Risk factors for heart failure in women with ischemia and no obstructive coronary artery disease.

Study objective: Women with ischemia and no obstructive coronary artery disease (INOCA) are at increased risk for heart failure (HF) hospitalizations, which is predominantly HF with preserved ejection fraction (HFpEF). We aimed to identify predictors for the development of heart failure HF in a deeply phenotyped cohort of women with INOCA and long-term prospective follow-up. Design setting and participants: Women enrolled in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) were evaluated for baseline characteristics including clinical history, medications, physical exam, laboratory data and angiographic data. Using a multivariate Cox analysis, we assessed the association between baseline characteristics and the occurrence of HF hospitalizations in 493 women with evidence of ischemia but no obstructive coronary disease, no prior history of HF, and available follow-up data. Results: During a median follow-up of 6-years, 18 (3.7%) women were hospitalized for HF. Diabetes mellitus and tobacco use were associated with HF hospitalization. In a multivariate analysis adjusting for known HFpEF predictors including age, diabetes, hypertension, tobacco use, and statin use, novel predictive variables included higher resting heart rate, parity and IL-6 levels and lower coronary flow reserve (CFR) and poor functional status. Conclusions: There is a considerable incidence of HF hospitalization at longer term follow-up in women with INOCA. In addition to traditional risk factors, novel risk variables that independently predict HF hospitalization include multi-parity, high IL-6, low CFR, and poor functional status. These novel risk factors may be useful to understand mechanistic pathways and future treatment targets for prevention of HFpEF.

Cardiac Imaging in Dialysis Patients.

There is a well-established yet unexplained high prevalence of cardiovascular morbidity and mortality in individuals with end-stage kidney disease receiving dialysis. Potential causes include changes in cardiac structure and function, with increased left ventricular mass index as the best established cardiac structural change associated with this increase in mortality. However, in recent years, new echocardiographic and cardiac magnetic resonance imaging techniques have emerged that may provide novel markers that may better explain the mechanisms underlying the cardiovascular morbidity and mortality observed in end-stage kidney disease. This review outlines advances in cardiac imaging and the current status of imaging modalities, including echocardiography, cardiac magnetic resonance imaging, and cardiac positron emission tomography, to identify dialysis patients at high risk for cardiovascular mortality.

Predicted Versus Observed Major Adverse Cardiac Event Risk in Women With Evidence of Ischemia and No Obstructive Coronary Artery Disease: A Report From WISE (Women's Ischemia Syndrome Evaluation).

Background Primary prevention risk scores are commonly used to predict cardiovascular (CVD) outcomes. The applicability of these scores in patients with evidence of myocardial ischemia but no obstructive coronary artery disease is unclear. Methods and Results Among 935 women with signs and symptoms of ischemia enrolled in WISE (Women's Ischemia Syndrome Evaluation), 567 had no obstructive coronary artery disease on angiography. Of these, 433 had had available risk data for 6 commonly used scores: Framingham Risk Score, Reynolds Risk Score, Adult Treatment Panel III, Atherosclerotic Cardiovascular Disease, Systematic Coronary Risk Evaluation, Cardiovascular Risk Score 2. Score-specific CVD rates were assessed. For each score, we evaluated predicted versus observed event rates at 10-year follow-up using c statistic. Recalibration was done for 3 of the 6 scores. The 433 women had a mean age of 56.9±9.4 years, 82.5% were white, 52.7% had hypertension, 43.6% had dyslipidemia, and 16.9% had diabetes mellitus. The observed 10-year score-specific CVD rates varied between 5.54% (Systematic Coronary Risk Evaluation) to 28.87% (Framingham Risk Score), whereas predicted event rates varied from 1.86% (Systematic Coronary Risk Evaluation) to 6.99% (Cardiovascular Risk Score 2). The majority of scores showed moderate discrimination (c statistic 0.53 for Atherosclerotic Cardiovascular Disease and Systematic Coronary Risk Evaluation; 0.78 for Framingham Risk Score) and underestimated risk (statistical discordance -58% for Adult Treatment Panel III; -84% for Atherosclerotic Cardiovascular Disease). Recalibrated Reynolds Risk Score, Atherosclerotic Cardiovascular Disease, and Framingham Risk Score had improved performance, but significant underestimation remained. Conclusions Commonly used CVD risk scores fail to accurately predict CVD rates in women with ischemia and no obstructive coronary artery disease. These results emphasize the need for new risk assessment scores to reliably assess this population.

Weight cycling and cardiovascular outcome in women with suspected ischemia: A report from the NHLBI-sponsored WISE Study.

