Outpatient Management of Patients With Angina With No Obstructive Coronary Arteries: How to Come to a Proper Diagnosis and Therapy

Two-thirds of women and one-third of men who undergo a clinically indicated coronary angiography for stable angina, have no obstructive coronary artery disease (CAD). Coronary vascular dysfunction is a highly prevalent underlying cause of angina in these so called “Angina with No Obstructive Coronary Arteries (ANOCA)” patients, foremost in middle aged women. Coronary vascular dysfunction encompasses various endotypes, namely epicardial and microvascular coronary spasms, impaired vasodilatation, and increased microvascular resistance. ANOCA patients, especially those with underlying coronary vascular dysfunction, have an adverse cardiovascular prognosis, poor physical functioning, and a reduced quality of life. Since standard ischemia detection tests and coronary angiograms are not designed to diagnose coronary vascular dysfunction, this ischemic heart disease is often overlooked and hence undertreated. But adequate diagnosis is vital, so that treatment can be started to reduce symptoms, reduce healthcare costs and improve quality of life and cardiovascular prognosis. The purpose of this review is to give a contemporary overview of ANOCA with focus on coronary vascular dysfunction. We will provide a possible work-up of patients suspected of coronary vascular dysfunction in the outpatient clinical setting, based on the latest scientific insights and international consensus documents. We will discuss the value of ischemia detection testing, and non-invasive and invasive methods to diagnose coronary vascular dysfunction. Furthermore, we will go into pharmacological and non-pharmacological therapeutic options including anti-anginal regimens and lifestyle interventions.

Myocardial SPECT Perfusion Defects in Angina Patients, Without Significant Epicardial Coronary Artery Disease. Can Pathological SPECT Affect Long-Term Prognosis?

Purpose: Patients with angina and a positive SPECT for reversible ischemia, with no or non-obstructive CAD on ICA represent a frequent clinical problem and predicting prognosis is challenging. Methods: A retrospective single center study focused on patients that underwent elective-ICA with angina and a positive SECT with no or non-obstructive CAD in the CathLab, during a seven-year period. Assessment of patients’ cardiovascular morbidity, mortality, and MACE during a follow-up period of at least three years after ICA, with the assist of a telephone questionnaire.Results: Data of all patients that underwent ICA for a period of 7 years (from January 1,2011 until December 31, 2017) in our hospital were analyzed. The patients that fulfilled the prespecified criteria were 569. At the telephone survey, 285(50.1%) were successfully contacted and agreed to participate. The mean age was 67.6 (SD8.8) years (35.4%female) and the mean follow-up time was 5.53years (SD1.85). Mortality rate was 1.7% (4 patients/non-cardiac causes) and 1,7% rate of revascularization. 31(10,9%) were hospitalized for cardiac reasons and 10,9% patients reported symptoms of HF (no patients with NYHA-Class above II). 21 had arrhythmic events and only two mild anginal symptoms. Noteworthy finding was, the mortality rate in the not-contacted group (12 out of 284, 4,2%), derived by public security records, did not differ significantly from the contacted-group. Conclusions: Patients with angina, a positive SPECT for reversible ischemia and no or non-obstructive CAD in ICA have very good long-term cardiovascular prognosis for at least 5 years.

Obesity Phenotypes and Electrocardiographic Characteristics in Physically Active Males: CHIEF Study

Background: Metabolically unhealthy obesity (MUO) has been associated with surface electrocardiographic (ECG) left ventricular hypertrophy (LVH), left atrial enlargement (LAE), and inferior T wave inversions (TWI) in the middle- and old-aged populations. However, the relationship between obesity phenotypes and these ECG abnormalities in physically active young adults is yet to be determined.Methods: A total of 2,156 physically active military males aged 18–50 in Taiwan were analyzed. Obesity and metabolically unhealthy status were, respectively, defined as the body mass index ≥27 kg/m2 and the presence of metabolic syndrome based on the ATPIII criteria for Asian male adults. Four groups were classified as the metabolically healthy non-obesity (MHNO, n = 1,484), metabolically unhealthy non-obesity (MUNO, n = 86), metabolically healthy obesity (MHO, n = 376), and MUO (n = 210). ECG-LVH was based on the Sokolow–Lyon and Cornell voltage criteria, ECG-LAE was defined as a notched P wave ≥0.12 s in lead II or a notch of ≥0.04 s, and inferior TWI was defined as one negative T wave axis in limb leads II, III, or aVF. Physical performance was evaluated by time for a 3-km run. Multiple logistic regression analysis with adjustment for age, smoking, alcohol drinking, and physical performance was utilized to investigate the associations between obesity phenotypes and the ECG abnormalities.Results: As compared to MHNO, MUNO, MHO, and MUO were associated with lower risk of Sokolow–Lyon-based ECG-LVH [odds ratios (OR) and 95% confidence intervals: 0.80 (0.51–1.25), 0.46 (0.36–0.58), and 0.39 (0.28–0.53), respectively; p for trend <0.001], and with greater risk of ECG-LAE [OR: 0.87 (0.44–1.72), 2.34 (1.77–3.10), and 3.02 (2.13–4.28), respectively; p for trend <0.001] and inferior TWI [OR: 2.21 (0.74–6.58), 3.49 (1.97–6.19), and 4.52 (2.38–8.60), respectively; p for trend <0.001]. However, no associations between obesity phenotypes and Cornell-based ECG-LVH were found.Conclusion: In physically active young males, obesity was associated with higher risk of ECG-LAE and inferior TWI, whereas the risk between obesity and ECG-LVH might vary by the ECG criteria, possibly due to a high prevalence of exercise induced-LVH in military and greater chest wall thickness in obesity. The cardiovascular prognosis of ECG-LVH in physically active obese adults requires further study.

