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Background: Renal injury induces major changes in plasma and cardiac metabolites. Using a small- animal in vivo model, we sought to identify a key metabolite whose levels are significantly modified following an acute kidney injury (AKI) and to analyze whether this agent could offer cardiac protection once an ischemic event has occurred., Methods and Results: Metabolomics profiling of cardiac lysates and plasma samples derived from rats that underwent AKI 1 or 7 days earlier by 5/6 nephrectomy versus sham-operated controls was performed. We detected 26 differential metabolites in both heart and plasma samples at the two selected time points, relative to sham. Out of which, kynurenic acid (kynurenate, KYNA) seemed most relevant. Interestingly, KYNA given at 10 mM concentration significantly rescued the viability of H9C2 cardiac myoblast cells grown under anoxic conditions and largely increased their mitochondrial content and activity as determined by flow cytometry and cell staining with MitoTracker dyes. Moreover, KYNA diluted in the drinking water of animals induced with an acute myocardial infarction, highly enhanced their cardiac recovery according to echocardiography and histopathology., Conclusion: KYNA may represent a key metabolite absorbed by the heart following AKI as part of a compensatory mechanism aiming at preserving the cardiac function. KYNA preserves the in vitro myocyte viability following exposure to anoxia in a mechanism that is mediated, at least in part, by protection of the cardiac mitochondria. A short-term administration of KYNA may be highly beneficial in the treatment of the acute phase of kidney disease in order to attenuate progression to reno-cardiac syndrom and to reduce the ischemic myocardial damage following an ischemic event., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bigelman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: We aimed to test the differences in peak VO 2 between males and females in patients diagnosed with heart failure (HF), using combined stress echocardiography (SE) and cardiopulmonary exercise testing (CPET)., Methods: Patients who underwent CPET and SE for evaluation of dyspnea or exertional intolerance at our institution, between January 2013 and December 2017, were included and retrospectively assessed. Patients were divided into three groups: HF with preserved ejection fraction (HF p EF), HF with mildly reduced or reduced ejection fraction (HF mr EF/HF r EF), and patients without HF (control). These groups were further stratified by sex., Results: One hundred seventy-eight patients underwent CPET-SE testing, of which 40% were females. Females diagnosed with HF p EF showed attenuated increases in end diastolic volume index ( P = 0.040 for sex × time interaction), significantly elevated E/e' ( P < 0.001), significantly decreased left ventricle (LV) end diastolic volume:E/e ratio ( P = 0.040 for sex × time interaction), and lesser increases in A-VO 2 difference ( P = 0.003 for sex × time interaction), comparing to males with HF p EF. Females diagnosed with HF mr EF/HF r EF showed diminished increases in end diastolic volume index ( P = 0.050 for sex × time interaction), mostly after anaerobic threshold was met, comparing to males with HF mr EF/HF r EF. This resulted in reduced increases in peak stroke volume index ( P = 0.010 for sex × time interaction) and cardiac output ( P = 0.050 for sex × time interaction)., Conclusions: Combined CPET-SE testing allows for individualized non-invasive evaluation of exercise physiology stratified by sex. Female patients with HF have lower exercise capacity compared to men with HF. For females diagnosed with HF p EF, this was due to poorer LV compliance and attenuated peripheral oxygen extraction, while for females diagnosed with HF mr EF/HF r EF, this was due to attenuated increase in peak stroke volume and cardiac output. As past studies have shown differences in clinical outcomes between females and males, this study provides an essential understanding of the differences in exercise physiology in HF patients, which may improve patient selection for targeted therapeutics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rozenbaum, Granot, Sadeh, Havakuk, Arnold, Shimiaie, Ghermezi, Barak, Ben Gal, Shacham, Keren, Topilsky and Laufer-Perl.)

Background: The causes of heart failure (HF) during high-grade atrioventricular block (AVB) are poorly understood. This study assessed the mechanisms of HF in patients with AVB., Methods: We studied patients presenting (between 2012 and 2016) with high-grade AVB not related to acute myocardial infarction. Patients with preexisting significant valvular heart disease were excluded. All patients underwent comprehensive echocardiographic evaluation during AVB, before pacemaker implantation. The diagnosis of HF was based on the Framingham criteria., Results: A total of 122 patients were included in the study, 50% male, average age 76 ± 13 years. Twenty-eight patients (23%) with AVB presented with HF. Univariate correlates associated with HF were decrease in cardiac output (CO) (odds ratio [OR] 0.68 [95% confidence interval 0.49-0.9] per L/min; P = 0.007), measures of impaired left ventricular (LV) compliance, and increase in diastolic mitral regurgitation (MR) volume (OR 1.04 [1.01-1.07] per cc; P = 0.0016). Ventricular rate during AVB and LV ejection fraction were not significantly associated with the presence of HF. By multivariate nominal logistic analysis, the best model associated with HF included diastolic MR volume (OR 1.04 [1.001-1.09]; P = 0.02), A-wave deceleration time (OR 0.96 [0.94-0.9]; P = 0.001), and CO (OR 0.92 [0.4-1.00]; P = 0.005) (χ 2  = 30.6; area under the receiver operating characteristic curve = 0.84; P < 0.0001 for the entire model)., Conclusions: In the setting of high-degree AVB, clinical HF occurrence correlates with impaired LV compliance and diastolic MR volume, but not with heart rate or LV ejection fraction. The cardiac performance of patients with poor LV compliance and high-volume diastolic MR may show maladjustment to slow heart rates, manifesting as low CO and HF., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Current methods do not allow a thorough assessment of causes associated with limited exercise capacity in patients with chronic obstructive pulmonary disease (COPD)., Methods: Twenty patients with COPD and 20 matched control subjects were assessed using combined cardiopulmonary and stress echocardiographic testing. Various echocardiographic parameters (left ventricular [LV] volumes, right ventricular [RV] area, ejection fraction, stroke volume, S', and E/e' ratio) and ventilatory parameters (peak oxygen consumption [Vo 2 ] and A-Vo 2 difference) were measured to evaluate LV and RV function, hemodynamics, and peripheral oxygen extraction (A-VO 2 difference)., Results: Significant differences (both between groups and for group-by-time interaction) were seen in exercise responses (LV volume, RV area, LV volume/RV area ratio, S', E/e' ratio, tricuspid regurgitation grade, heart rate, stroke volume, and Vo 2 ). The major mechanisms of reduced exercise tolerance in patients with COPD were bowing of the septum to the left in 12 (60%), abnormal increases in E/e' ratio in 12 (60%), abnormal stroke volume reserve in 16 (80%), low peak A-Vo 2 difference in 10 (50%), chronotropic incompetence in 13 (65%), or a combination of several mechanisms. Patients with COPD and poor exercise tolerance showed attenuated increases in stroke volume, heart rate, and A-Vo 2 difference and exaggerated changes in LV/RV ratio and LV compliance (ratio of LV volume to E/e' ratio) compared with patients with COPD with good exercise tolerance., Conclusions: Combined cardiopulmonary and stress echocardiographic testing can be helpful in determining individual mechanisms of exercise intolerance in patients with COPD. In patients with COPD, exercise intolerance is predominantly the result of chronotropic incompetence, limited stroke volume reserve, exercise-induced elevation in left filling pressure, and peripheral factors and not simply obstructive lung function. Limited stroke volume is related to abnormal RV contractile reserve and reduced LV compliance introduced through septal flattening and direct ventricular interaction., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Acute pulmonary embolism (PE) is considered to be one of the most common cardiovascular diseases with considerable mortality. Conflicting data imply possible role for echocardiography in assessing this disease., Objectives: To determine which of the echo parameters best predicts short-term and long-term mortality in patients with PE., Methods: We prospectively enrolled 235 patients who underwent computed tomography of pulmonary arteries (CTPA) and transthoracic Echocardiography (TTE) within < 24 hours. TTE included a prospectively designed detailed evaluation of the right heart including right ventricular (RV) myocardial performance index (RIMP), RV end diastolic and end systolic area, RV fractional area change, acceleration time (AT) of pulmonary flow and visual estimation. Interpretation and performance of TTE were blinded to the CTPA results., Results: Although multiple TTE parameters were associated with PE, all had low discriminative capacity (AUC < 0.7). Parameters associated with 30-day mortality in univariate analysis were acceleration time (AT) < 81 msec (P = 0.04), stroke volume < 44 cc (P = 0.005), and RIMP > 0.42 (P = 0.05). The only RV independent echo parameter associated with poor long-term prognosis (adjusted for significant clinical, and routine echo associates of mortality) was RIMP (hazard ratio 3.0, P = 0.04). The only independent RV echo parameters associated with mortality in PE patients were RIMP (P = 0.05) and AT (P = 0.05). Addition of RIMP to nested models eliminated the significance of all other parameters assessing RV function., Conclusions: Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE.