BACKGROUND: We previously reported in a cross-sectional analysis an adverse relationship between weight cycling and HDL-cholesterol but not angiographic obstructive coronary artery disease (CAD) among women undergoing coronary angiography for suspected ischemia in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE). We now examine the relationship between weight cycling and prospective adverse cardiovascular outcome in this group. METHODS: 795 women enrolled between 1996-2001 in the WISE undergoing coronary angiography for evaluation of suspected ischemia and followed for a median of 6.0 years (interquartile range = 3.4 years). Adverse outcome was defined as a composite of all-cause death, cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure. Weight cycling was defined as the intentional loss of at least 10 lbs. (4.5 kgs.) at least three times during the women's lifetime. RESULTS: Women (n = 224) who reported a history of weight cycling were younger; more often white and better educated compared those without this history. At baseline, women with a weight cycling history had lower HDL-C values, higher body mass index, larger waist circumferences and higher values for fasting blood sugar, but no difference in obstructive CAD prevalence or severity. There was an inverse relationship between weight cycling and adverse composite cardiovascular outcome, whereby fewer of women with a history of weight cycling experienced an adverse outcome as compared to non-cyclers (21% vs 29%, respectively, p = 0.03). CONCLUSIONS: Despite an adverse association with HDL-cholesterol in women undergoing coronary angiography for suspected ischemia, weight cycling was associated with a lower adverse outcome rate in women with suspected ischemia.

Left Ventricular Mass Change After Anthracycline Chemotherapy.

BACKGROUND: Myocardial atrophy and left ventricular (LV) mass reductions are associated with fatigue and exercise intolerance. The relationships between the receipt of anthracycline-based chemotherapy (Anth-bC) and changes in LV mass and heart failure (HF) symptomatology are unknown, as is their relationship to LV ejection fraction (LVEF), a widely used measurement performed in surveillance strategies designed to avert symptomatic HF associated with cancer treatment. METHODS AND RESULTS: We performed blinded, serial assessments of body weight, LVEF and mass, LV-arterial coupling, aortic stiffness, and Minnesota Living with Heart Failure Questionnaire measures before and 6 months after initiating Anth-bC (n=61) and non-Anth-bC (n=15), and in 24 cancer-free controls using paired t and χ2 tests and multivariable linear models. Participants averaged 51±12 years, and 70% were women. Cancer diagnoses included breast cancer (53%), hematologic malignancy (42%), and soft tissue sarcoma (5%). We observed a 5% decline in both LVEF (P<0.0001) and LV mass (P=0.03) in the setting of increased aortic stiffness and disrupted ventricular-arterial coupling in those receiving Anth-bC but not other groups (P=0.11-0.92). A worsening of the Minnesota Living with Heart Failure Questionnaire score in Anth-bC recipients was associated with myocardial mass declines (r=-0.27; P<0.01) but not with LVEF declines (r=0.11; P=0.45). Moreover, this finding was independent of LVEF changes and body weight. CONCLUSIONS: Early after Anth-bC, LV mass reductions associate with worsening HF symptomatology independent of LVEF. These data suggest an alternative mechanism whereby anthracyclines may contribute to HF symptomatology and raise the possibility that surveillance strategies during Anth-bC should also assess LV mass.

ACC/AATS/AHA/ASE/EACTS/HVS/SCA/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for the Treatment of Patients With Severe Aortic Stenosis: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

The American College of Cardiology collaborated with the American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons to develop and evaluate Appropriate Use Criteria (AUC) for the treatment of patients with severe aortic stenosis (AS). This is the first AUC to address the topic of AS and its treatment options, including surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). A number of common patient scenarios experienced in daily practice were developed along with assumptions and definitions for those scenarios, which were all created using guidelines, clinical trial data, and expert opinion in the field of AS. The 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines(1) and its 2017 focused update paper (2) were used as the primary guiding references in developing these indications. The writing group identified 95 clinical scenarios based on patient symptoms and clinical presentation, and up to 6 potential treatment options for those patients. A separate, independent rating panel was asked to score each indication from 1 to 9, with 1-3 categorized as "Rarely Appropriate," 4-6 as "May Be Appropriate," and 7-9 as "Appropriate." After considering factors such as symptom status, left ventricular (LV) function, surgical risk, and the presence of concomitant coronary or other valve disease, the rating panel determined that either SAVR or TAVR is Appropriate in most patients with symptomatic AS at intermediate or high surgical risk; however, situations commonly arise in clinical practice in which the indications for SAVR or TAVR are less clear, including situations in which 1 form of valve replacement would appear reasonable when the other is less so, as do other circumstances in which neither intervention is the suitable treatment option. The purpose of this AUC is to provide guidance to clinicians in the care of patients with severe AS by identifying the reasonable treatment and intervention options available based on the myriad clinical scenarios with which patients present. This AUC document also serves as an educational and quality improvement tool to identify patterns of care and reduce the number of rarely appropriate interventions in clinical practice.

