-TAVR Patients: A Prospective, Single-Center, Cohort, Pilot Study.

INTRODUCTION: Cardiac rehabilitation after transcatheter aortic valve replacement (TAVR) safely improves exercise tolerance, functional independence, and quality of life. However, barriers such as transportation, cost, and limited access to rehabilitation programs prohibits participation. In 2010, the Veterans Affairs Medical Center (VAMC) started a 12-week home-based cardiac rehabilitation (HBCR) program at 13 sites around the country to increase participation by reducing such barriers. We present the findings of HBCR in post-TAVR patients from the VAMC in Gainesville, FL, USA. METHODS: Fifty-nine patients who underwent TAVR between 2015 and 2018 at the Gainesville VA were offered HBCR. Forty-one patients enrolled, 28 completed the program, and 14 completed the surveys. We used various performance measures including Life's Simple 7 survey, 6-min Walk (6-MW), Duke Activity Survey Index (DASI), and Short Form-36 (SF-36) health survey to assess the pre and post-HBCR changes in emotional, functional, and physical well-being of the patients. RESULTS: Paired comparison of pre and post-HBCR using Wilcoxon signed-rank test revealed a statistically significant difference in the pre and post-HBCR scores for DASI, DASI-Mets, and SF-36 physical functioning (p values 0.05, 0.034, and 0.016, respectively), suggesting an improvement in the patients' physical functioning after participating in the HBCR program. CONCLUSIONS: In conclusion, our pilot study offers novel insight into the role of HBCR in improving physical health and well-being in post-TAVR patients while eliminating the barriers of transportation and access to cardiac rehabilitation programs.

Circulating SHBG (Sex Hormone-Binding Globulin) and Risk of Ischemic Stroke: Findings From the WHI.

Background and Purpose- Circulating levels of SHBG (sex hormone-binding globulin) have been inversely linked to obesity, diabetes mellitus, and other cardiometabolic disorders. It remains uncertain whether low SHBG is prospectively predictive of stroke risk, particularly in women. We investigated whether SHBG is associated with risk of incident ischemic stroke (IS) among women in the WHI (Women's Health Initiative). Methods- From an observational cohort of 161 808 postmenopausal women enrolled in the WHI at 40 sites across the United States from 1993 to 1998, we identified 13 192 participants free of prevalent stroke at baseline who were included in an ancillary study that measured serum SHBG. We used Cox proportional hazards regression, stratified by SHBG measurement assay, to assess IS risk across quintiles of SHBG (Q1-Q5), adjusting first for demographic variables (model 1), additionally for body mass index, hypertension, alcohol use, and smoking status (model 2), and for physical activity and reproductive risk factors (model 3). In sensitivity analyses, potential mediators (diabetes mellitus status, levels of estradiol, testosterone, and CRP [C-reactive protein]) were included. Results- Of 13 192 participants (mean age, 62.5 years; 67.4% non-Hispanic white, 18.5% black, 7.6% Hispanic, and 5.0% Asian), after following for an average of 11.6 years, 768 IS events were adjudicated. Compared with the highest quintile of SHBG levels (referent), women in the lowest SHBG quintile had a higher risk of IS in all 3 multivariable models (model 1: hazard ratio, 1.88 [95% CI, 1.47-2.41]; model 2: hazard ratio, 1.69 [95% CI, 1.30-2.20]; model 3: hazard ratio, 1.61 [95% CI, 1.19-2.19]; trend tests P<0.05 for all models). Including potential mediators such as diabetes mellitus, estradiol, and testosterone in the models attenuated but did not eliminate significant inverse associations between SHBG and IS. Conclusions- In this prospective cohort of postmenopausal women, there was a statistically significant inverse association between serum SHBG levels and IS risk, which supports the notion that SHBG could be used as a risk stratification tool for predicting IS in women.

Relationship between Invasive and Echocardiographic Transvalvular Gradients after Transcatheter Aortic Valve Replacement.

