Margo Minissian

AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update A Guideline From the American Heart Association and American College of Cardiology Foundation

Since the 2006 update of the American Heart Association (AHA)/American College of Cardiology Foundation (ACCF) guidelines on secondary prevention,1 important evidence from clinical trials has emerged that further supports and broadens the merits of intensive risk-reduction therapies for patients with established coronary and other atherosclerotic vascular disease, including peripheral artery disease, atherosclerotic aortic disease, and carotid artery disease. In reviewing this evidence and its clinical impact, the writing group believed it would be more appropriate to expand the title of this guideline to “Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease.” Indeed, the growing body of evidence confirms that in patients with atherosclerotic vascular disease, comprehensive risk factor management reduces risk as assessed by a variety of outcomes, including improved survival, reduced recurrent events, the need for revascularization procedures, and improved quality of life. It is important not only that the healthcare provider implement these recommendations in appropriate patients but also that healthcare systems support this implementation to maximize the benefit to the patient. Compelling evidence-based results from recent clinical trials and revised practice guidelines provide the impetus for this update of the 2006 recommendations with evidence-based results2–165 (Table 1). Classification of recommendations and level of evidence are expressed in ACCF/AHA format, as detailed in Table 2. Recommendations made herein are largely based on major practice guidelines from the National Institutes of Health and updated ACCF/AHA practice guidelines, as well as on results from recent clinical trials. Thus, the development of the present guideline involved a process of partial adaptation of other guideline statements and reports and supplemental literature searches. The recommendations listed in this document are, whenever possible, evidence based. Writing group members performed these relevant supplemental literature searches with key search phrases including but not limited …

2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents

James L. Januzzi, Jr, MD, FACC, Chair Luis C. Afonso, MBBS, FACC Anthony Bavry, MD, FACC Brendan M. Everett, MD, FACC Jonathan Halperin, MD, FACC Adrian Hernandez, MD, FACC Hani Jneid, MD, FACC Dharam J. Kumbhani, MD, SM, FACC Eva M. Lonn, MD, FACC James K. Min, MD, FACC Pamela B. Morris

Ranolazine Improves Angina in Women With Evidence of Myocardial Ischemia But No Obstructive Coronary Artery Disease

OBJECTIVES We conducted a pilot study for a large definitive clinical trial evaluating the impact of ranolazine in women with angina, evidence of myocardial ischemia, and no obstructive coronary artery disease (CAD). BACKGROUND Women with angina, evidence of myocardial ischemia, but no obstructive CAD frequently have microvascular coronary dysfunction. The impact of ranolazine in this patient group is unknown. METHODS A pilot randomized, double-blind, placebo-controlled, crossover trial was conducted in 20 women with angina, no obstructive CAD, and ≥ 10% ischemic myocardium on adenosine stress cardiac magnetic resonance (CMR) imaging. Participants were assigned to ranolazine or placebo for 4 weeks separated by a 2-week washout. The Seattle Angina Questionnaire and CMR were evaluated after each treatment. Invasive coronary flow reserve (CFR) was available in patients who underwent clinically indicated coronary reactivity testing. CMR data analysis included the percentage of ischemic myocardium and quantitative myocardial perfusion reserve index (MPRI). RESULTS The mean age of subjects was 57 ± 11 years. Compared with placebo, patients on ranolazine had significantly higher (better) Seattle Angina Questionnaire scores, including physical functioning (p = 0.046), angina stability (p = 0.008), and quality of life (p = 0.021). There was a trend toward a higher (better) CMR mid-ventricular MPRI (2.4 [2.0 minimum, 2.8 maximum] vs. 2.1 [1.7 minimum, 2.5 maximum], p = 0.074) on ranolazine. Among women with coronary reactivity testing (n = 13), those with CFR ≤ 3.0 had a significantly improved MPRI on ranolazine versus placebo compared to women with CFR > 3.0 (Δ in MPRI 0.48 vs. -0.82, p = 0.04). CONCLUSIONS In women with angina, evidence of ischemia, and no obstructive CAD, this pilot randomized, controlled trial revealed that ranolazine improves angina. Myocardial ischemia may also improve, particularly among women with low CFR. These data document approach feasibility and provide outcome variability estimates for planning a definitive large clinical trial to evaluate the role of ranolazine in women with microvascular coronary dysfunction. (Microvascular Coronary Disease In Women: Impact Of Ranolazine; NCT00570089).

A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve

Abstract Aims The mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling. Materials and results Randomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500–1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (−3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041). Conclusions In this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects. Trial registration clinicaltrials.gov Identifier: NCT01342029.

