Physiological Assessment with iFR prior to FFR Measurement in Left Main Disease.

Despite guideline-based recommendation of the interchangeable use of instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) to guide revascularization decision-making, iFR/FFR could demonstrate different physiological or clinical outcomes in some specific patient or lesion subsets. Therefore, we sought to investigate the impact of difference between iFR and FFR-guided revascularization decision-making on clinical outcomes in patients with left main disease (LMD). In this international multicenter registry of LMD with physiological interrogation, we identified 275 patients in whom physiological assessment was performed with both iFR/FFR. Major adverse cardiovascular event (MACE) was defined as a composite of death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The receiver-operating characteristic analysis was performed for both iFR/FFR to predict MACE in respective patients in whom revascularization was deferred and performed. In 153 patients of revascularization deferral, MACE occurred in 17.0% patients. The optimal cut-off values of iFR and FFR to predict MACE were 0.88 (specificity:0.74; sensitivity:0.65) and 0.76 (specificity:0.81; sensitivity:0.46), respectively. The area under the curve (AUC) was significantly higher for iFR than FFR (0.74; 95%CI 0.62-0.85 vs. 0.62; 95%CI 0.48-0.75; p = 0.012). In 122 patients of coronary revascularization, MACE occurred in 13.1% patients. The optimal cut-off values of iFR and FFR were 0.92 (specificity:0.93; sensitivity:0.25) and 0.81 (specificity:0.047; sensitivity:1.00), respectively. The AUCs were not significantly different between iFR and FFR (0.57; 95%CI 0.40-0.73 vs. 0.46; 95%CI 0.31-0.61; p = 0.43). While neither baseline iFR nor FFR was predictive of MACE in patients in whom revascularization was performed, iFR-guided deferral seemed to be safer than FFR-guided deferral.

The Safety and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors for Patients with Sarcopenia or Frailty: Double Edged Sword?

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) show cardiovascular protective effects, regardless of the patient's history of diabetes mellitus (DM). SGLT2is suppressed cardiovascular adverse events in patients with type 2 DM, and furthermore, SGLT-2is reduced the risk of worsening heart failure (HF) events or cardiovascular death in patients with HF. Along with these research findings, SGLT-2is are recommended for patients with HF in the latest guidelines. Despite these benefits, the concern surrounding the increasing risk of body weight loss and other adverse events has not yet been resolved, especially for patients with sarcopenia or frailty. The DAPA-HF and DELIVER trials consistently showed the efficacy and safety of SGLT-2i for HF patients with frailty. However, the Rockwood frailty index that derived from a cumulative deficit model was employed for frailty assessment in these trials, which might not be suitable for the evaluation of physical frailty or sarcopenia alone. There is no fixed consensus on which evaluation tool to use or its cutoff value for the diagnosis and assessment of frailty in HF patients, or which patients can receive SGLT-2i safely. In this review, we summarize the methodology of frailty assessment and discuss the efficacy and safety of SGLT-2i for HF patients with sarcopenia or frailty.

Sex Differences in Cardiac and Clinical Phenotypes and Their Relation to Outcomes in Patients with Heart Failure.

Biological sex is one of the major factors characterizing the heart failure (HF) patient phenotype. Understanding sex-related differences in HF is crucial to implement personalized care for HF patients with various phenotypes. There are sex differences in left ventricular (LV) remodeling patterns in the HF setting, namely, more likely concentric remodeling and diastolic dysfunction in women and eccentric remodeling and systolic dysfunction in men. Recently supra-normal EF (snLVEF) has been recognized as a risk of worse outcome. This pathology might be more relevant in female patients. The possible mechanism may be through coronary microvascular dysfunction and sympathetic nerve overactivation from the findings of previous studies. Further, estrogen deficit might play a significant role in this pathophysiology. The sex difference in body composition may also be related to the difference in LV remodeling and outcome. Lower implementation in guideline-directed medical therapy (GDMT) in female HFrEF patients might also be one of the factors related to sex differences in relation to outcomes. In this review, we will discuss the sex differences in cardiac and clinical phenotypes and their relation to outcomes in HF patients and further discuss how to provide appropriate treatment strategies for female patients.