Optimal Same-Day Platelet Inhibition in Patients Receiving Drug-Eluting Stents With or Without Previous Maintenance Thienopyridine Therapy: from the Evaluation of Platelet Inhibition in Patients Having A VerifyNow Assay (EPIPHANY) Trial.

We determined if high on-treatment platelet reactivity (HTPR) can be overcome on the day of percutaneous coronary intervention (PCI) in patients with or without previous maintenance thienopyridine therapy. Patients with HTPR, as defined as P2Y12 reaction units (PRU) >230, were switched to an alternate thienopyridine. Patients with HTPR undergoing PCI are at increased risk for ischemic complications. A total of 429 patients undergoing PCI with drug-eluting stents were enrolled. Patients on maintenance thienopyridine (n = 249) with PRU >230 were loaded with the alternative thienopyridine. Patients who were thienopyridine naïve (n = 180) were randomized to clopidogrel 600 (n = 90) or prasugrel 60 mg (n = 90). Patients with HTPR were loaded with the alternative agent. Patients on maintenance clopidogrel (n = 192) had a higher prevalence of HTPR compared with prasugrel (n = 57; 51% vs 4%, p <0.001). Patients on maintenance clopidogrel with HTPR (n = 98) who were loaded with prasugrel achieved PRU ≤230 in 97%. Thienopyridine-naïve patients loaded with clopidogrel had a higher prevalence of HTPR compared with prasugrel (37% vs 3%, p <0.001). Clopidogrel-loaded patients with HTPR (n = 33) who were reloaded with prasugrel achieved PRU ≤230 in 94%. All 3 prasugrel-loaded patients with HTPR treated with clopidogrel achieved PRU ≤230. Two patients experienced 30-day major adverse clinical events. One patient experienced Thrombolysis In Myocardial Infarction major bleeding. In conclusion, HTPR can be overcome in patients with and without previous maintenance thienopyridine therapy by identifying patients with HTPR and switching to an alternate thienopyridine.

The global cardiovascular magnetic resonance registry (GCMR) of the society for cardiovascular magnetic resonance (SCMR): its goals, rationale, data infrastructure, and current developments.

BACKGROUND: With multifaceted imaging capabilities, cardiovascular magnetic resonance (CMR) is playing a progressively increasing role in the management of various cardiac conditions. A global registry that harmonizes data from international centers, with participation policies that aim to be open and inclusive of all CMR programs, can support future evidence-based growth in CMR. METHODS: The Global CMR Registry (GCMR) was established in 2013 under the auspices of the Society for Cardiovascular Magnetic Resonance (SCMR). The GCMR team has developed a web-based data infrastructure, data use policy and participation agreement, data-harmonizing methods, and site-training tools based on results from an international survey of CMR programs. RESULTS: At present, 17 CMR programs have established a legal agreement to participate in GCMR, amongst them 10 have contributed CMR data, totaling 62,456 studies. There is currently a predominance of CMR centers with more than 10 years of experience (65%), and the majority are located in the United States (63%). The most common clinical indications for CMR have included assessment of cardiomyopathy (21%), myocardial viability (16%), stress CMR perfusion for chest pain syndromes (16%), and evaluation of etiology of arrhythmias or planning of electrophysiological studies (15%) with assessment of cardiomyopathy representing the most rapidly growing indication in the past decade. Most CMR studies involved the use of gadolinium-based contrast media (95%). CONCLUSIONS: We present the goals, mission and vision, infrastructure, preliminary results, and challenges of the GCMR. TRIAL REGISTRATION: Identification number on ClinicalTrials.gov: NCT02806193 . Registered 17 June 2016.

Rb-82 PET/CT left ventricular mass-to-volume ratios.

