Traditional Cardiovascular Risk Factors and Coronary Microvascular Dysfunction in Women and Men: A Single-Center Study.

INTRODUCTION: Coronary microvascular dysfunction (CMD) is common in patients with and without obstructive epicardial coronary artery disease (CAD). Risk factors for the development of CMD have not been fully elucidated, and data regarding sex-associated differences in traditional cardiovascular risk factors for obstructive CAD in patients with CMD are lacking. METHODS: In this single-center, prospective registry, we enrolled patients with nonobstructive CAD undergoing clinically indicated invasive assessment of coronary microvascular function between November 2019 and March 2023. Associations between coronary microvascular dysfunction, traditional cardiovascular risk factors, and sex were assessed using univariate and multivariate regression models. RESULTS: Overall, 245 patients with nonobstructive CAD were included in the analysis (62.9% female; median age 68 (interquartile range: 59, 75). Microvascular dysfunction was diagnosed in 141 patients (57.5%). The prevalence of microvascular dysfunction was similar in women and men (59.0% vs. 57.0%; p = 0.77). No association was found between traditional risk factors for coronary atherosclerosis and CMD regardless of whether CMD was structural or functional. In women, but not in men, older age and the presence of previous ischemic heart disease were associated with lower coronary flow reserve (ß = -0.29; p < 0.01 and ß = -0.15; p = 0.05, respectively) and lower resistive reserve ratio (ß = -0.28; p < 0.01 and ß = -0.17; p = 0.04, respectively). CONCLUSION: For the entire population, no association was found between coronary microvascular dysfunction and traditional risk factors for coronary atherosclerosis. In women only, older age and previous ischemic heart disease were associated with coronary microvascular dysfunction. Larger studies are needed to elucidate risk factors for CMD.

Outcomes of Patients Undergoing PCI of Ostial Coronary Lesions: A Single-Center Study.

INTRODUCTION: Ostial coronary lesions are a subset of proximal coronary lesions, which are relatively more difficult to treat and were associated with worse clinical outcomes in the early percutaneous coronary intervention (PCI) era. Data regarding the outcomes of ostial lesions' PCI in the contemporary era are lacking. METHODS: We conducted a single-center, all-comer, prospective registry study, enrolling patients undergoing PCI with the use of contemporary drug-eluting stents (DES) between July 2016 and February 2018. Included in the present analysis were only patients treated for proximal lesions. Clinical outcomes were compared between patients undergoing PCI of ostial versus proximal nonostial lesions. The primary endpoint was target vessel revascularization (TVR). Secondary endpoints included target lesion revascularization (TLR) and major cardiovascular adverse events (MACE) at 12 months. RESULTS: A total of 334 (84.7% male, 67.3 ± 10.7 years) patients were included, of which 91 patients were treated for ostial lesions and 243 were treated for proximal nonostial lesions. Baseline and procedural characteristics were similar between the two groups. At 12 months, TVR and TLR were numerically higher among patients undergoing PCI of ostial versus nonostial lesions without reaching statistical significance (5.5% vs. 3.3%; p = 0.35 and 4.4% vs. 2.5%; p = 0.47, respectively). The rate of MACE was similar between the two groups. CONCLUSION: In patients undergoing PCI with the use of contemporary DES, clinical outcomes were similar among patients treated for ostial compared to proximal nonostial lesions. Larger studies are required to further evaluate the performance of contemporary DES in this subset of lesions.

Arrhythmic storm from ischemic ventricular fibrillation treated with intravenous quinidine.

We present a case who developed an acute right ventricular infarction. The leads demonstrating ST-segment elevation were different than those expected based on previous publications. We explain why this happened with the aid of 3-dimentional imaging. Our case then developed an arrhythmic storm caused by ischemic ventricular fibrillation (VF). Emergency revascularization failed and the VF-storm failed to respond to sedation, lidocaine and amiodarone but responded to intravenous quinidine.