INTRODUCTION: Lower transcatheter aortic valve replacement (TAVR) pressure gradients have been reported after implantation of self-expanding valves compared with balloon-expandable valves; however, there is a paucity of data on the relationship between invasively measured transvalvular pressure gradients and Doppler-derived measurements. METHODS: From September 2013 to September 2018, patients with native aortic valve stenosis who had both intraoperative invasive and postoperative echocardiography transvalvular pressure gradients were included for analysis. We used parametric and nonparametric statistics to compare aortic gradients within and between groups. RESULTS: Of 171 patients, 152 (88.9%) patients had TAVR with a balloon-expandable valve and 19 (11.1%) with a self-expanding valve. Among all patients, the invasive aortic gradient was 7.8 ± 3.2 mmHg and the Doppler-derived aortic gradient was 11.0 ± 4.5 mmHg (p < 0.001). Among those who received a balloon-expandable valve, the invasive aortic gradient was 7.5 ± 3 mmHg and the Doppler aortic gradient was 11.4 ± 4.5 mmHg (p < 0.001). In contrast, among patients who received a self-expanding valve, the invasive aortic gradient was 10.3 ± 3.4 mmHg and the Doppler aortic gradient was 8.5 ± 4.6 mmHg (p = 0.18). CONCLUSIONS: Balloon-expandable valves were associated with lower invasive measurements versus post-TAVR Doppler gradients, while results were inconclusive regarding self-expanding valves.

Trend and Outcomes of Direct Transcatheter Aortic Valve Replacement from a Single-Center Experience.

INTRODUCTION: When transcatheter aortic valve replacement (TAVR) was introduced, pre-implantation balloon aortic valvuloplasty (BAV) was a routine part of the procedure. Smaller device profiles have resulted in selective use of BAV; however, there is a paucity of data about the trend in use of direct TAVR and the safety of this strategy. METHODS: All patients who underwent TAVR at a Veterans Affairs Medical Center from September 2013 to November 2016 were included in this retrospective analysis. We reviewed angiography films and verified with procedure reports to assess if direct TAVR was performed. Troponin T was assessed within 72 h after the TAVR. Multivariate analysis examined the association between direct TAVR and periprocedural myocardial infarction (MI) or 1-year mortality. RESULTS: Overall, 207 patients were available for analysis. The mean follow-up was 13.3 months. A balloon-expandable valve was used 93.2% of the time, and 35.3% of patients were treated with conscious sedation. Periprocedural MI or 1-year mortality occurred in 12.5% of the direct TAVR group versus 18.3% of the pre-implantation BAV group (p = 0.30). After controlling for potential confounding variables, direct TAVR was not associated with periprocedural MI or 1-year mortality. CONCLUSIONS: Direct TAVR appears to be safe and is not associated with periprocedural MI or 1-year mortality. With current generation devices, this strategy can be considered for most patients undergoing TAVR.

Non-PCI/CABG therapies for refractory angina.

Angina persists for many patients despite modern medical therapy and/or revascularization, and this is referred to as refractory angina. All patients with refractory angina must be treated with aggressive risk factor modification plus optimized medical management. ß-Blockers and nitrates are usually first-line agents; however most patients require multiple medications for refractory symptom control. Novel agents, such as ranolazine and ivabradine, as well as non-pharmacologic therapies, such as enhanced external counterpulsation and cardiac rehabilitation, may provide relief or reduction of angina. Other standard treatments such as antiplatelet therapy, lipid reduction therapy, blood pressure control, diabetes control, smoking cessation, and wei1ght control should be part of the management of refractory angina as well.

Improvement of Subjective Well-Being by Ranolazine in Patients with Chronic Angina and Known Myocardial Ischemia (IMWELL Study).

INTRODUCTION: We aimed to assess if ranolazine would improve angina symptoms among patients with documented myocardial ischemia. METHODS: Eligible subjects had chronic stable angina and at least one coronary stenosis with fractional flow reserve (FFR) ≤0.80 or at least one chronic total occlusion (CTO) without attempted revascularization. Subjects were randomized to oral ranolazine 500 mg twice daily for 1 week, then ranolazine 1000 mg twice daily for 15 weeks versus matching placebo. The primary end point was change in angina at 16 weeks as assessed by the Seattle Angina Questionnaire (SAQ). RESULTS: Between September 2014 and January 2016, 25 subjects were randomized to ranolazine versus 25 to placebo. The most common reason for eligibility was CTO (72%), while the remainder had myocardial ischemia documented by low FFR. The mean FFR was 0.57 ± 0.12. Sixty-eight percent of subjects were on two or more anti-angina medications at baseline. Study medication was discontinued in 32% (eight of 25) of the ranolazine group versus 36% (nine of 25) of the placebo group. By intention-to-treat, 46 subjects had baseline and follow-up SAQ data completed. Ranolazine was not associated with an improvement in angina compared with placebo at 16 weeks. The results were similar among 33 subjects that completed study medication. The incidence of ischemia-driven hospitalization or catheterization was 12% (three of 25) of the ranolazine group versus 20% (five of 25) in the placebo group (p > 0.05). CONCLUSIONS: In subjects with chronic stable angina and documented myocardial ischemia, ranolazine did not improve angina symptoms at 16 weeks. FUNDING: Gilead. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02265796).