Left ventricular (LV) mass:volume ratios indexed to body size (Mi/Vi) provide risk stratification for cardiac events. We sought to determine whether Rb-82 PET mass and volume indices are similar to MRI normal values for low likelihood subjects, and whether abnormal indices are related to abnormal myocardial blood flow (MBF). Data were analyzed retrospectively for 194 patients referred for rest/stress Rb-82 PET. LV EF, volume and mass values were calculated and mass:volume ratios were indexed to patients' height and weight. MBF was computed from the first pass dynamic component of PET data. 53 patients at low likelihood of CAD had PET Mi/Vi = 1.35 ± 0.27, consistent with the MRI literature range of 1.0-1.5. Compared to patients with normal indexed volume (Vi), patients with abnormally high Vi had lower rest MBF (0.56 ± 0.24 vs 0.93 ± 0.57 ml/g/min, p = 0.0001), and lower stress MBF (0.97 ± 0.52 vs. 1.83 ± 0.96 ml/g/min, p < 0.0001). Stress EF < 50% predicted abnormal Vi with 90% accuracy. Patients with Mi/Vi < 1.0 had abnormally low rest EF (45 ± 16% vs. 60 ± 15%, p < 0.0001) and low rest MBF (0.58 ± 0.25 vs. 0.96 ± 0.59 ml/g/min, p < 0.0001). In our study population, abnormal LV volume and mass correlated with lower rest and stress MBF and EF, suggesting that the pathophysiologic explanation of these patients' increased risk is more extensive obstructive CAD.

Relationships between left ventricular asynchrony and myocardial blood flow.

OBJECTIVE: 82Rb PET protocols enable determination of left ventricular asynchrony (LVAS) at rest and stress, along with myocardial blood flow (MBF). We hypothesized that in patients with resting LVAS, MBF differs between those with stress-induced LVAS improvement and those with stress-induced LVAS deterioration. METHODS: We retrospectively analyzed 82Rb rest/regadenoson stress PET studies of 195 patients evaluated for known or suspected coronary artery disease. MBF was computed from first-pass data; function and relative perfusion were computed from myocardial equilibrium data. LVAS was defined as phase contraction bandwidth (BW) above 82Rb gender-specific normal limits, with changes defined as BW moving into or out of normal ranges. RESULTS: Among the 195 patients, 64 had LVAS at rest, of whom 13 reverted to normal and 51 continued to have LVAS with stress. Patients who did not improve had lower stress MBF (1.04 ± 0.69 vs 1.58 ± 0.67, p = .02) and coronary flow reserve (1.94 ± 1.16 vs 3.04 ± 1.22, p = .01) than those who did improve. ROC analysis indicated that the parameter most strongly associated with improvement in asynchrony for patients with resting LVAS was reduction in MBF heterogeneity (ROC area (accuracy) = 84%, sensitivity = 92%, and specificity = 67%). CONCLUSION: LVAS is highly correlated with MBF and CVR, with stress-induced improvement in synchronicity most strongly associated with improved MBF homogeneity.

CTA Detection of Left Atrial Stasis and Thrombus in Patients with Atrial Fibrillation.

BACKGROUND: We investigated computed tomography (CT) angiography (CTA) in assessment of left atrial appendage (LAA) stasis and thrombus in preprocedural evaluation for atrial fibrillation (AF) ablation in a large community cohort. METHODS AND RESULTS: We reviewed CTA and transesophageal echocardiographic images obtained in 861 consecutive patients with a history of AF undergoing same-day CTA and transesophageal echocardiogram (TEE) before AF ablation at a single hospital (2006-2013). CTA findings of LAA filling defects from acquisitions without electrocardiogram gating were compared to TEE features of LAA stasis (grade 0-4) and thrombus. Stasis grade 0 or 1 by TEE in the absence of thrombus was defined as a negative result. In addition, LAA peak flow velocity was assessed by TEE. Average age was 61 ± 10 years and 75% were male. On CTA, 161 patients (19%) had LAA filling defects on CTA and 21 had ≥grade 2 stasis on TEE, including two with thrombus, resulting in a positive predictive value of only 13%. However, among 670 CTA-negative patients, 669 (99%) were negative for thrombus or stasis by TEE with one false-negative CTA in a patient with grade 2 stasis by TEE but no thrombus, yielding a negative predictive value of 99.9%. Slow LAA Doppler flow velocity was the most important determinant of false-positive CTA results in multivariate analysis (P < 0.0001) CONCLUSION: LAA filling defects on CT are associated with slow LAA flow velocity. AF patients without LAA filing defects on CT are free of significant stasis and thrombus on TEE. It may be possible to eliminate TEE in up to 80% of AF ablation patients based on negative CTA findings.

Collective impact of conventional cardiovascular risk factors and coronary calcium score on clinical outcomes with or without statin therapy: The St Francis Heart Study.