Catheter Induced Mechanical Suppression of Outflow-tract Arrhythmias: Incidence, Characteristics, and Significance.

BACKGROUND: The incidence, characteristics, and clinical significance of catheter-induced mechanical suppression (trauma) of ventricular arrhythmias originating in the outflow tract (OT) area have not been thoroughly evaluated. OBJECTIVES: To determine these variables among our patient cohort. METHODS: All consecutive patients with right ventricular OT (RVOT) and left ventricular OT (LVOT) arrhythmias ablated at two medical centers from 1998 to 2014 were included. Patients were observed for catheter-induced trauma during ablation procedures. Procedural characteristics, as well as response to catheter-induced trauma and long term follow-up, were recorded. RESULTS: During 288 ablations of OT arrhythmias in 273 patients (RVOT n=238, LVOT n=50), we identified 8 RVOT cases (3.3%) and 1 LVOT (2%) case with catheter-induced trauma. Four cases of trauma were managed by immediate radiofrequency ablation (RFA), three were ablated after arrhythmia recurrence within a few minutes, and two were ablated after > 30 minutes without arrhythmia recurrence. Patients with catheter-induced trauma had higher rates of repeat ablations compared to patients without: 3/9 (33%) vs. 12/264 (0.45%), P = 0.009. The three patients with arrhythmia recurrence were managed differently during the first ablation procedure (immediate RFA, RFA following early recurrence, and delayed RFA). During the repeat procedure of these three patients, no catheter trauma occurred in two, and in one no arrhythmia was observed. CONCLUSIONS: Significant catheter-induced trauma occurred in 3.1% of OT arrhythmias ablations, both at the RVOT and LVOT. Arrhythmia suppression may last > 30 minutes and may interfere with procedural success. The optimal mode of management following trauma is undetermined.

Prognostic significance of aortic valve gradient in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

OBJECTIVE: To evaluate the effect of baseline aortic valve gradient (AVG) both as a continuous and a categorical variable on mortality in patients undergoing transcatheter aortic valve replacement (TAVR), focusing on the high-gradient severe aortic stenosis (AS) patients. BACKGROUND: Identifying new predictors of mortality in the TAVR population can help refine risk stratification and improve the patient selection process for this procedure. So far, AVG has mainly been studied as a categorical variable and there is a paucity of data on its prognostic value as a continuous variable, especially in patients with high AVG AS, who constitute the majority of patients referred for TAVR. METHODS: We analyzed data on 1,224 consecutive symptomatic severe AS patients, who underwent TAVR at 3 centers. The relation between pre-TAVR AVG and mortality was evaluated among all patients and in patients with high AVGs (mean AVG ≥40 mm Hg) using the Cox proportional hazard model adjusting for multiple variables. RESULTS: During a mean follow-up of 1.8 years, baseline AVG was inversely associated with mortality in the entire cohort and in patients with high AVG AS. By multivariable analysis, patients with mean AVG 40-60 mm Hg and >60 mm Hg had a respective 38% (P = 0.010) and 61% (P < 0.001) reduction in mortality compared to patients with mean AVG <40 mm Hg. Every 10 mm Hg increase in mean AVG was associated with 20% reduction in mortality (P < 0.001). Analyses among patients with high (mean AVG >40 mm Hg) and very high AVG AS (mean AVG >60 mm Hg) yielded similar results (HR = 0.88, P = 0.031, and HR = 0.80, P = 0.019, per 10 mm Hg increase in AVG, respectively). Using peak AVGs and an analysis restricted to patients without reduced ejection fraction yielded consistent results. CONCLUSIONS: Baseline AVGs show an inverse association with mortality post-TAVR. These results were consistent also in patients with high-gradient AS, suggesting that AVG can be used to identify patients most likely to benefit from TAVR.

Increased CD11b+ cells and Interleukin-1 (IL-1) alpha levels during cardiomyopathy induced by chronic adrenergic activation.