ß1 Adrenergic Receptor Autoantibodies and IgG Subclasses: Current Status and Unsolved Issues.

A wide range of anti-myocardial autoantibodies have been reported since the 1970s. Among them, autoantibodies against the ß1-adrenergic receptor (ß1AR-AAb) have been the most thoroughly investigated, especially in dilated cardiomyopathy (DCM). Β1AR-Aabs have agonist effects inducing desensitization of ß1AR, cardiomyocyte apoptosis, and sustained calcium influx which lead to cardiac dysfunction and arrhythmias. Β1AR-Aab has been reported to be detected in approximately 40% of patients with DCM, and the presence of the antibody has been associated with worse clinical outcomes. The removal of anti-myocardial autoantibodies including ß1AR-AAb by immunoadsorption is beneficial for the improvement of cardiac function for DCM patients. However, several studies have suggested that its efficacy depended on the removal of AAbs belonging to the IgG3 subclass, not total IgG. IgG subclasses differ in the structure of the Fc region, suggesting that the mechanism of action of ß1AR-AAb differs depending on the IgG subclasses. Our previous clinical research demonstrated that the patients with ß1AR-AAb better responded to ß-blocker therapy, but the following studies found that its response also differed among IgG subclasses. Further studies are needed to elucidate the possible pathogenic role of IgG subclasses of ß1AR-AAbs in DCM, and the broad spectrum of cardiovascular diseases including HF with preserved ejection fraction.

Prognostic value of peripheral endothelial function on major adverse cardiovascular events above traditional risk factors.

AIMS: This study aims to identify whether adding peripheral microvascular dysfunction (PMED), a marker of atherosclerosis to established risk scores has an incremental prognostic value for major adverse cardiovascular events (MACE). METHODS AND RESULTS: This is a retrospective study of patients who underwent measuring peripheral arterial tonometry from 2006 to 2020. The optimal cut-off value of the reactive hyperaemia index (RHI) that had maximal prognostic value associated with MACE was calculated. Peripheral microvascular endothelial dysfunction was defined as the RHI lower than the cut-off. Traditional cardiovascular risk factors such as age, sex, congestive heart failure, hypertension, diabetes, stroke, and vascular disease were determined to calculate the CHA2DS2-Vasc score. The outcome was MACE defined as myocardial infarction, heart failure hospitalization, cerebrovascular events, and all-cause mortality. A total of 1460 patients were enrolled (average age 51.4 ± 13.6, 64.1% female). The optimal cut-off value of the RHI was 1.83 in the overall population and in females and males was 1.61 and 1.8, respectively. The risk of MACE during 7 [interquartile range (IQR): 5,11] years of follow-up was 11.2%. Kaplan-Meier analysis showed that lower RHI is associated with worse MACE-free survival (P < 0.001). Multivariate Cox proportional hazard analysis, controlling for classic cardiovascular risk factors or risk scores such as CHA2DS2-Vasc and Framingham risk score revealed that PMED is an independent predictor of MACE. CONCLUSION: Peripheral microvascular dysfunction predicts cardiovascular events. Non-invasive assessment of peripheral endothelial function may be useful in early detection and improving the stratification of high-risk patients for cardiovascular events.

Coronary Reactivity Assessment Is Associated With Lower Health Care-Associated Costs in Patients Presenting With Angina and Nonobstructive Coronary Artery Disease.

BACKGROUND: The financial burden linked to the diagnosis and treatment of patients with chest pain on the health care system is considerable. Angina and nonobstructive coronary artery disease (ANOCA) is common, associated with adverse cardiovascular events, and may lead to repeat testing or hospitalizations. Diagnostic certainty can be achieved in patients with ANOCA using coronary reactivity testing (CRT); however, its financial effect on the patient has not been studied. Our goal was to assess the effect of CRT on health care-related cost in patients with ANOCA. METHODS: Patients with ANOCA who underwent diagnostic coronary angiography (CAG) and CRT (CRT group) were matched to controls who had similar presentation but only underwent a CAG without CRT (CAG group). Standardized inflation-adjusted costs were collected and compared between the 2 groups on an annual basis for 2 years post the index date (CRT or CAG). RESULTS: Two hundred seven CRT and 207 CAG patients were included in the study with an average age of 52.3±11.5 years and 76% females. The total cost was significantly higher in the CAG group as compared with the CRT group ($37 804 [$26 933-$48 674] versus $13 679 [$9447-$17 910]; P<0.001). When costs are itemized and divided based on the Berenson-Eggers Type of Service categorization, the largest cost difference occurred in imaging (any type, including CAG; P<0.001), procedures (eg, percutaneous coronary intervention/coronary artery bypass grafting/thrombectomy) (P=0.001), and test (eg, blood tests, EKG; P<0.001). CONCLUSIONS: In this retrospective observational study, assessment of CRT in patients with ANOCA was associated with significantly reduced annual total costs and health care utilization. Therefore, the study may support the integration of CRT into clinical practice.