Late Paravalvular Aortic Regurgitation: Migration of the Valve or Late Recoil?

A 79-year-old man underwent trans-catheter aortic valve replacement for symptomatic severe aortic stenosis with a 26-mm Edwards SAPIEN XT valve. Immediately after valve deployment there was moderate amount of paravalvular leak. Post-dilation was performed with an additional 2 cc of volume, and the paravalvular leak was reduced to trace. Nine months later, trans-thoracic echocardiography revealed moderate to severe paravalvular leak and possible aortic migration of the valve. The patient was brought back for the treatment of the paravalvular leak which was suspected to be due to valve migration. However, fluoroscopy and trans-esophageal echocardiography showed good valve position. Measurement of late valve recoil in the Coplanar view using cine-angiographic analysis software showed that the lower third of the valve had the greatest late recoil (-1.74 mm, 6.55%), which presumably accounted for the progression of the paravalvular leak. Valve-in-valve trans-catheter aortic valve replacement was performed with a 26-mm SAPIEN 3 valve and the paravalvular leak was reduced to trace. This case displays late recoil as a likely mechanism for development of paravalvular leak after SAPIEN XT valve implantation. Our case illustrates that late recoil needs to be systematically evaluated in future studies, especially when trans-catheter aortic valve replacement is being expanded to lower risk and younger patients for whom the longevity and long-term performance of these valves is of critical importance.

Prognostic Significance of Asymptomatic Myocardial Ischemia in Women vs. Men.

BACKGROUND: Silent myocardial ischemia is a recognized but suboptimally studied condition in patients with and without known coronary artery disease. Limited work has focused on the association between silent myocardial ischemia and future prognosis however the majority of these analyses have focused mostly on male cohorts. As signs and symptoms of myocardial ischemia are known to be different in women, it is important to discuss and highlight any differences in association between silent myocardial ischemia and adverse cardiovascular outcomes based on gender. METHODS: The aim of this review is to summarize the current literature available discussing silent myocardial ischemia and potential gender differences. We searched English language studies on PUBMED and the Cochrane Database of Systematic Reviews from the database start dates to November 2015. CONCLUSION: As data on the presence of silent myocardial ischemia in women is limited, whether a differential association based on gender between this condition and cardiovascular prognosis remains unknown. Future studies should target women especially those without epicardial coronary disease and suspected coronary microvascular dysfunction.

Drug-eluting stents may not reduce target lesion revascularization in cardiac allograft vasculopathy.

OBJECTIVE: Although drug-eluting stent (DES) compared with bare metal stent (BMS) use reduces in-stent restenosis (ISR) in traditional coronary artery disease, its efficacy in cardiac allograft vasculopathy (CAV) has not been clearly established. BACKGROUND: CAV is a leading cause of mortality after the first year following cardiac transplantation. CAV treatment options are limited, and DES use has increased significantly in this population. METHODS: In a retrospective study of heart transplant patients at our institution who underwent percutaneous coronary intervention with a BMS or DES for CAV, we compared baseline characteristics, clinical outcomes, ISR, and target lesion revascularization (TLR). The primary end-point was angiographic ISR assessed by quantitative coronary angiography analyzed as both a binary (≤50% vs. >50%) and continuous variable (follow-up minimal luminal area [MLA]/baseline MLA). Secondary outcomes included TLR and a composite of death, myocardial infarction, heart failure, and retransplantation. RESULTS: In 45 patients with DES, BMS, or both, ISR assessed as a continuous variable was statistically different between the 2 stent groups (follow-up MLA/baseline MLA = 0.796 DES vs. 0.481 BMS; P = 0.0037). There was also a significant difference in ISR (10.8% for DES versus 30.7% for BMS) when assessed as a binary variable. There was no statistically significant difference in TLR or composite cardiovascular outcomes between groups when adjusted for traditional cardiovascular risk factors. CONCLUSIONS: ISR assessed as a continuous variable was significantly different between stent groups. However, this did not lead to a difference in TLR or cardiovascular outcomes. This hypothesis-generating finding suggests that patients with CAV may not necessarily need treatment with DES, which can be more costly and carries more potential risk than BMS.

Implementation of cardovascular cell therapy network trials: challenges, innovation and lessons learned from experience in the CCTRN.