Objective: Acute kidney injury (AKI) is a frequent complication in patients with ST segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). While AKI occurring post-PCI has been well studied, the incidence and clinical significance of early renal impairment evident on hospital admission prior to PCI and which resolves towards discharge has not been investigated., Methods: We retrospectively studied 2339 STEMI patients treated with primary PCI. The incidence of renal impairment and in-hospital complications as well as short and long-term mortality were compared between patients who did not develop renal impairment, patients who developed post-PCI AKI and those who presented with renal impairment on admission but improved their renal function during hospitalization (improved renal function). Improved renal function was defined as continuous and gradual decrease of ⩾ 0.3 mg/dL in serum creatinine levels obtained at hospital admission., Results: One hundred and nineteen patients (5%) had improved renal function and 230 patients (10%) developed post-PCI AKI. When compared with patients with no renal impairment, improved renal function and post-PCI AKI were associated with more complications and adverse events during hospitalization as well as higher 30-day mortality. Long-term mortality was significantly higher among those with post-PCI AKI (63/230, 27%) following STEMI than those without renal impairment (104/1990, 5%; p <0.001), but there was no significant difference in long term mortality between patients with no renal impairment and those with improved renal function (5% vs . 7.5%, p =0.17)., Conclusion: In STEMI patients undergoing primary PCI, the presence of renal impairment prior to PCI which resolves towards discharge is not uncommon and is associated with adverse short-term outcomes but better long-term outcomes compared with post-PCI AKI.

Aims: Asses the added value of quantitative evaluation of tricuspid regurgitation (TR), the proper cut-off value for severe TR and 'torrential TR' based on outcome data. The added value of quantitative evaluation of TR, and the cut-off values associated with increased mortality are unknown., Methods and Results: In patients with all-cause TR assessed both qualitatively and quantitatively by proximal iso-velocity surface area method, long-term and 1-year outcome analysis was conducted. Thresholds for excess mortality were assessed using spline curves, receiver-operating characteristic curves, and minimum P-value analysis. The study involved 676 patients with all-cause TR (age 73.9 ± 14 years, male 45%, ejection fraction 52.9 ± 14%). Effective regurgitant orifice (ERO) was strongly associated with decreased survival in unadjusted [hazard ratio (HR) 2.38 (1.79-3.01), P < 0.0001 per 0.1 cm2 increment] and adjusted [2.6 (1.25-5.0), P = 0.01] analyses. Quantitative grading was superior to qualitative grading in prediction of outcome (P < 0.01). The optimal cut-off value for the best separation in survival between groups of patients with severe vs. lesser degree of TR was 0.35 cm2 [P < 0.0001, HR =2.0 (1.5-2.7)]. ERO negatively impacted survival, even when including only the subgroup of patients with severe TR [HR 1.5 (1.01-2.3); P = 0.04]. The optimal threshold corresponding for the best separation for survival between groups of patients with severe vs. 'torrential' TR was 0.7 cm2 [P = 0.005, HR =2.6 (1.2-5.1)]., Conclusion: TR can be severe and even 'torrential' and is associated with excess mortality. Quantitative assessment of TR by ERO measurement is a powerful independent predictor of outcome, superior to standard qualitative assessment. The optimal cut-off above which mortality is increased is 0.35 cm2, similar albeit slightly lower than suggested in recent guidelines. Torrential TR >0.7 cm2 is associated with poorer survival compared to patients with severe TR (ERO > 0.4 cm2 and <0.7 cm2)., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objective: Monoclonal antibody derivatives are promising drugs for the treatment of various diseases due to their high matrix metalloproteinases (MMP) active site specificity. We studied the effects of a novel antibody, SDS3, which specifically recognizes the mature active site of MMP9/2 during ventricular remodeling progression in a mouse model of chronic volume overload (VO)., Methods: VO was induced by creating an aortocaval fistula (ACF) in 10- to 12-week-old C57BL male mice. The VO-induced mice were treated with either vehicle control (PBS) or with SDS3 twice weekly by intraperitoneal (ip) injection. The relative changes in cardiac parameters between baseline (day 1) and end-point (day 30), were evaluated by echocardiography. The effects of SDS3 treatment on cardiac fibrosis, cardiomyocyte volume, and cardiac inflammation were tested by cardiac staining with Masson's trichrome, wheat Germ Agglutinin (WGA), and CD45, respectively. Serum levels of TNFα and IL-6 with and without SDS3 treatment were tested by ELISA., Results: SDS3 significantly reduced cardiac dilatation, left ventricular (LV) mass, and cardiomyocyte hypertrophy compared to the vehicle treated animals. The antibody also reduced the heart-to-body weight ratio of the ACF animals to values comparable to those of the controls. Interestingly, the SDS3 group underwent significant reduction of cardiac inflammation and pro-inflammatory cytokine production, indicating a regulatory role for MMP9/2 in tissue remodeling, possibly by tumor necrosis factor alpha (TNFα) activation. In addition, significant changes in the expression of proteins related to mitochondrial function were observed in ACF animals, these changes were reversed following treatment with SDS3., Conclusion: The data suggest that MMP9/2 blockage with SDS3 attenuates myocardial remodeling associated with chronic VO by three potential pathways: downregulating the extracellular matrix proteolytic cleavage, reducing the cardiac inflammatory responses, and preserving the cardiac mitochondrial structure and function., Competing Interests: NO authors have competing interests

Objective: ST-segment elevation acute myocardial infarction (STEMI) in very young adults is uncommon. Many studies have focused on the cutoff of 45-50 years old to define young patients with STEMI leaving limited data on the group of very young patients aged less than 35 years old. We investigated the incidence of STEMI in different subgroups of young patients and focused on the characteristics, possible pathogenesis and outcomes in very young patients aged less than 35 years old., Methods: We retrospectively studied 792 STEMI patients aged less than 55 years who underwent successful primary PCI. We categorized patients as very young if they were or less 35 years old and as young if they were between 36 and 55 years old. Baseline characteristics, angiographic findings, as well as short- and long-term outcomes were compared between the two groups., Results: There were 46 (6%) very young patients (age ≤ 35 years) and 748 (94%) young patients (36 < age ≤ 55 years). Very young patients had fewer atherosclerotic risk factors than young patients, but there was no difference in short- or long-term outcomes. Overt hypercoagulable state was evident serologically (antiphospholipid antibodies) in 2/7 (29%) of screened patients and clinically (left ventricular thrombus or acute coronary thrombosis without an atherosclerotic plaque) in 6/46 patients (13%)., Conclusion: Very young patients with STEMI constitute a distinct subset of young patients with fewer atherosclerotic risk factors yet comparable outcomes. More efforts should be made screening for serologic and clinical evidence of hypercoagulability in this group of patients.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein released by renal tubular cells upon nephrotoxic or ischemic events and is considered an early marker of tubular damage. We aimed to demonstrate the presence of early renal injury detected by elevated NGAL levels taken before contrast administration in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI)., Patients and Methods: We prospectively included 88 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn immediately before PCI (baseline NGAL; NGAL1) and 24 h after PCI (NGAL2). Abnormal elevations in NGAL levels were defined using the cardiac surgery associated NGAL score (NGAL score) with NGAL levels at least 100 ng/ml, suggesting renal tubular damage. Patients were also assessed for the dynamics between NGAL2 and NGAL1 levels., Results: The mean age of the patients was 62 ± 13 years and 78% were men. A total of 50/88 (56%) patients had baseline NGAL level of at least 100, suggesting possible tubular damage before PCI. Only 10 patients progressed to clinical acute kidney injury during hospitalization, all of whom had baseline NGAL level of at least 100 (P < 0.001). Among patients with baseline NGAL at least 100, 28/50 (56%) showed a decrease in the NGAL level within 24 h, whereas only 9/50 (18%) showed an elevation in the NGAL level. In contrast, only 7/38 (19%) patients with baseline NGAL level less than 100 showed an elevation in NGAL levels within 24 h., Conclusion: Elevated NGAL levels before primary PCI suggesting renal tubular damage are common among STEMI patients. Further trials are needed to assess the complex cardio-renal interactions.

