Severe CAD Research Articles

CORONARY ARTERY DISEASE;

Objectives: To establish or refute any association between high Body Mass Index (BMI) and Coronary Artery Disease in South Punjab area of Pakistan. Background: Ischemic heart disease has a strong relation with high Body Mass Index (BMI). But still uncertainty persists about the association that exists between overweight (BMI 25-29.9 kg/m2) or obese patients (BMI >30 kg/m2). Design: Observational, Cross Sectional Study. Setting: Cardiac cath lab department of Multan Institute of cardiology Multan. Duration of Study: Six month tenure extending between January 2017 to June 2017. Methods: The study was conducted in cardiac cath lab department of Multan Institute of cardiology, Multan. Total of Four hundred and seventy eight patients (478) over a period of two months were included in the study. All patients were having a coronary angiography due to a medical indication. Their BMI was calculated by using standard formula. Results: Out of 478 patients 335 (70.1%) patients were having optimal weight. 123 (25.7%) were overweight, 12 (2.5%) were mildly obese, 8 (1.7%) were severely obese patients. Optimal weight patients had 12.5% normal coronary angiogram, 26.3 % had single vessel CAD, 20% had two vessel disease and 41.2% had severe triple vessel disease. Over weight patients had 17.9% normal coronary angiograms, single vessel CAD was seen in 26.8% patients, 21.9% patients had two vessel disease and 33.3% had severe triple vessel CAD. Mildly obese patients had 8.3% normal coronary angiograms, 50% had single vessel CAD, 25% had two vessel disease, and 16.7% had severe Triple vessel disease. Among severe obese patients 12.5% had normal coronary angiography, 25% had single vessel disease, 50% had two vessel disease, and 12.5% had severe triple vessel disease. Conclusion: Patients undergoing Coronary Angiogram in the region of south Punjab did not show any significant relationship between severity of CAD (Severe two vessels & severe Triple vessel disease) and BMI.

Correlation between Inflammatory Marker and Glycemic Control in Patients with Ischemic Heart Disease

Background: Recent evidence suggests that inflammatory markers and poor glycemic control are significantly associated with the development of cardiovascular complications. The purpose of this study was to determine the association between inflammatory marker (CRP) and glycemic status (HbA1c) in ischemic heart disease patients.
 Method: This cross sectional study was performed on 668 patients of ischemic heart disease in the Department of Cardiology, Dhaka Medical College Hospital, Dhaka, who underwent Coronary angiogram from January 2017 to December 2017. CRP value were divided into normal (<6 mg/L), borderline (6-10 mg/L) and high (>10 mg/L) and HbA1c was divided <6.5% and ≥6.5%. After performed Coronary angiography the extent of disease was divided into insignificant CAD of (<50% stenosis), significant CAD considered as >50% stenosis and single vessel, double vessel, triple vessel CAD and normal coronaries. The relationship between CRP with HbA1c was analyzed by Chi square test. ANOVA test was used to analyze the continuous variables, shown with mean and standard deviation. Pearson’s correlation coefficient was used to test the relationship between CRP and HbA1c in CAD patients. p value <0.05 was considered as statistically significant.
 Result: Most (65.0%) of the patients belonged to age 41-60 years. The mean age was found 51.4±10.7 years. Majority (82.3%) of patients were male. Among risk factors, highest (40.0%) patients had hypertension followed by 209 (31.3%) diabetes mellitus and 204 (30.5%) smoker. Positive correlation was found (r=0.220, p= 0.001) between HbA1c with CRP in CAD patients. High CRP was found 138(38.4%) in <6.5% HbA1c and 187(60.5%) in ≥6.5 percent HbA1c. The difference was statistically significant (p<0.05). Multi variable logistic regression was found high HbA1c, high CRP and diabetes mellitus were statistically significant (p<0.05) in severe CAD (Double and triple vessel) patient.
 Conclusion: Positive correlation was found between serum levels of CRP and HbA1c in CAD patients. Thus, aiming at good glycemic control and estimation of serum CRP levels will possibly be of help in planning early intervention, thereby preventing further complications which in turn may help preserve cardiac functions in ischemic heart disease patients.
 Bangladesh Heart Journal 2018; 33(2) : 100-105

Abstract 17414: Increased Activity of Brain Region Governing Stress Perception is Associated With Plaque Vulnerability and Vascular Inflammation in Acute Myocardial Infarction Population; Retrospective and Prospective Study Evaluated by 18 FDG-PET/CT and OCT