O004 Obstructive sleep apnoea severity is associated with parasympathetic withdrawal in coronary artery disease

Introduction Patients with Coronary Artery Disease (CAD) are exposed to myocardial ischemia and hypoxia, resulting in altered autonomic function. Obstructive sleep apnoea (OSA) is highly prevalent in CAD and is associated with increased sympathetic activity which could further exacerbate cardiovascular risk. We aimed to determine whether OSA severity is associated with altered autonomic function in CAD patients. Methods Patients presenting to the coronary care unit with CAD underwent level 2 portable polysomnography to assess the presence and severity of OSA. Autonomic function was calculated from continuous blood pressure and 3-lead ECG 5 minute recordings while awake. Mean spontaneous baroreceptor sensitivity (sBRS msec/mmHg); vagally mediated heart rate variability (HRV) markers (pNN50%, RMSSD, HF-HRV); and, sympathetically mediated vascular autonomic function (LF-BPV) were measured. Autonomic function was assessed in relation to OSA severity (Apnoea Hypopnea Index, AHI; oxygen desaturation index, ODI). Results OSA was present in 49/51 (96%) participants with CAD (age 54±9 years; BMI 28.9±5.4 kg/m2; male 41(77%)). No association was found between sBRS and AHI. There was a modest inverse correlation between AHI and vagally mediated HRV (RMSSD, r= -0.28 p=0.04; HF, r= -0.31 p=0.03). AHI positively correlated with LF-SBP (r=0.29, p=0.04) suggesting upregulation of sympathetic modulation. Linear regression analyses, adjusted for age, sex, and BMI, showed AHI was a determinant of parasympathetically modulated HRV measures (pNN50% -0.25(0.12), p=0.05). Conclusions In patients with CAD, increased AHI was associated with parasympathetic withdrawal suggesting that OSA could increase poor cardiovascular prognosis in this population.

Correlation between Heart Rate Variability and Claustrum Stimulation – Hypothesis, Experimental Studies and Future Perspectives

Heart rate variability (HRV) has long been associated with cardiovascular risk, especially after a myocardial infarction, but also in general. HRV refl ects and is used as a surrogate for the balance between sympathetic and parasympathetic systems in modulating the cardiovascular activity. A low HRV, traditionally associated to sympathovagal imbalance, is associated with a worse cardiovascular prognosis. Deep brain stimulation (DBS) is a surgical technique used for severe cases of Parkinson’s disease and other neurologic pathologies. DBS is performed in various areas of the brain and through different protocols. The claustrum, an area located between the external capsule and the insular cortex, was recently shown to be connected to Parkinson’s motor symptoms. As DBS in other regions of the brain has proven non-motor effects, like infl uencing the HRV, we sought to document the effect of claustrum stimulation on the sympatho-vagal balance (SVB). Our preliminary data indicates that claustrum stimulation inclines the SVB toward the latter, but more studies are required to observe the long-term effects of this type of stimulation.

