Intravascular lithotripsy compared to rotational atherectomy for the treatment of calcified distal left main coronary artery disease: A single center experience.

BACKGROUND: The safety and efficacy of intravascular lithotripsy (IVL) for the treatment of calcified distal left main (LM) disease remains unclear, especially compared to rotational atherectomy (RA). METHODS: We retrospectively analyzed the baseline clinical, angiographic, intravascular ultrasound (IVUS) characteristics and procedural outcomes of 107 patients who underwent distal LM percutaneous coronary intervention (PCI) with IVL (with or without adjunct atherectomy) versus RA alone for plaque modification before stenting at a single center between 2020 and 2022. RESULTS: A total of 50 patients underwent calcium modification with IVL with or without adjunct atherectomy and 57 with RA only. The mean age was 73 years and with a high prevalence of diabetes (58.9%), chronic kidney disease (42.1%), prior revascularization (coronary artery bypass graft surgery [36.4%] or prior PCI [32.7%]). Acute coronary syndrome was the primary indication for PCI in over 50% of the patients in both groups. Medina 1-1-1 LM bifurcation disease was identified in 64% and 60% of the IVL and RA groups (p = 0.64) respectively. Final minimum stent area in distal LM (>8.2 mm2 ), ostial LAD (>6.3 mm2 ) and ostial LCX (>5.0 mm2 ) were achieved in 96%, 85% and 89% of cases treated with IVL respectively and 93%, 93% and 100% of cases treated with RA respectively (LM p = 1.00; LAD p = 0.62; LCX; p = 1.00 for difference between the two groups). Procedural success (technical success without in-hospital major adverse events) was achieved in 98% of the IVL group and 86% of the RA-only group (p = 0.04). There were eight procedural complications (flow-limiting dissection, perforation, or slow/no-reflow) in the RA group compared to four in the IVL group (NS), and one patient in the RA required salvaged mechanical support compared to none in the IVL group. CONCLUSION: Plaque modification with coronary IVL appears to be efficacious and safe for the treatment of severely calcified distal LM lesions compared to RA only. Larger randomized studies are needed to confirm these findings.

Circulating progenitor cells and outcomes in patients with coronary artery disease.

BACKGROUND: Low quantities of circulating progenitor cells (CPCs), specifically CD34+ populations, reflect impairment of intrinsic regenerative capacity. This study investigates the relationship between subsets of CPCs and adverse outcomes. METHODS: 1366 individuals undergoing angiography for evaluation of coronary artery disease (CAD) were enrolled into the Emory Cardiovascular Biobank. Flow cytometry identified CPCs as CD45med blood mononuclear cells expressing the CD34 epitope, with further enumeration of hematopoietic CPCs as CD133+/CXCR4+ cells and endothelial CPCs as vascular endothelial growth factor receptor-2 (VEGFR2+) cells. Adjusted Cox or Fine and Gray's sub-distribution hazard regression models analyzed the relationship between CPCs and 1) all-cause death and 2) a composite of cardiovascular death and non-fatal myocardial infarction (MI). RESULTS: Over a median 3.1-year follow-up period (IQR 1.3-4.9), there were 221 (16.6%) all-cause deaths and 172 (12.9%) cardiovascular deaths/MIs. Hematopoietic CPCs were highly correlated, and the CD34+/CXCR4+ subset was the best independent predictor. Lower counts (≤median) of CD34+/CXCR4+ and CD34+/VEGFR2+ cells independently predicted all-cause mortality (HR 1.46 [95% CI 1.06-2.01], p = 0.02 and 1.59 [95% CI 1.15-2.18], p = 0.004) and cardiovascular death/MI (HR 1.50 [95% CI 1.04-2.17], p = 0.03 and 1.47 [95% CI 1.01-2.03], p = 0.04). A combination of low CD34+/CXCR4+ and CD34+/VEGFR2+ CPCs predicted all-cause death (HR 2.1, 95% CI 1.4-3.0; p = 0.0002) and cardiovascular death/MI (HR 2.0, 95% CI 1.3-3.2; p = 0.002) compared to those with both lineages above the cut-offs. CONCLUSIONS: Lower levels of hematopoietic and endothelial CPCs indicate diminished endogenous regenerative capacity and independently correlate with greater mortality and cardiovascular risk in patients with CAD.

