Prevalence and prognosis of genetically proven familial hypercholesterolemia in subjects with coronary artery disease and reduced ejection fraction.

Few studies have genetically screened variants related to familial hypercholesterolemia (FH) and investigated their survival impact in patients with coronary artery disease (CAD) and reduced left ventricular ejection fraction (EF). Patients with CAD and reduced EF (< 40%) were enrolled. Their genomic DNAs were sequenced for FH-related genes. All-cause and cardiovascular mortality data served as the major outcome. A total of 256 subjects were analyzed and 12 subjects (4.7%) carried FH-related genetic variants. After a median follow-up period of 44 months, 119 of the study subjects died. Cox survival analysis showed that carrying the FH genetic variant did not have a significant impact on the survival of CAD with reduced EF. However, higher estimated glomerular filtration rate (eGFR), better EF and beta blocker use were protective for a lower all-cause mortality. Further larger studies are needed to evaluate the impact of carrying the FH-related genetic variant on survival of CAD with reduced EF.

A Higher Estimated Glomerular Filtration Rate Is Associated with Better Survival in Subjects with Coronary Artery Disease and Heart Failure with a Mildly Reduced Ejection Fraction.

Subjects with coronary artery disease (CAD) have myocardial ischemia and associated abnormal left ventricular ejection fraction (EF). Heart failure with mildly reduced EF (41-49%) (HFmrEF) is a new subgroup of EF for heart failure. Although prognostic factors for CAD and HF with reduced EF are well known, fewer studies have been conducted on factors related to the survival of CAD and HFmrEF. We recruited study subjects with significant CAD and HFmrEF from our cardiac catheterization data bank. Data were recorded from traceable chart records from our hospital. All-cause and cardiovascular mortality were recorded until December 2019 and served as a follow-up outcome. A total of 348 subjects with CAD and HFmrEF were analyzed. The median duration of follow-up was 37 months. Seventy-eight subjects died during the follow-up period and 30 of them were due to cardiovascular causes. In univariate analyses, those who died were of older ages, and with a lower estimated glomerular filtration rate (eGFR) (47 ± 30 versus 71 ± 30 mL/minute/1.73 m2, P < 0.001), and lower usage of percutaneous coronary intervention (PCI) and beta blockers. In the Cox survival regression analysis, a higher eGFR (hazard ratio 0.980, P < 0.001) was protective, while older age and a higher serum total cholesterol (hazard ratio 1.006, P = 0.048) were related to all-cause mortality for CAD with HFmrEF. Furthermore, a higher eGFR was also associated with less cardiovascular mortality. In conclusion, for subjects with CAD and HFmrEF, a higher eGFR was protective and associated with a lower all-cause and cardiovascular mortality.

Plasma aryl hydrocarbon receptor associated with epicardial adipose tissue in men: a cross-sectional study.

BACKGROUND: Epicardial adipose tissue (EAT) is a type of ectopic fat with endocrine and paracrine functions. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that responds to environmental stimuli. AhR expression is associated with obesity. In this cross-sectional study, we aimed to determine the relationship between circulating AhR concentrations and EAT. METHODS: A total of 30 men with obesity and 23 age-matched men as healthy controls were enrolled. Plasma AhR concentrations were determined at fasting. The EAT thickness was measured on the free wall of the right ventricle from the basal short-axis plane by magnetic resonance imaging. RESULTS: The participants with obesity had a higher plasma AhR level than the controls (81.0 ± 24.5 vs. 65.1 ± 16.4 pg/mL, P = 0.010). The plasma AhR level was positively correlated with EAT thickness (correlation coefficient = 0.380, P = 0.005). After adjusting for fasting glucose levels, plasma AhR levels were still significantly associated with EAT thickness (95% CI 0.458‒5.357, P = 0.021) but not with body mass index (P = 0.168). CONCLUSION: Plasma AhR concentrations were positively correlated with EAT thickness on the free wall of the right ventricle in men. Further investigations are needed to evaluate the causal effects and underlying mechanisms between AhR and EAT.

Rotablation for Octogenarians in a Modern Cathlab: Short- and Intermediate-Term Results.