Modern Approaches to Lower Lipoprotein(a) Concentrations and Consequences for Cardiovascular Diseases

Lipoprotein(a) (Lp(a)) is a low density lipoprotein particle that is associated with poor cardiovascular prognosis due to pro-atherogenic, pro-thrombotic, pro-inflammatory and pro-oxidative properties. Traditional lipid-lowering therapy does not provide a sufficient Lp(a) reduction. For PCSK9 inhibitors a small reduction of Lp(a) levels could be shown, which was associated with a reduction in cardiovascular events, independently of the effect on LDL cholesterol. Another option is inclisiran, for which no outcome data are available yet. Lipoprotein apheresis acutely and in the long run decreases Lp(a) levels and effectively improves cardiovascular prognosis in high-risk patients who cannot be satisfactorily treated with drugs. New drugs inhibiting the synthesis of apolipoprotein(a) (an antisense oligonucleotide (Pelacarsen) and two siRNA drugs) are studied. Unlike LDL-cholesterol, for Lp(a) no target value has been defined up to now. This overview presents data of modern capabilities of cardiovascular risk reduction by lowering Lp(a) level.

Nuts: Natural Pleiotropic Nutraceuticals

Common nuts (tree nuts and peanuts) are energy-dense foods that nature has gifted with a complex matrix of beneficial nutrients and bioactives, including monounsaturated and polyunsaturated fatty acids, high-quality protein, fiber, non-sodium minerals, tocopherols, phytosterols, and antioxidant phenolics. These nut components synergize to favorably influence metabolic and vascular physiology pathways, ameliorate cardiovascular risk factors and improve cardiovascular prognosis. There is increasing evidence that nuts positively impact myriad other health outcomes as well. Nut consumption is correlated with lower cancer incidence and cancer mortality, and decreased all-cause mortality. Favorable effects on cognitive function and depression have also been reported. Randomized controlled trials consistently show nuts have a cholesterol-lowering effect. Nut consumption also confers modest improvements on glycemic control, blood pressure (BP), endothelial function, and inflammation. Although nuts are energy-dense foods, they do not predispose to obesity, and in fact may even help in weight loss. Tree nuts and peanuts, but not peanut butter, generally produce similar positive effects on outcomes. First level evidence from the PREDIMED trial shows that, in the context of a Mediterranean diet, consumption of 30 g/d of nuts (walnuts, almonds, and hazelnuts) significantly lowered the risk of a composite endpoint of major adverse cardiovascular events (myocardial infarction, stroke, and death from cardiovascular disease) by ≈30% after intervention for 5 y. Impressively, the nut-supplemented diet reduced stroke risk by 45%. As they are rich in salutary bioactive compounds and beneficially impact various health outcomes, nuts can be considered natural pleiotropic nutraceuticals.

Abstract P264: Protective Effects Of Angiotensin II Inhibitors In Lebanese SARS-COV2 Hospitalized Patients

Introduction: SARS-CoV2 leads to increased Angiotensin II resulting in worsened cardiovascular disease (CVD) outcome and prognosis. ACEIs and ARBs prescribed drugs could be a crucial player in SARS-COV2 prognosis, owing that ACE2 is one SARS-CoV2 binding site and that ACE2 expression in the cardiovascular system is markedly elevated following the treatment with ACEIs and ARBs. Hypothesis: We hypothesized that hospitalized SARS-COV2 Lebanese patients with varying stages of heart failure (A through C) taking ACEIs or ARBs will exhibit an overall better cardiovascular prognosis than control patients with comparable demographics but on other cardiovascular medications. Method: Lebanese patients (N=66) classified as heart failure A-C and admitted to AUBMC for SARS-CoV2 infection were recruited as a part of an ongoing clinical study. Patients were assigned to the control group (No ACEIs or ARBs) or the study sample group (on ACEIs or ARBs). Baseline characteristics including cardiovascular, inflammatory, respiratory and overall outcomes were collected from the patients’ medical charts and analyzed. Unadjusted associations on recruited patients are presented here. Adjusted analyses will be performed when a total of 200 patients is reached. Results: The average age of patients was 69±12.42. The total average weight was 84.24±15.59 Kg and significantly higher in ACEIs/ARBs group (p=0.032). Most patients were males (48 of 66) and patients on ACEIs/ARBs medication were 38 of 66. Heart failure stage, systolic and diastolic blood pressures and heart rate were comparable on presentation between patients on ACEIs/ARBs and controls. Unadjusted analysis showed a significantly higher percentage of death (p=0.024), mechanical ventilation (p=0.05), and elevated troponin (p=0.03) in the control group. A trend towards higher percentage of elevated NT-ProBNP and high levels of peak IL-6 were observed in the control group (p = 0.088 and p=0.076 respectively). All patients had elevated CRP on admission. SARS-CoV2 treatments were comparable between the two groups. Conclusion: Higher mortality and worsened prognosis were observed in the control groups when compared to the ACEIs/ARBs group. Ongoing recruitment is currently underway to perform adjusted analyses.