Background: Acute kidney injury (AKI) complicating transcatheter aortic valve implantation (TAVI) is relatively frequent and associated with significant morbidity. Previous studies have shown a higher 30-day and 1-year mortality risk in patients with periprocedural AKI. Our aim was to identify the prognostic impact of periprocedural AKI on long-term follow-up., Methods: This is a single-center prospective study evaluating patients undergoing TAVI for severe aortic stenosis. AKI was defined according to the Valve Academic Research Consortium 2 definition, as an absolute increase in serum creatinine ≥0.3 mg/dL or an increase >50% within the first week following TAVI. Mortality data were compared between patients who developed AKI and those who did not. Logistic and Cox regressions were used for survival analysis., Results: The final analysis included 1086 consecutive TAVI patients. AKI occurred in 201 patients (18.5%). During the follow-up period, 289 patients died. AKI was associated with an increased risk of 30-day mortality {4.5 versus 1.9% in the non-AKI group; hazard ratio [HR] 3.70 [95% confidence interval (CI) 1.35-10.13]}. Although 1-year mortality was higher in the AKI group in univariate analysis, it was not significant after a multivariate regression. AKI was a strong predictor of longer-term mortality [42.3 versus 22.7% for 7-year mortality; HR 1.71 (95% CI 1.30-2.25)]. In 189 of 201 patients we had data regarding recovery from AKI up to 30 days after discharge. In patients with recovery from AKI, the mortality rate was lower (38.2 versus 56.6% in the nonrecovery group; P = 0.022)., Conclusions: Periprocedural AKI following TAVI is a strong risk factor for short-term as well as long-term mortality (up to 7 years). Therefore more effort is needed to reduce this complication., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Aims: Tricuspid regurgitation (TR) is a frequent echocardiographic finding; however, its effect on outcome is unclear. The objectives of current study were to evaluate the impact of TR severity on heart failure hospitalization and mortality., Methods and Results: We retrospectively reviewed consecutive echocardiograms performed between 2011 and 2016 at the Tel-Aviv Medical Center. TR severity was determined using semi-quantitative approach including colour jet area, vena contracta width, density of continuous Doppler jet, hepatic vein flow pattern, trans-tricuspid inflow pattern, annular diameter, right ventricle, and right atrial size. Major comorbidities, re-admissions and all-cause mortality were extracted from the electronic health records. The final analysis included 33 305 patients with median follow-up period of 3.34 years (interquartile range 2.11-4.54). TR (≥mild) was present in 31% of our cohort. One-year mortality rates were 7.7% for patients with no/trivial TR, 16.8% for patients with mild TR, 29.5% for moderate TR, and 45.6% for patients with severe TR (P < 0.001). Univariate and multivariate analyses demonstrated a positive correlation between TR severity and overall mortality and rates of heart failure re-admission after adjustment for potential confounders. The proportional hazards method for overall mortality showed that patients with moderate [hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.02-1.3, P = 0.024] and severe TR (HR 1.43, 95% CI 1.08-1.88, P = 0.011) had a worse prognosis than those with no or minimal TR., Conclusions: The presence of any degree of TR is associated with adverse clinical outcome. At least moderate TR is independently associated with increased mortality., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: While the impact of mitral regurgitation (MR) prior to transcatheter aortic valve replacement (TAVR) has been intensively studied, the implications of post-procedural MR on outcome are unknown. We investigated the clinical and physiological impact of significant MR after TAVR., Methods: Clinical and echocardiographic data of 486 patients who underwent TAVR between March 2009 and December 2014 were evaluated. Clinical endpoints included overall mortality and combined endpoint of mortality, heart failure re-hospitalization and new atrial fibrillation. Echocardiographic parameters were analyzed at baseline, 30-day and 6-month after TAVR., Results: MR severity improved in 25%, worsened in 19% and did not change in 56% of patients 30-days post TAVR (p = 0.3). Post TAVR MR grade ≥ moderate was present in 16.1%. Predictive accuracy of post TAVR MR was low (AUC = 0.63). Median follow-up was 4.3 years (interquartile range, 2.5 to 6.1). Post TAVR MR grade ≥ moderate was associated with increased mortality and combined cardiac events (p = 0.013 and p < 0.001) even when adjusted for all clinical and echo parameters and when analyzed with propensity score matching. In patients with MR ≥ moderate, LV filling pressure and RV hemodynamics worsened 6 months post TAVR, while improving in patients with less significant post procedural MR., Conclusion: Post procedural, but not pre-procedural MR grade ≥ moderate was independently associated with mortality and adverse cardiac events after TAVR. Significant MR post TAVR resulted in adverse LV and RV remodeling and poor hemodynamic. Our study strengthens the rational for initiating early treatment to reduce post TAVR MR., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of renal tubular damage. We investigated the incidence and possible implications of elevated NGAL levels (suggesting renal damage) compared to both functional and damage markers (manifested as serum creatinine [sCr] elevation) and no NGAL/sCr change, among -ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI)., Methods: We included 131 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn 24 h following PCI. We used the terms NGAL(-) or NGAL(+) with levels ≥100 ng/mL suggesting renal tubular damage and the terms. sCr(-) or sCr(+) to consensus diagnostic increases in sCr defining acute kidney injury. Patients were also assessed for in hospital-adverse outcomes., Results: Of the study patients, 56 (42%) were NGAL(-)/sCr(-), 58 (44%) NGAL(+)/sCr(-), and 18 (14%) were both NGAL(+)/sCr(+). According to the 3 study groups, there was a stepwise increase in the proportion of left ventricular ejection fraction ≤45% (43 vs. 60. vs. 72%; p = 0.04), in-hospital adverse outcomes (9 vs. 14 vs. 56%; p < 0.001) and their combination. Specifically, more NGAL(+)/sCr(-) patients developed the composite endpoint when compared to NGAL(-)/sCr(-) patients (64 vs. 46%; OR 2.1, [95% CI 1.1-4.5], p = 0.05). A similar and consistent increase was observed in peak sCr, length of hospital stay, and C-reactive protein levels., Conclusions: Elevated NGAL levels suggesting renal tubular damage, increased inflammation, or both are common among STEMI patients and are associated with adverse outcomes even in the absence of diagnostic increase in sCr., (© 2020 S. Karger AG, Basel.)

Introduction and Objective: Neutrophil gelatinase-associated lipocalin (NGAL), a glycoprotein released by renal tubular cells, can be used as a marker of early tubular damage. We evaluated plasma NGAL level utilization for the identification of acute kidney injury (AKI) among ST-elevation myocardial infarction (STEMI) patients undergoing primary coronary intervention (PCI)., Methods: 131 STEMI patients treated with PCI were prospectively included. Plasma NGAL levels were drawn prior to PCI (0 h) and 24 h afterwards. AKI was defined per KDIGO criteria of serum creatinine increase. Receiver-operating characteristic (ROC) methods were used to identify optimal sensitivity and specificity for the observed NGAL range., Results: Overall AKI incidence was 14%. NGAL levels were significantly higher for patients with AKI at both 0 h (164 ± 42 vs. 95 ± 30; p < 0.001) and 24 h (142 ± 41 vs. 93 ± 36; p < 0.001). Per ROC curve analysis, an optimal cutoff value of NGAL (>120 ng/mL) predicted AKI with 80% sensitivity and specificity (AUC 0.881, 95%, CI 0.801-0.961, p < 0.001). In a multivariate logistic regression model, NGAL levels were independently associated with AKI at 0 h (OR 1.044, 95% CI 1.013-1.076; p = 0.005) and 24 h (OR 1.018, 95% CI 1.001-1.036; p = 0.04)., Conclusions: Elevated NGAL levels, suggesting renal tubular damage, are independently associated with AKI in STEMI patients undergoing primary PCI., (© 2020 S. Karger AG, Basel.)

