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Large clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia.The purpose of this study was to assess the effect of empagliflozin on left ventricular (LV) function and volumes, functional capacity, and quality of life (QoL) in nondiabetic HFrEF patients.In this double-blind, placebo-controlled trial, nondiabetic HFrEF patients (n = 84) were randomized to empagliflozin 10 mg daily or placebo for 6 months. The primary endpoint was change in LV end-diastolic and -systolic volume assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life.Empagliflozin was associated with a significant reduction of LV end-diastolic volume (-25.1 ± 26.0 ml vs. -1.5 ± 25.4 ml for empagliflozin vs. placebo, respectively; p 0.001) and LV end-systolic volume (-26.6 ± 20.5 ml vs. -0.5 ± 21.9 ml for empagliflozin vs. placebo; p 0.001). Empagliflozin was associated with reductions in LV mass (-17.8 ± 31.9 g vs. 4.1 ± 13.4 g, for empagliflozin vs. placebo, respectively; p 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 ± 4.2 vs. -0.1 ± 3.9; p 0.001). Patients who received empagliflozin had significant improvements in peak OEmpagliflozin administration to nondiabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status. (Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity? [ATRU-4] [EMPA-TROPISM]; NCT03485222).

Coronary revascularization is accomplished either by percutaneous coronary intervention (PCI), with low risk of immediate complications, or coronary artery bypass graft (CABG), with improved long-term, event-free survival attributable to use of the left internal mammary artery graft. Hybrid coronary revascularization (HCR) combines both. The left internal mammary artery graft is done by sternal-sparing approaches or by robotic-assisted, endoscopic surgery. HCR reduces bleeding, ventilator time, and length of stay compared with traditional CABG. Compared with PCI, HCR offers the durability and survival advantages of the left internal mammary artery. The large-scale National Heart, Lung, and Blood Institute-sponsored, randomized Hybrid Trial (Hybrid Coronary Revascularization Trial) was initiated to examine whether HCR is superior to multivessel PCI. However, enrollment was suboptimal, triggering premature study discontinuation. HCR integrates the positive features of both PCI and CABG, albeit requiring 2 procedures rather than 1. Adequately powered randomized trials are required to evaluate the outcomes and cost-effectiveness of HCR compared with CABG and multivessel PCI alone.

BACKGROUND: Hybrid PET/MR imaging has significant potential in cardiology due to its combination of molecular PET imaging and cardiac MR. Multi-tissue-class MR-based attenuation correction (MRAC) is necessary for accurate PET quantification. Moreover, for thoracic PET imaging, respiration is known to lead to misalignments of MRAC and PET data that result in PET artifacts. These factors can be addressed by using multi-echo MR for tissue segmentation and motion-robust or gated acquisitions. However, the combination of these strategies is not routinely available and can be prone to errors. In this study we examine the qualitative and quantitative impacts of multi-class MRAC compared to a more widely available, simple two-class MRAC for cardiac PET/MR. METHODS AND RESULTS: In a cohort of patients with cardiac sarcoidosis, we acquired MRAC data using multi-echo radial gradient-echo MR imaging. Water-fat separation was used to produce attenuation maps with up to 4 tissue classes including water-based soft tissue, fat, lung, and background air. Simultaneously acquired 18F-fluorodeoxyglucose PET data were subsequently reconstructed using each attenuation map separately. PET uptake values were measured in the myocardium and compared between different PET images. The inclusion of lung and subcutaneous fat in the MRAC maps significantly affected the quantification of 18F-fluorodeoxyglucose activity in the myocardium but only moderately altered the appearance of the PET image without introduction of image artifacts. CONCLUSIONS: Optimal MRAC for cardiac PET/MR applications should include segmentation of all tissues in combination with compensation for the respiratory-related motion of the heart. Simple two-class MRAC is adequate for qualitative clinical assessment.

Clinical, laboratory, and autopsy findings support an association between coronavirus disease-2019 (COVID-19) and thromboembolic disease. Acute COVID-19 infection is characterized by mononuclear cell reactivity and pan-endothelialitis, contributing to a high incidence of thrombosis in large and small blood vessels, both arterial and venous. Observational studies and randomized trials have investigated whether full-dose anticoagulation may improve outcomes compared with prophylactic dose heparin. Although no benefit for therapeutic heparin has been found in patients who are critically ill hospitalized with COVID-19, some studies support a possible role for therapeutic anticoagulation in patients not yet requiring intensive care unit support. We summarize the pathology, rationale, and current evidence for use of anticoagulation in patients with COVID-19 and describe the main design elements of the ongoing FREEDOM COVID-19 Anticoagulation trial, in which 3,600 hospitalized patients with COVID-19 not requiring intensive care unit level of care are being randomized to prophylactic-dose enoxaparin vs therapeutic-dose enoxaparin vs therapeutic-dose apixaban. (FREEDOM COVID-19 Anticoagulation Strategy [FREEDOM COVID]; NCT04512079).

