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BACKGROUND: Earlier studies among heart failure (HF) patients reported a paradox of reduced mortality rates in those with increased body mass index (BMI). Recently, however, it has been shown that obesity was not associated with better prognosis in certain groups. The aim of this study was to evaluate the 'obesity paradox' among patients included in the Heart Failure Survey in Israel (HFSIS). METHODS AND RESULTS: Clinical, demographic, and laboratory characteristics of 2,323 patients hospitalized with a diagnosis of acute or decompensated chronic HF in 25 public Israeli hospitals between March 1 and April 30, 2003, were categorized by BMI as: normal weight (18.5-24.9 kg/m(2); n = 837), overweight (25.0-29.9 kg/m(2); n = 877), or obese (>=30.0 kg/m(2); n = 574), excluding 35 patients with BMI <18.5 kg/m(2). Survival over 15 months was inversely related to BMI category. Age-adjusted mortality hazard ratio (HR) was 0.95 (95% confidence interval [CI] 0.79-1.14) for overweight patients and 0.70 (95% CI 0.55-0.88) for obese patients compared with normal-weight patients. After further adjustment for gender, ejection fraction, New York Heart Association functional class, ischemic heart disease, diabetes, hypertension, dyslipidemia, renal function, and medications (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, [beta]-blocker, spironolactone), obesity was associated with a nonsignificant HR of 0.79 (95% CI 0.59-1.05). Hypertension and dyslipidemia were also paradoxically associated with better survival in our model (HR 0.74, CI 0.59-0.92; and HR 0.77, CI 0.63-0.94; respectively; both P < .05). CONCLUSIONS: Our study falls in line with the obesity paradox observation (in obese but not overweight patients) in a large survey of HF patients, although this finding was not statistically significant on multivariate adjustment analysis. [ABSTRACT FROM AUTHOR]

Little is known about the natural history of non-significant mitral and tricuspid regurgitation (MR and TR) following surgical aortic valve replacement (SAVR) for aortic regurgitation (AR). We retrospectively analyzed 184 patients (median age 64 (IQR, 55-74) years, 76.6% males) who underwent SAVR for AR. Subjects with significant non-aortic valvulopathies, prior/concomitant valvular interventions, or congenital heart disease were excluded. The cohort was evaluated for MR/TR progression and, based on the latter's occurrence, for echocardiographic and clinical indices of heart failure and mortality. By 5.8 (IQR, 2.8-11.0) years post-intervention, moderate or severe MR occurred in 20 (10.9%) patients, moderate or severe TR in 25 (13.5%), and either of the two in 36 (19.6%). Patients who developed moderate or severe MR/TR displayed greater biventricular disfunction and functional limitation and were less likely to be alive at 7.0 (IQR, 3.4-12.1) years compared to those who did not (47.2 vs. 79.7%, p < 0.001). The emergence of significant MR/TR was associated with preoperative atrial fibrillation/flutter, symptomatic heart failure, and above-mild MR/TR as well as concomitant composite graft use, but not with baseline echocardiographic measures of biventricular function and dimensions, aortic valve morphology, or procedural aspects. In conclusion, among patients undergoing SAVR for AR, significant MR/TR developed in one fifth by six years, correlated with more adverse course, and was anticipated by baseline clinical and echocardiographic variables.

Background Little is known about the impact of transcatheter mitral valve edge-to-edge repair on changes in left ventricular ejection fraction (LVEF) and the effect of an acute reduction in LVEF on prognosis. We aimed to assess changes in LVEF after transcatheter mitral valve edge-to-edge repair for both primary and secondary mitral regurgitation (PMR and SMR, respectively), identify rates and predictors of LVEF reduction, and estimate its impact on prognosis. Methods and Results In this international multicenter registry, patients with both PMR and SMR undergoing transcatheter mitral valve edge-to-edge repair were included. We assessed rates of acute LVEF reduction (LVEFR), defined as an acute relative decrease of >15% in LVEF, its impact on all-cause mortality, major adverse cardiac event (composite end point of all-cause death, mitral valve surgery, and residual mitral regurgitation grade ≥2), and LVEF at 12 months, as well as predictors for LVEFR. Of 2534 patients included (727 with PMR, and 1807 with SMR), 469 (18.5%) developed LVEFR. Patients with PMR were older (79.0±9.2 versus 71.8±8.9 years; P <0.001) and had higher mean LVEF (54.8±14.0% versus 32.7±10.4%; P <0.001) at baseline. After 6 to 12 months (median, 9.9 months; interquartile range, 7.8-11.9 months), LVEF was significantly lower in patients with PMR (53.0% versus 56.0%; P <0.001) but not in patients with SMR. The 1-year mortality was higher in patients with PMR with LVEFR (16.9% versus 9.7%; P <0.001) but not in those with SMR ( P =0.236). LVEF at baseline (odds ratio, 1.03 [95% CI, 1.01-1.05]; P =0.002) was predictive of LVEFR for patients with PMR, but not those with SMR ( P =0.092). Conclusions Reduction in LVEF is not uncommon after transcatheter mitral valve edge-to-edge repair and is correlated with worsened prognosis in patients with PMR but not patients with SMR. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05311163.

Background: Cancellation of transesophageal echocardiography (TEE) tests leads to inefficient use of echocardiography laboratory (echo lab) time and wastes resources., Objectives: To identify the causes of same-day TEE cancellations in hospitalized patients, to formulate a TEE order screening protocol, and to evaluate its efficacy at implementation., Methods: We performed a prospective analysis of inpatients referred to a single tertiary hospital echo lab for TEE study by inpatient wards. A comprehensive screening protocol emphasizing active participation of all links directly involved in the chain of inpatient TEE referral was developed and implemented. Comparison of pre- and post-implementation of the new screening protocol on two consecutive periods of 6 months on TEE cancellation rates out of total ordered TEEs stratified by cause categories was performed., Results: : In total, 304 inpatient TEE procedures were ordered during the initial observation period; 54(17.8%) were canceled on the same day. The most common cancellation reasons were equally respiratory distress and patient not in fasted state (20.4% of total cancellations and 3.6% of all scheduled TEEs for each cause). Following implementation of the new screening process, total TEEs ordered (192) and cancelled (16) dropped significantly. A decrease in the rate of each cancellation category was observed, with statistical significance achieved for the overall cancellation rate (8.3% vs. 17.8%, P = 0.003), but not for the individual cancellation categories in split analysis., Conclusions: A concerted effort to implement a comprehensive screening questionnaire significantly reduced same-day cancellations of scheduled TEEs.