Backgrounds: Chronic mental stress is a major risk factor of coronary artery disease, but there is a lack of direct mechanistic evidence between brain amygdala activity, a neural stress center, versus plaque vulnerability in acute coronary syndrome. In this study, we aimed to evaluate whether brain amygdala activity in AMI patients assessed by 18 F-FDG PET/CT could be associated with vascular inflammation in carotid beds and high-risk coronary plaque features evaluated by OCT. Methods and Results: In retrospective analysis, the patients who underwent 18 F-FDG PET/CT and CAG at Korea University Guro Hospital (Seoul, Korea). Among 1802 patients underwent 18 F-FDG PET/CT from October 1 2009 to 31 December 31 2015, 230 patients received CAG. After excluding 36 patients who had active cancer or brain disease, 198 were stratified according to degree of coronary severity by syntax score [none (n=159); mild to moderate (n=26); severe (n=13)]. Brain amygdalar activity on PET was quantified as target-to-background ratio (TBR) of standardized uptake value (amygdalar SUV max /temporal SUV mean ). The amygdalar TBR was significantly higher in patients with severe coronary disease rather than those without coronary stenosis or mild to moderate stenosis assessed by syntax score (P=0.03). Intriguingly, among 13 patients with severe CAD, the amygdalar TBR significantly increased in the 6 patients presented as AMI compared to non-MI patients (P=0.03). In following prospective study, we performed 18 F-FDG PET/CT in AMI patients underwent percutaneous coronary intervention within index admission period, and in patients with chronic stable angina (CSA) as control. The plaque morphology in non-culprit segment of infarct-related artery (IRA) was estimated by OCT in AMI patients. Brain amygdalar TBR was significantly higher in AMI patients compared to CSA patients (p<0.05). In AMI patients, amygdalar activity was significantly associated with vascular inflammation quantified as carotid TBR (p<0.05). The increased amygdalar activity was associated with high-risk plaque characteristics of non-culprit segments of IRA. Conclusions: The amygdalar activity assessed by 18 F-FDG PET/CT was significantly higher in patients with AMI than CSA. This amygdalar activity was related to vulnerable plaque characteristics of IRA. Our results suggest that brain emotional activity in ACS could contribute to plaque instability in pan-vascular beds.

OC14 CONCOMITANT TRANS-AORTIC TRANSCATHETER AORTIC VALVE IMPLANTATION AND COMPLETE OFF-PUMP CORONARY ARTERY REVASCULARIZATION IN HIGH-RISK PATIENTS

Treatment of concomitant aortic stenosis and coronary artery disease represents a challenge in elderly high-risk patients with unsuitable peripheral anatomy to percutaneous access for TAVI. Our aim was to investigate efficacy, safety and mid-term clinical outcomes of concomitant Trans-Aortic TAVI and OPCAB. Methods: Between April2011 and January2016, 41 patients underwent simultaneous Tao-TAVI through a median sternotomy and OPCAB. High surgical risk profile did not permit conventional AVR and surgical revascularisation. PCI was considered unsuitable, because of LAD-proximal lesions and/or high SYNTAX-score. Primary endpoints were mortality and cerebro-vascular event rate. Results: Mean age was 82.6 ± 4.1 years with logistic-EuroSCORE and STS-score 19.19 ± 13.58% and 6.28 ± 3.57%. Average number of distal anastomoses was 2.7; TAo-TAVI was performed using either Sapien XT or Sapien 3 devices in 85.4% and 14.6% respectively, with a success rate of 95.1%. None paravalvular leak (PVL) ≥2/4 was observed with mean prosthesis gradient of 9.6 ± 3.8 mmHg. Conversion to CPB was required in 4.9% and pace-maker implantation in 4.9%. No cerebro-vascular accident were noted neither in-hospital stay (14.9 ± 5.0 days) or during total follow up (mean 17,26 months). In-hospital mortality was 7,32% and survival rate at 6,18 months was 84,35% and 77,86%, respectively. Conclusions: Considering high surgical risk, Simultaneous TAo-TAVI and OPCAB have become realistic treatment alternative and could represent a reasonable option in high-risk patients with severe AS and CAD and unsuitable peripherical access, permitting CPB avoidance.

ESC/EAS clinical guidance recommendations: impact on patient eligibility for PCSK9 inhibitor therapy