BACKGROUND: Systemic CD11b+ cells have been associated with several cardiac diseases, such as chronic heart failure. OBJECTIVES: To assess the levels of circulating CD11b+ cells and pro-inflammatory cytokines in cardiomyopathy induced by chronic adrenergic stimulation. METHODS: Male Lewis rats were injected with low doses of isoproterenol (isoprel) for 3 months. Cardiac parameters were tested by echocardiography. The percentage of CD11b+ cells was tested by flow cytometry. The levels of inflammatory cytokines in the sera were determined by an inflammation array, and the expression levels of cardiac interleukin-1 (IL-1) receptors were analyzed by real-time polymerase chain reactions. Cardiac fibrosis and inflammation were determined by histological analysis. RESULTS: Chronic isoprel administration resulted in increased heart rate, cardiac hypertrophy, elevated cardiac peri-vascular fibrosis, reduced fractional shortening, and increased heart weight per body weight ratio compared to control animals. This clinical presentation was associated with accumulation of CD11b+ cells in the spleen with no concomitant cardiac inflammation. Cardiac dysfunction was also associated with elevated sera levels of IL-1 alpha and over expression of cardiac IL-1 receptor type 2. CONCLUSIONS: CD11b+ systemic levels and IL-1 signaling are associated with cardiomyopathy induced by chronic adrenergic stimulation. Further studies are needed to define the role of systemic immunomodulation in this cardiomyopathy.

Differential Effects of Colchicine on Cardiac Cell Viability in an in vitro Model Simulating Myocardial Infarction.

OBJECTIVES: We aimed to examine the effects of colchicine, currently in clinical trials for acute myocardial infarction (AMI), on the viability of cardiac cells using a cell line model of AMI. METHODS: HL-1, a murine cardiomyocyte cell line, and H9C2, a rat cardiomyoblast cell line, were incubated with TNFα or sera derived from rats that underwent AMI or sham operation followed by addition of colchicine. In another experiment, HL-1/H9C2 cells were exposed to anoxia with or without subsequent addition of colchicine. Cell morphology and viability were assessed by light microscopy, flow cytometry and Western blot analyses for apoptotic markers. RESULTS: Cellular viability was similar in both sera; however, exposing both cell lines to anoxia reduced their viability. Adding colchicine to anoxic H9C2, but not to anoxic HL-1, further increased their mortality, at least in part via enhanced apoptosis. Under any condition, colchicine induced detachment of H9C2 cells from their culture plates. This phenomenon did not apply to HL-1 cells. CONCLUSIONS: Colchicine enhanced cardiomyoblast mortality under in vitro conditions mimicking AMI and reduced their adherence capability. HL-1 was not affected by colchicine; nevertheless, no salvage effect was observed. We thus conclude that colchicine may not inhibit myocardial apoptosis following AMI.

Down-Regulation of Cardiac Erythropoietin Receptor and its Downstream Activated Signal Transducer Phospho-STAT-5 in a Rat Model of Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is often accompanied by impairment of cardiac function that may lead to major cardiac events. Erythropoietin (EPO), a kidney-produced protein, was shown to be beneficial to heart function. It was suggested that reduced EPO secretion in CKD may play a role in the initiation of heart damage. OBJECTIVES: To investigate molecular changes in the EPO/ erythropoietin receptor (EPO-R) axis in rat cardiomyocytes using a rat model for CKD. METHODS: We established a rat model for CKD by kidney resection. Cardiac tissue sections were stained with Masson's trichrome to assess interstitial fibrosis indicating cardiac damage. To evaluate changes in the EPO/EPO-R signaling cascade in the myocardium we measured cardiac EPO and EPO-R as well as the phosphorylation levels of STAT-5, a downstream element in this cascade. RESULTS: At 11 weeks after resection, animals presented severe renal failure reflected by reduced creatinine clearance, elevated blood urea nitrogen and presence of anemia. Histological analysis revealed enhanced fibrosis in cardiac sections of CKD animals compared to the sham controls. Parallel to these changes, we found that although cardiac EPO levels were similar in both groups, the expression of EPO-R and the activated form of its downstream protein STAT-5 were significantly lower in CKD animals. CONCLUSIONS: CKD results in molecular changes in the EPO/EPO-R axis. These changes may play a role in early cardiac damage observed in the cardiorenal syndrome.