Percutaneous Closure of a Giant Aortocoronary Saphenous Vein Graft Aneurysm With Fistulous Connection to the Right Atrium.

Saphenous vein graft (SVG) aneurysms are rare but can be associated with significant morbidity and mortality. This case illustrates a percutaneous approach for the management of SVG aneurysm with a fistulous connection to the right atrium.

A single healthcare experience with Impella RP.

OBJECTIVES: To understand the predictors of survival and indications for Impella RP in a single healthcare experience. BACKGROUND: The Impella RP can be used to temporarily support patients with right ventricular (RV) dysfunction after left ventricular assist device (LVAD) placement or myocardial infarction (MI). However, recent postmarket approval data have raised concerns of higher than expected mortality with this device. METHODS: A retrospective chart review and analysis of all patients that underwent Impella RP placement in the Emory Healthcare system between January 2016 and December 2018 were performed. Patients were classified according to the indication. RESULTS: A total of 39 patients underwent Impella RP placement. Six patients were post-LVAD, 9 were implanted for massive pulmonary embolism with persistent shock, 8 for postcardiac surgery RV failure (non-LVAD), 11 for RV failure post-MI, and 5 for new or worsening nonischemic cardiomyopathy. The worst survival was noted in MI-related cardiogenic shock group and in patients who presented with cardiac arrest (3/12). All observed deaths were due to persistent refractory shock. There was no device related death. Survival improved during the last year of experience compared to the first 2 years. CONCLUSION: This study supports the selective use of the Impella RP, with a higher than national reported survival rate (49% vs. 28.6%). Indication appears to be an important factor determining survival.

Preventive Cardiology as a Subspecialty of Cardiovascular Medicine: JACC Council Perspectives.

Although significant progress has been made to reduce the global burden of cardiovascular disease, efforts have focused primarily on treatment of manifest disease rather than on prevention of events. An enormous opportunity exists to transition focus from intervention to providing equal attention to prevention of cardiovascular disease. The nascent specialty of "preventive cardiology" is emerging from the background of long-established services such as lipid, diabetes, hypertension, and general cardiology clinics. It is incumbent on the cardiology community to invest in cardiovascular prevention because past gains are threatened with the rising tide of obesity and diabetes. Now is the time to establish a dedicated preventive cardiology subspecialty to train the clinicians of the future. This American College of Cardiology Council Perspective aims to define the need for preventive cardiology as a unique subspecialty, broaches controversies, provides a structure for future training and education, and identifies possible paths forward to professional certification.

Provider Specialty, Anticoagulation, and Stroke Risk in Patients With Atrial Fibrillation and Cancer.

BACKGROUND: It is unknown whether early cardiology involvement shortly after atrial fibrillation (AF) diagnosis is associated with favorable outcomes in AF patients who have cancer. OBJECTIVES: The purpose of this study was to examine the relationship between early cardiology involvement after AF diagnosis in patients with history of cancer. METHODS: This study examined associations of early cardiology involvement with oral anticoagulation use, stroke, and bleeding among nonvalvular AF patients (n = 388,045; mean age 68 ± 15 years; 59% male) with a history of cancer (past or active) from the MarketScan database (2009 to 2014). International Classification of Disease-9th Revision-Clinical Modification codes in any position were used to identify cancer diagnosis prior to AF diagnosis. Provider specialty and filled anticoagulant prescriptions 3 months prior to and 6 months after AF diagnosis were obtained. Poisson regression models were used to compute the probability of an oral anticoagulant prescription fill, and Cox regression was used to estimate the risks of stroke and major bleeding. RESULTS: A total of 64,016 (17%) AF patients had a history of cancer. Cardiology involvement was less likely to occur among patients with a history of cancer than those without (relative risk [RR]: 0.92 [95% confidence interval (CI): 0.91 to 0.93]). Patients with history of cancer were less likely to fill prescriptions for anticoagulants (RR: 0.89 [95% CI: 0.88 to 0.90]) than those without cancer, and similar results were observed across cancer types. Patients with cancer were more likely to fill prescriptions for anticoagulants (RR: 1.48 [95% CI: 1.45 to 1.52]) if seen by a cardiologist. A reduced risk of stroke (hazard ratio: 0.89 [95% CI: 0.81 to 0.99]) was observed among all cancer patients who were seen by a cardiology provider, without an increased risk of bleeding (hazard ratio: 1.04 [95% CI: 0.95 to 1.13]). Similar results were observed when the analysis was stratified by active versus remote history of cancer. CONCLUSIONS: Although AF patients with cancer were less likely to see a cardiologist, or fill anticoagulant prescriptions, cardiology involvement was associated with increased anticoagulant prescription fills and favorable AF-related outcomes in AF patients with cancer.