Limited data on gender differences by ethnicity after percutaneous coronary intervention (PCI) exist. In this prospective cohort study, we examined gender differences in 1-year outcomes among patients from 4 ethnic groups who underwent PCI from 2010 to 2016 at a tertiary center. The primary outcome was 1-year major adverse cardiovascular events (MACE) defined as composite of all-cause death, nonfatal myocardial infarction (MI), or target lesion revascularization. Secondary outcomes included composite of death or MI and individual components of MACE. Baseline characteristics and outcomes were compared between gender in each ethnic group. The study included 16,361 patients: 7,881 whites (26.1% women), 1,943 blacks (47.3% women), 2,621 Asians (22.6% women), and 3,916 Hispanics (39.3% women). Women were older with more co-morbidities than men. Unadjusted, women had higher incidence of 1-year MACE than men among whites and Asians but not blacks or Hispanics, which was driven by a greater incidence of death in white women and greater incidence of MI in Asian women compared with male counterparts. After adjustment, findings showed similar risk of 1-year MACE in women versus men in whites, Asians, and Hispanics (Whites: hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.78 to 1.16; Asians: HR 1.14, 95% CI 0.77 to 1.67; Hispanics: HR 0.97, 95% CI 0.74 to 1.27). Black women had lower risk of 1-year MACE compared with black men (HR 0.67, 95% CI 0.46 to 0.97), driven by lower risk of death or MI. In conclusion, this study suggests that risk factors account for adverse events in women after PCI.

Background High-intensity statins (HIS) are recommended for secondary prevention following percutaneous coronary intervention (PCI). We aimed to describe temporal trends and determinants of HIS prescriptions after PCI in a usual-care setting. Methods All patients with age ≤75 years undergoing PCI between January 2011 and May 2016 at an urban, tertiary care center and discharged with available statin dosage data were included. HIS were defined as atorvastatin 40 or 80 mg, rosuvastatin 20 or 40 mg, and simvastatin 80 mg. Results A total of 10,495 consecutive patients were included. Prevalence of HIS prescriptions nearly doubled from 36.6% in 2011 to 60.9% in 2016 (P Conclusion Although the rate of HIS prescriptions after PCI has increased in recent years, important heterogeneity remains and should be addressed to improve practices in patients undergoing PCI.

Background: SGLT2 inhibitors (SGLT2i) improve prognosis in HFrEF patients. We recently demonstrated in a porcine model of non-diabetic HFrEF that empagliflozin (EMPA) ameliorates adverse cardiac remodeling and improves LV systolic function. However, the effect of EMPA on left atrial (LA) dilatation has not yet been studied Hypothesis:: Empagliflozin ameliorates left atrial dilatation in non-diabetic HFrEF patients Methods: The EMPATROPISM clinical trial investigated the efficacy and safety of EMPA in non-diabetic HFrEF patients. 84 patients were randomized to EMPA 10mg daily for 6 months or placebo on top of optimal medical treatment, and were evaluated with cardiac magnetic resonance (CMR). LA Volumes were quantified by CMR using the Simpson method (the number of slices in the usual short axis SSFP cine sequence was increased to cover both LV and the whole of LA. The primary endpoint was change in LVEDV. Prespecified secondary endpoints were changes in maximal and minimal LA volumes (ΔMax LA Vol and ΔMin LA Vol) at the end of 6 months between both arms Results: 80 patients completed the follow up period. There were no differences at baseline in LVEDV (220±75 vs 209±68mL for EMPA vs placebo, p=0.5) or LVEF (36±8 vs 37±8%, p=0.7). There were no differences at baseline in both groups in either maximal or minimal LA volume (Table). In the primary endpoint, EMPA-treated patients showed decrease in LVEDV and increase in LVEF (ΔLVEDV -25±25 vs -1±25mL, p Conclusions: In HFrEF patients without diabetes, treatment with empagliflozin ameliorates left atrial dilatation. As LA volume is a surrogate for chronic filling pressures, this reduced LA volume suggest improved diastolic function with EMPA

Background: SGLT2 inhibitors (SGLT2i) improve prognosis in HFrEF patients. We recently demonstrated in a porcine model of non-diabetic HFrEF that empagliflozin (EMPA) ameliorates adverse cardiac remodeling and improves LV systolic function. However, the effect of EMPA on interstitial myocardial fibrosis (IMF) and aortic stiffness has not yet been studied Hypothesis: Empagliflozin ameliorates IMF and aortic stiffness in non-diabetic HFrEF patients Methods: The EMPATROPISM clinical trial (NCT 03485222) investigated the efficacy and safety of EMPA in non-diabetic HFrEF patients. 84 patients were randomized to EMPA 10mg daily for 6 months or placebo on top of optimal medical treatment, and were evaluated with cardiac magnetic resonance (CMR). IMF was assessed by CMR using extracellular volume (ECV) by T1 mapping. Aortic stiffness was quantified by pulse wave velocity (PWV) by CMR. The primary endpoint was change in LVEDV. Prespecified secondary endpoints were changes in ECV (ΔECV) and PWV (ΔPWV) at 6 months between both arms Results: 80 patients completed the follow up period. There were no differences at baseline in LVEDV (220±75 vs 209±68mL for EMPA vs placebo, p=0.5) or LVEF (36±8 vs 37±8%, p=0.7). There were no differences at baseline in both groups in either ECV or PWV (Table). In the primary endpoint, EMPA-treated patients showed decrease in LVEDV and increase in LVEF (ΔLVEDV -25±25 vs -1±25mL, p Conclusions: In HFrEF patients without diabetes, treatment with empagliflozin ameliorates IMF and aortic stiffness. This may explain the benefits of SGLT2i in HFrEF even in the absence of diabetes

Background Thromboembolic disease is common in coronavirus disease-2019 (COVID-19). There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postm...