Background: There are limited reports on the treatment of complex calcified lesions using rotational atherectomy (RA) in octogenarians, particularly in high-risk patients. Objective: To evaluate procedural and clinical outcomes of RA in octogenarians. Methods: Consecutive RA patients from 2010 to 2018 were selected from our catheterization laboratory database, stratified into two groups (≥ or < 80 years old), and analyzed. Results: A total of 411 patients (269 males and 142 females) with a mean age of 73.8 ± 11.3 years were enrolled, of whom 153 were ≥ 80 years old and 258 were < 80 years old. Most of the patients displayed high-risk features. The baseline Syntax scores were high in both groups, and most lesions were heavily calcified (96.1% vs. 97.3%, p = 0.969, respectively). The use of hemodynamic support intra-aortic balloon pump was more frequent in the octogenarians (21.6% vs. 11.6%, p = 0.007), but the RA completion rate was similarly high (95.9% vs. 99.1%, p = 0.842). There was no difference in acute complications. The total/cardiovascular (CV) death rate within one year was higher in the octogenarians, along with higher major adverse cardiovascular event (MACE)/CV MACE rates in the first month. Cox regression analysis showed that age ≥ 80 years, acute coronary syndrome, ischemic cardiomyopathy/shock, multi-vessel disease and serum creatinine were all predictors of MACE, and that these factors plus peripheral artery disease were predictors of all-cause mortality in these patients. Conclusions: RA is feasible with a very high success rate in high-risk octogenarians with complex anatomies, and with equal safety and no increase in complications. The higher rates of all-cause death and MACE were attributed to an older age and other traditional risk factors.

A cluster of heritable pulmonary arterial hypertension cases in a family with all three siblings carrying the same novel AQP1 c.273C>G variant-a case report.

Approximately 25%-30% of patients diagnosed with idiopathic pulmonary arterial hypertension (PAH) have a clustered underlying Mendelian genetic cause and should be classified as heritable PAH (HPAH). The sixth World Symposium on Pulmonary Hypertension listed AQP1 as a PAH-related gene. AQP1 and its protein product Aquaporin-1 (AQP1) are found in abundance within pulmonary artery smooth muscle cells. Here, we report a family affected by HPAH with all three siblings carrying the same novel missense variant of AQP1 c.273C>G (p.Ile91Met). The youngest brother and the older sister both had dyspnea and edema and were diagnosed with HPAH about 10 years ago. In 2021, they received genetic tests that revealed all three siblings carried the same novel variant of AQP1 (c.273C>G). The brother in between these two siblings, although originally claimed to be asymptomatic, raised awareness. He then sought medical examination and confirmed the diagnosis of HPAH as well. This report on all three siblings carrying the same novel variant of AQP1 (c.273C>G) highlighted the importance of genetic testing and counseling for family members when PAH was first detected.

Lower All-Cause Mortality for Coronary Heart or Stroke Patients Who Adhere Better to Mediterranean Diet-An NHANES Analysis.

Consuming a Mediterranean-style diet (MED) is helpful for primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, few studies have compared mortality in ASCVD subjects with different degrees of adherence to the MED diet or have evaluated the contributions of individual diet components. We analyzed National Health and Nutrition Examination Survey (NHANES) participants with a history of coronary heart disease (CHD) or stroke (N = 2052) in a period from 1999 to 2010. Their individual vital status was linked to the National Death Index till the end of 2011. The level of adherence to the MED diet was quantified using a 9-point evaluation score (aMED score). Cox regression models were used to compare the different levels of adherence to the MED diet, and contributions of individual components of the MED diet on cardiovascular, cancer, and all-cause mortality. Among the 2052 subjects with CHD or stroke, 29.0% (596 of 2052) died after a median follow-up of 5.6 years. In Cox regression analysis, higher absolute aMED score (HR 0.798, p = 0.0079) or above median aMED score (score 4-9) (HR 0.646, p = 0.0013) was negatively associated with all-cause mortality. Among various components of the MED diet, intake of more whole grains or nuts was significantly associated with a lower all-cause mortality. In contrast, a higher aMED score was not associated with less cardiovascular mortality. In a secondary analysis that excluded deaths within 2 years of the NHANES study entry, the above median aMED score (score 4-9) was negatively associated with both all-cause and cardiovascular mortality. In conclusion, subjects with a history of CHD or stroke adhering better to the MED diet in the NHANES study had a lower all-cause mortality during follow-ups. Consuming more whole grains or nuts had a lower all-cause mortality. The protective effect of adherence to the MED diet on decreasing cardiovascular mortality was seen only after excluding those who died within first two years of the NHANES study entry.