Background: Primary pericardial mesothelioma is an extremely rare disease. Prognosis is poor, with little effects of chemo- or radio-therapy. The majority of cases is diagnosed at autopsy., Case Summary: A 22-year-old man, who presented with recurrent pericarditis and large pericardial effusion 2 months after a second BNT162b2 COVID-19 vaccine, underwent pericardiocentesis and pericardial window. Pathology specimen of pericardium revealed benign mesothelial inflammation, consistent with acute pericarditis. Four months later, he presented with a large pericardial mass manifesting in heart failure and underwent urgent pericardiectomy. A new pathology specimen immunostaining and fluorescence in situ hybridization analysis revealed pericardial mesothelioma. Despite intensive care, the patient died 3 weeks later., Discussion: Primary pericardial mesothelial should be considered in the differential diagnosis of refractory recurrent pericarditis, even with prior biopsy-proven pericarditis or when a putative trigger (COVID-19 mRNA prior vaccination) is suspected, as was the case in this patient. Tumour diagnosis and identification consist of multimodal imaging and laboratory tests. A multidisciplinary, individualized care approach should be performed., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Transthoracic echocardiography (TTE) is the gold standard for aortic stenosis (AS) assessment. Transesophageal echocardiography (TEE) provides better resolution, but its effect on AS assessment is unclear. To answer this question, we studied 56 patients with ≥moderate AS. Initial TTE (TTE1) was followed by conscious sedation with simultaneous TEE and TTE2. Based on conservative versus actionable implication, AS types were dichotomized into group A, comprising moderate and normal-flow low-gradient, and group B, comprising high gradient, low ejection fraction low-flow low-gradient, and paradoxical low-flow low-gradient AS. Paired analysis of echocardiographic variables and AS types measured by TEE versus TTE2 and by TEE versus TTE1 was performed. TEE versus simultaneous TTE2 comparison demonstrated higher mean gradients (31.7 ± 10.5 vs 27.4 ± 10.5 mm Hg) and velocities (359 ± 60.6 vs 332 ± 63.1 cm/s) with TEE, but lower left ventricular outflow velocity-time-integral (VTI 1 ) (18.6 ± 5.1 vs 20.2 ± 6.1 cm), all p <0.001. This resulted in a lower aortic valve area (0.8 ± 0.21 vs 0.87 ± 0.28 cm 2 ), p <0.001, and a net relative risk of 1.86 of group A to B upgrade. TEE versus (awake state) TTE1 comparison revealed a larger decrease in VTI 1 because of a higher initial awake state VTI 1 (22 ± 5.6 cm), resulting in similar Doppler-velocity-index and aortic valve area decrease with TEE, despite a slight increase in mean gradients of 0.8 mm Hg (confidence interval -1.44 to 3.04) and velocities of 10 cm/s (confidence interval -1.5 to 23.4). This translated into a net relative risk of 1.92 of group A to B upgrade versus TTE1. In conclusion, TEE under conscious sedation overestimates AS severity compared with both awake state TTE and simultaneous sedation state TTE, accounted for by different Doppler insonation angles obtained in transapical versus transgastric position., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: In view of inconsistencies in threshold values of severe aortic stenosis (AS) hemodynamic indices, it is unclear what is the relative contribution of each variable in a binary classification of AS based on aortic valve replacement (AVR) indication. We aimed to assess relative discriminative value and optimal threshold of each constituent hemodynamic parameter for this classification and confirm additional prognostic value., Methods: Echocardiography studies of 168 patients with ≥ moderate AS were included. AS types were dichotomized into Group-A, comprising moderate and Normal-Flow Low-Gradient (NFLG), and Group-B, comprising High-Gradient(HG), Low Ejection Fraction Low-Flow Low-Gradient(Low EF-LFLG), and Paradoxical Low-Flow Low-Gradient(PLFLG) AS. Aortic valve area (AVA), Doppler velocity index (DVI), peak aortic velocity, mean gradient, stroke volume index and transaortic flow rate(TFR) were assessed for A/B Group discrimination value and optimal thresholds were determined. Dichotomized values were assessed for predictive value for AVR or death., Results: C-statistic values for binary AS classification was .74-.9 for the tested variables. AVA and DVI featured the highest score, and SVI the lowest one. AVA≤.81 cm 2 and DVI≤.249 had 87.6% and 86% respective sensitivity for Group B patients, and a similar specificity of 80.9%. During a mean follow-up of 9.1±10.1 months, each of the tested dichotomized variables except for SVI predicted AVR or death on multivariate analysis., Conclusion: An AVA value ≤.81 cm 2 or a DVI ≤ .249 threshold carry the highest discriminative value for severe AS in patients with aortic stenosis, translating into an independent prognostic value, and can be helpful in making clinical decisions., (© 2021 Wiley Periodicals LLC.)