TRPV2 is a well-conserved channel protein expressed in almost all tissues. Cardiomyocyte TRPV2 is expressed in the intercalated disks of the cardiac sarcomeres, where it is involved in maintaining the proper mechanoelectric coupling and structure. It is also abundantly expressed in the intracellular pools, mainly the endoplasmic reticulum. Under pathological conditions, TRPV2 is translocated to the sarcolemma, where it mediates an abnormal [Ca] 2+ entry that may contribute to disease progression. In addition, an intracellularly diffused TRPV2 expression is present in resident cardiac macrophages. Upon infection or inflammation, TRPV2 is engaged in early phagosomes and is, therefore, potentially involved in protecting the cardiac tissue. Following acute myocardial infarction, a profound elevated expression of TRPV2 is observed on the cell membrane of the peri-infarct macrophages. The macrophage TRPV2 may harbor a detrimental effect in cardiac recovery by increasing unfavorable migration and phagocytosis processes in the injured heart. Most reports suggest that while cardiac TRPV2 activation may be beneficial under specific physiological conditions, both cardiac- and macrophage-related TRPV2 blocking can significantly ameliorate disease progression in various pathological states. To verify this possibility, the time frame of TRPV2 overexpression and its mediated signaling need to be fully characterized in both cardiomyocyte and cardiac macrophage populations.

Background: Elderly individuals ( ≥ 75 years) constitute an increasing proportion of patients presenting with myocardial infarction treated with primary percutaneous coronary intervention (PCI), but only limited data are available regarding the incidence and prognostic implications of acute kidney injury (AKI) in this group of patients., Objective: To evaluate the incidence and prognostic implications of AKI in older adults ( ≥ 75 years) with ST-segment elevation myocardial infarction (STEMI) treated with primary PCI., Patients and Methods: A retrospective cohort, observational, single-center study of consecutive 416 older patients with STEMI (≥ 75 years) treated with primary PCI between January 2008 and August 2017 was conducted. AKI was defined as an increase of at least 0.3 mg/dl in serum creatinine within 48 h following admission., Results: A total of 96/416 (23%) patients developed AKI. The occurrence of AKI was associated with adverse in-hospital outcomes, higher 30 days (25 vs. 6%; P < 0.001), and long-term mortality (46 vs. 17%; hazard ratio: 3.2; 95% confidence interval: 2.1-4.7; P < 0.001). Among patients with AKI, 46/96 (48%) demonstrated recovery of renal function at hospital discharge. Lack of renal function recovery at discharge (50/96 patients; 52%) was associated with the occurrence of new or progression of baseline chronic kidney disease., Conclusion: Among older patients with STEMI undergoing primary PCI, AKI is a frequent complication associated with adverse renal short-term and long-term outcomes.

Background: Current guidelines for the treatment of ST-segment elevation myocardial infarction (STEMI) recommend a door-to-balloon time (DBT) of ≤ 90 min for patients undergoing primary percutaneous coronary intervention (PCI). We aimed to investigate the possible impact of further reduction in DBT intervals beyond the 90 min cutoff on short and long-term outcomes among STEMI patients undergoing primary PCI., Methods: We retrospectively studied 889 STEMI patients (median age 61 years, 83% men) who underwent successful primary PCI and had a DBT of ≤ 90 min. Patients were stratified according to DBT into 2 groups: < 60 min and 60-90 min. Patients records were assessed for the occurrence of in-hospital complications, 30-day and 1-year mortality., Results: Patients having DBT < 60 min (n = 608, 68%) were more likely to present earlier, in daytime and weekdays, and had better post-procedural left ventricular ejection fraction and lower 30-day mortality (3% vs. 6%, p = 0.03). Mortality over 1-year was significantly lower among patients having DBT < 60 compared to DBT of 60-90 min (4.6% vs. 9.6%, p = 0.004). In a binary logistic regression model DBT < 60 min was associated with 51% risk reduction for 1-year mortality (OR 0.49, 95% CI 0.25-0.93, p = 0.03)., Conclusions: Among STEMI patients undergoing primary PCI within 90 min of admission DBT < 60 min was independently associated with better 1-year mortality.

Background: Red blood cell distribution width (RDW), which is routinely reported in complete blood counts, is a measure of the variability in size of circulating erythrocytes. RDW is an independent predictor of prognosis in patients with cardiovascular diseases. We evaluated the short- and long-term prognostic value of RDW in a large cohort of transcatheter aortic valve implantation (TAVI) patients., Methods: The impact of RDW on outcome was determined prospectively in 1029 consecutive patients with severe aortic stenosis (AS) undergoing transfemoral TAVI. The cohort was divided into 2 groups according to RDW above and below 15.5%. Collected data included patient characteristics, medical background, left ventricle ejection fraction (LVEF), frailty score, Society of Thoracic Surgeons (STS) score, periprocedural laboratory results, and long-term (up to 7.5 years) clinical outcomes., Results: The mean age (±SD) was 83.1±6.3 years, mean STS score was 4.2±3.1% and mean estimated LVEF was 55.7±8.4%. Mean pre-TAVI RDW levels were 15.3±3.2%. Patients with RDW≤15.5% (n=683) and RDW>15.5% (n=346) had a 1-year mortality rate of 6% and 17%, respectively (p=0.001) and a 5-year mortality rate of 20% and 38%, respectively (p<0.001). Baseline RDW>15.5% was independently associated with all-cause mortality (hazard ratio 1.83, 95% confidence interval 1.44-2.32, p<0.001)., Conclusions: Elevated RDW is a strong independent marker and predictor of short- and long-term mortality following TAVI, that might present a relevant future supplement to current preprocedural risk scores. Additional research is needed to clarify the mechanisms responsible for this finding., (Copyright © 2019. Published by Elsevier Ltd.)