Coronary microvascular dysfunction in heart failure patients.

Coronary microcirculation has multiple layers of autoregulatory function to maintain resting flow and augment hyperemic flow in response to myocardial demands. Functional or structural alterations in the coronary microvascular function are frequently observed in patients with heart failure with preserved or reduced ejection fraction, which may lead to myocardial ischemic injury and resultant worsening of clinical outcomes. In this review, we describe our current understanding of coronary microvascular dysfunction in the pathogenesis of heart failure with preserved and reduced ejection fraction.

Deferred Versus Performed Revascularization for Left Main Coronary Disease With Hemodynamic Significance.

BACKGROUND: The majority of randomized controlled trials of revascularization decision-making excludes left main coronary artery disease (LMD). Therefore, contemporary clinical outcomes of patients with stable coronary artery disease and LMD with proven ischemia remain poorly understood. The aim of this study was to assess the long-term clinical outcomes of physiologically significant LMD according to the treatment strategies of revascularization versus revascularization deferral. METHODS: In this international multicenter registry of stable LMD interrogated with the instantaneous wave-free ratio, patients with physiologically significant ischemia (instantaneous wave-free ratio ≤0.89) were analyzed according to the coronary revascularization (n=151) versus revascularization deferral (n=74). Propensity score matching was performed to adjust for baseline clinical characteristics. The primary end point was a composite of death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization of left main stem. The secondary end points were as follows: cardiac death or spontaneous LMD-related myocardial infarction; and ischemia-driven target lesion revascularization of left main stem. RESULTS: At a median follow-up period of 2.8 years, the primary end point occurred in 11 patients (14.9%) in the revascularized group and 21 patients (28.4%) in the deferred group (hazard ratio, 0.42 [95% CI, 0.20-0.89]; P=0.023). For the secondary end points, cardiac death or LMD-related myocardial infarction occurred significantly less frequently in the revascularized group (0.0% versus 8.1%; P=0.004). The rate of ischemia-driven target lesion revascularization of left main stem was also significantly lower in the revascularized group (5.4% versus 17.6%; hazard ratio, 0.20 [95% CI, 0.056-0.70]; P=0.012). CONCLUSIONS: In patients who underwent revascularization for stable coronary artery disease and physiologically significant LMD determined by instantaneous wave-free ratio, the long-term clinical outcomes were significantly improved as compared with those in whom revascularization was deferred.

Reactive Oxygen Species in the Aorta and Perivascular Adipose Tissue Precedes Endothelial Dysfunction in the Aorta of Mice with a High-Fat High-Sucrose Diet and Additional Factors.