Background: We have previously reported an increased risk for non-hematological malignancies in young patients with moderate or severe aortic stenosis (AS). These findings were the result of a post-hoc analysis from a large echocardiography database and needed verification. Our aim was to determine, using a different study population, whether young patients with AS are at increased risk for cancer., Methods: A large echocardiographic database was used to identify patients (age ≥ 20 years) with moderate or severe AS (study group) and patients without aortic stenosis (comparative group). The new occurrence of non-hematological malignancies was determined after the index date (first echo with moderate or severe AS or first recorded echo in the control group)., Results: The final study group included 7013 patients with AS and 98,884 without AS. During a median follow-up of 6.9 years (3.0-11.1) there were 10,705 new cases of non-hematological cancer. The crude incidence rate of cancer was higher in AS compared to non-AS patients (22.3 vs. 13.7 per 1000 patient-year, crude HR 1.58 (95%CI 1.46-1.71). After adjustment for relevant covariates, there was no difference between groups (HR 0.93, 95% CI 0.86-1.01). Only patients in the lowest age quartile (20-49.7 years), had an increased adjusted risk of cancer (HR 1.91, 95%CI 1.08-3.39). The HR for the risk of cancer associated with AS was inversely proportional to age (P < 0.001 for the interaction between AS and age)., Conclusions: Young patients with moderate or severe AS may have an increased risk for cancer. Cancer surveillance should be considered for young patients with AS., (© 2021. The Author(s).)

Objectives: The purpose of this study was to examine the impact of residual mitral regurgitation (MR) on mortality in patients undergoing transcatheter aortic valve replacement (TAVR)., Background: MR is common in patients undergoing TAVR. Data on optimal management of patients with significant MR after TAVR are limited., Methods: The registry consisted of 16 TAVR centers (n = 7,303). Outcomes of patients with ≥ moderate versus lesser grade MR after TAVR were compared., Results: In 1,983 (27.2%) patients, baseline MR grade was ≥ moderate. MR regressed in 874 (44.1%) patients and persisted in 1,109 (55.9%) after TAVR. Four-year mortality was higher for those with MR persistence, but not for those with MR regression after TAVR, compared with nonsignificant baseline MR (43.8% vs. 35.1% vs. 32.4%; hazard ratio [HR]: 1.38; p = 0.008; HR: 1.02; p = 0.383, respectively). New York Heart Association functional class III to IV after TAVR was more common in those with MR persistence vs. regression (14.4% vs. 3.9%; p < 0.001). In a propensity score-matched cohort (91 patients' pairs), with significant residual MR after TAVR who did or did not undergo staged mitral intervention, staged intervention was associated with a better functional class through 1 year of follow-up (82.4% vs. 33.3% New York Heart Association functional class I or II; p < 0.001), and a numerically lower 4-year mortality, which was not statistically significant (64.6% vs. 37.5%; HR: 1.66; p = 0.097)., Conclusions: Risk stratification based on improvement in MR and symptoms after TAVR can identify patients at increased mortality risk after TAVR. These patients may benefit from a staged transcatheter mitral intervention, but this requires further proof from future studies. (Transcatheter Treatment for Combined Aortic and Mitral Valve Disease. The Aortic+Mitral TRAnsCatheter [AMTRAC] Valve Registry [AMTRAC]; NCT04031274)., Competing Interests: Funding Support and Author Disclosures Dr. Barbanti has received consultant fees from Edwards Lifesciences. Dr. Grasso has served as a proctor for Abbott Vascular. Dr. De Backer has received research grants and consultant fees from Abbott and Boston Scientific. Dr. Andreas has served as a proctor for Abbott and Edwards Lifesciences; and has received advisory board fees from Medtronic. Dr. Estévez-Loureiro has served as a consultant for Abbott Vascular and Boston Scientific. Dr. Amat-Santos has served as a proctor for Boston Scientific. Dr. Nombela-Franco has received consultant fees from Edwards Lifesciences; and has served as a proctor for Abbott. Dr. Søndergaard has received consultant fees and institutional research from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr. Van Mieghem has received research grant support from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, PulseCath BV, and Daiichi-Sankyo; and has received advisory fees from Abbott, Boston Scientific, Ancora, Medtronic, PulseCath BV, and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Fever following transcatheter aortic valve implantation (TAVI) is a common phenomenon, attributed mostly to inflammatory response which may impact outcome. Systemic inflammatory response may be triggered by multiple factors, most associated with the TAVI procedure itself. However, there are no data regarding the incidence of fever following TAVI in contemporary era with newer generation devices. Our primary objective was to measure temporal trends in fever incidence and features following TAVI., Methods: We analyzed a retrospective cohort of 802 consecutive patients who underwent TAVI at our institution between November 2008 and February 2018. We identified and characterized all patients who developed fever (>38.0°C from any cause) within the first 72 h following the procedure and analyzed incidence and characteristics stratified into 3 time frames: 2008-2014, 2014-2016, and 2016-2018., Results: Following TAVI, 190 (23.7%) patients developed fever (mean age 82.3 ± 5.2 years, 64.2% female). An infectious etiology was evident in only 32.1% of cases. The frequency decreased gradually and significantly across timeframes (32.8, 23.6, and 14.5%, respectively, p < 0.001). In a multivariate regression analysis, 1st generation CoreValve (HR 1.91; CI 95% 1.2-3.04, p = 0.006) was found to be associated with higher incidence of fever in addition to female gender, vascular complications, transfemoral access, and reduced GFR., Conclusions: Fever incidence post TAVI decreased significantly throughout the last decade. The higher rate of fever in the early years of TAVI was likely associated with first-generation devices, vascular complications, and reduced GFR., (© 2021 S. Karger AG, Basel.)