Cardiac Hypertrophy and Cardiac Cell Death in Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is a prevalent clinical condition affecting 15% of the general population. Cardiorenal syndrome (CRS) type 4 is characterized by an underlying CKD condition leading to impairment of cardiac function and increased risk for major cardiovascular events. To date, the mechanisms leading from CKD to CRS are not completely understood. In particular, it is unclear whether the pathological changes that occur in the heart in the setting of CKD involve enhanced cell death of cardiac cells. OBJECTIVES: To assess whether CKD may mediate loss of cardiac cells by apoptosis. METHODS: We established rat models for CKD, acute myocardial infarction (acute MI), left ventricular dysfunction (LVD), and sham. We measured the cardiac-to-body weight as well as kidney-to-body weight ratios to validate that renal and cardiac hypertrophy occur as part of disease progression to CRS. Cardiac cells were then isolated and the percent of cell death was determined by flow cytometry following staining with annexin-FITC and propidium iodide. In addition, the levels of caspase-3-dependent apoptosis were determined by Western blot analysis using an anti-cleaved caspase-3 antibody. RESULTS: CKD, as well as acute MI and LVD, resulted in significant cardiac hypertrophy. Nevertheless, unlike the increased levels of cell death observed in the acute MI group, in the CKD group, cardiac hypertrophy was not associated with induction of cell death of cardiac cells. Caspase-3 activity was even slightly reduced compared to sham-operated controls. CONCLUSIONS: Our data show that while CKD induces pathological changes in the heart, it does not induce cardiac cell death.

Smoking and Respiratory Diseases in Patients with Coronary Microvascular Dysfunction.

BACKGROUND: Coronary microvascular disease (CMD) is common in patients with and without obstructive coronary artery disease, and is associated with adverse clinical outcomes. Respiratory-related variables are associated with pulmonary and systemic microvascular dysfunction, while evidence about their relationship with CMD is limited. We aim to evaluate respiratory-related variables as risk factors of CMD. METHODS: This is an observational, single-center study enrolling consecutive patients undergoing invasive evaluation of coronary microvascular function in the catheterization laboratory. Patients with evidence of obstructive coronary artery disease or with missing data were excluded. Associations between respiratory-related variables and indices of CMD were assessed using univariate and multivariate regression models. RESULTS: Overall, 266 patients (mean age 67 ± 11 years, 59% females) were included in the current analysis. Of those, 155 (58%) had evidence of CMD. Among the respiratory variables, independent predictors of CMD were current smoking (adjusted odds ratio [AOR] 2.5; 95% confidence interval [CI], 1.2-5; P = .01) and obstructive sleep apnea (AOR 5.7; 95% CI, 1.2-26; P = .03), while chronic obstructive pulmonary disease was not. Among ever-smokers, higher smoking pack-years was an independent risk factor for CMD (median 35 vs 25 pack-years, AOR 1.09; 95% CI, 1.04-1.13; P < .01), and was associated with higher rates of pathologic index of microcirculatory resistance and resistive reserve ratio. CONCLUSION: In patients undergoing invasive coronary microvascular evaluation, current smoking and obstructive sleep apnea are independently associated with CMD. Among smokers, higher pack-years is a strong predictor for CMD. Our findings should raise awareness for prevention and possible treatment options.

Coronary microvascular dysfunction in patients with Takotsubo syndrome.