BACKGROUND AND AIMS: The efficacy of statin therapy remains unknown in patients eligible for statin therapy with and without elevated coronary calcium score (CAC). The study sought to evaluate how cardiovascular risk factors, expressed in terms of statin eligibility for primary prevention, and CAC modify clinical outcomes with and without statin therapy. METHODS: We conducted a post-hoc analysis of the St. Francis Heart Study treatment trial, a double-blind, placebo-controlled randomized controlled trial of atorvastatin (20 mg), vitamin C (1 g), and vitamin E (1000 U) daily, versus placebos in 990 asymptomatic individuals with CAC ≥ 80th percentile for age and gender. Primary cardiovascular outcomes included non-fatal myocardial infarction or coronary death, coronary revascularization, stroke, and peripheral arterial revascularization. We further stratified the treatment and placebo groups by eligibility (eligible when statin indicated) for statin therapy based on 2013 ACC/AHA guidelines and based on CAC categories. RESULTS: After a median follow-up of 4.8 years, cardiovascular events had occurred in 3.9% of the statin treated but not eligible, 4.6% of the untreated and not eligible, 8.9% of the treated and eligible and 13.4% of the untreated and eligible groups, respectively (p<0.001). Low CAC (<100) occurred infrequently in statin eligible subjects (≤4%) and was associated with low 10-year event rate (<1 per 100 person-years). In contrast, high CAC (>300) occurred frequently in more than 35% of the statin not eligible subjects and was associated with a high 10-year event rate (≥17 per 100 person-years). Risk prediction improved significantly when both clinical risk profile and CAC score were combined (net reclassification index p = 0.002). CONCLUSIONS: Under the current statin treatment guidelines a small number of statin eligible subjects with low CAC might not benefit from statin therapy within 5 years. However, the statin not eligible subjects with high CAC have high event rate attributing to loss of opportunity for effective primary prevention.

Effect of Outflow Tract Contributions to 82Rb-PET Global Myocardial Blood Flow Computations.

UNLABELLED: Algorithms are able to compute myocardial blood flow (MBF) from dynamic PET data for each of the 17 left ventricular segments, with global MBF obtained by averaging segmental values. This study was undertaken to compare MBFs with and without the basal-septal segments. METHODS: Data were examined retrospectively for 196 patients who underwent rest and regadenoson-stress (82)Rb PET/CT scanning for evaluation of known or suspected coronary artery disease. MBF data were acquired in gated list mode and rebinned to isolate the first-pass dynamic portion. Coronary vascular resistance (CVR) was computed as mean arterial pressure divided by MBF. MBF inhomogeneity was computed as the ratio of SD to mean MBF. Relative perfusion scores were obtained using (82)Rb-specific normal limits applied to polar maps of myocardial perfusion generated from myocardial equilibrium portions of PET data. MBF and CVRs from 17 and 14 segments were compared. RESULTS: Mean MBFs were lower for 17- than 14-segment means for rest (0.78 ± 0.50 vs. 0.85 ± 0.54 mL/g/min, paired t test P < 0.0001) and stress (1.50 ± 0.88 vs. 1.67 ± 0.96 mL/g/min, P < 0.0001). Bland-Altman plots of MBF differences versus means exhibited nonzero intercept (-0.04 ± 0.01, P = 0.0004) and significant correlation (r = -0.64, P < 0.0001), with slopes significantly different from 0.0 (-7.2% ± 0.6% and -8.3% ± 0.7% for rest and stress MBF; P < 0.0001). Seventeen-segment CVRs were higher than 14-segment CVRs for rest (159 ± 86 vs. 147 ± 81 mm Hg/mL/g/min, paired t test P < 0.0001) and stress CVR (85 ± 52 vs. 76 ± 48 mm Hg/mL/g/min, P < 0.0001). MBF inhomogeneity correlated significantly (P < 0.0001) with summed perfusion scores, but values correlated significantly more strongly for 14- than 17-segment values for rest (r = 0.67 vs. r = 0.52, P = 0.02) and stress (r = 0.69 vs. r = 0.47, P = 0.001). When basal segments were included in MBF determinations, perfusion inhomogeneity was greater both for rest (39% ± 10% vs. 31% ± 10%, P < 0.0001) and for stress (42% ± 12% vs. 32% ± 11%, P < 0.0001). CONCLUSION: Averaging 17 versus 14 segments leads to systematically 7%-8% lower MBF calculations, higher CVRs, and greater computed inhomogeneity. Consideration should be given to excluding basal-septal segments from standard global MBF determination.