Since the diagnosis of cardiac amyloidosis (CA) is often delayed, echocardiographic findings are frequently indicative of advanced cardiomyopathy. We aimed to describe early echocardiographic features in patients subsequently diagnosed with CA. Preamyloid diagnosis echocardiographic studies were screened for structural and functional parameters and stratified according to the pathogenetic subtype (immunoglobulin light-chain [AL] or amyloid transthyretin [ATTR]). Abnormalities were defined based on published guidelines. Our cohort included 75 CA patients of whom 42 (56%) were diagnosed with AL and 33 (44%) with ATTR. Forty-two patients had an earlier echocardiography exam available for review. Patients presented with increased wall thickness (1.3 [interquartile range {IQR} 1.0, 1.5] cm) ≥3 years before the diagnosis of CA and relative wall thickness was increased (0.47 [IQR 0.41, 0.50]) ≥7 years prediagnosis. One to 3 years before CA diagnosis restrictive left ventricular (LV) filling pattern was present in 19% of patients and LV ejection fraction ≤50% was present in 21% of patients. Right ventricular dysfunction was detected concomitantly with disease diagnosis. The echocardiographic phenotype of ATTR versus AL-CA showed increased relative wall thickness (0.74 [IQR 0.62, 0.92] versus 0.62 [IQR 0.54, 0.76], p = 0.004) and LV mass index (144 [IQR 129, 191] versus 115 [IQR 105, 146] g/m 2 , p = 0.020) and reduced LV ejection fraction (50 [IQR 44, 58] versus (60 [IQR 53, 60]%, p = 0.009) throughout the time course of CA progression, albeit survival time was similar. In conclusion, increased wall thickness and diastolic dysfunction in CA develop over a time course of several years and can be diagnosed in their earlier stages by standard echocardiography., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Sedation can impact aortic stenosis (AS) classification, which depends on left ventricular ejection fraction (<≥ [less than or greater than and/or equal to] 50%), aortic valve area (AVA<≥ 1 cm 2 ), mean pressure gradient (<≥ 40 mm Hg), peak velocity <≥ 400 cm/sec, and stroke volume index (SVI <≥35 mL/m 2 ). We compared AS classification by transthoracic echo (TTE) during wakefulness versus sedation., Methods: Immediately following a baseline TTE performed during wakefulness, another TTE was done during sedation delivered for a concomitant transesophageal study in 69 consecutive patients with AS (mean age 78 ± 7 years, 32 males). AVA was calculated through the continuity equation using the relevant hemodynamic parameters measured by each TTE study and same left ventricular outflow tract. AS class was defined as moderate, severe high gradient (HG), low ejection fraction low flow low gradient (LF-LG), paradoxical LF-LG (PLFLG), and normal flow low gradient (NF-LG). Based on conservative versus invasive treatment implication, AS classes were aggregated into group A (moderate AS and NFLG) and group B (HG, low-EF LF-LG, and PLFLG)., Results: During sedation, systolic and diastolic blood pressure decreased by 14.3 ± 29 and 8 ± 22 mm Hg, respectively, mean pressure gradient from 30.4 ± 10.9 to 27.2 ± 10.8 mm Hg, peak velocity from 345.3 ± 57.7 to 329.3 ± 64.8 cm/m 2 , and SVI from 41.5 ± 11.3 to 38.3 ± 11.8 mL/m 2 (all P < .05). Calculated AVA was similar (delta = -0.009 ± 0.15 cm 2 ). Individual discrepancies in hemodynamic parameters between the paired TTE studies resulted in an overall 17.4% rate of AS intergroup misclassification with sedation, with a relative risk of 1.09 of downgrade misclassification from group B to A versus upgrade misclassification (P < .001)., Conclusions: Sedation TTE assessment downgrades AS severity in a significant proportion of patients, with a conversely smaller proportion of patients being upgraded, and therefore cannot be a substitute for wakefulness assessment., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: The MitraClip procedure is becoming an acceptable alternative for high-risk patients with mitral regurgitation (MR) due to functional (FMR) or degenerative (DMR) disease and suitable mitral anatomy., Objectives: To evaluate the results of MitraClip at our institute in carefully selected patients., Methods: We conducted a retrospective analysis of medical records and echocardiography data from January 2012 to December 2017., Results: A total of 39 MitraClip procedures in 37 patients (aged 75 ± 12 years, 9 women) was performed. Twenty-four patients presented with FMR, 12 with DMR, and 1 with combined pathology. One-day post-procedure MR was moderate to low in 86.1% of patients, with immediate device success in 88.8%. MR at 1 year was moderate to low in 79% at 1 year. Survival at 1 year was 86% and at 2 years 69.4%. Peri-procedural (< 1 week) death and MitraClip failure occurred in one and three patients, respectively. New York Heart Association score improved to class 1 or 2 in 37% of patients at 1 year vs. one patient at baseline. Post-procedural systolic pulmonary pressure was reduced from 53 (range 48-65) to 43 (range 36-52) mmHg at 1 month with a subsequent plateau at follow-up, to 41 (34-57) mmHg at 6 months, and to 47 (38-50) at 12 months., Conclusions: MitraClip in severe MR resulted in modest improvement in functional status and pulmonary pressure with a small risk of immediate procedural complications. Outcomes are encouraging considering the natural course of MR and the risks of surgical intervention.