This paper will review myocardial infarction with non-obstructive coronary arteries (MINOCAs) briefly, and then focus on the imaging tools that should be employed when caring for patients with suspected MINOCA. Diagnostic imaging has a critical role in assessing patients with suspected or confirmed MINOCA. The extent at which these diagnostic tests are used in any given patient will depend on the clinical acumen for the underlying condition, as well as the available resources. There are myriad conditions that can lead to MINOCA; further testing to exclude other underlying causes of myocardial injury is crucial. Cardiovascular imaging may assist in identifying the etiological cause in cases where MINOCA remains the most likely diagnosis. A systematic approach to the diagnostic assessment will help to uncover the underlying diagnosis, guide therapy, and provide the patient and their families with appropriate feedback.

International audience; Purpose: Our study investigated the impact of coronary artery calcification (CAC) and systemic inflammation on risks for major adverse cardiovascular events (MACE) following percutaneous coronary intervention (PCI).Background: CAC and systemic inflammation are known to be associated with an increased risk of cardiovascular events.Methods: A total of 17,711 consecutive patients who underwent PCI in our hospital between January 1, 2009 and December 31, 2015 were categorized according to the degree of CAC (moderate/severe vs. none/mild) and high-sensitivity C-reactive protein (hsCRP) level (≥2 vs.

Coronary revascularization is accomplished either by percutaneous coronary intervention (PCI), with low risk of immediate complications, or coronary artery bypass graft (CABG), with improved long-term, event-free survival attributable to use of the left internal mammary artery graft. Hybrid coronary revascularization (HCR) combines both. The left internal mammary artery graft is done by sternal-sparing approaches or by robotic-assisted, endoscopic surgery. HCR reduces bleeding, ventilator time, and length of stay compared with traditional CABG. Compared with PCI, HCR offers the durability and survival advantages of the left internal mammary artery. The large-scale National Heart, Lung, and Blood Institute-sponsored, randomized Hybrid Trial (Hybrid Coronary Revascularization Trial) was initiated to examine whether HCR is superior to multivessel PCI. However, enrollment was suboptimal, triggering premature study discontinuation. HCR integrates the positive features of both PCI and CABG, albeit requiring 2 procedures rather than 1. Adequately powered randomized trials are required to evaluate the outcomes and cost-effectiveness of HCR compared with CABG and multivessel PCI alone.

OBJECTIVES We aimed to evaluate the early and one-year outcomes of Impella-supported high-risk nonemergent percutaneous coronary intervention (PCI). BACKGROUND The evidence for the use of mechanical circulatory support (MCS) devices in high-risk nonemergent PCI is limited and nonconclusive. METHODS We performed a single-center retrospective study including all patients who underwent high-risk nonemergent PCI supported by Impella 2.5/CP at our institution between January 2009 and June 2018. This patient population was propensity score matched with subjects undergoing PCI with no MCS. The primary endpoint was major adverse cardiac events (MACE: all-cause death, myocardial infarction [MI], and target lesion revascularization) at one-year follow-up. RESULTS Two-hundred fifty patients undergoing Impella-supported nonemergent PCI were matched to 250 controls. The two groups were well balanced in terms of clinical and angiographic characteristics. Left main PCI was performed more frequently among Impella-supported patients (26% vs. 11%, p

Introduction: Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare coronary artery anomaly that carries 90% mortality in the first year of life when left untreated. The diagnosis of ALCAPA is rare in adulthood, and it includes a broad spectrum of clinical manifestations, including sudden cardiac death (SCD). Case report: We report a rare case of resuscitated sudden cardiac arrest in a 55-year-old female, who was diagnosed with ALCAPA and underwent successful surgical correction and implantable cardioverter defibrillator (ICD) implantation for secondary prevention. Discussion: ALCAPA diagnosis is not confined to childhood, and it represents a rare cause of life-threatening arrhythmias and SCD in the adult population. Surgical correction is recommended, regardless of age, presence of symptoms or inducible myocardial ischemia. Multimodality imaging is crucial for diagnosis, management planning and follow up. Assessment of the risk of recurrent ventricular arrhythmias, despite full revascularization, should be performed in all adults with ALCAPA. Myocardial scar detected via late gadolinium enhancement represents a potential irreversible substrate for ventricular arrhythmias, and it provides additional information to evaluate indication of an ICD for secondary prevention.

The adipokine resistin has been proposed to link obesity, insulin resistance and diabetes. We have previously reported that diabetic hearts express high levels of resistin while overexpression of resistin in adult rat hearts gives rise to a phenotype resembling diabetic cardiomyopathy. The transcriptional regulation of resistin in diabetic cardiac tissue is currently unknown. This study investigated the mechanism of resistin upregulation and the role of Serca2a in its transcriptional suppression. We demonstrate that restoration of Ca2+ homeostasis in diabetic hearts, through normalization of Serca2a function genetically and pharmacologically, suppressed resistin expression via inhibition of NFATc. H9c2 myocytes stimulated with high-glucose concentration or Ca2+ time-dependently increased NFATc and resistin expression while addition of the Ca2+ chelator BAPTA-AM attenuated this effect. NFATc expression was enhanced in hearts from ob/ob diabetic and from cardiac-specific Serca2a−/− mice. Similarly, NFATc increased resistin expression in myocytes cultured in low glucose while the NFATc inhibitor VIVIT blocked glucose-induced resistin expression, suggesting that hyperglycemia/diabetes induces resistin expression possibly through NFATc activation. Interestingly, overexpression of Serca2a or VIVIT mitigated glucose-stimulated resistin and NFATc expression and enhanced AMPK activity, a downstream target of resistin signaling. NFATc direct activation of resistin was verified by resistin promoter luciferase activity and chromatin-immunoprecipitation analysis. Interestingly, activation of Serca2a by a novel agonist, CDN1163, mirrored the effects of AAV9-Serca2a gene transfer on resistin expression and its promoter activity and AMPK signaling in diabetic mice. These findings parse a role for Ca2+ in resistin transactivation and provide support that manipulation of Serca2a-NFATc-Resistin axis might be useful in hyper-resistinemic conditions.