Cardiac magnetic resonance imaging myocardial perfusion reserve index assessment in women with microvascular coronary dysfunction and reference controls

OBJECTIVE We sought to comparatively assess cardiac magnetic resonance imaging (CMRI) myocardial perfusion reserve index (MPRI) in women with confirmed microvascular coronary dysfunction (MCD) cases and reference control women. BACKGROUND Women with signs or symptoms of myocardial ischemia in the absence of obstructive coronary artery disease (CAD) frequently have MCD which carries an adverse prognosis. Diagnosis involves invasive coronary reactivity testing (CRT). Adenosine CMRI is a non-invasive test that may be useful for the detection of MCD. METHODS Fifty-three women with MCD confirmed by CRT and 12 age- and estrogen-use matched reference controls underwent adenosine CMRI. CMRI was assessed for MPRI, calculated using the ratio of myocardial blood flow at hyperemia/rest for the whole myocardium and separately for the 16 segments as defined by the American Heart Association. Statistical analysis was performed using repeated measures ANOVA models. RESULTS Compared to reference controls, MCD cases had lower MPRI values globally and in subendocardial and subepicardial regions (1.63±0.39 vs. 1.98±0.38, P=0.007, 1.51±0.35 vs. 1.84±0.34, P=0.0045, 1.68±0.38 vs. 2.04±0.41, P=0.005, respectively). A perfusion gradient across the myocardium with lower MPRI in the subendocardium compared to the subepicardium was observed for both groups. CONCLUSIONS Women with MCD have lower MPRI measured by perfusion CMRI compared to reference controls. CMRI may be a useful diagnostic modality for MCD. Prospective validation of a diagnostic threshold for MPRI in patients with MCD is needed.

A Randomized Controlled Trial of Acupuncture in Stable Ischemic Heart Disease Patients

BACKGROUND Heart rate variability (HRV) is reduced in stable ischemic heart disease (SIHD) patients and is associated with sudden cardiac death (SCD). We evaluated the impact of traditional acupuncture (TA) on cardiac autonomic function measured by HRV in SIHD patients. METHODS We conducted a randomized controlled study of TA, sham acupuncture (SA), and waiting control (WC) in 151 SIHD subjects. The TA group received needle insertion at acupuncture sites, the SA group received a sham at non-acupuncture sites, while the WC group received nothing. The TA and SA groups received 3 treatments/week for 12 weeks. 24-Hour, mental arithmetic stress, and cold pressor (COP) HRV was collected at entry and exit, along with BP, lipids, insulin resistance, hs-CRP, salivary cortisol, peripheral endothelial function by tonometry (PAT), and psychosocial variables. RESULTS Mean age was 63 ± 10; 50% had prior myocardial infarction. Comparison of WC and SA groups demonstrated differences consistent with the unblinded WC status; therefore by design, the control groups were not merged. Exit mental stress HRV was higher in TA vs. SA for markers of parasympathetic tone (p ≤ 0.025), including a 17% higher vagal activity (p=0.008). There were no differences in exit 24-hour or COP HRV, BP, lipids, insulin resistance, hs-CRP, salivary cortisol, PAT, or psychosocial variables. CONCLUSIONS TA results in intermediate effects on autonomic function in SIHD patients. TA effect on HRV may be clinically relevant and should be explored further. These data document feasibility and provide sample size estimation for a clinical trial of TA in SIHD patients for the prevention of SCD. CONDENSED ABSTRACT We conducted a randomized, single-blind trial of traditional acupuncture (TA) vs. sham acupuncture (SA) vs waiting control (WC) in stable ischemic heart disease (SIHD) patients to evaluate cardiac autonomic function measured by heart rate variability (HRV). Exit mental stress HRV was higher in the TA compared to SA group for time and frequency domain markers of parasympathetic tone (all p ≤ 0.025), including a 17% higher vagal activity (p=0.008). These data document feasibility and provide sample size estimation for an outcome-based clinical trial of TA in SIHD patients for the prevention of sudden cardiac death.