Background: Late tricuspid regurgitation is a common finding in patients with rheumatic valvular disease after mitral valve replacement surgery. However, the long-term benefit of concomitant tricuspid valve annuloplasty has not been established in this population., Methods: This was a single-center retrospective study in a tertiary hospital. The final cohort included 285 rheumatic patients who underwent either isolated mitral valve replacement (147 patients) or mitral valve replacement with concomitant tricuspid valve annuloplasty (138 patients). Tricuspid regurgitation severity grade was assessed according to current echocardiography guidelines and graded using a 0 to 3 scale (none or trivial, mild, moderate, severe)., Results: Patients were followed for a total median duration of 10.8 (interquartile range, 6.8 to 14.5) years. The majority of patients undergoing mitral valve replacement were women, with a median age at operation of 59 (interquartile range, 48 to 68) years. Patients undergoing concomitant tricuspid valve annuloplasty had a 3.4-fold odds of improving their tricuspid regurgitation grade at long-term follow-up by multivariate logistic regression. Furthermore, concomitant tricuspid valve annuloplasty was independently associated with a long-term survival benefit in patients with preoperative moderate or severe tricuspid regurgitation (hazard ratio, 0.44; 95% confidence interval, 0.23 to 0.87; p = 0.018)., Conclusions: This study demonstrates good long-term results in patients with rheumatic heart disease undergoing mitral valve replacement with concomitant tricuspid valve annuloplasty., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Transthoracic echocardiography (TTE) is the standard method for evaluating the severity of aortic stenosis (AS), while transesophageal echocardiography (TEE) is useful for morphologic characterization. The study aim was to assess the impact of complementary TEE to TTE in refining hemodynamic assessment of AS severity., Methods: A retrospective analysis was conducted of sequential TTE and TEE studies performed in 100 patients with moderate or severe AS confirmed on prior TTE. The left ventricular outflow tract (LVOT) velocity-time-integral (VTI1) and the aortic valve velocity-time integral (VTI2) were measured for both modalities. The highest values of VTI1 and VTI2 and mean gradients and peak velocities were selected from the sequential TTE/TEE study for indexed aortic valve area (AVAi) calculation and AS severity determination through an integrated assessment., Results: AVAi determined by TTE was not significantly different from that determined by TEE (mean difference -0.008 cm2; p = 0.38). The dimensionless velocity index (DVI) was higher when assessed by TTE than by TEE (mean difference 0.0126 ± 0.04; p = 0.003). Using the integrated AS assessment, six of 13 patients with a TTE-based diagnosis of moderate AS were re-classified as severe AS. A slight lowering of the recommended TTE-derived DVI threshold for severe AS, from 0.25 to 0.24, improved the ability to discriminate moderate versus severe AS, as determined by the integrated assessment., Conclusions: TEE integrated with TTE may improve the detection of severe AS, particularly in patients with moderate AS criteria assessed by TTE, but with a DVI ratio ≤0.24.

Transcatheter aortic valve implantation (TAVI) is an established treatment for severe aortic stenosis in patients at high or prohibitive surgical risk. Nevertheless, long-term clinical and echocardiographic data are still lacking. We carried out an analysis of 560 consecutive patients who underwent TAVI at our institution from 2008 to 2016 to evaluate temporal changes in TAVI characteristics, predictors of 1-year and long-term outcomes, and to compare the performance of the early- and new-generation valve systems. With time, we have adopted lower risk threshold for patient selection and have been using conscious sedation and transfemoral access preferentially (p <0.001 for all). The incidence of greater than mild PVL decreased from 16% to 7.6%, p = 0.029. Within 5 years, 47% of the patients died, the majority (78%) due to noncardiac causes. Independent predictors of 1-year death included periprocedural aspects (i.e., vascular complications, stroke, and PVL), whereas death occurring later than 1 year was solely related to baseline co-morbidities. Transvalvular gradients and residual regurgitation remained nonclinically significant for up to 5 years of follow-up. New-generation valves were associated with less PVL compared with propensity score-matched early-generation valves (p <0.001). In conclusion, TAVI utilization at our institution has progressed to include lower risk patients with transfemoral access becoming applicable in the great majority. Poor long-term survival is attributable to population factors rather than to procedural factors. Intermediate- and long-term hemodynamics are excellent. PVL has diminished significantly with the new-generation valves. Efforts to improve long- and short-term outcomes remain a therapeutic challenge., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Patients with suspected dissection of the thoracic aorta require immediate diagnostic evaluation so that urgent therapeutic interventions can begin. We present a case of aortic dissection with an atypical initial presentation mimicking acute pericarditis, in which the correct diagnosis was made on the basis of the suprasternal view of transthoracic echocardiography.

Compared to patients with normal renal function, the prevalence of atrial fibrillation (AF) in chronic kidney disease (CKD) is increased, as is consequently the stroke prevalence in these patients. This increased risk of stroke in patients with CKD is caused not only by the increased prevalence of AF, but also by associated co-morbidities, and inherent platelet and vascular dysfunction. Paradoxically, imbalance in the same factors also increases the bleeding risk, imposing a dilemma as to whether anticoagulation should be prescribed or deferred, particularly in patients with end-stage renal disease (ESRD), in whom the bleeding diathesis and thromboembolic predisposition are most recalcitrant. Unfortunately, it is in this vulnerable population, in whom therapeutic options are most limited, that evidence-based studies relating to stroke prophylaxis are scarce, discordant and based only on registry observations. Pending randomized controlled studies on this issue, we will review important epidemiologic data and major recent registry-based studies that the clinician has to weigh when making the best decision on the issue of the prophylactic use of warfarin in patients with CKD with AF, focusing on patients with end-stage renal disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To explore the relation between the baseline aortic valve gradient (AVG) as a continuous variable and clinical outcomes following transcatheter aortic valve implantation (TAVI) in general and specifically in patients with high-gradient aortic stenosis (AS)., Methods: We reviewed 317 consecutive patients who underwent TAVI at our institution. We investigated the relation between AVG as a continuous/categorical variable and outcome among all patients and in patients without low-flow low-gradient AS, using the Cox proportional hazard model adjusting for multiple prognostic variables., Results: Patients had a peak AVG of 79.9 ± 22.8 mm Hg (mean 50.5 ±15.7). During a mean follow-up of 2.7 years, AVG was inversely associated with mortality and mortality or cardiac hospitalization. Every 10-mm-Hg increase in peak AVG was associated with 18% reduction in mortality (p = 0.003) and 19% reduction in mortality/cardiac hospitalization (p < 0.001). Every 10-mm-Hg increase in mean AVG was associated with a 24% reduction in both outcomes (p = 0.005 and p < 0.001). Subgroup analysis of patients with left-ventricular ejection fraction >40% or peak AVG >64 mm Hg yielded similar results., Conclusions: Mean and peak baseline AVGs are directly associated with improved outcomes after TAVI; AVG can be used to select the patients most likely to benefit from TAVI., (© 2016 S. Karger AG, Basel.)