Background Patients undergoing percutaneous mechanical circulatory support (pMCS)-assisted percutaneous coronary intervention (PCI) represent a high-risk group vulnerable to complications and readmissions. Hypothesis Thirty-day readmissions after pMCS-assisted PCI are common among patients with comorbidities and account for a significant amount of healthcare spending. Methods Patients undergoing PCI and pMCS (Impella, TandemHeart, or intra-aortic balloon pump) for any indication between January 1, 2012, and November 30, 2014, were selected from the Nationwide Readmissions Database. Patients were identified using appropriate ICD-9-CM codes. Clinical risk factors and complications were analyzed for association with 30-day readmission. Results Our analysis included 29 247 patients, of which 4535 (15.5%) were readmitted within 30 days. On multivariate analysis, age ≥ 65 years, female sex, hypertension, diabetes, chronic lung disease, heart failure, prior implantable cardioverter-defibrillator, liver disease, end-stage renal disease, and length of stay ≥5 days during index hospitalization were independent predictors of 30-day readmission. Cardiac etiologies accounted for ~60% of readmissions, of which systolic or diastolic heart failure (22%), stable coronary artery disease (11.1%), acute coronary syndromes (8.9%), and nonspecific chest pain (4.0%) were the most common causes. In noncardiac causes, sepsis/septic shock (4.6%), hypotension/syncope (3.2%), gastrointestinal bleed (3.1%), and acute kidney injury (2.6%) were among the most common causes of 30-day readmissions. Mean length of stay and cost of readmissions was 4 days and $16 191, respectively. Conclusions Thirty-day readmissions after pMCS-assisted PCI are common and are predominantly associated with increased burden of comorbidities. Reducing readmissions for common cardiac etiologies could save substantial healthcare costs.

Residual atherothrombotic risk remains higher in patients with versus without diabetes mellitus (DM) despite statin therapy. The underlying mechanisms are unclear. This is a retrospective post-hoc analysis of the YELLOW II trial, comparing patients with and without DM (non-DM) who received rosuvastatin 40 mg for 8–12 weeks and underwent intracoronary multimodality imaging of an obstructive nonculprit lesion, before and after therapy. In addition, blood samples were drawn to assess cholesterol efflux capacity (CEC) and changes in gene expression in peripheral blood mononuclear cells (PBMC). There was a significant reduction in low density lipoprotein-cholesterol (LDL-C), an increase in CEC and beneficial changes in plaque morphology including increase in fibrous cap thickness and decrease in the prevalence of thin cap fibro-atheroma by optical coherence tomography in DM and non-DM patients. While differential gene expression analysis did not demonstrate differences in PBMC transcriptome between the two groups on the single-gene level, weighted gene coexpression network analysis revealed two modules of coexpressed genes associated with DM, Collagen Module and Platelet Module, related to collagen catabolism and platelet function respectively. Bayesian network analysis revealed key driver genes within these modules. These transcriptomic findings might provide potential mechanisms responsible for the higher cardiovascular risk in DM patients.

Studies have shown worse outcome for women compared with men after percutaneous coronary intervention (PCI), especially in the presence of diabetes mellitus (DM). We aimed to investigate the risk of ischemic events after PCI in women versus men stratified by the presence or absence of DM. A total of 17,154 consecutive patients from a single-center PCI registry enrolled from January 2009 to December 2014 were categorized accordingly: female/non-DM, female/DM, male/non-DM, and male/DM. End points included death and myocardial infarction (MI) at 1 year. Of the overall population, 15% (n = 2,631) were female/non-DM, 17% (n = 2,891) were female/DM, 38% (n = 6,483) were male/non-DM, and 30% (n = 5,149) were male/DM. Within the 4 study groups, female/DM had the highest risk, whereas female/non-DM and male/DM showed similar risks and male/non-DM showed lowest risk for death (4.64% vs 3.08% vs 2.93% vs 2.31%; p-trend0.0001 over all groups and p = 0.69 between female/non-DM and male/DM, respectively) and MI (4.15% vs 3.99% vs 3.71% vs 2.55%; p trend0.0001 over all groups and p = 0.97 between female/non-DM and male/DM, respectively). After multivariate adjustment findings were largely unchanged suggesting highest risk for adverse events in diabetic women compared with other groups and comparable risks for death and MI in nondiabetic women compared with diabetic men. In conclusion, these findings highlight the combined influence of DM and female gender as strong determinants of post-PCI risk while also illustrating "risk equivalence" between nondiabetic women versus diabetic men.