Aims: We aimed to analyse the association between right haemodynamic parameters, right ventricular (RV) dysfunction parameters, and outcomes in patients with preserved ejection fraction (EF)., Methods and Results: Retrospective analysis of right haemodynamic (systolic pulmonary pressure and end-diastolic pulmonary pressure based on tricuspid regurgitation (TR) velocity at pulmonary valve opening time), and RV parameters including size (end-diastolic and end-systolic area), function (RV fractional area change, Tei index, Tricuspid Annular Plane Systolic Excursion, and speckle tracking derived free wall strain), from 557 consecutive patients with preserved EF [EF ≥ 50%; age 64.9 + 20; 52% female; co-morbidity Charlson index 4.7 (2.9, 6.4)]. All cause and cardiac mortality were retrospectively analysed and correlated to echo haemodynamic and co-morbid parameters. TR velocity at pulmonary valve opening time and calculated end-diastolic pulmonary artery pressure were obtainable in 71% of patients. The best haemodynamic univariate predictor of mortality was calculated end-diastolic pulmonary artery pressure [hazard ratio 1.06 (1.04-1.07); P < 0.0001], superior to TR peak velocity and systolic pulmonary artery pressure. Elevated end-diastolic pulmonary artery pressure was associated with all cause and cardiac mortality even when adjusted for all significant clinical (age, gender, and Charlson index), and echo (stroke volume index, left atrial volume index, systolic pulmonary pressure, E/e', and Tei index) parameters. Tei index was superior to all other RV functional parameters (P < 0.05 for all parameters)., Conclusion: TR velocity at pulmonary valve opening time and calculated end-diastolic pulmonary artery pressure are obtainable in most patients, and add prognostic information on top of clinical and routine haemodynamic and diastolic parameters., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Although the natural history of aortic stenosis (AS) depends on the severity of symptoms, the prognostic significance of AS clinical progression in patients who underwent aortic valve replacement is less clear. Here, we studied the correlation between the severity of AS presenting symptoms and survival after transcatheter aortic valve implantation (TAVI). We evaluated long-term survival of a consecutive cohort of severe AS patients (n = 862, mean Society of Thoracic Surgeons score 4.16 ± 2.9) who underwent transfemoral TAVI from 2009 to 2016. Patients were classified as having severe symptoms (i.e., angina, syncope, or heart failure, n = 424) or mild symptoms (i.e., dizziness, fatigue, effort dyspnea, chest discomfort, n = 438). No differences in device success nor in-hospital complications were found between groups. During a median follow-up of 2.84 (1.9 to 4.5) years, survival at 1, 3, and 5 years in the entire cohort, was 89% ± 1.1%, 75% ± 1.6%, and 59% ± 2.1%, respectively. Severe symptoms were associated with higher mortality (hazard ratio 1.54, 95% confidence intervals 1.230 to 1.939, p <0.001). The 1-, 3-, and 5-year survival was 94% ± 1.9%, 81% ± 3.3%, and 71% ± 4.3% in patients with angina, 92% ± 3.3%, 75% ± 5.6%, and 56% ± 8.2% in patients with syncope and 77% ± 3%, 54% ± 3.7%, and 41% ± 4.1% in patients with heart failure, respectively, (p <0.001). Heart failure symptoms emerged as independent predictor of mortality (hazard ratio 1.66, 1.28 to 2.17, p <0.001), regardless of left ventricular ejection fraction. The severity of AS symptoms affects survival after TAVI and overt heart failure independently predicts early mortality. Early intervention after diagnosis of severe AS is crucial to reduce the unfavorable effects of clinical progression on survival after TAVI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Limited data are present on persistent renal impairment following acute kidney injury (AKI) among ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). We evaluated the incidence and prognostic implications of acute kidney disease (AKD), defined as reduced kidney function for the duration of between 7 and 90 days after exposure to an AKI initiating event, as well as long-term renal outcomes among STEMI patients undergoing primary PCI who developed AKI., Patients and Methods: We retrospectively studied 225 consecutive STEMI patients who developed AKI. Patients were assessed for the occurrence of AKD and long-term renal outcomes on the basis of serum creatinine levels measured at 7 days/hospital discharge and within 90-180 days of renal insult. Mortality was assessed at 90 days and over a period of 1271±903 days (range: 2-2130 days) following the renal insult., Results: Progression to AKD occurred in 81/225 (36%) patients and was associated with higher 90-day (35 vs. 11%, P<0.001) and long-term mortality (35 vs. 17%, P<0.001). Normalization of serum creatinine to a level equal/lower than hospital admission level at more than 90 days from renal insult occurred in 41% of patients with AKD, whereas 59% of these patients showed new/progressed chronic kidney disease. In contrast, only 7% of patients without AKD showed the progression of pre-existing renal disease while, in the rest, the serum creatinine level remained stable., Conclusion: Progression to AKD following an acute renal insult in STEMI is frequent and associated with worse survival and adverse long-term renal outcomes.

Purpose: To demonstrate the possible association of statin therapy with C reactive protein (CRP) serial measurements in ST elevation myocardial infarction (STEMI) patients., Materials and Methods: STEMI patients between 2008 and 2016 with available CRP data from admission were divided into two groups according to pre-admission statin therapy. A second CRP measurement was noted following primary coronary intervention (within 24 h from admission). The difference between the two measurements was designated ΔCRP., Results: The cohort consisted of 1134 patients with a median age of 61 (IQR52-70), 81% males. Patients on statins prior to admission (336/1134, 26%) were more likely to have CRP levels within normal range (≤5 mg/l) compared to patients without prior treatment, both at admission (75 vs. 24%, p = 0.004) and at 24 h (70 vs. 48%, p = 0.029). The prevalence of patients with pre-admission statin therapy decreased as ΔCRP increased (p = 0.004; n = 301). The likelihood of ΔCRP to be above 5 mg/l in patients with pre-admission statin therapy was reduced after age and gender adjustments (OR 0.54, 95% CI 0.32-0.92, p = 0.023) and in multivariate (OR 0.57, 95% CI 0.33-0.99, p = 0.048) analysis., Conclusions: Pre-admission statin therapy is associated with a less robust inflammatory response in STEMI patients, highlighting statin's pathophysiological importance.

Background: There are limited data regarding the effect of long-standing hyperglycemia on the occurrence of acute kidney injury (AKI) in ST segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI)., Methods: We retrospectively studied 723 STEMI patients undergoing primary PCI. Patients were stratified into two groups according to glycated hemoglobin (HbA1c) levels as a marker of prolonged hyperglycemia: those with HbA1c < 7% and those with HbA1c ≥7%. Medical records were reviewed for the occurrence of AKI., Results: HbA1c levels ≥7% were found in 225/723 (31%) of patients. The occurrence of AKI was significantly higher among patients with HbA1c levels ≥7% (32/225, 14%) compared to patients with HbA1c levels < 7% (32/498, 6%; p = 0.001). Patients with chronic kidney disease (CKD) and HbA1c ≥7% had an eight-fold increase in the incidence of AKI compared to patients with HbA1c < 7% and no CKD (32 vs. 4%). In a multivariable regression model, HbA1c ≥7% was independently associated with AKI (OR 1.92, 95% CI 1.09-3.36, p = 0.02)., Conclusion: HbA1c ≥7% was associated with a higher likelihood of AKI in STEMI patients treated with primary PCI., (© 2019 S. Karger AG, Basel.)

Background:: Acute kidney injury is associated with adverse outcomes after acute ST elevation myocardial infarction (STEMI). It remains unclear, however, whether subclinical increase in serum creatinine that does not reach the consensus criteria for acute kidney injury is also related to adverse outcomes in STEMI patients undergoing primary percutaneous coronary intervention., Methods:: We conducted a retrospective study of 1897 consecutive STEMI patients between January 2008 and May 2016 who underwent primary percutaneous coronary intervention, and in whom acute kidney injury was not diagnosed throughout hospitalization. We investigated the incidence of subclinical acute kidney injury (defined as serum creatinine increase of ≥ 0.1 and < 0.3 mg/dl) and its relation to a composite end point of adverse in hospital outcomes., Results:: Subclinical acute kidney injury was detected in 321 patients (17%). Patients with subclinical acute kidney injury had increased rate of the composite end point of adverse in-hospital events (20.3% vs. 9.7%, p<0.001), a finding which was independent of baseline renal function. Individual components of this end point (occurrence of heart failure, atrial fibrillation, need for mechanical ventilation and in-hospital mortality) were all significantly higher among patients with subclinical acute kidney injury ( p< 0.05 for all). In a multivariable regression model subclinical acute kidney injury was independently associated with higher risk for adverse in-hospital events (odds ratio 1.92.6, 95% confidence interval: 1.23-2.97, p=0.004)., Conclusions:: Among STEMI patients treated with primary percutaneous coronary intervention, small, subclinical elevations of serum creatinine, while not fulfilling the consensus criteria for acute kidney injury, may serve as a significant biomarker for adverse outcomes.

Cardiotoxicity from cancer therapy has become a leading cause of morbidity and mortality in cancer survivors. The most commonly used definition is cancer therapeutic related cardiac dysfunction defined as a left ventricular ejection fraction (LVEF) reduction of >10%, to a value below 50%. However, according to the recent American and European Society of Echocardiography, global longitudinal strain (GLS) is the optimal parameter for early detection of subclinical left ventricular dysfunction. The objective of this study was to evaluate the frequency of GLS reduction in patients with active cancer and its correlation to other echocardiographic parameters. Data were collected as part of the International Cardio-Oncology Registry. All patients performed at least 2 echocardiograms including GLS. We evaluated the frequency of GLS reduction (≥10% relative reduction), its correlation to LVEF reduction and whether there are other predicting echocardiographic parameters. In 64 consecutive patients, 12 (19%) had ≥10% GLS relative reduction, of which 75% had no concomitant ejection fraction reduction. There were no significant differences in the baseline cardiac risk factors (hypertension, diabetes, hyperlipidemia, or smoking). Treatment with Doxorubicin, Pertuzumab, or Ifosfamide was significantly more frequent in patients GLS reduction. No other echocardiographic parameters, including diastolic function or systolic pulmonary artery pressure were significant predictors for GLS reduction. In conclusion, our study demonstrates that GLS reduction is frequent in active cancer patients, precedes LVEF reduction and cannot be anticipated by other echocardiographic parameters. Using GLS routinely during therapy may lead to an early diagnosis of cardiotoxicity., (Copyright © 2018. Published by Elsevier Inc.)