Metabolic syndrome (Mets) is the major contributor to the onset of metabolic complications, such as hypertension, type 2 diabetes mellitus (DM), dyslipidemia, and non-alcoholic fatty liver disease, resulting in cardiovascular diseases. C57BL/6 mice on a high-fat and high-sucrose diet (HFHSD) are a well-established model of Mets but have minor endothelial dysfunction in isolated aortas without perivascular adipose tissue (PVAT). The purpose of this study was to evaluate the effects of additional factors such as DM, dyslipidemia, and steatohepatitis on endothelial dysfunction in aortas without PVAT. Here, we employed eight-week-old male C57BL/6 mice fed with a normal diet (ND), HFHSD, steatohepatitis choline-deficient HFHSD (HFHSD-SH), and HFHSD containing 1% cholesterol and 0.1% deoxycholic acid (HFHSD-Chol) for 16 weeks. At week 20, some HFHSD-fed mice were treated with streptozocin to develop diabetes (HFHSD-DM). In PVAT-free aortas, the endothelial-dependent relaxation (EDR) did not differ between ND and HFHSD (p = 0.25), but in aortas with PVAT, the EDR of HFHSD-fed mice was impaired compared with ND-fed mice (p = 0.005). HFHSD-DM, HFHSD-SH, and HFHSD-Chol impaired the EDR in aortas without PVAT (p < 0.001, p = 0.019, and p = 0.009 vs. ND, respectively). Furthermore, tempol rescued the EDR in those models. In the Mets model, the EDR is compromised by PVAT, but with the addition of DM, dyslipidemia, and SH, the vessels themselves may result in impaired EDR.

Physiology-guided PCI versus CABG for left main coronary artery disease: insights from the DEFINE-LM registry.

There have been no studies comparing clinical outcomes of physiology-guided revascularization in patients with unprotected left main coronary disease (ULMD) between percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG). The aim of this study was to assess the long-term clinical outcomes between PCI and CABG of patients with physiologically significant ULMD. From an international multicenter registry of ULMD patients interrogated with instantaneous wave-free ratio (iFR), we analyzed data from 151 patients (85 PCI vs. 66 CABG) who underwent revascularization according to the cutoff value of iFR ≤ 0.89. Propensity score matching was employed to adjust for baseline clinical characteristics. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were the individual components of the primary endpoint. Mean age was 66.6 (± 9.2) years, 79.2% male. Mean SYNTAX score was 22.6 (± 8.4) and median iFR was 0.83 (IQR 0.74-0.87). After performing propensity score matching analysis, 48 patients treated with CABG were matched to those who underwent PCI. At a median follow-up period of 2.8 years, the primary endpoint occurred in 8.3% in PCI group and 20.8% in CABG group, respectively (HR 3.80; 95% CI 1.04-13.9; p = 0.043). There was no difference in each component of the primary event (p > 0.05 for all). Within the present study, iFR-guided PCI was associated with lower cardiovascular events rate in patients with ULMD and intermediate SYNTAX score, as compared to CABG. State-of-the-art PCI vs. CABG for ULMD. Study design and primary endpoint in patients with physiologically significant ULMD. MACE was defined as the composite of all-cause death, non-fatal myocardial infarction, and target lesion revascularization. The blue line denotes the PCI arm, and the red line denotes the CABG arm. PCI was associated with significantly lower risk of MACE than CABG. CABG: coronary artery bypass grafting; iFR: instantaneous wave-free ratio; MACE: major adverse cardiovascular events; PCI: percutaneous coronary intervention; ULMD: unprotected left main coronary artery disease.

Ventricular arrhythmias in patients with prior aortic valve intervention: Characteristics, ablation and outcomes.

INTRODUCTION: Data regarding ventricular tachycardia (VT) or premature ventricular complex (PVC) ablation in patients with aortic valve (AV) intervention (AVI) is limited. Catheter ablation (CA) can be challenging given perivalvular substrate in the setting of prosthetic valves. We sought to investigate the characteristics, safety, and outcomes of CA in patients with prior AVI and ventricular arrhythmias (VA). METHODS: We identified consecutive patients with prior AVI (replacement or repair) who underwent CA for VT or PVC between 2013 and 2018. We investigated the mechanism of arrhythmia, ablation approach, perioperative complications, and outcomes. RESULTS: We included 34 patients (88% men, mean age 64 ± 10.4 years, left ventricular (LV) ejection fraction 35.2 ± 15.0%) with prior AVI who underwent CA (22 VT; 12 PVC). LV access was obtained through trans-septal approach in all patients except one patient who had percutaneous transapical access. One patient had combined retrograde aortic and trans-septal approach. Scar-related reentry was the dominant mechanism of induced VTs. Two patients had bundle branch reentry VTs. In the VT group, substrate mapping demonstrated heterogeneous scar that involved the peri-AV area in 95%. Despite that, the site of successful ablation included the periaortic region only in 6 (27%) patients. In the PVC group, signal abnormalities consistent with scar in the periaortic area were noted in 4 (33%) patients. In 8 (67%) patients, the successful site of ablation was unrelated to the periaortic area. No procedure-related complications occurred. The survival and recurrence-free survival rate at 1 year tended to be lower in VT group than in PVC group (p = .06 and p = .05, respectively) with a 1-year recurrence-free survival rate of 52.8% and 91.7%, respectively. No arrhythmia-related death was documented on long-term follow-up. CONCLUSION: CA of VAs can be performed safely and effectively in patients with prior AVI.