Transcatheter aortic valve implantation (TAVI) is an established technique for the treatment of severe symptomatic aortic stenosis. Data on long-term TAVI outcomes, both hemodynamic and clinical, in real-world practice settings are limited. We aim to explore the long-term clinical results in patients with severe symptomatic aortic stenosis using multiple catheter-based options: 360 TAVI-treated patients were followed up for ≤5 years. The Medtronic CoreValve was used in 71% and the Edwards SAPIEN in 26%. The primary end point was all-cause mortality during follow-up. Outcomes were assessed based on the Valve Academic Research Consortium 2 criteria. The mean ± SD patient age was 82.1 ± 6.9 years (56.4% women). The Society of Thoracic Surgeons score was 7.5 ± 4.7. The clinical efficacy end point and time-related valve safety at 3 years was 50% and 81.7%, respectively. The calculated 3- and 5-year survival rates were 71.6% and 56.4%, respectively. Five-year follow-up data were obtained for 54 patients alive; 96.2% of alive patients were in the New York Heart Association class I and II, 4 years after TAVI. No gender differences in all-cause mortality rates were observed (p = 0.58). In multivariate analysis, hospitalization 6 months previous to TAVI (hazard ratio [HR] 1.92, 95% confidence interval [CI] 1.17 to 3.15, p = 0.01), frailty (HR 1.89, 95% CI 1.11 to 3.2, p = 0.02), acute kidney injury (HR 1.93, 95% CI 1.03 to 3.61, p = 0.04), and moderate or more paravalvular aortic regurgitation after TAVI (HR 4.26, 95% CI 2.54 to 7.15, p <0.001) were independent predictors for all-cause mortality. In conclusion, long-term outcomes of TAVI are encouraging. Prevention and early identification of paravalvular leak and acute renal failure after the procedure would improve short- and long-term outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: We hypothesized that the guideline-recommended peak anti-Xa levels for pregnant women with mechanical prosthetic heart valves (MPHVs) receiving adjusted dose low-molecular-weight heparin (LMWH) are associated with subtherapeutic trough levels and consequently with an inadequate level of anticoagulation., Background: Low-molecular-weight heparin is often used for anticoagulation in pregnant women including those with MPHV. American College of Cardiology/American Heart Association guidelines recommend monitoring of plasma anti-Xa factor peak levels and adjustment of the dose to achieve peak levels of 0.7 to 1.2 U/mL. In spite of these recommendations, cases of valve thrombosis during pregnancy continue to occur., Methods and Results: We studied 30 pregnant patients receiving anticoagulation for various indications with adjusted dose LMWH given subcutaneously twice a day which had both trough and peak anti-Xa levels throughout pregnancy for a total of 187 paired determinations. The recommended peak anti-Xa levels (0.7-1.2 U/mL) were obtained in 123 (66%) of the measurements but in 80% of them, the trough levels were found to be subtherapeutic (<0.6 U/mL). Subtherapeutic trough levels were found in 8 (73%) of the 11 measurements with peak levels of 0.7 to 0.79 U/mL, 17 (74%) of the 23 of 0.8 to 0.89 U/mL, 21 (72%) of the 29 of 0.9 to 0.99 U/mL, and 28 (44%) of the 63 of 1.0 to 1.2 U/mL. There were 42 measurements with peak anti-Xa levels >1.2 U/mL and even in these cases, 13 (31%) of the trough levels were found to be subtherapeutic., Conclusions: Anticoagulation with adjusted dose LMWH aimed to achieve guideline-recommended peak levels of anti-Xa for patients with MPHVs is commonly associated with subtherapeutic trough levels. Routine measurement of trough anti-Xa levels is therefore advisable in women with MPHV treated with LMWH during pregnancy to assure adequate level of anticoagulation., (© The Author(s) 2014.)

Left atrial appendage (LAA) occlusion or ligation by percutaneously implanted devices is increasingly an alternative management option for atrial fibrillation, particularly for patients who are intolerant or have contraindications for anticoagulation. Echocardiography plays an important part in screening, guidance of implantation, and after-device assessment. Assessment of LAA anatomy suitable for device implantation, thrombus exclusion, guidance of transseptal puncture, localization of catheter, guidance of device deployment, and after-device assessment are all important functions of echocardiography. This article reviews the role of echocardiography in device-based LAA occlusion or ligation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The pathophysiology of aortic stenosis (AS) involves inflammatory features including infiltration of the aortic valve (AV) by activated macrophages and T cells, deposition of lipids, and heterotopic calcification., Objectives: To evaluate the correlation between white blood cell (WBC) differential count and the occurrence and progression of AS., Methods: We identified in our institutional registry 150 patients with AS who underwent two repeated echo studies at least 6 months apart. We evaluated the association between the average of repeated WBC differential counts sampled during the previous 3 years and subsequent echocardiographic AS indices., Results: There was no significant difference in total WBC, lymphocyte or eosinophil count among mild, moderate or severe AS groups. There was a progressive decrease in monocyte count with increasing AS severity (P = 0.046), more prominent when comparing the mild and severe groups. There was a negative correlation between AV peak velocity or peak or mean gradient and monocyte count in the entire group (r = -0.31, -0.24, and -0.25 respectively, all P < 0.01). Similar partial correlations controlling for age, gender, hypertension, smoking, dyslipidemia and ejection fraction remained significant. The median changes over time in peak velocity and peak gradients in AS patients were 0.44 (0-1.3) m/sec/ year and 12 (0-39) mmHg/year, respectively. There was no correlation between any of the WBC differential counts and the change in peak velocity or peak gradient per year., Conclusions: Severe AS is associated with decreased total monocyte count. These findings may provide further clues to the mechanism underlying the pathogenesis of aortic stenosis.

Effective anticoagulation is critical in patients with mechanical prosthetic heart valve (MPHV), but remains challenging in pregnancy because both oral anticoagulation and heparins are associated with important fetal and maternal risks. A 33-year-old high-risk pregnant woman presented with MPHV thrombosis during early pregnancy. Resolution of the thrombus and eventual resumption of normal prosthetic mitral valve function was obtained through treatment with low-molecular weight heparin (LMWH). This case of early pregnancy MPHV thrombosis emphasized the importance of adequate initial coagulation prior to pregnancy and the potential need to extend measurements to both peak and trough levels to assure an adequate level of anticoagulation in women with MPHV treated with LMWH during pregnancy.