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been demonstrated to significantly reduce the risk of recurrent adverse vascular events in high-risk patients with a history of coronary, cerebral, or peripheral artery disease. The primary barrier to the use of these drugs is their cost. Use of these drugs in the highest-risk patients would improve their cost-effectiveness. A clinical guidance for the use of these drugs based on vascular risk was recently published.Objectives: To determine how clinical guidance recommendations would impact the numbers of patients eligible to receive PCSK9 inhibitor therapy.Methods: 2000 consecutive patients admitted to an academic medical center referred to a cardiology consult service with documented atherosclerotic cardiovascular disease (ASCVD) were evaluated for PCSK9 inhibitor eligibility using the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) clinical guidance recommendations. Any patient with ASCVD with an LDL-C >140 mg/dl was considered eligible for PCSK9 inhibitor therapy. Patients with an LDL-C >100 mg/dl had to meet additional criteria to be eligible. These criteria included (1) diabetes with target organ damage or another risk factor; (2) severe or extensive CAD; or (3) progressive/accelerated ASCVD, ischemic stroke, or revascularization in the coronary, cerebral, or peripheral arterial system within 2 years of a previous ASCVD event.Results: Mean age was 64.9 ± 12.7 years; 66% were men and 34% were women; 80% were white, 9% were black, 10% were Latino and 1% other. Eligibility for PCSK9 inhibitor therapy included 163 patients with LDL-C >140 mg/dl and 892 patients with LDL-C >100 mg/dl with additional risk factors. Additional risk factors were diabetes plus comorbidity in 318 patients; severe or extensive CAD in 317 patients; and progressive/accelerated ASCVD in 257 patients. The total number of patients eligible for PCSK9 inhibitor therapy using the ESC/EAS criteria was 1055 (53%).Conclusions: Previous studies have estimated 15 to 25% of patients with a history of vascular disease to be eligible for PCSK9 inhibitors. In this high-risk cardiac population, over 50% of patients would be PCSK9 inhibitor eligible. The cost to treat this proportion of patients would represent an overwhelming burden to any health system using current drug costs. Medication access coordinators need to play a critical role in the selection and evaluation of patients eligible for PCSK9 inhibitor therapy to maximize cost-efficiency of this therapy.

Suicide Left Ventricle: the Importance of Continuing Beta Blockers In Cardiogenic Shock Post-TAVR

Case report A 76 yo Female with PMHx of severe aortic stenosis, CAD, and HTN presented to the ER with worsening dypsnea and underwent TAVR procedure without complications. Within 48 hours post-op, her BP dropped to 70s/20s. All antihypertensive medications, including atenolol were discontinued and vasopressors were started. Patient developed new onset atrial fibrillation with rapid ventricular response a few hours after stopping atenolol and subsequently went into cardiogenic shock. Despite the addition of digoxin, amiodarone, cardioversion, and 3 different vasopressors, her hemodynamics were refractory to interventions. The severe hypoperfusion led to multiorgan failure and she passed away 10 days post-TAVR. TEE, TTE, and angiography did not indicate coronary artery occlusion or complications of the new valve apparatus and surrounding structures as causes of her collapse. Conclusion Labile hemodynamics post-TAVR are well known complications that are documented in literature. Such complications can lead to hemodynamic collapse, i.e, cardiogenic shock, and is termed “suicide left ventricle”. This phenomenon is largely due to the sudden afterload reduction from valve replacement. It is of conventional practice to discontinue all antihypertensive medications in the setting of shock, including beta blockers. However, the physiology of the left ventricle in aortic stenosis post-TAVR is unique and counterintuitive. The chronically hypertrophied left ventricle in AS requires the negative ionotropy effect of beta blockers to increase filling time, and thus increasing cardiac output. Positive inotropes (such as digoxin, beta agonists, phosphodiesterase inhibitors like milrinone) would force the ventricle to pump more forcefully against an already narrow chamber, thus decreasing cardiac output. A few cases in literature have shown the use of beta blockers despite cardiogenic shock post-TAVR, and hemodynamics were subsequently improved and left suicide ventricle was prevented. Our case highlights the detrimental effect of taking away negative ionotropy and adding positive inotropy in a post-TAVR patient. It is Class I recommendation by the ACC/AHA guidelines to continue beta blockers on the day of TAVR or within 24 H before the time of procedure, and we would like to stress the importance of continuing beta blockers in cases of cardiogenic shock post-TAVR as well as avoiding positive inotropes in these patients.

Concise Review: The Regenerative Journey of Pericytes Toward Clinical Translation.

Coronary artery disease (CAD) is the single leading cause of death worldwide. Advances in treatment and management have significantly improved patient outcomes. On the other hand, although mortality rates have decreased, more people are left with sequelae that require additional treatment and hospitalization. Moreover, patients with severe nonrevascularizable CAD remain with only the option of heart transplantation, which is limited by the shortage of suitable donors. In recent years, cell‐based regenerative therapy has emerged as a possible alternative treatment, with several regenerative medicinal products already in the clinical phase of development and others emerging as competitive preclinical solutions. Recent evidence indicates that pericytes, the mural cells of blood microvessels, represent a promising therapeutic candidate. Pericytes are abundant in the human body, play an active role in angiogenesis, vessel stabilization and blood flow regulation, and possess the capacity to differentiate into multiple cells of the mesenchymal lineage. Moreover, early studies suggest a robustness to hypoxic insult, making them uniquely equipped to withstand the ischemic microenvironment. This review summarizes the rationale behind pericyte‐based cell therapy and the progress that has been made toward its clinical application. We present the different sources of pericytes and the case for harvesting them from tissue leftovers of cardiovascular surgery. We also discuss the healing potential of pericytes in preclinical animal models of myocardial ischemia (MI) and current practices to upgrade the production protocol for translation to the clinic. Standardization of these procedures is of utmost importance, as lack of uniformity in cell manufacturing may influence clinical outcome. Stem Cells 2018;36:1295–1310

The Role of Impella for Hemodynamic Support in Patients With Aortic Stenosis.