Background The relative outcomes of intravascular ultrasound (IVUS)–guided percutaneous coronary intervention (PCI) compared with angiography-guided PCI with drug-eluting stent (DES) in complex lesions have not been established. We sought to compare the efficacy and safety of IVUS-guided PCI with angiography-guided PCI in patients with complex coronary lesions treated with DES. Methods Electronic databases were searched to identify all randomized trials comparing IVUS-guided vs angiography-guided DES implantation. We evaluated major adverse cardiac events (MACE), all-cause and cardiovascular death, myocardial infarction, target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis outcomes at the longest reported follow-up. Random-effects modeling was used to calculate pooled relative risk (RR) and 95% CIs. Results Eight trials comprising 3,276 patients (1,635 IVUS-guided and 1,641 angiography-guided) enrolling only patients with complex lesions were included. Mean follow-up was 1.4±0.5years. Compared with angiography-guided PCI, patients undergoing IVUS-guided PCI had significantly lower MACE (RR 0.64, 95% CI 0.51-0.80, P =.0001), TLR (RR 0.62, 95% CI 0.45-0.86, P =.004), and TVR (RR 0.60, 95% CI 0.42-0.87, P =.007). There were no significant differences for stent thrombosis, cardiovascular death, or all-cause death. In meta-regression analysis, IVUS-guided PCI was of greatest benefit in reducing MACE in patients with acute coronary syndromes, diabetes, and long lesions. Conclusions The present meta-analysis demonstrates a significant reduction in MACE, TVR, and TLR with IVUS-guided DES implantation in complex coronary lesions.

El reemplazo de valvulas aorticas transcateter es una opcion de tratamiento excelente para pacientes con estenosis aortica severa sintomatica y riesgo alto o intermedio para cirugia. Con base en evidencia cientifica solida en reemplazo de valvulas aorticas transcateter, obtenida de estudios clinicos aleatorios y con ya cerca de ocho anos ˜ de experiencia comercial, ?por que importaria pensar en la durabilidad de estas valvulas y por que esta duda acaba de salir a la luz publica?

AIMS Patients with human immunodeficiency virus (HIV) infection have an increased risk of acute myocardial infarction (MI), and 6.5-15% of mortality in this population is attributable to cardiovascular disease. However, the angiographic pattern of coronary artery disease (CAD) in patients with HIV undergoing percutaneous coronary intervention (PCI) remains unknown. We sought to assess and describe the angiographic features and burden of CAD in patients with HIV as compared to those without HIV infection. METHODS AND RESULTS This is a retrospective, single-centre study comparing 93 patients with HIV infection who underwent PCI between 2003 and 2011 with 93 control patients without HIV infection matched for age (±3 years), gender, diabetes, and year of PCI (±2 years). Quantitative coronary angiography (QCA) was performed for all treated lesions at baseline and following PCI in both groups. One-year clinical outcomes post PCI were also analysed and compared. The mean age for both study populations was 57 years; patients with HIV were more likely to present with ST-segment elevation myocardial infarction (STEMI). Patients had a similar extent of CAD as measured by the presence of multivessel disease as well as SYNTAX score; however, patients with HIV were more likely to have lesions in the proximal segment of the respective coronary artery. While both groups mostly displayed none/mild calcified lesions, HIV+ patients had longer and fewer stenotic lesions. Clinical outcomes at one year were similar. CONCLUSIONS While HIV+ patients were more likely to present with STEMI, detailed coronary angiographic analysis revealed less complex lesions and favourable anatomy. This paradox may suggest alterations in genesis and progression of atherosclerosis in this clinical setting.

Background: Despite extensive evidence demonstrating the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects remain elusive.Objectives: This study as...

Diabetes mellitus (DM) and chronic kidney disease (CKD) separately are known to facilitate the progression of medial arterial calcification (MAC) in patients with symptomatic peripheral artery disease (PAD), but their combined effect on MAC and associated mediators of calcification is not well studied. The association of MAC and calcification inducer bone morphogenetic protein (BMP-2) and inhibitor fetuin-A, with PAD, is well known. Our aim was to investigate the association of MAC with alterations in BMP-2 and fetuin-A protein expression in patients with PAD with DM and/or CKD. Peripheral artery plaques (50) collected during directional atherectomy from symptomatic patients with PAD were evaluated, grouped into no-DM/no-CKD ( n = 14), DM alone ( n = 10), CKD alone ( n = 12), and DM+CKD ( n = 14). MAC density was evaluated using hematoxylin and eosin, and alizarin red stain. Analysis of inflammation, neovascularization, BMP-2 and fetuin-A protein density was performed by immunohistochemistry. MAC density, inflammation grade and neovessel content were significantly higher in DM+CKD versus no-DM/no-CKD and CKD ( p < 0.01). BMP-2 protein density was significantly higher in DM+CKD versus all other groups ( p < 0.01), whereas fetuin-A protein density was significantly lower in DM+CKD versus all other groups ( p < 0.001). The combined presence of DM+CKD may be associated with MAC severity in PAD plaques more so than DM or CKD alone, as illustrated in this study, where levels of calcification mediators BMP-2 and fetuin-A protein were related most robustly to DM+CKD. Further understanding of mechanisms involved in mediating calcification and their association with DM and CKD may be useful in improving management and developing therapeutic interventions.