Background: Despite having a similar large extent of atherosclerotic coronary affliction, some patients suffer of recurrent cardiac events, whereas others remain asymptomatic., Hypothesis: We hypothesized the existence of a systemic "signature" that could distinguish "vulnerable" patients with preexisting coronary atherosclerosis from those having similar risk factors and atheromatous burden, but no history of clinically evident plaque rupture/erosion., Methods: Twenty three patients who had at least two prior myocardial infarctions ("vulnerable group") were matched in respect to their background and coronary atherosclerosis extent with twenty one patients without a history of previous myocardial infarction who underwent routine coronary angiography before valvular surgery. We studied a panel of cytokines, antibodies and hormones including IL-6, IL-10, IL-12, antibodies to β2 glycoprotein I (β2GPI), antibodies to oxidized-LDL, adiponectin and resistin, along with levels of circulating EPCs and Tregs., Results: A significantly higher level of Treg cells was present in the control (73.4%±4) than in the "vulnerable patient" group (62.2%±10.7), p<0.001. IL-10 level was also significantly higher in the control than in the vulnerable patients (2.6±1.2 pg/ml versus 0.9±0.1 pg/ml respectively, p=0.03). There was no significant difference in the circulating levels of the other cytokines, hormones or EPCs between the two groups., Conclusion: Regulatory T cells and serum IL-10 may discriminate "vulnerable" versus stable patients and may have a protective role against plaque rupture in patients with coronary atherosclerosis., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Cardiac tamponade can be a lethal complication in the cardiac catheterization laboratory. Patients with obstructive hypertrophic cardiomyopathy are particularly vulnerable to the hemodynamic effects of tamponade because of their heightened sensitivity to ventricular load in the generation of forward stroke volume. Cardiac tamponade should be distinguished from the normal effects of respiration on dynamic outflow tract obstruction in these patients. This recognition not only ensures an accurate hemodynamic diagnosis, but it also will expedite timely therapy for patients in need., (Copyright © 2010 Wiley-Liss, Inc.)

Background: ST-elevation myocardial infarction is caused by occlusive coronary thrombosis where antecedent plaque disruption occurs. When treating STEMI the main goal is to achieve prompt reperfusion of the infarction area. Several studies have demonstrated the efficacy of an aspiration device before percutaneous coronary intervention in patients with acute myocardial infarction., Objectives: To determine the added value of thrombus aspiration prior to primary PCI by comparing AMI patients with totally occluded infarct-related artery treated with routine primary PCI to those treated with extraction device prior to primary PCI., Methods: The study group comprised 122 consecutive patients with AMI and a totally occluded infarct artery (TIMI flow 0) who underwent primary PCI. The patients were divided into two groups: 68 who underwent primary PCI only (control group) and 54 who underwent primary thrombus extraction with an extraction device before PCI (extraction group). Baseline clinical and lesion characteristics were similar in both groups. Final TIMI grade flow and myocardial blush as well as 1 year mortality, target lesion revascularization, recurrent myocardial infarction, unstable angina and stroke were compared between the two groups., Results: Primary angiographic results were better for the extraction group versus the control group: final grade 3 TIMI flow was 100% vs. 95.6% (P= 0.03) and final grade 3 myocardial blush grade 50% vs. 41.18% (although Pwas not significant). Long-term follow-up total MACE showed a nonsignificant positive trend in the extraction group (12.96% vs. 24.71%, P= 0.26)., Conclusions: The use of extraction devices for intracoronary thrombectomy during primary PCI in patients with totally occluded infarct artery significantly improved epicardial reperfusion in the infarct-related vessel and showed a trend for more favorable long-term outcome.

Aim: To compare the predictive power of different endothelial progenitor cell (EPC) phenotypic markers for future cardiovascular events., Methods: Peripheral blood was collected from 76 consecutive patients with acute coronary syndromes (ACS) who underwent percutaneous coronary intervention in our institute. The various EPC phenotypes of peripheral blood mononuclear cells were CD34+CD133+, CD34+KDR+, and CD 133+KDR+. The outcome endpoint included cardiovascular mortality, recurrent ACS, and hospitalization for decompensated heart failure during a 24-mo follow-up period., Results: CD34+CD133+ cells (P = 0.034), but not CD34+KDR+ (P = 0.35) or CD 133+KDR+ cells (P = 0.19), were found to predict recurrent ACS. We found no correlation between EPCs measured by any of the three phenotypic combinations of accepted CD markers and the total combination of these separate outcomes., Conclusion: The EPC CD34+CD133+ phenotype, but not the CD34+KDR+ or the CD 133+KDR+ phenotypes, is predictive of future adverse cardiovascular outcomes.

Isolated ventricular non-compaction is a frequently underdiagnosed rare congenital cardiomyopathy. The importance of diagnosing this cardiomyopathy lies especially in asymptomatic patients, screening relatives of index cases in order to focus on their follow-up, and searching for criteria warranting prophylactic anticoagulation, implantable cardioverter defibrillator and anti-remodeling drugs such as angiotensin-converting inhibitors. We present the clinical and imaging characteristics of this entity and discuss some of the therapeutic dilemmas involving these patients.

The no-reflow phenomenon after successful coronary artery perfusion is caused by a myocardial perfusion defect due to impaired blood flow in the microvascular bed. This phenomenon is more prevalent among acute myocardial infarction patients who have additional cardiovascular risk factors, and its presence constitutes an independent negative prognostic sign. The impaired microvascular myocardial blood flow is caused by microemboli and by intracellular processes taking place during the reperfusion phase. In the last few years, many studies have been published regarding new diagnostic and treatment modalities based on a better understanding of the pathophysiological processes implicated.