The goal of this review is to discuss the effects of Impella (Abiomed, Danvers, MA), to support in the hemodynamics of patients with severe aortic stenosis, and to explore the clinical scenarios in which the use of Impella may be beneficial in this setting. The management of patients with severe aortic stenosis who go on to develop left ventricular failure and cardiogenic shock remains an important clinical challenge associated with increased morbidity and mortality. Once considered a relative contraindication, the use of Impella in severe aortic stenosis has now been proven feasible and demonstrated promising results in selected high-risk patients. The use of Impella to provide hemodynamic support maybe considered in patients with aortic stenosis in cardiogenic shock or those with severe left ventricular dysfunction and CAD who require high-risk PCI and or balloon aortic valvuloplasty. Impella is also an attractive option in selected cases of hemodynamic collapse during TAVR.

Gender Differences in Clinical, Angiographic and Procedural Profiles between Young Patients with Acute Coronary Syndrome undergoing Percutaneous Coronary Intervention

Background: Acute coronary syndrome (ACS) is increasingly prevalent among young patients, particularly in South Asia, where young patients are known to present with multiple risk factors and gender-based differences in angiographic profiles. This study aimed to compare gender differences in clinical, angiographic and procedural profiles between young patients with ACS undergoing percutaneous coronary intervention (PCI).Methods: This prospective observational study was done at the National Institute of Cardiovascular Diseases (NICVD) from April 2016 to March 2017. 190 young patients with ACS undergoing PCI were included. Clinical, angiographic and procedural variables were compared and statistically analyzed.Results: The mean age of young females and males was 43.8±6.9 years and 40.1±4.3 years respectively (p<<0.001). Young women had significantly more risk factors of hypertension (62.1% vs 33.7%, p<0.001) and diabetes (57.9% vs 31.6%, p<0.001) in comparison to young men. Smoking was significantly greater among young males (70.5% vs 0%, p<0.001). Young females had significantly better mean ejection fraction (EF) (48.4±9.3% vs 45.1±10.4%, p=0. 02). Left main coronary artery (3.2% vs. 1.1%, p=0.61) and left anterior descending artery (51.6% vs. 45.3%, p=0.38) were more frequently involved among young females. Young males showed angiographically more severe CAD and greater frequency of multivessel CAD with higher DVD (22.1%vs 18.9%, p=0.58) and TVD (18.9%vs 11.6%, p=0.15).Conclusion: Significantly more young women with ACS presented with hypertension and diabetes than young males. However, they had better ejection fraction and less severe angiographic profiles.Cardiovasc. j. 2018; 10(2): 113-120

Semiautomatic Volumetry of Low Attenuation of Thoracic Aortic Plaques on Curved Planar Reformations Using MDCT Angiographic Data with 0.5 mm Collimation.

To evaluate the relationship of aortic low attenuation plaque volume (LAPV) on multidetector computed tomography (MDCT) with the abdominal aortic aneurysm (AAA), the coronary arterial disease (CAD, ≥50% stenosis), severe (≥90% stenosis) CAD, hypertension, and long-term (≥10 years) hypertension. Curved planar reformations (CPR) of three segments (the ascending, the arch, and the upper descending aorta) of the thoracic aorta were generated with attenuation-dependent color codes to measure LAPV with 0~29 HU and total noncalcified plaque volume (TNPV) with 0~150 HU in 95 patients. Correlation coefficients were employed to assess the impact of each LAPV and TNPV on AAA, CAD, severe CAD, hypertension, and long-term hypertension. Each Mean LAPV/cm and TNPV/cm was statistically greater in the aortic arch than the ascending (p < 0.001 on each) or the proximal descending segment (p < 0.001 on each). LAPV in the aortic arch has moderate correlations with AAA, severe CAD, and long-term hypertension (r = 0.643, 0.639, 0.662, resp.). Plaque volumes in each aortic segment can be measured clinically and the increasing LAPV in the arch may be a significant factor associated with the development of severe atherosclerosis underlying AAA, severe CAD, and long-term hypertension.

Serum Adiponectin Levels and Severity of Coronary Artery Disease by Gensini Score

Background: Ischemic heart disease is the most common cause of death all over the world; its rate is expected to be accelerated in the next decade. Adiponectin is a protein hormone that modulates a number of metabolic processes, including glucose regulation and acid oxidation. Objective: To correlate serum levels of adiponectin and CAD severity assessed by Gensini score. Subjects and methods: Ninety subjects were recruited from catheterization unit (36 subjects with normal coronary arteries and 54 patients with CAD) and they were subdivided into four groups according to the number of affected vessel. Their modified Gensini score was calculated according to the severity of coronary lesions. Blood samples were withdrawn to measure adiponectin levels. Results: Adiponectin levels were lower in patients with CAD than those with normal coronary arteries group by a highly significant statistically value (P<0.001). A significant negative correlation was found between adiponectin levels and modified Gensini score (r= -0.903; P<0.001). Adiponectin levels were significantly lower in patients with multi-vessels disease compared to patients with twovessel disease and single-vessel disease. Conclusion: Adiponectin levels are lower in patients with CAD in comparison to group without CAD. The lower the levels the more severe CAD will be. So, measurement of adiponectin levels may be helpful in risk stratification of patients with CAD.