BACKGROUND: The pathophysiology of Takotsubo syndrome (TTS) remains incompletely understood. While coronary microvascular dysfunction (CMD) is a potential pathophysiologic mechanism, evidence is limited. OBJECTIVES: We sought to evaluate CMD in patients with TTS. METHODS: Consecutive patients diagnosed with TTS were included and underwent coronary angiography with invasive microvascular function evaluation, including fractional flow reserve, Coronary Flow Reserve (CFR), Index of Microcirculatory Resistance (IMR), and Resistive Reserve Ratio (RRR). Patients had an echocardiography evaluation during their index admission and at approximately 6 weeks. RESULTS: Thirty patients were included (mean age 74 ±9, 90 % female). Twenty-five patients (83 %) had at least one abnormal coronary microvascular function parameter. Abnormal parameters included CFR<2.5 in 20 patients (67 %), IMR>25 in 18 patients (60 %), and RRR<3.5 in 25 (83 %). Longer time from symptoms to angiography correlated with a higher CFR (r = 0.51, P<0.01), and had an area under the receiver operating characteristic curve of 0.793 (95 % CI 0.60-0.98) for pathologic CFR. Patients with emotional trigger had a lower rate of pathologic IMR compared with non-emotional trigger (36 % vs 81 %, p = 0.01). Follow up echocardiography performed at a median of 1.5 months (IQR 1.15-6) showed an improvement in left ventricular ejection fraction for all patients (from mean of 40 % to 57 %). CONCLUSION: CMD was present in most patients with TTS. The role of microvascular function in TTS may vary according to the clinical presentation and RRR may be more sensitive for the diagnosis of CMD in TTS.

Conduction disorders following transcatheter aortic valve replacement using acurate Neo2 transcatheter heart valve: A propensity matched analysis.

BACKGROUND: The ACURATE neo2 transcatheter aortic valve was developed to improve paravalvular leak (PVL) rates while maintaining low rates of conduction disturbances and permanent pacemaker implantation (PPMI) seen with its predecessor. We aimed to compare conduction disturbances rates of transcatheter aortic valve replacement (TAVR) using ACURATE Neo2 with other commonly used valves. METHODS: A retrospective analysis of the Israeli TAVR registry between the years 2014-2023 was performed to compare conduction disturbances and PVL rates, and procedural outcomes, among patients treated with ACURATE neo2, Edwards Sapien 3 (S3), and Evolut PRO valves. Propensity score matching was performed to compare groups with similar characteristics. RESULTS: Following exclusion of patients with non-femoral access, unknown valve type, older-generation valves, and less commonly used valves or (n = 4387), our analysis included 3208 patients undergoing TAVR using ACURATE neo2, Edwards S3, and Evolut PRO valves. Propensity matched groups comprised 169 patients each. Rates of any conduction disturbances [left bundle branch block (LBBB), atrioventricular block, or PPMI] were lower in the ACURATE neo2 group compared to both other valves [15.8 %, S3-37.5 % (p < 0.001), Evolut PRO-27.5 % (p = 0.02)] as were LBBB rates [9.0 %, S3-31.3 % (p < 0.001); Evolut PRO-20.1 % (p = 0.01). Atrioventricular block and PPMI rates were lower without statistical significance, as were rates of above-moderate PVL. CONCLUSIONS: In this analysis, TAVR using ACURATE neo2 was associated with a lower composite rate of conduction disturbances in comparison to the Evolut PRO and Edwards S3 valves, mainly due to lower left bundle branch block rates, with non-significantly lower rates of PPMI and PVL.

Effect of vitamin D analogues on acute cardiorenal syndrome: a laboratory rat model.