Effect of Cigarette Smoking on Risk for Adverse Events in Patients With Heart Failure and Preserved Ejection Fraction.

Smoking is an important risk factor in the development of heart failure with preserved ejection (HFpEF), and previous reports have identified smoking as a significant predictor of death in this population. However, the relation between smoking and heart failure-specific outcomes has not been examined in patients with HFpEF. This analysis included 1,717 patients (mean age = 71 ± 10 years; 50% men; 78% white) with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial from the Americas. Smoking was ascertained by self-reported history and categorized as never, former, or current. Multivariable Cox regression was used to examine the risk of hospitalization for heart failure, death, and cardiovascular death across smoking categories. There were 116 current smokers (7%), 871 former smokers (51%), and 729 never smokers (42%) in this analysis. Current smoking was associated with an increased risk of hospitalization for heart failure (never: hazard ratio [HR] 1.0; former: HR 1.25, 95% confidence interval [CI] 0.99 to 1.57; current: HR 1.68, 95% CI 1.08 to 2.61), death (never: HR 1.0; former: HR 1.02, 95% CI 0.81 to 1.29; current: HR 1.82, 95% CI 1.19 to 2.78), and cardiovascular death (never: HR 1.0; former: HR 1.00, 95% CI 0.74 to 1.35; current: HR 1.85, 95% CI 1.09 to 3.24) compared with former or never smokers in a multivariable model adjusted for cardiovascular risk factors. A similar increased risk of hospitalization for heart failure (former: HR 1.0; current: HR 1.54, 95% CI 1.01, 2.36), death (former: HR 1.0; current: HR 1.81, 95% CI 1.19, 2.75), and cardiovascular death (former: HR 1.0; current: HR 1.76, 95% CI 1.04, 2.98) was observed for current smokers when we limited the analysis to those with a history of smoking. In conclusion, current smoking is associated with an increased risk for adverse outcomes in HFpEF, including hospitalization for heart failure. Smoking cessation strategies possibly have a role to reduce the risk for adverse cardiovascular outcomes in patients with HFpEF.

Progenitor Cells and Clinical Outcomes in Patients With Acute Coronary Syndromes.

RATIONALE: Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS). OBJECTIVE: We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS. METHODS AND RESULTS: In 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31-2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18-5.13) increase in all-cause mortality, P=0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS. CONCLUSIONS: CPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality.

Association between low diastolic blood pressure and subclinical myocardial injury.

BACKGROUND: Coronary arteries perfuse cardiac myocytes during diastole. We hypothesized that marked lowering of diastolic blood pressure (DBP) is associated with increased risk of subclinical myocardial injury (SC-MI). METHODS: This analysis included 6107 participants without history of cardiovascular disease (CVD) from the third National Health and Nutrition Examination Survey. SC-MI was determined by a validated electrocardiogram-based scoring system. Logistic regression was used to examine the cross-sectional association between DBP (< 70, 70-80 mmHg (reference group), and > 80 mmHg; and per each 10 mmHg decrease, separately) with SC-MI across levels of systolic blood pressure (SBP) (< 120, 120-139, or > 140 mmHg). RESULTS: In a multivariable model, DBP < 70 mmHg was associated with a higher risk of SC-MI [OR (95% CI) 1.40 (1.02, 1.94)] in participants with SBP > 140 mmHg. This association was consistent in subgroups stratified by age, race, diabetes, hypertension, obesity and smoking, but was stronger in women than in men [OR (95% CI) 1.58 (1.06, 2.37) vs. 1.10 (0.62, 1.94), respectively; interaction p value = 0.006]. Also, among participants with SBP > 140 mmHg, every 10 mmHg decrease in DBP was associated with a 12% increased odds of SC-MI [OR (95% CI) 1.12 (1.01, 1.23)]. No significant associations between DBP and SC-MI were observed in those with SBP < 120 mmHg or 120-139 mmHg, or between DBP > 80 mmHg and SC-MI in any of SBP levels. CONCLUSIONS: Low DBP < 70 mmHg in those with SBP > 140 mmHg carries higher risk of SC-MI, especially in women. Further research is needed to understand the therapeutic implications of these findings.