Clonal Hematopoiesis of Indeterminate Potential Is Associated With Coronary Microvascular Dysfunction In Early Nonobstructive Coronary Artery Disease.

BACKGROUND: Clonal hematopoiesis (CH) of indeterminate potential (CHIP) is a risk factor for cardiovascular disease. The relationship between CHIP and coronary microvascular dysfunction (CMD) is unknown. The current study examines the association between CHIP and CH with CMD and the potential relationships in risk for adverse cardiovascular outcomes. METHODS: In this retrospective observational study, targeted next-generation sequencing was performed for 177 participants with no coronary artery disease who presented with chest pain and underwent routine coronary functional angiogram. Patients with somatic mutations in leukemia-associated driver genes in hematopoietic stem and progenitor cells were examined; CHIP was considered at a variant allele fraction ≥2%; CH was considered at a variant allele fraction ≥1%. CMD was defined as coronary flow reserve to intracoronary adenosine of ≤2. Major adverse cardiovascular events considered were myocardial infarction, coronary revascularization, or stroke. RESULTS: A total of 177 participants were examined. Mean follow-up was 12±7 years. A total of 17 patients had CHIP and 28 had CH. Cases with CMD (n=19) were compared with controls with no CMD (n=158). Cases were 56±9 years, were 68% women, and had more CHIP (27%; P=0.028) and CH (42%; P=0.001) than controls. CMD was associated with independent risk for major adverse cardiovascular events (hazard ratio, 3.89 [95% CI, 1.21-12.56]; P=0.023), and 32% of this risk was mediated by CH. The risk mediated by CH was ≈0.5× as large as the direct effect of CMD on major adverse cardiovascular events. CONCLUSIONS: In humans, we observe patients with CMD are more likely to have CHIP, and nearly one-third of major adverse cardiovascular events in CMD are mediated by CH.

D-Dimer beyond Diagnosis of Pulmonary Embolism: Its Implication for Long-Term Prognosis in Cardio-Oncology Era.

Venous thromboembolism (VTE) is a common comorbidity of cancer, often referred to as cancer-associated thrombosis (CAT). Even though its prevalence has been increasing, its clinical picture has not been thoroughly investigated. In this single-center retrospective observational study, 259 patients who were treated for pulmonary embolism (PE) between January 2015 and December 2020 were available for analysis. The patients were divided by the presence or absence of concomitant malignancy, and those with malignancy (N = 120, 46%) were further classified into active (N = 40, 15%) and inactive groups according to the treatment status of malignancy. In patients with malignancy, PE was more often diagnosed incidentally by computed tomography or D-dimer testing, and the proportion of massive PE was lower. Although D-dimer levels overall decreased after the initiation of anticoagulation therapy, concomitant malignancy was independently associated with higher D-dimer at discharge despite the lower severity of PE at onset. The patients with malignancy had a poor prognosis during post-discharge follow-up. Active malignancy was independently associated with major adverse cardiovascular events (MACE) and major bleeding. D-dimer at discharge was an independent predictor of mortality even after adjustment for malignancy. This study's findings suggest that CAT-PE patients might have hypercoagulable states, which can potentially lead to a poorer prognosis.

A Low Arginine/Ornithine Ratio is Associated with Long-Term Cardiovascular Mortality.