The cardiovascular cell therapy network was developed by the National Heart, Lung and Blood Institute to design and conduct clinical trials to advance the field of cardiovascular (CV) cell-based therapy. The Cardiovascular Cell Therapy Network successfully completed three clinical trials involving approximately 300 subjects across five centers and six satellites. Although the concept of a network within clinical trials research is not new, the knowledge gained in the implementation of such large-scale trials, particularly in novel therapeutic areas such as cell therapy is not often detailed in the literature. The purpose of this communication is to summarize key factors in achieving network goals and share the knowledge gained to promote success in future cardiovascular disease cell therapy trials and networks.

Efficacy and safety of unfractionated heparin plus glycoprotein IIb/IIIa inhibitors during revascularization for an acute coronary syndrome: a meta-analysis of randomized trials performed with stents and thienopyridines.

BACKGROUND: Early studies of glycoprotein IIb/IIIa inhibitors (GPIs) demonstrated benefit during percutaneous coronary intervention for acute coronary syndromes (ACS). Since their introduction, the magnitude of benefit of GPIs has become unclear. HYPOTHESIS: We hypothesized that adding a GPI to unfractionated heparin in ACS patients treated with stents and thienopyridines is beneficial. METHODS: We searched the MEDLINE, Cochrane, and clinicaltrials.gov databases for randomized clinical trials that studied the use of GPIs during ACS. We required that patients be randomly assigned to unfractionated heparin plus a GPI versus unfractionated heparin plus placebo (or control). Additional inclusion criteria included the use of coronary stents and periprocedural thienopyridines. Outcomes were assessed at 30 days. Random effects DerSimonian-Laird summary risk ratios (RR) and 95% confidence intervals (CIs) were constructed. RESULTS: Sixteen studies with 7611 patients were included. Myocardial infarction was 3.1% with GPI versus 4.4% with control (RR = 0.74; 95% CI, 0.59-0.94, P = 0.014); revascularization, 1.7% versus 2.7% (RR = 0.64; 95% CI, 0.46-0.89, P = 0.008); major bleeding, 2.5% versus 2.1% (RR = 1.21; 95% CI, 0.89-1.63, P = 0.22); minor bleeding, 5.5% versus 4.1% (RR = 1.37; 95% CI, 1.06-1.78, P = 0.016); and mortality, 2.2% versus 2.9% (RR = 0.79; 95% CI, 0.59-1.06, P = 0.12), respectively. CONCLUSIONS: Among ACS patients treated with stents and thienopyridines, GPIs were associated with reduced myocardial infarction and revascularization. Minor, but not major bleeding was increased with GPIs. Mortality was similar between the groups. © 2011 Wiley Periodicals, Inc. Supporting information may be found in the online version of this article This work was supported by an unrestricted grant from the Florida Heart Research Institute, which had no role in the study design, data collection, analysis, or interpretation, manuscript writing, or decision to proceed with publication. Anthony A Bavry has received research support from Novartis Pharmaceuticals and serves as a contractor for American College of Cardiology Cardiosource. The other authors have no funding, financial relationships, or conflicts of interest to disclose.

Efficacy and safety of glycoprotein IIb/IIIa inhibitors during elective coronary revascularization: a meta-analysis of randomized trials performed in the era of stents and thienopyridines.

OBJECTIVES: The purpose of this study was to investigate the efficacy and safety of glycoprotein IIb/IIIa inhibitors (GPIs) during elective percutaneous coronary intervention (PCI). BACKGROUND: Studies have documented that GPIs are useful during PCI; however, much of this research was conducted before the routine use of coronary stents and thienopyridines. METHODS: We searched the MEDLINE, Cochrane clinical trials, and ClinicalTrials.gov databases from inception for studies that randomly assigned patients undergoing elective PCI to a GPI versus control. Trials were included if stents and thienopyridines were used routinely and clinical outcomes were reported. Outcomes were assessed within 30 days. A DerSimonian-Laird model was used to construct random effects summary risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Our search yielded 22 studies with 10,123 patients. The incidence of nonfatal myocardial infarction was 5.1% with GPI versus 8.3% with control (RR: 0.66, 95% CI: 0.55 to 0.79, p < 0.0001). Major bleeding was 1.2% versus 0.9% (RR: 1.37, 95% CI: 0.83 to 2.25, p = 0.22), minor bleeding was 3.0% versus 1.7% (RR: 1.70, 95% CI: 1.28 to 2.26, p < 0.0001), and mortality was 0.3% versus 0.5% (RR: 0.70, 95% CI: 0.36 to 1.33, p = 0.27), respectively. CONCLUSIONS: In the current era of elective PCI performed with stents and thienopyridines, GPIs provide clinical benefit. These agents reduce nonfatal myocardial infarction without a notable increase in major bleeding; however, they increase the risk of minor bleeding. All-cause mortality is not reduced.