Sex Differences in Circulating Progenitor Cells.

BACKGROUND: Lower levels of circulating progenitor cells (PCs) reflect impaired endogenous regenerative capacity and are associated with aging, vascular disease, and poor outcomes. Whether biologic sex and sex hormones influence PC numbers remains a subject of controversy. We sought to determine sex differences in circulating PCs in both healthy persons and patients with coronary artery disease, and to determine their association with sex hormone levels. METHODS AND RESULTS: In 642 participants (mean age 48 years, 69% women, 23% black) free from cardiovascular disease, we measured circulating PC counts as CD45med+ mononuclear cells coexpressing CD34 and its subsets expressing CD133, chemokine (C-X-C motif) receptor 4, and vascular endothelial growth factor receptor 2 epitopes using flow cytometry. Testosterone and estradiol levels were measured. After adjustment for age, cardiovascular risk factors, and body mass, CD34+ (ß=-23%, P<0.001), CD34+/CD133+ (ß=-20%, P=0.001), CD34+/chemokine (C-X-C motif) receptor 4-positive (ß=-24%, P<0.001), and CD34+/chemokine (C-X-C motif) receptor 4-positive/CD133+ (ß=-21%, P=0.001) PC counts, but not vascular endothelial growth factor receptor 2-positive PC counts were lower in women compared with men. Estradiol levels positively correlated with hematopoietic, but not vascular endothelial growth factor receptor 2- positive PC counts in women (P<0.05). Testosterone levels and PC counts were not correlated in men. These findings were replicated in an independent cohort with prevalent coronary artery disease. CONCLUSIONS: Women have lower circulating hematopoietic PC levels compared with men. Estrogen levels are modestly associated with PC levels in women. Since PCs are reflective of endogenous regenerative capacity, these findings may at least partly explain the rise in adverse cardiovascular events in women with aging and menopause.

Association between oxidative stress and atrial fibrillation.

BACKGROUND: Oxidative stress (OS) may be a key mechanism underlying the development of atrial fibrillation (AF) in experimental studies, but data in humans remain limited. OBJECTIVE: Systemic OS can be estimated by measurements of circulating levels of the aminothiols including glutathione, cysteine, and their oxidized products. We tested the hypothesis that the redox potentials of glutathione (EhGSH) and cysteine will be associated with prevalent and incident AF. METHODS: Plasma levels of aminothiols were measured in 1439 patients undergoing coronary angiography, of whom 148 (10.3%) had a diagnosis of AF. After a median follow-up of 6.3 years, 104 of 917 patients (11.5%) developed incident AF. Multivariate logistic regression and Cox regression models were used to determine whether OS markers were independent predictors of prevalent and incident AF after adjustment for traditional risk factors, heart failure, coronary artery disease, and high-sensitivity C-reactive protein level. RESULTS: For each 10% increase in EhGSH, the odds of prevalent AF was 30% higher (odds ratio [OR] 1.3; 95% confidence interval [CI] 1.1-1.7; P = .02) and 90% higher (OR 1.9; 95% CI 1.3-2.7; P = .004) when the median was used as a cutoff. The EhGSH level above the median was more predictive of chronic AF (OR 4.0; 95% CI 1.3-12.9; P = .01) than of paroxysmal AF (OR 1.7; 95% CI 1.1-2.7; P = .03). Each 10% increase in EhGSH level was associated with a 40% increase in the risk of incident AF (hazard ratio 1.4; 95% CI 1.1-1.7; P = .01). CONCLUSION: Increased OS measured by the redox potentials of glutathione is associated with prevalent and incident AF. Therapies that modulate OS need to be investigated to treat and prevent AF.

Progenitor Cells and Clinical Outcomes in Patients With Heart Failure.