AIMS: The long-term prognostic value of the bioavailability of L-arginine, an important source of nitric oxide for the maintenance of vascular endothelial function, has not been investigated fully. We therefore investigated the relationship between amino acid profile and long-term prognosis in patients with a history of standby coronary angiography. METHODS: We measured the serum concentrations of L-arginine, L-citrulline, and L-ornithine by high-speed liquid chromatography. We examined the relationship between the L-arginine/L-ornithine ratio and the incidence of all-cause death, cardiovascular death, and major adverse cardiovascular events (MACEs) in 262 patients (202 men and 60 women, age 65±13 years) who underwent coronary angiography over a period of ≤ 10 years. RESULTS: During the observation period of 5.5±3.2 years, 31 (12%) patients died, including 20 (8%) of cardiovascular death, while 32 (12%) had MACEs. Cox regression analysis revealed that L-arginine/L-ornithine ratio was associated with an increased risk for all-cause death (unadjusted hazard ratio, 95% confidence interval) (0.940, 0.888-0.995) and cardiovascular death (0.895, 0.821-0.965) (p＜0.05 for all). In a model adjusted for age, sex, hypertension, hyperlipidemia, diabetes, current smoking, renal function, and log10-transformed brain natriuretic peptide level, cardiovascular death (0.911, 0.839-0.990, p=0.028) retained an association with a low L-arginine/ L-ornithine ratio. When the patients were grouped according to an L-arginine/L-ornithine ratio of 1.16, the lower L-arginine/L-ornithine ratio group had significantly higher incidence of all-cause death, cardiovascular death, and MACEs. CONCLUSION: A low L-arginine/L-ornithine ratio may be associated with increased 10-year cardiac mortality.

Circulating Progenitor Cells Are Associated With Bioprosthetic Aortic Valve Deterioration: A Preliminary Study.

Background Mechanisms underlying bioprosthetic valve deterioration are multifactorial and incompletely elucidated. Reparative circulating progenitor cells, and conversely calcification-associated osteocalcin expressing circulating progenitor cells, have been linked to native aortic valve deterioration. However, their role in bioprosthetic valve deterioration remains elusive. This study sought to evaluate the contribution of different subpopulations of circulating progenitor cells in bioprosthetic valve deterioration. Methods and Results This single-center prospective study enrolled 121 patients who had peripheral blood mononuclear cells isolated before bioprosthetic aortic valve replacement and had an echocardiographic follow-up ≥2 years after the procedure. Using flow cytometry, fresh peripheral blood mononuclear cells were analyzed for the surface markers CD34, CD133, and osteocalcin. Bioprosthetic valve deterioration was evaluated by hemodynamic valve deterioration (HVD) using echocardiography, which was defined as an elevated mean transprosthetic gradient ≥30 mm Hg or at least moderate intraprosthetic regurgitation. Sixteen patients (13.2%) developed HVD during follow-up for a median of 5.9 years. Patients with HVD showed significantly lower levels of reparative CD34+CD133+ cells and higher levels of osteocalcin-positive cells than those without HVD (CD34+CD133+ cells: 125 [80, 210] versus 270 [130, 420], P=0.002; osteocalcin-positive cells: 3060 [523, 5528] versus 670 [180, 1930], P=0.005 respectively). Decreased level of CD34+CD133+ cells was a significant predictor of HVD (hazard ratio, 0.995 [95% CI, 0.990%-0.999%]). Conclusions Circulating levels of CD34+CD133+ cells and osteocalcin-positive cells were significantly associated with the subsequent occurrence of HVD in patients undergoing bioprosthetic aortic valve replacement. Circulating progenitor cells might play a vital role in the mechanism, risk stratification, and a potential therapeutic target for patients with bioprosthetic valve deterioration.

Invasive aortic pulse pressure is linked to cardiac allograft vasculopathy after heart transplantation.