Association of Visceral Adiposity Index Score with the Severity of Coronary Artery Disease in Patients with Ischemic Heart Disease

Background: Ischemic Heart Disease (IHD) is the leading cause of death throughout the world and obesity especially visceral adiposity (central obesity has significant influence for its development &amp; progression. Visceral adiposity index (VAI) is a novel sex specific index which had significant correlation with visceral adiposity.Objectives: To evaluate the impact of cut-off points of VAI defining visceral adipose dysfunction (VAD) on the angiographic severity of coronary artery disease in patients of IHD.Methods: A total of 100 patients with IHD were divided into Case (of which 50 patients of IHD with VAD positive) and Control group (of which 50 patients of IHD with VAD negative). Then clinical, biochemical, echocardiographic and coronary artery angiographic indexes (determined by Gensini score) were acquired in relation to VAI.Results: VAD positive group had more significant form of coronary artery disease in term of Gensini score than VAD negative group.The mean level of Visceral Adiposity Index (VAI) was observed 3.1±0.9 and 2.1±0.6 in significant CAD (Gensini score ?36) and insignificant CAD (Gensini score&lt;36) respectively. The difference of mean VAI between the significant and insignificant CAD groups were statistically significant (p=&lt;0.001). First group (VAD positive) also had more CAD risk factors like hypertension, diabetes mellitus and dyslipidemia which were significantly higher than second group (VAD negative) (p=0.02, 0.002, 0.01). Univariate and multivariate analysis revealed that out of the 8 variables hypertension, dyslipidemia, diabetes mellitus, waist circumference and visceral adiposity index were found to be the independently significant predictors of severe CAD patients with ORs being 1.61 vs. 1.52, 1.97 vs. 1.36, 2.19 vs. 1.97, 1.94 vs. 1.61 and 3.89 vs. 3.49 respectively. Thus the VAI was found to be more strong predictor of the severity of CAD.Conclusion: VAI is a simple indicator of visceral adipose mass &amp; was markedly associated with the severity of coronary artery disease in IHD patients.Bangladesh Heart Journal 2017; 32(1) : 36-39

Sensitive Troponin I and Stress Testing in the Emergency Department for the Early Management of Chest Pain Using 2-Hour Protocol.

Despite improvements in identifying high-risk patients with non-ST segment ACS (acute coronary syndrome), low risk patients presenting with atypical chest pain and non-diagnostic Electrocardiogram (ECG) continued to undergo unnecessary admissions and testing. Since 1992, our chest pain protocol included using 4-hour serial biomarkers from ED admission in combination with stress testing to evaluate these patients. Our study aimed at determining whether a new accelerated diagnostic protocol using sensitive cardiac troponin I (cTnI) 2 hours after admission to the ED followed by stress testing is safe and effective in emergency settings, allowing for appropriate triage, earlier discharge and reducing costs. We conducted a single center randomized trial at Presence St. Francis Hospital Chest pain center in Evanston, Illinois enrolling sixty-four consecutive patients with atypical chest pain and non-diagnostic ECG, participants were randomized to accelerated 2 hrs protocol or our pre-existing 4-hrs protocol. Sixty patients completed the protocol and were randomized to either a 2-hour (29 patients) or 4-hour protocol using both I-STAT and PATHFAST cTnI (31 Patients). Troponin I was evaluated at 0 and at 2 hours from ED presentation with and additional draw for patients in the 4-hour rule out-group. Patients with normal serial biomarkers were then evaluated with stress testing and qualified for earlier discharge if the stress test was negative, while those with a positive biomarker at any time were admitted. Thirty-six patients had exercise treadmill stress test and 24 patients had either nuclear or Echo stress test. Fifty-three patients had a normal stress test and were discharged home. One patient in the 4-hour group with normal serial troponins developed ventricular tachycardia/fibrillation during the recovery period of a regular stress test. Six patients had a positive PATHFAST cTnI and a normal I-STAT cTnI at 2-hours. Two out of these six patients evaluated by coronary angiography. One patient had severe tortuous coronaries but no significant obstructive lesion and one had a severe CAD who needed Coronary artery bypass grafting (CABG). Three of the six patients had a normal stress test and one patient decided to leave without further testing. None of the patients with a normal stress test had a major cardiac event or adverse cardiac outcome at six-month follow up. This study demonstrates that the 2 hours accelerated protocol using high sensitivity Troponin assay at 0 and 2 hours with comprehensive clinical evaluation and ECG followed by stress testing might be successful in identifying low-risk patient population who may benefit from early discharge from ED reducing associated costs and length of stay.