Background: Severe aortic stenosis (AS) and severe tricuspid regurgitation (TR) may coexist. The aim of this study was to determine the change in right ventricular (RV) function and TR after surgical aortic valve replacement combined with tricuspid valve repair (SAVR+TVr), transcatheter aortic valve replacement (TAVR), or conservative management and compare outcomes dependent on RV functional parameters and treatment allocation., Methods: A retrospective analysis was conducted in 147 consecutive patients with severe AS and TR of baseline and 6-month clinical and echocardiographic parameters, including quantitative estimation of RV size and function (end-diastolic and end-systolic areas, tricuspid annular plane systolic excursion, fractional area change, and Tei index)., Results: SAVR+TVr and TAVR were associated with superior reduction in TR jet area after 6 months (P = .01 for time × group interaction) compared with conservative therapy. However, RV function (tricuspid annular plane systolic excursion and stroke volume) improved after TAVR but not after SAVR+TVr (P = .007 and P = .02 for time × group interaction, respectively). Conservative therapy for combined AS and TR was associated with >80% mortality in <4 years. TAVR and SAVR+TVr were associated with improved survival compared with conservative therapy (P < .0001), without significant difference between each other. Quantitative RV functional parameters were associated with poor outcomes, including tricuspid annular plane systolic excursion (P = .002), Tei index (P = .02), and RV fractional area change (P = .03)., Conclusions: In this nonrandomized, retrospective, observational study, SAVR+TVr and TAVR were associated with reductions in TR in patients with severe AS combined with severe TR. Importantly, RV function improved after TAVR but not after SAVR+TVr. Patients with severe AS and TR have a very poor prognosis with conservative therapy. When contemplating invasive procedures, assessment should include quantitative functional RV parameters., (Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Recent reports have demonstrated the adverse effects of venous congestion on renal function in patients with heart failure. None of these trials, however, has evaluated the effect of acute myocardial ischemia on the occurrence of acute kidney injury (AKI)., Methods: We conducted a retrospective study of 1336 ST segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) between June 2012 and June 2016. Comprehensive echocardiographic examination was performed within 72 h of hospital admission. Non-invasive evaluation of central venous pressure (CVP) was estimated from measurements of inferior vena cava diameter and its collapsibility. Intermediate-high CVP was defined as ≥ 8 mm/Hg. Patients were stratified according to left ventricular ejection fraction (LVEF) and CVP and assessed for AKI., Results: Intermediate-high CVP was associated with AKI both in patients with LVEF greater than 45% and those with 45% or lower. Patients having LVEF ≤ 45% and intermediate-high CVP had a 10-fold increase in the incidence of AKI compared to patients with LVEF > 45% and normal CVP (39 vs. 4%). In a multivariable logistic regression model, intermediate-high CVP was independently associated with AKI (OR = 2.73, 95% CI 1.54-4.87; p = 0.001). Other variables associated with AKI included LVEF ≤ 45% (OR = 2.37, 95%CI 1.25-4.51; p = 0.008), time to reperfusion, mechanical ventilation and chronic kidney disease., Conclusions: Among STEMI patients undergoing PCI, the utilization of simple echocardiographic measurements (LVEF and CVP) may be useful for early identification of those at high risk for AKI.

Objective: Delay in seeking medical care following symptom onset in patients with acute ST-elevation myocardial infarction (STEMI) is related to increased morbidity and mortality. Actual trends of prehospital delays in patients hospitalized with STEMI have not been well characterized. We evaluated trends in the length of time that had elapsed from symptom onset to hospital presentation among STEMI patients admitted to our hospital., Patients and Methods: We retrospectively studied 2203 consecutive patients hospitalized for acute STEMI who underwent primary percutaneous coronary intervention (PCI) between January 2008 and December 2016. Information on the delay in time from symptom onset to presentation at hospital was extracted from the patients' medical records., Results: Over the 9-year study period, the median duration of prehospital delay for patients undergoing primary PCI showed significant variations, being maximal between the years 2013 and 2014 (150 vs. 90 min, respectively, P<0.001). A significant increase was found in the proportion of patients with prehospital delay less than 2 h, being maximal between the years 2011 and 2013 (64 vs. 47%, P=0.001). An opposite trend was found for decrease in patients with prehospital delay more than 6 h, being maximal between 2008 and 2015 (32 vs. 23%, P=0.001). Multivariate logistic regression model showed that older age, diabetes, female sex, and first STEMI were associated independently with prehospital delay more than 2 h., Conclusion: Prehospital delay periods for patients undergoing primary PCI showed variations over time. More efforts are needed to educate at-risk populations about seeking early medical assistance.

Background: Mitochondria hold crucial importance in organs with high energy demand especially the heart. We investigated whether chronic kidney disease (CKD), which eventually culminates in cardiorenal syndrome, could affect cardiac mitochondria and assessed the potential involvement of angiotensin II (AngII) in the process., Methods: Male Lewis rats underwent 5/6 nephrectomy allowing CKD development for eight months or for eleven weeks. Short-term CKD rats were administered with AngII receptor blocker (ARB). Cardiac function was assessed by echocardiography and cardiac sections were evaluated for interstitial fibrosis and cardiomyocytes' hypertrophy. Electron microscopy was used to explore the spatial organization of the cardiomyocytes. Expression levels of mitochondrial content and activity markers were tested in order to delineate the underlying mechanisms for mitochondrial pathology in the CKD setting with or without ARB administration., Results: CKD per-se resulted in induced cardiac interstitial fibrosis and cardiomyocytes' hypertrophy combined with a marked disruption of the mitochondrial structure. Moreover, CKD led to enhanced cytochrome C leakage to the cytosol and to enhanced PARP-1 cleavage which are associated with cellular apoptosis. ARB treatment did not improve kidney function but markedly reduced left ventricular mass, cardiomyocytes' hypertrophy and interstitial fibrosis. Interestingly, ARB administration improved the spatial organization of cardiac mitochondria and reduced their increased volume compared to untreated CKD animals. Nevertheless, ARB did not improve mitochondrial content, mitochondrial biogenesis or the respiratory enzyme activity. ARB mildly upregulated protein levels of mitochondrial fusion-related proteins., Conclusions: CKD results in cardiac pathological changes combined with mitochondrial damage and elevated apoptotic markers. We anticipate that the increased mitochondrial volume mainly represents mitochondrial swelling that occurs during the pathological process of cardiac hypertrophy. Chronic administration of ARB may improve the pathological appearance of the heart. Further recognition of the molecular pathways leading to mitochondrial insult and appropriate intervention is of crucial importance., Competing Interests: The authors have declared that no competing interests exist.

Background: Acute kidney injury (AKI) following acute ST elevation myocardial infarction (STEMI) is associated with adverse outcomes. The recently proposed KDIGO criteria suggested modifications to the consensus classification system for AKI, namely lowering the threshold of increase in absolute serum creatinine and extending the time frame for AKI detection to 7 days. We evaluated the incidence, risk factors, and long-term mortality associated with AKI as classified by the KDIGO definition in a large single center cohort of consecutive STEMI patients., Methods: We retrospectively studied 2122 consecutive STEMI patients undergoing primary percutaneous coronary intervention (PCI). Recruited patients were admitted between January 2008 and May 2016 to the cardiac intensive care unit with the diagnosis of acute STEMI. We compared the utilization of the KDIGO and consensus criteria for the diagnosis of AKI and its relation to long term mortality., Results: The KDIGO criteria allowed the identification of more patients as having AKI (10.6 vs. 5.6%, p < 0.001) compared to the consensus criteria. Even mild elevation of serum creatinine (≥ 0.3 mg/dL) was associated with a marked increase in all-cause mortality (HR 4.7, 95% CI 3.1-6.43, p < 0.001). Patients with AKI whose renal function resolved prior to hospital discharge still had significantly higher mortality compared to patients with no AKI (23 vs. 8%, HR 3.1, 95% CI 2.09-4.90, p < 0.001)., Conclusion: KDIGO criteria is more sensitive than the consensus criteria in defining AKI in STEMI patients and identifying populations at risk for long term adverse outcomes.