Whole Exome Sequencing of Patients With Heritable and Idiopathic Pulmonary Arterial Hypertension in Central Taiwan.

Background: Genetic variants could be identified in subjects with idiopathic and heritable pulmonary arterial hypertension (PAH). The 6th World Symposium on Pulmonary Hypertension (WSPH) provided a list of genes with evidence of association with PAH. However, reports using whole exome sequencing (WES) from southeastern Asian PAH cohorts were scarce. Methods: Subjects with idiopathic and heritable PAH (N = 45) from two medical centers in central Taiwan were screened for PAH related gene variants. The genomic DNA was prepared from peripheral blood lymphocytes. We performed WES for all patients enrolled in this study. All identified gene variants were validated by polymerase-chain reaction and Sanger sequencing. The clinical and hemodynamic data were compared between bone morphogenetic protein receptor type-2 (BMPR2) gene variants carriers vs. non-carriers. Results: Eight patients (8/45 = 17.8%) was identified carrying BMPR2 gene variants and 8 patients (8/45 = 17.8%) had other WSPH-listed PAH-related gene variants (1 with ACVRL1, 1 with ENG, 1 with SMAD9, 1 with SMAD1, 1 with ATP13A3 and 3 with AQP1). In addition, a total of 14 non-WSPH-listed PAH-related genetic variant sites (ABCC8, NOTCH1, NOTCH2, NOTCH3, JAG1, BMP10, GGCX, FBLN2, ABCA3 and PTGIS) were found in this PAH cohort. Subjects carrying BMPR2 gene variant (N = 8) were younger at diagnosis of PAH (30 ± 11 vs 49 ± 13 years, p = 0.001) than the non-carrier group (N = 37). BMPR2 variant carriers had a trend toward having higher mean pulmonary arterial pressure (PAP) (61 ± 19 vs. 51 ± 13 mmHg, p = 0.076) than the non-carriers upon initial diagnosis. Pulmonary vascular resistance, right atrial pressure, cardiac output, as well as functional class were similar between BMPR2 variant carriers and non-carriers at initial diagnosis. Conclusions: We identified 17.8% of patients with BMPR2 gene variants and 17.8% subjects with other 6th WSPH-listed PAH-related gene variants in a Taiwanese idiopathic and heritable PAH cohort. PAH patients carrying BMPR2 variants presented at a younger age with a trend toward having higher mean PAP at initial diagnosis.

Newly diagnosed diabetes based on an oral glucose tolerance test predicts cardiovascular outcomes in patients with coronary artery disease: An observational study.

Diabetes is prevalent in patients with coronary artery disease (CAD). Using the oral glucose tolerance test (OGTT), abnormal glucose regulation can be detected early in CAD patients without known diabetes. In the present study, we assessed the impact of abnormal glucose regulation on the long-term cardiovascular outcomes of patients with established CAD. Patients hospitalized for a scheduled angiography due to angina were enrolled in Taichung Veterans General Hospital. Fasting plasma glucose (FPG) and 2-hour postload glucose (2hPG) were assessed using the OGTT. Hemoglobin A1c (HbA1c) and other biochemical analyses were assessed using fasting blood samples. During a median follow-up period of 4.6 years, a composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke was recorded as the primary endpoint. In 682 enrolled patients who completed the follow-up, there were 16 myocardial infarction events, 12 stroke events, and 58 deaths as composite endpoints. According to FPG and 2hPG, patients with newly diagnosed diabetes had a 2-fold higher risk for the composite endpoint than those in the normal glucose group (hazard ratio [HR], 2.011; 95% confidence interval (CI), 1.101-3.673; P = .023); however, prediabetes was not significantly associated with the composite endpoint (HR, 1.452; 95% CI, 0.788-2.675; P = .232). On the other hand, patients with diabetes diagnosed by FPG and HbA1c did not have a significantly higher risk for the composite endpoint than those in the normal glucose group (HR, 1.321; 95% CI, 0.686-2.545; P = .405). A 2hPG ≥7.8 mmol/L was a significant predictor for the composite endpoint (odds ratio, 1.743; 95% CI, 1.060-2.863; P = .028) after adjusting for age, sex, and estimated glomerular filtration rate. Diabetes, but not prediabetes, detected via OGTT is associated with a significantly increased risk for the composite endpoint in patients with established CAD. The 2hPG provided a greater predictive power for the composite endpoint than fasting glucose and HbA1c.