BACKGROUND: Vitamin D has been shown to induce beneficial effects on cardiovascular and renal morbidity by regulating inflammation and tissue fibrosis. OBJECTIVES: To evaluate the effect of vitamin D analogues on cardiac function and fibrosis in an animal model of cardiorenal syndrome. METHODS: Unilateral nephrectomy was performed and myocardial infarction induced in rats. The rats were treated with vitamin D receptor activator (VDRA, paricalcitol, 40 ng/250 g x 3/week) versus a vehicle. A third group of animals, which served as the control, underwent sham surgery and received no treatment. After 4 weeks of treatment, cardiac function and fibrosis were assessed by trans-thoracic echo and histology, respectively. As a parameter of systemic inflammation, previously shown to be altered in acute coronary syndrome, T regulatory (Treg) cell levels were measured by flow cytometry. Renal dysfunction was documented by standard laboratory tests. RESULTS: After 4 weeks of treatment, no significant improvement in cardiac function parameters was noted following VDRA administration. VDRA treatment did not significantly alter Treg cell systemic levels. Consistently, despite a trend toward less extent of myocardial fibrosis, we found no clear beneficial effects of VDRA on myocardial tissue inflammation and remodeling. CONCLUSIONS: Vitamin D treatment showed no beneficial effects on cardiac function parameters and fibrosis in an animal model of cardiorenal syndrome.

First-Phase Ejection Fraction and Long-Term Survival in Patients Who Underwent Transcatheter Aortic Valve Implantation.

Early recognition of deteriorating left ventricular function plays a key prognostic role in patients with aortic stenosis (AS). First-phase ejection fraction (EF1), the ejection fraction (EF) up to time of maximal contraction, has been suggested for detection of early left ventricular dysfunction in patients with AS with preserved EF. This work aims to evaluate the predictive value of EF1 for assessment of long-term survival in patients with symptomatic severe AS and preserved EF who undergo transcatheter aortic valve implantation (TAVI). We included 102 consecutive patients (median age 84 years [interquartile range 80 to 86 years]) who underwent TAVI between 2009 and 2011. Patients were retrospectively stratified into tertiles by EF1. Device success and procedural complications were defined according to the Valve Academic Research Consortium-3 criteria. Mortality data were retrieved from a computerized interface of the Israeli Ministry of Health. Baseline characteristics, co-morbidities, clinical presentation, and echocardiographic findings were similar among groups. The groups did not differ significantly regarding device success and in-hospital complications. During a potential follow-up period of >10 years, 88 patients died. Kaplan-Meier analysis (log-rank p = 0.017) followed by multivariable Cox regression analysis showed that EF1 predicted long-term mortality independently, either as continuous variable (hazard ratio 1.04, 95% confidence interval 1.01 to 1.07, p = 0.012) or for each decrease in tertile group (hazard ratio 1.40, 95% confidence interval 1.05 to 1.86, p = 0.023). In conclusion, low EF1 is associated with a significant decrease in adjusted hazard for long-term survival in patients with preserved EF who undergo TAVI. Low EF1 might delineate a population at great risk who would benefit from prompt intervention.

Vascular Complications in Transcatheter Aortic Valve Replacement With Plug-Based vs Suture-Based Closure Devices.

BACKGROUND: There are conflicting data regarding the efficacy and safety of suture vs plug-based vascular closure devices (VCDs) for large-bore catheter management in patients undergoing transcatheter aortic valve replacement (TAVR). We compared the rates of vascular complications (VCs) associated with 2 commonly used VCDs in a large cohort of patients undergoing TAVR. METHODS: We conducted a single-centre, all-comer, prospective registry study, enrolling patients undergoing TAVR for symptomatic severe aortic stenosis (AS) between the years 2009 and 2022. Clinical outcomes were compared between patients undergoing closure of the femoral access point using the MANTA VCD (M-VCD) (Teleflex, Wayne, PA) vs the ProGlide VCD (P-VCD) (Abbott Vascular, Abbott Park, IL). The main outcome measures were researcher adjudicated events of VARC-2 defined major and minor VCs. RESULTS: Overall, 2368 patients were enrolled in the registry; 1315 (51.0% male, 81.0 ± 7.0 years) patients were included in the current analysis. P-VCD was used in 813 patients, whereas M-VCD was used in 502 patients. In-hospital VCs were more frequent in the M-VCD vs the P-VCD group (17.3% vs 9.8%; P < 0.001). This outcome was mainly driven by elevated rates of minor VCs in the M-VCD group, whereas no significant difference was observed for major VCs (15.1% vs 8.4%; P < 0.001 and 2.2% vs 1.5%; P = 0.33, respectively). CONCLUSIONS: In patients undergoing TAVR for severe AS, M-VCD was associated with higher rates of VCs. This outcome was mainly driven by minor VCs. The rate of major VCs was low in both groups.