Elevated resting heart rate is associated with the severity of coronary artery disease in non-treated patients who underwent coronary angiography: potential role of lipoprotein subfractions

Objective: To assess the association between resting heart rate (RHR) and lipoprotein subfractions to provide potential evidence for the relationship between RHR and severity of CAD.Methods: A total of 1119 consecutive non-treated subjects scheduled for coronary angiography were enrolled. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) separation were performed by Lipoprint System. The link of RHR with lipoprotein subfractions was assessed.Results: Increased RHR was significantly associated with higher triglyceride, total cholesterol, non-HDL-cholesterol, and apolipoprotein B (all p < .01). Furthermore, data indicated that higher RHR was related to more severe CAD (all p < .05). In the following linear regression models, we observed that higher RHR (HRh bpm) was significantly associated with lower large HDL (β = –0.073, p = .024) and higher small LDL subfraction (β = 0.103, p = .005) after adjusting for potential confounders.Conclusions: Increased RHR was associated with more severe CAD, which may be partly due to the significant relation to atherogenic lipoprotein subfractions.

Impact of polymorphism rs7041 and rs4588 of Vitamin D Binding Protein on the extent of coronary artery disease

Background and Aim25-hydroxyvitamin D deficiency represents a widespread social problem but also an emerging risk factor for cardiovascular disease. Genetic variants of the Vitamin D Binding Protein (VDBP), the main transporter of vitamin D in the bloodstream, have been shown to account for a significant variability in the levels and systemic effects of vitamin D. We investigated whether the single nucleotide polymorphisms, rs7041 and rs4588, of VDBP are associated to the prevalence and extent of coronary artery disease. Methods and ResultsA consecutive cohort of patients undergoing coronary angiography in a single centre were included. Significant CAD was defined as at least 1 stenosis >50%, severe CAD for as left main and/or three-vessel disease. VDBP genetic status was assessed by polymerase chain reaction and restriction fragment length polymorphism technique.We included 1080 patients, 57% carried the mutated G allele of rs7041, whereas 22% carried the A allele of rs4588. Higher levels of C- reactive protein were observed in the carriers of G allele of rs7041 (p = 0.02), whereas 25-hydroxyvitamin D levels were similar across groups. A higher prevalence of lesions in the left anterior descending artery and a longer lesion length were observed in “A” carriers for rs4588 (p = 0.04 and p = 0.03, respectively). On the contrary, a higher prevalence of bifurcation lesions and chronic occlusions was observed in G carriers (p = 0.002 and p = 0.01 respectively). Both polymorphisms of VDBP did not affect the prevalence of CAD (rs7041: 79.1% TT vs 80.3% TG vs 78.5% GG, p = 0.81; rs4588 = 80.3% CC vs 78.5% AC + AA, p = 0.49) and severe CAD, (rs7041: 31.1% TT % vs 31.3% TG vs 30.6% GG, p = 0.88; rs4588: 32.2% CC vs 29.3% AC + AA, p = 0.31). Results were confirmed at multivariate analysis, for both rs7041 and rs4588. However, when including the levels of 25-hydroxyvitamin D in the multivariate model, we observed that 25(OH)D status and not genetic variants of VDBP were significantly associated with CAD (25-hydroxyvitamin D OR [95% CI] = 0.99 [0.97–1.0], p = 0.05; rs7041 TG: OR [95% CI] = 1.26 [0.73–2.19], p = 0.41; rs7041 GG: OR [95% CI] = 1.25 [0.82–1.91], p = 0.30; rs4588 AC + AA: OR [95% CI] = 0.76 [0.51–1.13], p = 0.18). ConclusionThis study showed in a large cohort of patients undergoing coronary angiography, that the polymorphisms rs7041 and rs4588 of VDBP are not associated with the levels of 25-hydroxyvitamin D nor with the prevalence and extent of CAD. In fact, 25-hydroxyvitamin D levels but not VDBP genetic status independently predicted the occurrence of coronary lesions at angiography.

Routine CT angiography to detect severe coronary artery disease prior to transcatheter aortic valve replacement.

Patients undergoing TAVR undergo routine CT angiography (CTA) to assess aorto-iliac pathology and annular dimensions. While coronary CTA may exclude severe CAD in younger patients, its efficacy in defining CAD severity prior to TAVR may be limited. We retrospectively studied 50 consecutive patients undergoing both invasive coronary angiography (ICA) and routine pre-TAVR CTA. Severe CAD was defined as ≥50% stenosis by quantitative coronary angiography and compared to a blinded CTA visual estimation of ≥50% stenosis. The analysis was confined to four segments: left main and three proximal to mid major coronaries to maximize myocardial territory at risk. Coronary assessment was performed using standard reconstructed ECG phases from pre-TAVR chest CTA on a Philips 256 iCT scanner. Nearly ¾ of patients were ≥75 years old, 57% were female, half were diabetic and 45% had prior PCI. By ICA, 49% had significant coronary calcification. The incidence of severe proximal to mid vessel CAD by ICA was 39%. Similarly, a third of patients required PCI prior to TAVR. CTA was unable to exclude severe proximal to mid vessel CAD in 88% of patients in all four segments: non-diagnostic CTA readings were mainly due to calcification (60%) or motion artifact (28%). Non-diagnostic coronary CTA readings ranged from 25 to 72% according to segment analyzed: only the left main segment had diagnostic quality CTA in the majority of patients (p < 0.01). PCI is performed frequently prior to TAVR based upon invasive coronary angiographic assessment. Routine chest CTA algorithms do not provide adequate diagnostic information to exclude severe CAD, primarily due to severe coronary calcification in the TAVR population.