Background: Electrocardiography abnormalities are a common finding in athletes. To facilitate the differentiation of physiological adaptation versus pathological remodeling, a series of guidelines has emerged in the past decade that attempt to improve specificity while maintaining a high sensitivity. Recently, T wave inversion in the athletic population gained more attention, resulting in accelerated research leading to novel findings not yet integrated into clinical practice. We aim to simplify the knowledge to date and integrate it into one easy to use practical flowchart.

Objectives: We have recently shown that the transient receptor potential vanilloid 2 (TRPV2) channel is exclusively upregulated in rat/murine peri-infarct monocytes/macrophages following an acute myocardial infarction (AMI), and that this overexpression might be detrimental for cardiac recovery. We aimed to characterize the expression levels of TRPV2 in peripheral blood mononuclear cells (PBMCs) of AMI patients relative to individuals with normal coronaries, and to analyze potential associations with inflammatory and cardiac ischemic markers., Methods: Patients who underwent coronary angiography due to AMI or chest pain were prospectively included. PBMCs were isolated from whole blood by Ficoll gradient centrifugation. TRPV2 expression was analyzed by real-time PCR. C-reactive protein (CRP) and troponin I (TpI) levels were determined at the central chemistry laboratory; interleukin 6 and insulin-like growth factor (IGF)-1 levels were tested by ELISA., Results: Following AMI, the number of TRPV2-expressing PBMCs was reduced when compared to in patients with normal coronaries. An inverse correlation was documented between the numbers of circulating macrophages and TRPV2 expression. Additionally, TRPV2 expression was inversely correlated with CRP and TpI and directly correlated with serum IGF-1., Conclusions: We assume that peripheral TRPV2 downregulation occurs concomitantly with the accumulation of TRPV2-white blood cells in the peri-infarct zone. TRPV2 may thus represent a novel target for treatment in the acute phase after MI., (© 2018 S. Karger AG, Basel.)

Aims: Shift work disrupts the normal circadian rhythm and is associated with risk factors for coronary artery disease (CAD) and a higher incidence of CAD morbidity and mortality. Cardiac computed tomography angiography (CCTA) is a robust noninvasive modality for assessing the presence, extent, and severity of CAD. We sought to investigate whether shift workers are prone to a higher burden of CAD compared to non-shift workers., Methods: We conducted a historically prospective study in consecutive patients who underwent CCTA and answered a telephonic questionnaire. Due to significant differences in age and gender, we compared 89 well-matched pairs of shift workers and non-shift workers with the use of propensity scores., Results: Our cohort consisted of 349 participants, of whom 94 (26.9%) were shift workers. The mean age was 50.7 years, and 62.5% were males. After pairing, we showed that shift workers had a higher prevalence of CAD than non-shift workers (74.2 vs. 53.9%, respectively, p = 0.01), and a lower prevalence of coronary calcium scores of zero (46.8 vs. 63.4%, respectively, p = 0.034). Stenosis >50% was more prevalent in shift workers than in non-shift workers (20.2 vs. 11.2%, respectively, p = 0.006), and the extent of CAD (defined as the presence of ≥1-vessel disease) tended to be higher in shift workers than in non-shift workers (25.8 vs. 13.5%, respectively, p = 0.06)., Conclusions: In this CCTA study, we showed in a well-matched cohort of consecutive patients that shift workers had a higher prevalence and extent of CAD than non-shift workers., (© 2017 S. Karger AG, Basel.)

Background: The outcome of tricuspid regurgitation (TR) remains unclear because of heterogeneity of etiology and the contradictory results of outcome studies. The aim of this study was to evaluate the clinical outcomes of TR in patients with pulmonary hypertension (PH) and normal left systolic function, stratified to patients with post- or precapillary PH., Methods: In patients with no left valvar disease (isolated) functional TR, preserved left systolic function (ejection fraction ≥ 50%), and PH (systolic pulmonary pressure > 50 mm Hg), TR was assessed both qualitatively (grade) and semiquantitatively using the vena contracta method, and retrospective analysis of long-term outcomes was conducted. Patients with severe comorbid diseases were excluded., Results: The study included 245 patients (age 80.5 years, 37% men, ejection fraction 57%, all with pulmonary systolic pressure > 50 mm Hg). At least moderate to severe TR was diagnosed in 178 patients, and their outcomes were compared with those of 67 patients with the same characteristics and less than mild TR. At least moderate to severe TR was associated with lower survival, independent of all characteristics, right ventricular size or function, comorbidity, or pulmonary pressure (P = .03 for grade and P = .02 for vena contracta). Cox proportional-hazard analysis with interaction terms for TR severity and etiology of PH (post- vs precapillary) showed that the etiology of PH did not affect the association of TR with outcome (P = .90 for the interaction term)., Conclusions: At least moderate to severe isolated TR is independently associated with excess mortality in patients with preserved systolic function and PH, warranting heightened attention to diagnosis and grading. This is irrespective of etiology (pre- or postcapillary) of PH. Semiquantitative assessment of TR by vena contracta is an independent associate of outcome, superior to standard qualitative assessment., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: The present study was designed to assess the underlying mechanism of decline in effort capacity seen with aging., Methods: We analyzed 250 healthy senior patients (≥65 years) with an ejection fraction ≥60% who underwent a stress echocardiogram test. The seniors (aged 65-94) were divided into 3 equal age groups (groups 1, 2, and 3), and their echo characteristics at rest and peak exercise (measured and calculated) were compared., Results: Diastolic function at rest declined significantly (E lateral, E septal, E/E', A) with age, while other rest parameters were similar. There was a significant reduction in peak cardiac output (CO) associated with age (time × age group interaction; P < .05), which was attributed to the combination an attenuated stroke volume (SV) and heart rate (HR) response. The decline in effort capacity with age was the product of the combined effect of cardiac (reduced LVEDV and HR response) and noncardiac (reduction in arteriovenous difference; P = .02 for interaction) causes., Conclusion: The cardiovascular system undergoes several age-related changes. Decline in effort capacity is an ongoing process of aging and consists of several changes in the cardiac and noncardiac systems, comprising a decline in CO and its components, specifically the peak exercise LVEDV, peak heart rate, and the ability of the muscles to extract enough oxygen for the necessary effort., (© 2017, Wiley Periodicals, Inc.)

Background: Diastolic mitral regurgitation (DMR) results from atrioventricular conduction disturbances, acute aortic regurgitation, and/or marked elevation of left ventricular filling pressure. Generally benign, in some clinical circumstances DMR has presumed to result in hemodynamic decompensation. The aforementioned causes of DMR are frequently encountered in patients treated by transcatheter aortic valve replacement (TAVR) but its clinical significance in this setting has not been studied. We sought to investigate the incidence of DMR and its prognostic implications following TAVR., Methods: Baseline clinical and echocardiographic variables from a prospective TAVR registry were analyzed to determine the correlates of post-procedural DMR and its impact on late outcomes (all-cause mortality and the composite of mortality and readmission due to heart failure)., Results: Of 267 patients undergoing TAVR, post-procedural DMR was present in 25 (9.3%). Independent predictors of DMR included pacemaker implantation [OR=2.7 (95%CI 1.03-6.50)], post-procedural systolic MR and aortic regurgitation [OR=3.7 (1.20-10.80) and OR=4.1 (1.50-10.60), respectively], and use of self-expanding bioprostheses [OR=4.9 (1.60-21.0)]. The incidence of the combined endpoint of death and/or readmission for heart failure was higher in patients with versus those without DMR (25% vs. 41%, respectively, p=0.08), although this association did not attain statistical significance on multivariable analyses. Interaction term analysis indicated a trend toward a heightened risk for the composite endpoint among patients with post-procedural aortic regurgitation (≥moderate) in whom DMR occurred (χ 2 2.94, p=0.09)., Conclusions: Although DMR following TAVR is common (occurring in approximately 1 of 10 patients), it is not independently associated with an increased risk of death and/or readmission for heart failure. Therefore, DMR post TAVR is more likely a marker of cardiac dysfunction than a causative factor., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

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.