Accelerated renal fibrosis in cardiorenal syndrome is associated with long-term increase in urine neutrophil gelatinase-associated lipocalin levels.

BACKGROUND: Cardiac events are the main cause of death among patients with end-stage renal failure. Even a mild renal disease is currently considered a major risk factor for cardiovascular complications following myocardial infarction (MI). The aim of the present study was to detect histological, sera and urine characteristics of kidney injury in cardiorenal syndrome (CRS) compared to chronic kidney disease (CKD) with an intact cardiac function. METHODS: We employed a rat model for CRS, in which an acute MI (AMI) was induced 4 weeks after establishment of subtotal nephrectomy. Four weeks later, left ventricular function was assessed by echocardiography and changes in renal performance were examined using histological and biochemical parameters. RESULTS: Increased interstitial fibrosis as well as renal inflammation were observed in renal sections derived from CRS rats, compared to subtotal nephrectomy (CKD)-only animals. Moreover, we found that even though AMI on the background of CKD was not associated with a further decrease in creatinine clearance or a further increase in sera BUN levels compared to CKD only, a significant long-term elevation in urine neutrophil gelatinase-associated lipocalin (Ngal) levels was detectable post-MI induction. CONCLUSIONS: AMI in the CKD setting is associated with accelerated renal fibrosis and long-term elevated urine Ngal values, suggesting that cardiac dysfunction contributes to accelerated intrinsic kidney injury in CKD. The data indicate that elevated urine Ngal may potentially serve as an early non-invasive laboratory parameter for a left ventricular dysfunction-related renal injury.

The cardiorenal syndrome: a mutual approach to concomitant cardiac and renal failure.

Heart failure (HF) accompanied by renal failure, termed cardiorenal syndrome (CRS), encompasses both the development and worsening of renal insufficiency secondary to HF as well as the harmful effects of impaired renal function on the cardiovascular system, and remains a universalclinical challenge. CRS was recently classified into subtypes depending on the etiologic and chronologic interactions between cardiac and renal dysfunctions. The mechanisms underlying the CRS are multifactorial, including hemodynamic alterations, neurohormonal effects, and inflammatory components. However, despite enhanced understanding and awareness of CRS, further elucidation of the mechanisms involved and the appropriate treatment approaches are clearly warranted. CRS is a difficult condition to manage, as treatment to relieve congestive symptoms of HF is limited by a further decline in renal functions, itself a major independent predictor of long-term cardiac morbidity. In order to perform a proper clinical investigation and implement appropriate treatmentthat will minimize subsequent progression of heart and kidney injury, a comprehensive approach to these two pathologies is crucial. In the present review we discuss current theories behind the mechanistic evolution of the CRS as well as therapeutic issues regarding this multifaceted condition.

Interleukin-33 augments Treg cell levels: a flaw mechanism in atherosclerosis.

BACKGROUND: Atherosclerosis is a well-established inflammatory disease in which T helper 1 (Th1) cells play a key role. Regulatory T (Treg) cells drive a shift from Th1 to Th2 response and were shown to be reduced in atherosclerosis. ST2/interleukin (IL)-33 signal was found to promote Th2 response, attenuating atherosclerotic plaque progression. OBJECTIVES: To evaluate the effect of IL-33 on Treg cell number. METHODS: We employed flow cytometry to determine Treg cell number, as well as ST2 levels, among splenocytes of C57BL/61 vs ApoE-/- mice. Soluble ST2 (sST2) levels were detected by enzyme-linked immunosorbent assay. RESULTS: IL-33 contributed to an increase in Treg cells, but this association was attenuated in ApoE knockout (ApoE-/-) atherosclerotic mice. As a possible mechanism we demonstrated a reduction in the levels of CD4+ST2+ cells by flow cytometry, which is cotemporary to the previously described decrease in Treg cells in ApoE-/- mice. Additionally, the serum level of the soluble ST2 (sST2) decoy receptor was higher in ApoE-/- mice than in control animals. CONCLUSIONS: Our results suggest that a repressed ST2/ IL-33 signaling may contribute to the decrease in Treg cells observed in atherosclerosis.