The SGLT2 inhibitor empagliflozin reduced cardiovascular mortality by 38% and heart failure (HF) hospitalizations by 35% in diabetic patients. We have recently demonstrated the efficacy of empagliflozin in ameliorating HF and improving cardiac function in a non-diabetic porcine model of HF mediated via a switch in myocardial metabolism that enhances cardiac energetics. Therefore, we hypothesized that the cardiac benefits of empagliflozin can also be extended to non-diabetic HF patients. The EMPA-TROPISM clinical trial is a randomized, double-blind, parallel group, placebo-controlled, trial comparing the efficacy of and safety of empagliflozin in non-diabetic HF patients. Eighty patients with stable HF for over 3 months, LVEF

BACKGROUND In patients treated with bare metal stents and first-generation drug-eluting stents (DES) smaller stent diameter (SD) has been associated with worse long term outcomes after percutaneous coronary intervention (PCI). Data on the impact of small SD on outcomes after PCI with second-generation DES is scarce. METHODS Consecutive patients treated with second-generation DES between 2010 and 2016 were included in a single tertiary center. Patients were grouped according to SD: ≤2.50 mm, 2.75 ≤ 3.00 mm, 3.25 ≤ 3.50 mm, and >3.50 mm. One-year event rates were estimated using the Kaplan-Meier method and adjusted hazard ratios were generated using Cox regression analysis. The primary endpoint was major adverse cardiac events (MACE; death, myocardial infarction [MI], or target vessel revascularization [TVR]). RESULTS Of the 17,607 patients who underwent PCI with second-generation DES, 32.6% (n = 5,741) had SD ≤2.5 mm, 39.1% (n = 6,890) had SD 2.75 ≤ 3.0 mm, 22.2% (n = 3,910) had SD 3.25 ≤ 3.5 mm, and 6.1% (n = 1,066) had SD >3.5 mm. At 1 year, MACE rates were 10.5%, 9.5%, 8.0%, and 8.0%, respectively, with increasing SD (p = .006). TVR rates decreased with increasing SD (7.2%, 5.8%, 4.7%, and 3.3%, respectively [p

Intensive low-density lipoprotein cholesterol (LDL-C) reduction with statins is recommended after elective percutaneous coronary intervention (PCI). We aimed to evaluate adherence to guideline-recommended statin therapy (GRST) and the rate of residual cholesterol risk (RCR) at follow-up after elective PCI. All patients who underwent elective PCI between January 2010 and May 2016 were prospectively included in this single-center study. GRST was defined as high-intensity statin (HIS) therapy for patients ≤75 years old and moderate-intensity statin (MIS) or HIS therapy for patients75 years. RCR at follow-up was defined as50% decrease in LDL-C with HIS or30% with MIS for statin-naïve patients and as LDL-C70 mg/dL for nonstatin-naïve patients. A total of 2,653 patients were included, with 1,304 (49.2%) discharged with GRST. There was a significant increase in the number of patients discharged with GRST over time from 44.2% in 2010 to 63.0% in 2016 (p0.001). Conversely, RCR at follow-up was present in 1,120 patients (42.2%) overall and remained stable over time. Risk factors of RCR at follow-up were female gender (odds ratio [OR]: 1.38; 95% confidence interval [CI] 1.13 to 1.70), previous myocardial infarction (OR: 1.37; 95% CI 1.12 to 1.64), smoking (OR: 1.30; 95% CI 1.01 to 1.67), higher LDL-C level at baseline (OR: 1.22; 95% CI 1.18 to 1.25). The presence of RCR was associated with an increased adjusted risk of death within 1 year of the second LDL-C measurement (adjHR: 2.78; 95% CI 1.15 to 6.67). In conclusion, although the rate of GRST at discharge has improved significantly over time in patients who underwent elective PCI, the prevalence of RCR at follow-up has not changed appreciably suggesting that further implementation of guidelines as well as novel or more intensive pharmacotherapy may be warranted.

ResumenLa isquemia miocárdica puede ser irreversible o reversible dependiendo de diferentes factores moleculares y fisiológicos. En la isquemia miocárdica irreversible se presentan tres tipos de muerte celular a nivel miocárdico: la necrosis, la apoptosis y la autofagia; mientras en la isquemia reversible la restauración de la función de los miocitos está determinada por factores como el restablecimiento temprano del flujo sanguíneo coronario y fenómenos de pre y posacondicionamiento isquémico. Conceptos como el miocardio aturdido (disfunción mecánica temporal luego de una lesión isquémica pero con flujo sanguíneo normal en ausencia de cualquier lesión irreversible) y el miocardio hibernante (región miocárdica viable, sin contractilidad) son formas quiescentes de la función cardiaca y explican un poco la capacidad del miocardio de restablecer su funcionamiento normal luego de un episodio de isquemia.AbstractMyocardial ischemia can be irreversible or reversible depending on multiple molecular and physiological factors. In irreversible myocardial ischemia there are three types of cell death on a myocardial level: necrosis, apoptosis and autophagy; whereas in reversible ischemia the restoration of the myocytes is determined by factors such as early recovery of coronary blood flow and pre- and postischemic conditioning phenomena. Concepts such as stunned myocardium (temporary mechanical dysfunction following an ischemic episode but with normal blood flow and without irreversible damage) and hibernating myocardium (viable myocardial region without contractility) are quiescent forms of the cardiac function and explain the ability of the myocardium to resume its normal functioning after an ischemic episode.