Sustained Hemodynamic and Clinical Improvements for a Patient With Idiopathic Pulmonary Arterial Hypertension Over 1.5 Years After Balloon Atrial Septostomy: A Case Report.

Balloon atrial septostomy (BAS) is an indicated treatment for subjects with idiopathic pulmonary arterial hypertension (IPAH), particularly for those with advanced right heart failure before bridging to lung transplantation. The mid-term clinical and hemodynamic benefits of BAS are not well studied. Here, we present a young female patient with IPAH who received maximal target medication and was admitted to our hospital due to advanced right heart failure. She had transition of subcutaneous to intravenous (IV) prostacyclin analogs (PA) injection and was registered for lung transplantation. The baseline mean right atrium (RA) pressure was 14 mmHg. BAS was performed with a balloon of 6 mm under intracardiac echocardiography (ICE) guidance. Systemic cardiac output (CO) (2.9-3.5 L/min) and oxygen delivery (OD) (291-318 ml/min) both increased after the BAS. Right heart failure was alleviated to function class II. One and a half years later, she received cardiac catheterization again. The second baseline mean RA pressure was 5 mmHg, left atrium (LA) pressure was 2 mmHg, and systemic CO was 3.3 L/min. These data indicated sustained hemodynamic improvements. The second course of BAS was performed under ICE guidance with a balloon of 8 mm. After the second BAS, her RA pressure was 3 mmHg, LA pressure was 3 mmHg, and CO was 3.4 L/min. In conclusion, BAS and IV PA infusion were effective in maintaining mid-term hemodynamic benefits and in stabilizing the critical right heart failure in a patient with IPAH over a 1.5-year period.

The Procedural and Clinical Outcomes of Rotational Atherectomy in Patients Presenting With Acute Myocardial Infarction.

Background: Rotational atherectomy (RA) is an indispensable tool used for calcified lesion preparation in percutaneous coronary intervention (PCI). However, use of RA in the setting of acute myocardial infarction (AMI) is challenged with limited clinical data. Objectives: This study aims to retrospectively investigate the procedural results, periprocedural complications, and clinical outcomes of RA in patients with AMI. Methods: All possible consecutive patients who received RA in AMI from January 2009 to March 2018 in a single tertiary center were analyzed retrospectively. Patients without AMI during the study period were also enrolled for comparison. Results: A total of 121 patients with AMI (76.0 ± 10.8 years, 63.6% males) and 290 patients without AMI were recruited. Among the AMI group, 81% of patients had non-ST-elevation myocardial infarction (NSTEMI) and 14% presented with cardiogenic shock. RA could be completed in 98.8% of patients in the AMI group and 98.3% in the non-AMI group (p = 1.00). The periprocedural complication rates were comparable between the AMI and non-AMI groups. The risks of in-hospital, 30-day, 90-day, and 1-year cardiovascular major adverse cardiac events (CV MACE) were significantly higher in the AMI group compared with the non-AMI group (in-hospital 13.2 vs. 2.8%, p < 0.001; 30-day 14.2 vs. 4.5%, p < 0.001; 90-day 20.8 vs. 6.9%, p < 0.001; 1-year 30.8 vs. 19.1%, p = 0.01). AMI at initial presentation and cardiogenic shock were predictors for both in-hospital CV MACE and 1-year CV MACE in multivariable binary logistic regression analysis. Other predictors for 1-year CV MACE included serum creatinine level and triple vessel disease. Conclusion: RA in patients with AMI is feasible with a high procedural completion rate and acceptable periprocedural complications. Given unstable hemodynamics and complex coronary anatomy, the in-hospital and 1-year MACE rates remained higher in patients with AMI compared with patients without AMI.

Rotablation in Patients with Advanced Renal Insufficiency through End-Stage Renal Disease: Short- and Intermediate-Term Results.