Intermediate CD14++CD16+ monocyte predicts severe coronary stenosis and extensive plaque involvement in asymptomatic individuals.

Circulating leukocyte subtypes and monocyte subsets are independent predictors of cardiovascular events. We hypothesized that an increased leukocyte subtype would predict severe coronary stenosis and extensive plaque involvement. We retrospectively analyzed clinical, laboratory, and coronary CT data in a total of 588 asymptomatic adults (69% men; mean age, 57 ± 9years) undergoing a general health check-up. Intermediate CD14++CD16+ monocyte count had the strongest association with mixed and calcified plaque scores, whereas the numbers of neutrophils and classical CD14++CD16- monocytes were significantly associated with non-calcified plaque score. Only high CD14++CD16+ monocyte count (>12cells/μL) significantly predicted extensive plaque involvement [odds ratio 3.16 (95% confidence interval 1.84-5.43), P < 0.001; quartile 4 vs. 1-3] and severe coronary stenosis [3.67 (1.84-7.33), P < 0.001; quartile 4 vs. 1-3] after adjustments for Framingham Risk Score (FRS), metabolic syndrome, and C-reactive protein. The CD14++CD16+ monocyte count, when added to FRS, significantly reclassified 30.4 and 26.7% of the overall and 50.2 and 36.2% of the intermediate-risk population (FRS 6-20%) for predicting extensive plaque involvement and severe coronary stenosis, respectively. Thus, in asymptomatic individuals, intermediate CD14++CD16+ monocyte could independently predict severe CAD and improve risk stratification.

Chronic Inhibition of Complement C1s By TNT009 Produces Sustained, Complete Remission in Patients with Severe, Transfusion-Dependent Cold Agglutinin Disease (CAD)

Background: We recently presented that the humanized anti-complement C1s monoclonal antibody, TNT009, rapidly stoppedhemolysisand correctedanemiain patients with severe CAD in an ongoing Phase 1b clinical trial. After completion of washout from protocol treatment, these patients suffered relapse of CAD with a drop inhemoglobinto pre-dose levels. We now report on the clinical experience of their extended re-treatment under the Named Patient provision of the Austrian Drug Act, which provided the occasion: 1) to explore lower dose regimens and alternative dosing schedules; 2) to try to recapitulate the initial success of complete remission under protocol treatment; 3) to test the durability of response with a longer term maintenance treatment with TNT009.Methods: In order to test a lower dose regimen of TNT009, the Phase 1b trial dosing of 60 mg/kg IV once weekly for both loading and maintenance was reduced to 45 mg/kg IV once weekly (4x) followed by maintenance with 45 mg/kg every other week. A simplified dosing regimen was then tried, using a single priming dose of 60 mg/kg on Day 0 followed by 60 mg/kg every other week (biweekly) thereafter beginning on Day 7. This TNT009 biweekly maintenance with 60 mg/kg was continued indefinitely to test the durability of the effect, to monitor for safety, and to serially assess their hematologic response to TNT009.Results:All infusions were well tolerated without premedication and without relevant adverse effects. TNT009 re-exposure immediately decreased CH50 activity and increased complement C4 levels, confirming the rapid onset ofpharmacodynamiceffect. The concordant and sustained effect of TNT009 on hematologic parameters related tohemolysisandanemiasis illustrated in the composite Figure 1 for the first patient treated, C1001. This patient has undergone three treatment episodes with TNT009: weekly dosing at 60 mg/kg under the Phase 1b protocol (left); weekly → biweekly 45 mg/kg (center); 60 mg/kg on Day 0 and biweekly thereafter starting on Day 7 (right). Note that the CH50 serves as apharmacodynamicmarker for the effective inhibition of the classical complement pathway by TNT009. Each new episode of treatment with TNT009 induced remission ofhemolyticanemia, and relapse occurred following washout (60 mg/kg weekly x 4) orpharmacodynamicbreakthrough (45 mg/kg maintenance regimen). Although it appears that the reduced dose maintenance regimen of 45 mg/kg biweekly does not suffice to maintain full C1s inhibition, there is no evidence oftachyphylaxisas restoration of full dose treatment at 60 mg/kg biweekly was able to restore remission again.A similar pattern of results was observed in the other patients offered Named Patient treatment with TNT009, but with two instructive exceptions. Patient C1004 had unsuspected erythropoietin deficiency and did not achieve complete normalization ofhemoglobinuntil concomitant treatment with erythropoietin was begun. Patient C1003 did not have CAD but Cold Agglutinin Syndrome (CAS) secondary to an extensivelymphoplasmacyticlymphoma (LPL). Initially she was treated with TNT009 monotherapy and did not respond. TNT009 was then stopped and her LPL was treated withibrutinib, resulting in a gradual amelioration of heranemiauntil anintercurrentinfection triggered relapse of herhemolyticanemia. At that time re-treatment with TNT009 (whileibrutinibwas continued) quickly normalized her hematologic parameters. Eventually TNT009 was able to increasehemoglobinlevels to >12 g/dLin all 5 of 5 treated patients.Conclusion:TNT009 was previously shown to induce rapid correction ofhemolyticanemiain severe CAD patients in a Phase 1b trial. It has now been shown that subsequent washout of TNT009 leads to relapse in all patients, and that re-induction of remission by TNT009 is possible in all. Long-term maintenance of remission can be achieved by dosing TNT009 at 60 mg/kg biweekly, the dose regimen to be tested in larger-scale clinical trials of CAD. [Display omitted] DisclosuresGilbert:Truenorth Therapeutics, Inc.: Employment, Equity Ownership. Panicker:Truenorth Therapeutics, Inc.: Employment. Parry:Truenorth Therapeutics, Inc.: Employment, Equity Ownership. Jaeger:Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses.