Background: Circulating CD34+ endothelial progenitor cells (EPCs) are capable of differentiating into mature endothelial cells to assist in angiogenesis and vasculogenesis. We sought to quantify the numbers of apoptotic progenitors in patients with congestive heart failure., Methods and Results: Peripheral blood mononuclear cells were isolated by Ficoll density-gradient from 58 patients with various degrees of heart failure and 23 matched controls. Apoptosis in progenitor CD34+ cells was assessed using the Annexin V-PE/PI detection kit, and FACS analysis was performed with triple staining for CD34, annexin-V and propidium iodide. The percentage of early and late apoptotic progenitor cells was determined in the subject groups and was correlated with clinical characteristics. While there was no significant difference in total CD34 positive cells or early apoptotic progenitors between control subjects and CHF patients (p = 0.42) or between severe and mild/moderate CHF groups (p = 0.544), there was an elevated number of late apoptotic progenitors in the severe CHF group compared with the mild/moderate CHF group (p = 0.03). Late apoptotic progenitors were significantly increased in CHF patients as compared to matched controls. There was also an inverse correlation between late apoptotic progenitors and ejection fraction (r = -0.252, p = 0.028) as well as a positive association with NYHA class (r = 0.223, p = 0.046)., Conclusion: Severe heart failure patients exhibited higher numbers of late apoptotic progenitors, and this was positively associated with NYHA class and negatively correlated with ejection fraction. This finding may shed light on the numerous factors governing the pathophysiology of CHF.

The role of vascular endothelium in cardiovascular disorders is well recognized. Mature endothelial cells contribute to the repair of endothelial injury, but only with a limited capacity. This has led to growing interest and further investigation into circulating endothelial progenitor cells (EPCs) and their role in vascular healing, repair and postnatal neovascularization. Recent studies have shown that EPCs are affected both in number and function by several cardiovascular risk factors as well as various cardiovascular disease states. Here, we aim to provide an overview of EPCs in humans, from methods of assessment to quantification and functional properties in numerous cardiovascular conditions. In addition, we hope to offer some perspective on the potential diagnostic and therapeutic aspects of EPCs.

Background: Progenitor CD34 cells are capable of differentiating into endothelial cells and play a role in neoangiogenesis. Circulating CD34+ cells and endothelial progenitor cells are increased in acute coronary syndrome (ACS) patients possibly because of peripheral mobilization. We tested the hypothesis that circulating apoptotic progenitors are detectable in healthy subjects and altered in ACS patients., Methods and Results: Peripheral blood mononuclear cells were isolated by Ficoll density gradient from 53 patients with ACS undergoing coronary angiography and 27 healthy subjects. Apoptosis in progenitor CD34+ cells was assessed using the Annexin V-PE/7-AAD detection kit, and fluorescence-activated cell sorter analysis was performed with triple staining for CD34, annexin-V, and 7-AAD. The percentage of apoptotic CD34+ progenitors was determined in the 2 subject groups and correlated with clinical characteristics. The percentage of apoptotic CD34+ progenitor cells was significantly increased in patients with ACS as compared with healthy subjects and was associated with the extent of coronary stenosis by angiography. There was no significant correlation between apoptotic progenitor CD34+ cells and the other parameters that we examined (age, smoking, hypertension, hyperlipidemia, diabetes mellitus, ejection fraction, creatinine levels, or taking any of the various medications, including beta blockers, thiazides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium blockers, nitrates, or statins)., Conclusion: We established for the first time to our knowledge an assay to detect circulating apoptotic progenitor cells using fluorescein isothiocyanate-anti-CD34 MAb, annexin V-PE, and 7-AAD and found that apoptotic CD34+ cells are increased in ACS patients and in patients with more extensive coronary artery disease. This novel assay may shed new light on the factors governing the hemostasis of progenitor CD34+ cells.

Background: The generation of large quantities of nitric oxide (NO) is implicated in the pathogenesis of anaphylactic shock. The source of NO, however, has not been established and conflicting results have been obtained when investigators have tried to inhibit its production in anaphylaxis., Objective: The aim of this study was to analyze the expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in a mouse model of anaphylaxis., Methods: BALB/c mice were sensitized and challenged with ovalbumin to induce anaphylaxis. Tissues were removed from the heart and lungs, and blood was drawn at different time points during the first 48 hours after induction of anaphylaxis. The Griess assay was used to measure nitric oxide generation. Nitric oxide synthase expression was examined by reverse transcriptase polymerase chain reaction and immunohistochemistry., Results: A significant increase in iNOS mRNA expression and nitric oxide production was evident as early as 10 to 30 minutes after allergen challenge in both heart and lungs. In contrast, expression of eNOS mRNA was not altered during the course of the experiment., Conclusion: Our results support involvement of iNOS in the immediate physiological response of anaphylaxis.

Erythropoietin and its receptor, a cytokine hormone long-known for its pro-erythropoietic effect, has been found to be expressed on a variety of tissues, including the cardiovascular system. Recent experimental studies in the ischemia-reperfusion model have demonstrated that erythropoietin has a significant cardioprotective and pro-angiogenic effect. This effect is quantified by a reduction in the relative infarct and apoptosis area and improved recovery of mechanical function. Despite potentially detrimental effects, erythropoietin has been used extensively in the last decade for treatment of anemia associated with chronic renal failure, and it has been found to be a safe drug in humans. The potential role of erythropoietin in the treatment of ischemic heart disease in humans has yet to be demonstrated in preliminary clinical trials.

The glycoprotein erythropoietin was originally discovered as a principal regulator that promotes the survival, proliferation and differentiation of erythroid progenitor cells. Despite potentially detrimental effects, such as increased blood pressure and hyperviscosity, recombinant human erythropoietin has been demonstrated to be a safe drug, as millions of anemia sufferers have received it over the last decade as a form of treatment. Recently, erythropoietin receptors have been discovered in a variety of tissues, including the cardiovascular system, and erythropoietin has been demonstrated to have a beneficial effect in congestive heart failure patients with anemia. The purpose of this review is to summarize the pleiotropic cardioprotective effects of erythropoietin in the cardiovascular system and to evaluate its potential role as a biomarker in these disorders.