Objective: Patients with advanced renal insufficiency are at high risk of coronary artery disease (CAD) and complex lesions. Treating complex calcified lesion with rotational atherectomy (RA) in these patients might be associated with higher risks and poorer outcomes. This study was set to evaluate features and outcomes of RA in these patients. Method: Consecutive patients who received coronary RA from April 2010 to April 2018 were queried from the Cath Lab database. The procedural details, angiography, and clinical information were reviewed in detail. Results: A total of 411 patients were enrolled and divided into Group A (baseline serum creatinine <5 mg/dl, n = 338) and Group B (baseline serum creatinine ≥ 5 mg/dl through ESRD, n = 73). Most patients had high-risk features (65.7% of acute coronary syndrome (ACS), 14.1% of ischemic cardiomyopathy, and 5.1% of cardiogenic shock). Group B patients were significantly younger (66.8 ± 11.4 vs. 75.2 ± 10.7 years, p < 0.001) and had more RCA and LCX but less LAD treated with RA. No difference was found in lesion location, vessel tortuosity, bifurcation lesions, chronic total occlusion, total lesion length, or total lesion numbers between the two groups. Less patients in Group B obtained completion of RA (95.9% vs 99.1%, p=0.037). There was no difference in the incidence of procedural complication or acute contrast-induced nephropathy. Group B patients had more deaths and MACE while in the hospital. The MACE and CV MACE were also higher in Group B patients at 180 days and one year, mostly due to TLR and TVR. Multivariate regression analysis showed that ACS, age, peripheral artery disease (PAD), advanced renal insufficiency, ischemic cardiomyopathy/shock, and high residual SYNTAX score were independent risk factors for in-hospital MACE, whereas ACS, advanced renal insufficiency, ischemic cardiomyopathy/shock, triple-vessel disease, and PAD independently predicted MACE at 6 months. Conclusions: Rotablation is feasible, safe, and could be carried out with very high success rate in very-high-risk patients with advanced renal dysfunction through ESRD without an increase in procedural complication.

Rotational atherectomy for chronically and totally occluded coronary lesions: A propensity score-matched outcomes study.

Background: Despite advances being made in techniques and devices, certain chronic total occlusion (CTO) lesions remain uncrossable or undilatable. Rotational atherectomy (RA) is usually necessary for such lesions to achieve successful revascularization. Methods: Information regarding consecutive patients who underwent coronary RA was retrieved from the catheterization laboratory database. Patients who underwent RA for CTO lesion refractory using other conventional devices were recruited, with propensity score-matched cases serving as controls. Results: A total of 411 patients underwent coronary RA in the study period. Most patients had high-risk features (65.7% had acute coronary syndrome (ACS), 14.1% ischemic cardiomyopathy, and 5.1% cardiogenic shock), while only 20.2% of the patients had stable angina. Among them, 44 patients underwent RA for CTO lesions (CTO group), whereas the propensity score matched controls consist of 37 patients (non-CTO group). The baseline characteristics, high-risk features, coronary artery disease (CAD) vessel numbers, left ventricular function and biochemistry profiles of both groups were the same except for more patients with diabetes (67.6% vs. 45.5%, p = 0.046) in the non-CTO group and more 1.25 mm burr uses in the CTO group. There were no significant differences in acute procedural outcomes or incidence of acute contrast-induced nephropathy (CIN), and no patient demanded emergent CABG or died during the procedure. There was no significant difference in major adverse cardiovascular events (MACE), CV MACE or individual components between the two groups in the hospital, at 30, 90, and 180 days or at 1 year. Conclusion: In comparison with the propensity risk factor scores-matched controls, there was no difference in procedural complications, acute CIN or clinical outcomes during various stages of RA for CTO lesions. RA for CTO patients was highly efficient and showed safety and outcome profiles similar to those for non-CTO lesions.

Shorter (GT)n repeats in the haem-oxygenase 1 gene promoter are associated with better mid-term survival in subjects with coronary artery disease and abnormal ejection fraction.