BACKGROUND: Endogenous regenerative capacity, assessed as circulating progenitor cell (PC) numbers, is an independent predictor of adverse outcomes in patients with cardiovascular disease. However, their predictive role in heart failure (HF) remains controversial. We assessed the relationship between the number of circulating PCs and the pathogenesis and severity of HF and their impact on incident HF events. METHODS AND RESULTS: We recruited 2049 adults of which 651 had HF diagnosis. PCs were enumerated by flow cytometry as CD45med+ blood mononuclear cells expressing CD34, CD133, vascular endothelial growth factor receptor-2, and chemokine (C-X-C motif) receptor 4 epitopes. PC subsets were lower in number in HF and after adjustment for clinical characteristics in multivariable analyses, a low CD34+ and CD34+/CXCR+ cell count remained independently associated with a diagnosis of HF (P<0.01). PC levels were not significantly different in reduced versus preserved ejection fraction patients. In 514 subjects with HF, there were 98 (19.1%) all-cause deaths during a 2.2±1.5-year follow-up. In a Cox regression model adjusting for clinical variables, hematopoietic-enriched PCs (CD34+, CD34+/CD133+, and CD34+/CXCR4+) were independent predictors of all-cause death (hazard ratio 2.0, 1.6, 1.6-fold higher mortality, respectively; P<0.03) among HF patients. Endothelial-enriched PCs (CD34+/VEGF+) were independent predictors of mortality in patients with HF with preserved ejection fraction only (hazard ratio, 5.0; P=0.001). CONCLUSIONS: PC levels are lower in patients with HF, and lower PC counts are strongly and independently predictive of mortality. Strategies to increase PCs and exogenous stem cell therapies designed to improve regenerative capacity in HF, especially, in HF with preserved ejection fraction, need to be further explored.

Vitamin D, Low-Grade Inflammation and Cardiovascular Risk in Young Children: A Pilot Study.

Vitamin D has anti-inflammatory properties, and deficiency is prevalent in children. There is a paucity of data regarding vitamin D status and its correlation with low-grade inflammation and vasculature. We prospectively enrolled 25 children, 9-11 years old (13 male); 21 obese. Eight atherosclerosis-promoting risk factors were scored as categorical variables with the following thresholds defining abnormality: body mass index Z score ≥ 1.5; systolic blood pressure ≥ 95th percentile (for age, sex, and height); triglyceride ≥ 100 mg/dL; low-density lipoprotein cholesterol (LDL-C) ≥ 110 mg/dL; high-density lipoprotein cholesterol ≤ 45 mg/dL; hemoglobin A1C (HBA1C) ≥ 5.5; 25-hydroxyvitamin D [25(OH) D] ≤ 30 ng/mL, and tobacco smoke exposure. High-sensitivity C-reactive protein (hsCRP) was measured to assess low-grade inflammation and classified as low- (<1 mg/L), average- (1-3 mg/L), and high-risk (>3 to <10 mg/L) groups. The proportion of children within each hsCRP group who had above threshold risk factors was calculated. Carotid artery ultrasound was performed to measure carotid artery intima-media thickness (CIMT). Median (range) for 25(OH) D was 24 (17-45) ng/mL. Eighteen were either 25 (OH) D deficient (<20 ng/mL) or insufficient (20-30 ng/mL), and seven were sufficient (>30 ng/mL). hsCRP was 1.7 (0.2-9.1) mg/L, with 11 being <1.0 mg/L, 8 between 1.0-3.0 and 6 > 3.0 to < 10.0 mg/L. Risk factor score was 3.9 ± 1.7 out of eight. 25(OH) D levels did not correlate with hsCRP or CIMT. While vitamin D deficiency, inflammation, and risk factors coexist at a very young age, causative mechanisms remain unclear.

Asymptomatic coronary artery disease in type II diabetes.

Coronary artery disease is a major cause of morbidity and mortality in patients with diabetes mellitus and remains one of the largest burdens on health care resources. Prevalence of asymptomatic CAD in this population is high and poses a diagnostic challenge due to lack of overt clinical complaints. At this time there is no clear algorithm to screen for silent myocardial ischemia in diabetics. In this article we review various diagnostic tools available for assessment and propose a step wise approach for risk stratification in these patients.