Does the use of polymer-free drug eluting stents improve clinical outcomes of patients undergoing percutaneous coronary interventions?

BACKGROUND: Implantation of drug eluting stents (DES) is the mainstay treatment for patients requiring percutaneous coronary intervention (PCI). The polymer coating of DES has been associated with inflammatory response, increased arterial injury and long-term in-stent restenosis and thrombosis. Polymer-free stents (PFS) were designed to overcome limitations of polymer-coated stents (PCS). Our aim was to compare clinical outcomes of patients undergoing PCI with PFS versus contemporary PCS. METHODS: This is a prospective, open-label registry study enrolling consecutive all-comers patients admitted to a single center and undergoing PCI using contemporary DES. Clinical outcomes were compared between patients treated with PFS and PCS. The primary endpoint was target lesion revascularization (TLR) at 12 months. Subgroup analyses were conducted for diabetic and nondiabetic patients. RESULTS: Overall, 1664 patients were included: 928 (55.8%) of which were treated with PFS and 736 (44.2%) with PCS for 2046 and 1462 lesions, respectively. At 12 months, TLR rates were not significantly different between the groups (1.7% vs. 2.3% for PFS and PCS, respectively, P = 0.48). The use of PFS did not improve clinical outcomes among diabetic patients in comparison with PCS. Target vessel revascularization and major adverse cardiac events rates were also similar between groups, regardless of diabetes status. CONCLUSION: Newer generation DES offer excellent results in diabetic and nondiabetic patients without significant differences in outcomes between PCS and PFS.

Impact of Valve Size on Paravalvular Leak and Valve Hemodynamics in Patients With Borderline Size Aortic Valve Annulus.

Background: Transcatheter heart valve (THV) selection for transcatheter aortic valve implantation (TAVI) is crucial to achieve procedural success. Borderline aortic annulus size (BAAS), which allows a choice between two consecutive valve sizes, is a common challenge during device selection. In the present study, we evaluated TAVI outcomes in patients with BAAS according to THV size selection. Methods: We performed a retrospective study including patients with severe aortic stenosis (AS) and BAAS, measured by multi-detector computed tomography (MDCT), undergoing TAVI with self-expandable (SE) or balloon-expandable (BE) THV from the Israeli multi-center TAVI registry. The aim was to evaluate outcomes of TAVI, mainly paravalvular leak (PVL) and valve hemodynamics, in patients with BAAS (based on MDCT) according to THV sizing selection in between 2 valve sizes. In addition, to investigate the benefit of shifting between different THV types (BE and SE) to avoid valve size selection in BAAS. Results: Out of 2,352 patients with MDCT measurements, 598 patients with BAAS as defined for at least one THV type were included in the study. In BAAS patients treated with SE-THV, larger THV selection was associated with lower rate of PVL, compared to smaller THV (45.3 vs. 64.5%; pv = 0.0038). Regarding BE-THV, larger valve selection was associated with lower post-procedural transvalvular gradients compared to smaller THV (mean gradient: 9.9 ± 3.7 vs. 12.5 ± 7.2 mmHg; p = 0.019). Of note, rates of mortality, left bundle branch block, permanent pacemaker implantation, stroke, annular rupture, and/or coronary occlusion did not differ between groups. Conclusion: BAAS is common among patients undergoing TAVI. Selection of a larger THV in these patients is associated with lower rates of PVL and optimized THV hemodynamics with no effect on procedural complications. Additionally, shift from borderline THV to non-borderline THV modified both THV hemodynamics and post-dilatation rates.