BACKGROUND: Haem oxygenase (HO)-1 is a rate-limiting enzyme for degrading haem into carbon monoxide. Subjects with longer GT repeats in the HO-1 gene (HMOX1) promoter are more likely to have coronary artery disease (CAD) and cardiovascular events. METHODS: We retrospectively enrolled CAD subjects with an abnormal ejection fraction (EF) <50% from our catheterisation data (N = 670). Polymerase chain reactions were performed for amplifying the HMOX1 promoter GT repeating segment to determine the number of repeats. RESULTS: In a median follow-up period of 40 months, 213 patients died. The distribution of genotype for HMOX1 promoter GT repeating segments SS, SL, and LL were significantly different (p < 0.001) between the dead (44.6%, 36.2%, 19.2%, respectively) and the survived (53.8%, 37.4%, 8.8%, respectively) (S allele: ≤30 repeats, L allele: >30 repeats). In Cox regression analysis, carrier of S allele (hazard ratio 0.665, p = 0.027), a higher EF (hazard ratio 0.037, p = 0.001), and revascularization with PCI were all negatively associated with all-cause death in subjects with CAD and abnormal EF. CONCLUSIONS: Carrier of shorter (GT)n repeats of HMOX1 gene promoter was negatively correlated with death events in CAD patients with abnormal EF.

Transcarotid Transcatheter Aortic Valve Replacement in an Octogenarian With Complex Type B Aortic Dissection and Aneurysm: A Case Report.

We report the case of an octogenarian with severe aortic valve stenosis, chronic kidney disease (CKD) and heart failure. Due to advanced CKD, we used a 3-dimensional transesophageal echocardiogram for sizing the device before transcatheter aortic valve replacement (TAVR). Noncontrast computed tomography found complex aortic dissection involving the arch, descending thoracic aorta, and abdominal aorta. TAVR was approached via the right carotid artery using a CoreValve. There was no cerebral vascular event. Renal function was well preserved. Transcarotid TAVR can be performed safely with complex type B aortic dissection. Three-dimensional transesophageal echocardiogram provides an alternative sizing solution in advanced CKD.

Nous décrivons ici le cas d'un octogénaire présentant une sténose sévère de la valve aortique, une néphropathie chronique et une insuffisance cardiaque. En raison de sa néphropathie chronique de stade avancé, nous avons eu recours à l'échocardiographie tridimensionnelle par voie transœsophagienne pour déterminer la taille du dispositif devant être utilisé avant le remplacement valvulaire aortique par cathéter (RVAC). Une tomodensitométrie sans contraste a révélé une dissection aortique complexe touchant l'arc aortique, l'aorte thoracique descendante et l'aorte abdominale. Le RVAC a été effectué par l'artère carotide droite à l'aide du système CoreValve. Il n'y a pas eu d'accident vasculaire cérébral. La fonction rénale a été bien préservée. Le RVAC par voie transcarotidienne peut être réalisé sans danger dans le cas d'une dissection aortique de type B complexe. L'échocardiographie tridimensionnelle par voie transœsophagienne constitue une solution de rechange pour déterminer la taille du dispositif chez les patients atteints de néphropathie chronique à un stade avancé.

Familial Hypercholesterolemia Genetic Variations and Long-Term Cardiovascular Outcomes in Patients with Hypercholesterolemia Who Underwent Coronary Angiography.

BACKGROUND: Familial hypercholesterolemia (FH) has been associated with early coronary artery disease (CAD) and increased risk of atherosclerotic cardiovascular disease. However, the prevalence of FH and its long-term outcomes in a CAD-high-risk cohort, defined as patients with hypercholesteremia who underwent coronary angiography, remains unknown. Besides, studies regarding the impact of genetic variations in FH on long-term cardiovascular (CV) outcomes are scarce. METHODS AND RESULTS: In total, 285 patients hospitalized for coronary angiography with blood low-density lipoprotein cholesterol (LDL-C) levels ≥ 160 mg/dL were sequenced to detect FH genetic variations in LDL receptors apolipoprotein B and proprotein convertase subtilisin/kexin type 9. Risk factors associated with long-term CV outcomes were evaluated. The prevalence of FH was high (14.4%). CAD and early CAD were significantly more prevalent among FH variation carriers than non-carriers, despite comparable blood LDL-C levels. Moreover, the FH variation carriers also underwent more revascularization after a mean follow-up of 6.1 years. Multivariate logistic regression demonstrated that FH genetic variation was associated with increased incidence of cardiovascular disease and mortality (odds ratio = 3.17, p = 0.047). Two common FH variants, LDLR c.986G>A and LDLR c.268G>A, showed the most significant impacts on high blood LDL-C levels and early-onset CAD. CONCLUSIONS: Our results indicate that FH genetic variants may exhibit differential effects on early-onset CAD and revascularization risks in patients undergoing coronary angiography. FH genetic information might help identify high-risk patients with typical CAD symptoms for appropriate intervention.