CHA2DS2-VASc-HSF score – New predictor of severity of coronary artery disease in 2976 patients

BackgroundCHADS2 and CHA2DS2-VASc scores have been used for assessing prognostic risk of thromboembolism in non valvular atrial fibrillation patients. They include similar risk factors for the development of CAD To increase the likelihood of determining CAD severity, the CHA2DS2-VASc-HS and CHA2DS2-VASc-HSF score comprising of hyperlipidemia, smoking and family history respectively in addition to the components of the CHA2DS2-VASc score and male instead of female gender. The aim was to investigate whether these risk scores can be used to predict CAD severity. Methods and resultsA total of 2976 consecutive patients who underwent coronary angiography were enrolled in the study. Presence of >50% stenosis in a coronary artery was assessed as significant CAD. Of the patients,804 had normal coronary angiograms and served as group 1. The remaining 2172 patients with coronary stenosis were further classified into 2 groups according to CAD with stenosis of <50% or >50%: 834 patients with mild CAD as group 2 and 1338 patients with severe CAD as group 3. The scores were significantly different among the 3 groups. All the four scores correlated significantly with the number of diseased and the Gensini score. ConclusionCHADS2, CHA2DS2-VASc, and especially CHA2DS2-VASc-HS and CHA2DS2-VASc-HSF scores could be considered predictive of the risk of severe CAD with CHA2DS2-VASc-HSF the best scoring scheme to predict CAD severity. The risk scoring systems may play an important role as predictive models because they are simple and can be easily applied by physicians without any additional costs in routine practice.

Value of global longitudinal strain by two dimensional speckle tracking echocardiography in predicting coronary artery disease severity.

BackgroundSignificant coronary artery stenosis might cause persistently impaired longitudinal left ventricle (LV) function at rest. LV global longitudinal strain (LVGLS) can be accurately assessed by 2D speckle-tracking strain echocardiography(2D-STE).ObjectiveWe aimed to evaluate the diagnostic accuracy of LV global longitudinal strain obtained by 2D-STE in prediction of severity of CAD.MethodsEighty patients with suspected stable angina pectoris were included. They underwent transthoracic echocardiography (TTE) to measure LV ejection fraction, 2-D-STE to measure GLS and coronary angiography (CA). The patients were divided into two groups: group 1 (58 patients) with significant (>70%) CAD, and group 2 (22 patients) with non-significant (<70%) CAD. Images were obtained in the apical long-axis, four-chamber, and two chamber views. Regional longitudinal systolic strain was measured in 17 myocardial segments and averaged to provide global longitudinal strain (LVGLS).ResultsThere was significant decrease in GLS in group 1 compared to group 2 (−11.86 ± 2.89% versus −18.65 ± 0.79%, P < 0.000). The optimal cutoff value of GLS for prediction of significant CAD was −15.6% [AUC 0.88, 95% CI 0.78–0.96 p < 0.000]. The sensitivity, specificity and accuracy of GLS for detecting significant CAD were 93.1%, 81.8%,and 90% respectively.There was a significant positive correlation between GLS and EF (r = 0.33; p = 0.036).There was incremental significant decrease in GLS with increasing number of coronary vessels involved.ConclusionMeasurement of global longitudinal strain using 2D speckle tracking echocardiography is sensitive and accurate tool in the prediction of severe CAD.