ResumenLa isquemia miocárdica es el conjunto de una serie de fenómenos fisiológicos que se manifiesta por condiciones clínicas como isquemia silente, angina estable y síndromes coronarios agudos. Diversos mecanismos de la regulación del flujo sanguíneo, la demanda miocárdica, la liberación de adenosina y la función del endotelio en las arterias coronarias son claves para mantener la irrigación miocárdica y han sido la base fisiológica para el desarrollo de pruebas de detección de isquemia como lo es el flujo de reserva fraccional, que hoy día hace parte de las recomendaciones de las guías.AbstractMyocardial ischaemia as a whole is a series of physiological phenomena manifested by clinical conditions such as silent ischaemia, stable angina and acute coronary syndromes. Various blood flow regulation mechanisms, myocardial demand, adenosine release and endothelial function in the coronary arteries are vital for maintaining myocardial irrigation, and have been the physiological basis for tests like fractional flow reserve, developed to detect ischaemia, that today forms part of the guideline recommendations.

Neointimal cellular proliferation of fibroblasts and myofibroblasts is documented in coronary artery restenosis, however, their role in peripheral arterial disease (PAD) restenosis remains unclear. Our aim was to investigate the role of fibroblasts, myofibroblasts, and collagens in restenotic PAD.Nineteen PAD restenotic plaques were compared with 13 de novo plaques. Stellate cells (HE), fibroblasts (FSP-1), myofibroblasts (α-actin/vimentin/FSP-1), cellular proliferation (Ki-67), and apoptosis (caspase-3 with poly ADP-ribose polymerase) were evaluated by immunofluorescence. Collagens were evaluated by picro-sirius red stain with polarization microscopy. Smooth muscle myosin heavy chain (SMMHC), IL-6 and TGF-β cytokines were analyzed by immunohistochemistry.Restenotic plaques demonstrated increased stellate cells (2.7 ± 0.15 vs.1.3 ± 0.15) fibroblasts (2282.2 ± 85.9 vs. 906.4 ± 134.5) and myofibroblasts (18.5 ± 1.2 vs.10.6 ± 1.0) p = 0.0001 for all comparisons. In addition, fibroblast proliferation (18.4% ± 1.2 vs.10.4% ± 1.1; p = 0.04) and apoptosis (14.6% ± 1.3 vs.11.2% ± 0.6; p = 0.03) were increased in restenotic plaques. Finally, SMMHC (2.6 ± 0.12 vs.1.4 ± 0.15; p = 0.0001), type III collagen density (0.33 ± 0.06 vs. 0.17 ± 0.07; p = 0.0001), IL-6 (2.08 ± 1.7 vs.1.03 ± 2.0; p = 0.01), and TGF-β (1.80 ± 0.27 vs. 1.11 ± 0.18; p = 0.05) were increased in restenotic plaques.Our study suggests proliferation and apoptosis of fibroblast and myofibroblast with associated increase in type III collagen may play a role in restenotic plaque progression. Understanding pathways involved in proliferation and apoptosis in neointimal cells, may contribute to future therapeutic interventions for the prevention of restenosis in PAD.

In the drug eluting stent (DES) era, repeat in-stent restenosis (ISR) of the same coronary lesion, despite percutaneous coronary intervention (PCI), is a rare but challenging problem that has not been reported. We aim to describe what we propose as the occurrence of "resistant"-ISR (R-ISR) in the DES era, including angiographic patterns and outcomes. We defined R-ISR as the recurrence of an ISR episode after successful treatment of the same lesion. We identified 276 consecutive patients with 291 lesions who had R-ISR between May 2003 and June 2012. Quantitative coronary angiography (QCA) was performed for the first and second ISR episodes. Outcomes at one year, including death, myocardial infarction (MI), and target lesion failure (TLF), were analyzed. Patients with R-ISR had a high frequency of diabetes (62%), chronic kidney disease (39%), bifurcation lesions (51%), and moderate to severe calcified lesions (52%). The most common pattern of R-ISR was focal (77%). R-ISR lesions were treated with DES implantation (55%) or balloon-only strategy (45%). The mortality rate and TLF at 2-years were 9.3% and 51% respectively. The overall 2-year TLF rate did not vary with the originally implanted stent, angiographic pattern (focal versus diffuse), or revascularization strategy. R-ISR appears to consist predominantly of focal lesions and occurs in patients at high clinical and angiographic risk, conceivably owing to their unique diabetic and coronary calcification profile. Clinical outcomes are suboptimal irrespective of angiographic pattern or treatment strategy, indicating the recalcitrant nature of the disease, and need for aggressive treatment of cardiovascular risk factors and novel interventional approaches. In the drug eluting stent (DES) era, repeat in-stent restenosis (ISR) of the same lesion, despite percutaneous coronary intervention, is a rare and challenging problem. We described the "resistant"-ISR (R-ISR) phenomena in the DES era, i.e. the recurrence of an ISR after a successful treatment of that same episode. We identified 276 consecutive patients with R-ISR, who presented with a high clinical and angiographic risk, conceivably owing to their unique diabetic and coronary calcification profile. The most common pattern of R-ISR was focal. The overall 2-year TLF rate exceeded 50% and did not vary significantly with the original stent implanted, angiographic pattern, or type of percutaneous revascularization. © 2016 Wiley Periodicals, Inc.