BACKGROUND: Pulse pressure (PP) has been linked to an increased risk of extent of coronary atherosclerosis and cardiovascular events. This study aimed to investigate the contribution of aortic PP on cardiac allograft vasculopathy (CAV) progression, and cardiovascular events after heart transplantation (HTx). METHODS: A total of 330 HTx patients (mean age 49 ± 25 years, 70.0% male) undergoing routine serial coronary intravascular ultrasound (IVUS) studies and had invasive aortic PP were enrolled. The median time from HTx to first IVUS was 13.6 months. CAV progression was assessed by IVUS as the changes (Δ) in plaque volume divided by the segment length (PV/SL), adjusted for the time between IVUS (median, 3.99 years; interquartile range, 1.99-7.20 years), and was defined as ΔPV/SL ≥0.50 mm3/mm/year. Major adverse cardiovascular event (MACE) was defined as any incidence of mortality, myocardial infarction, coronary revascularization, heart failure hospitalization, or re-transplantation. RESULTS: Recipient age, recipient sex, and renal dysfunction were independent determinant of high aortic PP (≥ 50 mmHg). High aortic PP was an independent determinant of CAV progression [odds ratio, 1.72; 95% confidence interval (CI), 1.01-2.93; p = 0.045]. Both high aortic PP (HR 1.46, 95% CI 1.01-2.11, p = 0.044) and high baseline CAV grade on angiogram (≥1, HR 1.50, 95% CI 1.03-2.21, p = 0.037) were independently associated with MACEs over 12 years. CONCLUSION: In post-HTx patients, high aortic PP was significantly associated with plaque progression. Both aortic PP and CAV grade are independently associated with MACE during long-term follow-up. These findings suggest that arterial stiffness and CAV can be important predictors of MACEs.

Coronary microvascular dysfunction is an independent predictor of developing cancer in patients with non-obstructive coronary artery disease.

AIMS: Cardiovascular disease and cancer share common pathogenesis and risk factors. Coronary microvascular dysfunction (CMD), reflecting impaired coronary microvascular dilation in response to stress, is related to a higher risk of major cardiovascular events; however, its association with cancer has not been explored. METHODS AND RESULTS: A retrospective study on 1042 patients with non-obstructive coronary artery diseases (NOCADs) was performed. Data regarding demographic, clinical history, diagnostic coronary reactivity test, and cancer occurrence were collected. Coronary microvascular dysfunction was defined as coronary flow reserve (the ratio of hyperaemic blood flow to resting blood flow) ≤2.5. Thirty-four per cent had CMD (67.4% female and the average age was 52.4 ± 12.2 years). Of 917 patients with no history of cancer, 15.5% developed cancer during follow-up [median of 9 (4, 16) years]. Kaplan-Meier analysis showed that CMD patients had lower cancer-free survival compared with those without CMD (log-rank P = 0.005). Cox proportional hazard analyses showed that after adjusting for age, sex, hypertension, diabetes, smoking, and glomerular filtration rate, CMD is independently associated with cancer [hazard ratio, 1.4; 95% confidence interval (CI), 1.09-2.04; P = 0.04]. The rate of major adverse cardiovascular events (MACE) was significantly higher in CMD patients compared with that in non-CMD patients who had a previous history of cancer [odds ratio (OR), 2.5; 95% CI, 1-6.2; P = 0.04] and those with no history of cancer (OR, 1.4; 95% CI, 1.01-1.9; P = 0.044). CONCLUSION: Coronary microvascular dysfunction is associated with cancer incidence in patients presenting with NOCADs. This study emphasizes follow-up in patients with CMD to evaluate the risk of MACE as well as potential malignant diseases.

Human Gut Microbiota in Coronary Artery Disease: A Systematic Review and Meta-Analysis.

In recent years, the importance of the gut microbiome in human health and disease has increased. Growing evidence suggests that gut dysbiosis might be a crucial risk factor for coronary artery disease (CAD). Therefore, we conducted a systematic review and meta-analysis to determine whether or not CAD is associated with specific changes in the gut microbiome. The V3-V4 regions of the 16S rDNA from fecal samples were analyzed to compare the gut microbiome composition between CAD patients and controls. Our search yielded 1181 articles, of which 21 met inclusion criteria for systematic review and 7 for meta-analysis. The alpha-diversity, including observed OTUs, Shannon and Simpson indices, was significantly decreased in CAD, indicating the reduced richness of the gut microbiome. The most consistent results in a systematic review and meta-analysis pointed out the reduced abundance of Bacteroidetes and Lachnospiraceae in CAD patients. Moreover, Enterobacteriaceae, Lactobacillus, and Streptococcus taxa demonstrated an increased trend in CAD patients. The alterations in the gut microbiota composition are associated with qualitative and quantitative changes in bacterial metabolites, many of which have pro-atherogenic effects on endothelial cells, increasing the risk of developing and progressing CAD.