Dyslipidemia, Not Inflammatory Markers or Adipokines, Contributes Significantly to a Higher SYNTAX Score in Stable Coronary Artery Disease (from the Taichung CAD Study).

BACKGROUND: The SYNTAX score is an index of coronary severity used to determine the revascularization strategy of a patient. Our previous study confirmed that the SYNTAX score is helpful in predicting major adverse cardiac events in patients with stable coronary artery disease (CAD). However, few studies have comprehensively investigated the predictors for SYNTAX scores in patients with stable CAD, including conventional risk factors, lipid parameters, inflammatory markers and adipokines. METHODS: The coronary severities of 181 revascularization-naïve CAD patients who had received coronary angiograms were coded using SYNTAX scores. Conventional risk factors, inflammatory markers, and adipokines were investigated in order to determine the independent predictors for SYNTAX severity in the patients with stable CAD. RESULTS: The SYNTAX severity score was divided according to the generally accepted criterion (low: ≤ 22, intermediate-high: ≥ 23). In univariate comparisons, the intermediate-high SYNTAX group had a significantly higher low-density lipoprotein cholesterol (LDL-C) level compared to the low SYNTAX score group (p = 0.046). In binary logistic regression, LDL-C, total cholesterol, ratio of total cholesterol/high-density lipoprotein cholesterol (HDL-C) and pre- admission statin use were significant predictors for a higher SYNTAX severity score in the patients with stable CAD. In contrast, circulating adipokines, high-sensitivity C-reactive protein and HDL-C alone were not. CONCLUSIONS: In revascularization-naïve CAD patients, dyslipidemia, including elevated LDL-C, total cholesterol, total cholesterol/HDL-C ratio and pre-index admission statin use, were associated with an intermediate-high SYNTAX severity score.

Postchallenge glucose increment was associated with hemoglobin glycation index in subjects with no history of diabetes.

We investigated the association between postchallenge glucose increment and hemoglobin glycation index (HGI), the difference between observed and predicted glycated hemoglobin (HbA1c), in subjects with no history of diabetes. We enrolled 1381 subjects who attended our outpatient clinic for an oral glucose tolerance test (OGTT) to screen for diabetes. HGI was defined as observed HbA1c minus predicted HbA1c. The predicted HbA1c was calculated by entering fasting plasma glucose (FPG) level into an equation [HbA1c(%)=FPG(mg/dL)*0.029+2.9686] determined from an HbA1c versus FPG regression analysis using data from an independent cohort of 2734 subjects with no history of diabetes. The association between 2-hour glucose increment and HGI was analyzed using linear regression analyses with adjustment of relevant parameters. Overall, the proportions of subjects with normal glucose tolerance, pre-diabetes, and newly diagnosed diabetes were 42.3%, 41.3%, and 16.4%, respectively. Compared with subjects who had an HGI≤0, subjects with an HGI>0 had a lower FPG (95.0±13.3 vs 98.5±15.3 mg/dL, p<0.001) but a higher 2-hour plasma glucose (151.1±52.8 vs 144.6±51.4 mg/dL, p=0.027) and 2-hour glucose increment (56.1±46.1 vs 46.1±45.0 mg/dL, p<0.001). The 2-hour glucose increment after an OGTT was independently associated with HGI (ß coefficient 0.003, 95% CI 0.002 to 0.003, p<0.001). Our findings suggested that postchallenge glucose increment was independently associated with HGI in subjects with no history of diabetes.

Subjects with coronary artery disease and reduced ejection fraction have longer (GT)n repeats in the heme-oxygenase 1 gene promoter.