Objectives The aim of this study was to identify the predictors of side branch (SB) ostial stenosis developed after provisional stenting of the main vessel (MV) using optical coherence tomography (OCT). Background Provisional stenting remains the main approach to treatment of bifurcation lesions; however, it may result in the narrowing of SB ostium. There is little information about underlying plaque morphology of the MV lesion and its potential impact on the SB after provisional stenting. Methods Patients with stable coronary disease with angiographic MV lesion not involving SB were included in a prospective single center study. The primary outcome was significant SB ostium stenosis (SBOS), defined as residual stenosis of >50% after MV stenting. Results Thirty bifurcation lesions in 30 patients were analyzed in the study. Poststenting significant SBOS was observed in 30% of patients. The MV lesions with SBOS > 50% were characterized by a higher prevalence of lipid rich plaques (100 vs. 64%, p = 0.040) and spotty calcifications (60 vs. 0%, p = 0.005). Maximal lipid arcs were greater (257° vs. 132°, p = 0.001) and lipid volume index was higher (1380 vs. 574, p = 0.012) in the SBOS >50% group. Multivariate logistic regression analysis identified maximal lipid arc (odds ratio (OR): 1.014, p = 0.038) and the presence of lipid plaque contralateral to SB ostium (OR: 8.14, p = 0.046) before stenting as independent predictors of significant SBOS after PCI. Conclusions High lipid content of the MV lesion and a contralateral location of lipid in the bifurcation area may contribute to SBOS after provisional stenting. © 2016 Wiley Periodicals, Inc.

This review discusses the possibilities offered by new modalities of non-invasive and invasive coronary imaging in an effort to optimize risk stratification for coronary artery disease, and identify subgroups at high risk that may benefit from an aggressive, personalized approach, with access to a growing number of novel drugs and interventions. Special emphasis is placed on the progress of novel invasive imaging techniques such as near infrared spectroscopy and optical coherence tomography that can reliably identify thin-capped fibroatheromas. Multiple trials are exploring the feasibility of these techniques to guide modulation of risk factor control and treatment of non-flow limiting lesions at high risk of destabilization and progression in patients undergoing clinically mandated angioplasty of angiographically critical lesions. Asymptomatic patients at high risk of cardiovascular ischaemic events may also benefit, with the intermediate step of a wider application of calcium score and angiography with multi-slice computed tomography, by a selective use of invasive imaging.

Objective We compared 1-year outcomes in insulin-treated diabetes mellitus (ITDM) and non-ITDM patients compared to nondiabetic (DM) patients following contemporary percutaneous coronary intervention (PCI). Background ITDM is associated with extensive atherosclerotic disease and worse cardiovascular prognosis compared to non-ITDM patients. Methods We evaluated PCI patients at a large tertiary center from 2010 to 2016, grouped according to diabetes and treatment status at baseline. One-year major adverse cardiac events (MACE) were defined as a composite of death, myocardial infarction (MI), or target vessel revascularization. Outcomes were adjusted using multivariable Cox regression methods. Results During the study period, 16,889 patients underwent PCI including 13.7% ITDM, 34.0% non-ITDM, and 52.3% non-DM patients. Patients with DM were younger, including more females and non-white patients, with higher body mass index and greater prevalence of prior revascularization and chronic kidney disease. Compared to others, ITDM patients more often presented with acute coronary syndrome, in-stent restenosis, or severe lesion calcification. There were no differences in discharge rates of dual antiplatelet therapy and statins, whereas beta-blockers were more commonly prescribed in DM patients. At 1-year, both ITDM and non-ITDM patients had greater risk of MACE compared with non-DM patients, and ITDM conferred greater adjusted risk than non-ITDM (ITDM = HR: 2.11, 95% CI [1.79,2.50]; non-ITDM = HR: 1.27, 95%CI [1.09,1.47]). Conclusions The negative prognostic effect of DM following contemporary PCI is heightened in the presence of insulin treatment, compared to non-DM patients. Focus on secondary prevention, prescription of and adherence to optimal medical therapy is necessary for post-PCI risk reduction.

OBJECTIVES The aim of the study was to identify the predictors of side branch (SB) compromise in severely calcified bifurcation lesions treated with orbital atherectomy (OA). BACKGROUND SB compromise remains a major complication of bifurcation lesion percutaneous coronary intervention (PCI). Higher prevalence of lipid-rich plaques and spotty calcification by optical coherence tomography (OCT) and SB ostial stenosis by angiography have been previously suggested as predictors of SB occlusion after main vessel (MV) stenting. METHODS Patients with chronic stable angina and severely calcified bifurcation lesions, in whom provisional stenting strategy was planned, were enrolled in the study. OA was used for lesion preparation in all cases. OCT imaging of the MV was performed before and after stenting. SB compromise was defined as a composite of SB occlusion (TIMI flow grade ≤ 2) and SB intervention after MV stenting. RESULTS Thirty stable CAD patients with 30 severely calcified bifurcation lesions were included in the study. Twelve patients (40%) had a compromised SB after MV stenting. Compromised SB was characterized by a greater angiographic diameter stenosis (55.4 ± 8.1% vs. 35.0 ± 14.4%, P

Plaque rupture, defined as direct exposure of the necrotic core to flowing blood, is a major cause of arterial thrombosis, acute myocardial infarction, and sudden coronary death. A highly thrombogenic necrotic core is separated from the lumen by a thin fibrous cap that is the last barrier between