Heart failure hospitalization in women with signs and symptoms of ischemia: A report from the women's ischemia syndrome evaluation study

BACKGROUND Women with signs and symptoms of ischemia, no obstructive coronary artery disease, and preserved left ventricular ejection fraction enrolled in the National Heart Lung and Blood Institute (NHLBI) sponsored Womens Ischemia Syndrome Evaluation (WISE) study have an unexpectedly high rate of subsequent heart failure (HF) hospitalization. We sought to verify and characterize the HF hospitalizations. METHODS A retrospective chart review was performed on 223 women with signs and symptoms of ischemia, undergoing coronary angiography for suspected coronary artery disease followed for 6±2.6years. Data were collected from a single site in the WISE study. RESULTS At the time of study enrollment, the women were 57±11years of age, all had preserved left ventricular ejection fraction, and 81 (36%) had obstructive CAD (defined as >50% stenosis in at least one epicardial artery). Among the 223 patients, 25 (11%) reported HF hospitalizations, of which 14/25 (56%) had recurrent HF hospitalizations (>2 hospitalizations). Medical records were available in 13/25 (52%) women. Left ventricular ejection fraction was measured in all verified cases and was found to be preserved in 12/13 (92%). HF hospitalization was not related to obstructive CAD. CONCLUSION Among women with signs and symptoms of ischemia undergoing coronary angiography for suspected obstructive CAD, HF hospitalization at 6-year follow-up was predominantly characterized by a preserved ejection fraction and not associated with obstructive CAD.

Adverse Pregnancy Conditions, Infertility, and Future Cardiovascular Risk: Implications for Mother and Child

Adverse pregnancy conditions in women are common and have been associated with adverse cardiovascular and metabolic outcomes such as myocardial infarction and stroke. As risk stratification in women is often suboptimal, recognition of non-traditional risk factors such as hypertensive disorders of pregnancy and premature delivery has become increasingly important. Additionally, such conditions may also increase the risk of cardiovascular disease in the children of afflicted women. In this review, we aim to highlight these conditions, along with infertility, and the association between such conditions and various cardiovascular outcomes and related maternal risk along with potential translation of risk to offspring. We will also discuss proposed mechanisms driving these associations as well as potential opportunities for screening and risk modification.

Diastolic dysfunction measured by cardiac magnetic resonance imaging in women with signs and symptoms of ischemia but no obstructive coronary artery disease

BACKGROUND Women with chest pain and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD), diagnosed by invasive coronary reactivity testing (CRT). The relationship between CMD and diastolic function measured by cardiac magnetic resonance imaging (CMR) is not well described. METHODS 41 women with suspected CMD underwent CRT and CMR. Left ventricular end-diastolic pressure (LVEDP), coronary flow reserve (CFR) and coronary blood flow (CBF) were measured invasively. Resting CMR of these women and 20 reference controls was assessed for LV mass, septal wall thickness, ejection fraction (LVEF), end-diastolic volume (EDV), peak filling rate (PFR) and time-to-peak-filling rate (tPFR). Pearson correlations and linear regression models were made. RESULTS Mean age was 55±9, all had LVEF≥50%, and 16/41 (40%) had LVEDP>15mmHg. CMD (CFR<2.5 or CBF<50%) was present in 34/41 (83%) women. tPFR (mean 178±110ms) and PFR (mean 3.2±0.64 EDV/s) were not significantly different in women with or without CMD. tPFR increased with age (r=0.37, p=0.017) and septal wall thickness (r=0.47, p=0.002), while PFR decreased with age (r=-0.45, p=0.003). There was an inverse relationship between CFR and tPFR (r=-0.3, p=0.058). Increasing mass was associated with decreasing CBF (p=0.02). Compared to controls, cases had lower LVEF (p=0.049) and lower EDV (p=0.0002). CONCLUSION In women with signs and symptoms of ischemia but no obstructive coronary artery disease, CMD and elevated LVEDP are prevalent. While non-endothelial dependent CMD may be related to diastolic dysfunction, further investigation is needed regarding links between CMD, diastolic dysfunction and the development of heart failure with preserved LVEF.

Adverse pregnancy outcomes and cardiovascular risk factor management.

Cardiovascular disease (CVD) is the leading health threat to American women. In addition to establish risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a womans risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger women often use their obstetrician/gynecologist as their primary health provider, this is an opportune time to diagnose and treat CVD risk factors early. Embedding preventive care providers such as nurse practitioners or physician assistants within OB/GYN practices can be considered, with referral to family medicine or internist for ongoing risk assessment and management. The American Heart Association (AHA)/American Stroke Association (ASA) stroke prevention guidelines tailored to women recommend that women with a history of pre-eclampsia can be evaluated for hypertension and other CVD risk factors within 6 months to 1-year post-partum. Given the burden and impact of CVD on women in our society, the entire medical community must work to establish feasible practice and referral patterns for assessment and treatment of CVD risk factors.