Heme oxygenase (HO)-1 is a rate-limiting enzyme for degrading heme into carbon monoxide. Longer (GT)n repeat of the HO-1 gene (HMOX1) promoter has a lower transcription rate. Subjects with longer GT repeats in the HMOX1 promoter are more likely to have coronary artery disease (CAD) and cardiovascular events. We retrospectively enrolled CAD subjects with an abnormal ejection fraction (EF) < 50% from our catheterization data (N = 670). Polymerase chain reactions were performed for amplifying the HMOX1 promoter GT repeating segment to determine the number of repeats. Two subgroups, reduced EF < 40% (N = 256), and mid-range EF 40-49% (N = 414), were compared. The distribution of genotypes of SS, SL and LL were significantly different in reduced EF (29%, 48%, 23%) vs. mid-range EF CAD (64%, 30%, 5%) (S allele: ≤ 30 repeats, L allele: > 30 repeats) (p < 0.001). The patients with reduced EF had a significantly longer average (GT)n (median 27.5 vs. 26.5, p = 0.004) than those with the mid-range EF. In multivariate analysis, the carrier of L allele (odds ratio 4.437, p < 0.001) was a significant predictor for the diagnosis of reduced vs. mid-range EF CAD. In conclusion, CAD patients with reduced EF had longer HMOX1 promoter (GT)n repeats than those with mid-range EF.

Case Report: Leaflet Thrombosis After Transcatheter Aortic Valve Replacement With Worsening Heart Failure-A Successful Resolution Using Non-vitamin K Antagonist Oral Anti-coagulant.

Background: Transcatheter aortic valve replacement (TAVR) is indicated for treating symptomatic severe aortic valve stenosis (AS) with intermediate-to-high surgical risks. Few reports are available on managing leaflet thrombosis after TAVR with worsening heart failure. Case Summary: A 77-year-old man with severe AS and coronary artery disease (CAD) received a successful TAVR with Edwards Sapien 3 valve. A year later, the patient developed a worsening heart failure with pulmonary edema, new-onset atrial fibrillation (Af), an increase in mean trans-aortic valve pressure gradient to 48 mmHg, worsening mitral regurgitation (MR), and pulmonary hypertension (PH). The response of the patient to intravenous diuretics and inotropic treatments was poor. Multi-slice CT (MDCT) revealed hypo-attenuated thrombus and thickened transcatheter heart valve leaflets. A non-vitamin K antagonist oral anti-coagulant (NOAC) was added to treat the new-onset Af and leaflet thrombosis on top of the con-current single antiplatelet for CAD. A series of follow-up echocardiograms showed a progressive decrease in trans-aortic valve pressure gradient to 17 mmHg and reductions in MR and PH. Three months after the NOAC treatment, MDCT revealed the resolution of hypo-attenuated thrombus and thickened leaflets. Symptoms of heart failure were also improved gradually. Discussion: Worsening heart failure or an increase in trans-aortic valve pressure gradient after TAVR warranted further MDCT studies. Leaflet thrombosis can be resolved after using NOAC as in our present case.

Incidence and Mechanisms of Coronary Perforations during Rotational Atherectomy in Modern Practice.

OBJECTIVE: Heavy calcifications remain formidable challenges to PCI, even for well-experienced operators. However, rotational atherectomy (RA)-induced coronary perforations (CPs) still could not be obviated. This study was to explore incidence and mechanisms of RA-induced CP in real-world practice. Knowing why CPs occur in RA should help operators avert such mishaps. METHOD: Patients who received coronary RA from April 2010 to December 2019 with keywords related to perforations were retrieved from database. The procedure details, angiography, and clinical information were reviewed in detail. RESULTS: A total of 479 RAs were performed with 11 perforations in 10 procedures among 9 patients documented. The incidence of RA-induced CP was 2.1%. The RA vessels were distributed in different territories, including first diagonal branch. Most CPs could be treated conservatively, but prolonged profound shock predisposed to poor outcome. CPs caused by rotawire tip occurred in 18.2% of cases, inappropriately sized burrs in 18.2% of cases, and rotawire damage with subsequent transection and perforation in another 18.2% of cases. A total of 5 (45.5%) perforations were caused by unintended and unnoticed bias cutting into noncalcified plaques (4, 36.4%) or through calcified vessel wall (1, 9.1%). The mechanisms for certain CPs were unique and illustrated in diagrams. CONCLUSION: CPs due to RA occur in certain percentage of patients. The mechanisms for CPs are diverse. Wire damage with subsequent transection could occur due to inappropriately repetitive burr stress on the wire body. A significant portion was due to unintended and unnoticed bias cutting into noncalcified plaque or through calcified vessel wall.