Background: Since the advent of primary percutaneous coronary intervention (PCI), studies have reported a declining incidence of left ventricular thrombus (LVT) following ST-elevation myocardial infarction (STEMI). We investigated the incidence and outcomes of early (pre-discharge) LVT in the contemporary era of PCI practice in a large cohort of STEMI patients., Methods: We retrospectively studied 2071 consecutive STEMI patients who underwent successful primary PCI. Screening echocardiography was performed within 24-48 h of admission. Patients with anterior STEMI were treated with intravenous heparin for 24-48 h until a first echocardiography test was performed. Patients with reduced ejection fraction (EF) ≤40% had a repeat test before hospital discharge (days 5-7). Heparin was continued in case of significant left ventricular dysfunction (EF < 35%) or apical akinesis or dyskinesis, until a second test ruled out LVT., Results: LVT was diagnosed before hospital discharge in 31/2071 patients (1.5%), 28 of whom (90%) had anterior STEMI. Only 2/31 patients with LVT (6.5%) developed embolic events before discharge and 1/31 (3.2%) had an episode of upper gastrointestinal bleeding that required blood transfusion. There was no significant difference between the two groups regarding in-hospital STEMI-related complications, short- and long-term mortality. All LVTs resolved in subsequent echocardiograms within 6 months of discharge., Conclusions: We report a low incidence of early LVT following STEMI. Further studies are needed to assess the efficacy and safety of a limited in-hospital anticoagulation protocol in STEMI patients with reduced EF.

Background: During the last few years there is a shift from performing Transcatheter Aortic Valve Replacement (TAVR) under general anesthesia towards conscious sedation and local anesthesia only. In the vast majority of centers, sedation is guided by a qualified anesthesiologist. In our center, all TAVR procedures are being performed under local anesthesia and mild sedation, however, since September 2014, a large portion of TAVR procedures are being performed under local anesthesia without the presence of an anesthesiologist. Here we compare 30days outcome of patients undergoing TAVR with and without the presence of anesthesiologist in the catheterization laboratory., Methods and Results: From September 2014 through April 2016, 324 patients (mean age 82.8±6) with severe symptomatic aortic stenosis were assigned to transfemoral TAVR with (150 patients) or without (174 patients) the attendance of an anesthesiologist. Baseline clinical and echocardiographic characteristics were similar between the groups. No difference in procedural and 30-day mortality, vascular complications, and major/life threatening bleeding were observed between the groups (p>0.1, for all)., Conclusions: The presence of an anesthesiologist in the catheterization laboratory during transfemoral TAVR procedures did not significantly change 30-day outcome., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Atrial fibrillation (AF) is a well-known complication in the setting of ST elevation myocardial infarction (STEMI). Data on the long-term prognostic implications of New-Onset AF (NOAF) complicating STEMI in the era of complete revascularization remains controversial. Our aim therefore was to evaluate the long-term prognosis of prior AF (pAF) and new-onset AF (NOAF) in STEMI patients undergoing percutaneous coronary intervention (PCI)., Methods: We studied 1657 consecutive STEMI patients hospitalized in the cardiac intensive care unit during 2008-2014. We reviewed patient records for the occurrence of pAF and NOAF. NOAF was defined as AF occurring within 30days of the STEMI episode. Patients were followed for a mean period of 3.4±2.1years., Results: Within our cohort 77 (4.6%) patients had pAF and 47 (2.8%) had NOAF. Patients with any AF were older and had a reduced systolic ejection fraction. Thirty-day mortality and all-cause mortality rates were significantly higher in patients with pAF in comparison to those without AF (9.1% vs. 2.2% p<0.001 and 31.2% vs. 9.4%, p<0.001, respectively). NOAF showed a trend for increased all-cause mortality (17% vs. 9.1%, p=0.07) and 30-days mortality (6.4% vs. 2.1%. p=0.09). In a multivariate regression model, pAF but not NOAF was a predictor of mortality throughout the follow-up period (HR 2.02, 95% CI 1.2 to 3.1, p=0.005 and HR 1.1, 95% CI 0.56 to 2.2, p=0.75, respectively)., Conclusions: Prior AF and not new-onset AF is an independent predictor of both short and long term mortality in patients treated with PCI., (Copyright © 2017. Published by Elsevier B.V.)

Background: Positive fluid balance has been associated with adverse outcomes in patients admitted to general intensive care units. We analysed the relationship between a positive fluid balance and its persistence over time in terms of in-hospital outcomes among ST elevation myocardial infarction (STEMI) patients complicated by cardiogenic shock., Methods: We retrospectively studied fluid intake and output for 96 hours following hospital admission in 48 consecutive adult patients with STEMI complicated by cardiogenic shock, all undergoing primary angioplasty. Daily and accumulated fluid balance was registered at up to 96 hours following admission. The cohort was stratified into two groups based on the presence or absence of positive fluid balance on day 4. Patients' records were assessed for in-hospital adverse outcomes, as well as 30-day all-cause mortality., Results: A positive fluid balance was present in 19/48 patients (40%). Patients with positive fluid balance were older and more likely to be treated by intra-aortic balloon counter-pulsation and antibiotics. These patients were more likely to develop acute kidney injury and to need new intubation and were less likely to have renal function recovery as well as successful weaning from mechanical ventilation ( p < 0.05 for all). Patients with positive fluid balance had higher 30-day mortality (68% vs. 10%; p < 0.001). In a multivariate Cox regression model, for every 1-L increase in positive fluid balance, the adjusted risk for 30-day mortality increased by 24% (hazard ratio: 1.24, 95% confidence interval: 1.07-1.42; p = 0.003)., Conclusions: A positive fluid balance was strongly associated with higher 30-day mortality in STEMI complicated by cardiogenic shock.

Purpose: We analyzed the relationship between a positive fluid balance and its persistence over time on acute kidney injury (AKI) development, severity and resolution among ST elevation myocardial infarction (STEMI) patients complicated by cardiogenic shock., Methods: We retrospectively studied the cumulative fluid balance intake and output at 96h following hospital admission in 84 consecutive adult patients with STEMI complicated by cardiogenic shock. The cohort was stratified into two groups, based on the presence or absence of positive fluid balance on day 4. Patients' records were assessed for the development of AKI, AKI severity and recovery., Results: Patients having positive fluid balance were more likely to develop a more severe AKI stage (52% vs. 13%; p<0.001), were less likely to have recovery of their renal function (29% vs. 75%, p=0.001), and demonstrated positive correlation between the amount of fluid accumulated and the rise in serum creatinine (R=0.42, p=0.004). For every 1l increase in positive fluid balance, the adjusted possibility for recovery of renal function decreased by 21% (OR=0.796, 95% CI 0.67-0.93; p=0.006)., Conclusions: A positive fluid balance was strongly associated with higher stage AKI and lower rate of AKI recovery in STEMI complicated by cardiogenic shock., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The new European Society of Cardiology guidelines reclassified heart failure according to left ventricular ejection fraction, recognizing patients with mid-range EF (mrEF; 40% to 49%) as a distinct group. We sought to investigate the clinical profile, in-hospital outcomes, and long-term mortality of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention who had mrEF. We conducted a retrospective study of 2,086 consecutive patients with STEMI between December 2007 and June 2016 who underwent primary percutaneous coronary intervention and had a comprehensive echocardiographic examination performed within 72 hours of hospital admission. Patients were stratified according to their left ventricular ejection fraction-mrEF (40% to 49%), reduced EF (rEF; <40%), and preserved EF (pEF; ≥50%) groups and evaluated for baseline characteristics, in-hospital outcomes, as well as for long-term mortality. A total of 858 of 2,086 patients (41%) had mrEF, 215 of 2086 (10%) had rEF, and 1,013 of 2,086 (48%) had pEF. Patients with mrEF had nearly similar baseline co-morbidities and similar 30-day mortality compared with patients with pEF (2% vs 1%, p = 0.17). In a univariate analysis, long-term mortality was higher compared with those with pEF (9.8% vs 7.2%, p <0.01). In a multivariate Cox regression model, mrEF was independently associated with increased long-term mortality risk compared with pEF (hazard ratio 1.4, 95% CI 1.02 to 1.93, p = 0.04). In conclusion, among STEMI patients, those with mrEF at presentation constitute a distinct group in terms of baseline characteristics, in-hospital outcomes, and long-term mortality., (Copyright © 2017 Elsevier Inc. All rights reserved.)