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1.
Cardiol J ; 30(3): 422-430, 2023.
Article in English | MEDLINE | ID: mdl-34581429

ABSTRACT

BACKGROUND: While the combination of a small aortic valve area (AVA) and low mean gradient is frequently labeled 'low-flow low-gradient aortic stenosis (AS)', there are two potential causes for this finding: underestimation of mean gradient and underestimation of AVA. METHODS: In order to investigate the prevalence and causes of discordant echocardiographic findings in symptomatic patients with AS and normal left ventricular (LV) function, we evaluated 72 symptomatic patients with AS and normal LV function by comparing Doppler, invasive, computed tomography (CT) LV outflow tract (LVOT) area, and calcium score (CaSc). RESULTS: Thirty-six patients had discordant echocardiographic findings (mean gradient < 40 mmHg, AVA ≤ 1 cm²). Of those, 19 had discordant invasive measurements (true discordant [TD]) and 17 concordant (false discordant [FD]): In 12 of the FD the mean gradient was > 30 mmHg; technical pitfalls were found in 10 patients (no reliable right parasternal Doppler in 6). LVOT area by echocardiography or CT could not differentiate between concordants and discordants nor between TD and FD (p = NS). CaSc was similar in concordants and FD (p = 0.3), and it was higher in true concordants than in TD (p = 0.005). CaSc positive predictive value for the correct diagnosis of severe AS was 95% for concordants and 93% for discordants. CONCLUSIONS: Discordant echocardiographic findings are commonly found in patients with symptomatic AS. Underestimation of the true mean gradient due to technical difficulties is an important cause of these discrepant findings. LVOT area by echocardiography or CT cannot differentiate between TD and FD. In the absence of a reliable and compete multi-window Doppler evaluation, patients should undergo CaSc assessment.


Subject(s)
Aortic Valve Stenosis , Transcatheter Aortic Valve Replacement , Humans , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/surgery , Echocardiography , Ventricular Function, Left , Severity of Illness Index , Stroke Volume
2.
J Am Soc Echocardiogr ; 35(10): 1028-1036, 2022 10.
Article in English | MEDLINE | ID: mdl-35817379

ABSTRACT

BACKGROUND: Contemporary data on the independent association of severe tricuspid regurgitation (TR) with excess mortality are needed. The aims of this study were to describe contemporary outcomes of patients with severe TR and to identify outcome modifiers. METHODS: Consecutive echocardiographic reports linked to clinical data from the largest medical center in Israel (2007-2019) were reviewed. The primary outcome was all-cause mortality. Cox regression and propensity score matching models were applied. RESULTS: The final cohort included 97,096 patients. Mild, moderate, and severe TR was documented in 27,147 (28%), 2,844 (3%) and 1,805 (2%) patients, respectively. During a median follow-up period of 5 years (interquartile range, 2-8 years), 22,170 patients (23%) died. Kaplan-Meier survival analysis demonstrated an increased risk for death with an increasing degree of TR (log-rank P < .001). Propensity score matching of 1,265 patients with severe TR and matched control subjects showed that compared with those with nonsevere TR, patients with severe TR were 17% more likely to die (95% CI, 1.05-1.29; P = .003). The association of severe TR with survival was dependent on estimated right ventricular (RV) pressure, with a more pronounced effect among patients with estimated systolic pressure ≤ 40 mm Hg (hazard ratio, 2.12 vs 1.04; P for interaction < .001). A landmark subanalysis of 17,967 patients demonstrated that RV function deterioration on follow-up echocardiography modified the association of severe TR with survival. It was more significant among patients with preserved and stable RV function (P for interaction = .035). CONCLUSIONS: The outcome of severe TR is modified by RV pressure and function. Once RV function deteriorates, differences in the outcomes of patients with and without severe TR are less pronounced.


Subject(s)
Tricuspid Valve Insufficiency , Big Data , Echocardiography , Humans , Retrospective Studies , Tricuspid Valve Insufficiency/complications , Tricuspid Valve Insufficiency/diagnostic imaging , Ventricular Function, Right , Ventricular Pressure
3.
Isr Med Assoc J ; 24(3): 144-150, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35347925

ABSTRACT

BACKGROUND: Estimated frequency of aortic stenosis (AS) in those over 75 years of age is 3.4%. Symptomatic patients with severe AS have increased morbidity and mortality and aortic valve replacement should be offered to improve life expectancy and quality of life. OBJECTIVES: To identify whether systolic time intervals can identify severe AS. METHODS: The study comprised 200 patients (mean age 79 years, 55% men). Patients were equally divided into normal, mild, moderate, or severe AS. All patients had normal ejection fraction. Acceleration time (AT) was defined as the time from the beginning of systolic flow to maximal velocity; ejection time (ET) was the time from onset to end of systolic flow. The relation of AT/ET was calculated. Death or aortic valve intervention were documented. AT increased linearly with the severity of AS, similar to ET and AT/ET ratio (P for trend < 0.05 for all). Receiver-operator characteristic curve analysis demonstrated that AT can identify severe AS with a cutoff ≥ 108 msec with 100% sensitivity and 98% specificity, while a cutoff of 0.34 when using AT/ET ratio can identify severe AS with 96% sensitivity and 94% specificity. Multivariate analysis adjusting to sex, stroke volume index, heart rate, and body mass index showed similar results. Kaplan-Meier curve for AT ≥ 108 and AT/ET ≥ 0.34 predicted death or aortic valve intervention in a 3-year follow-up. CONCLUSIONS: Acceleration time and AT/ET ratio are reliable measurements for identifying patients with severe AS. Furthermore, AT and AT/ET were able to predict aortic valve replacement or death.


Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis , Aged , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/surgery , Female , Humans , Male , Quality of Life , Systole
4.
J Am Soc Echocardiogr ; 35(4): 378-386.e3, 2022 04.
Article in English | MEDLINE | ID: mdl-34915134

ABSTRACT

BACKGROUND: Data on the independent association of moderate aortic stenosis (AS) with excess mortality, even when it does not progress to severe AS, are limited. The aims of this study were to evaluate the association of moderate AS with poor survival and to identify clinically important modifiers of that association. METHODS: Consecutive patients who underwent echocardiographic evaluation between 2007 and 2019 were included. All-cause mortality and cancer data were available for all patients from national registries. Cox regression survival models were applied, with censoring of patients who developed metastatic cancer, developed more than moderate AS, or underwent aortic valve intervention during follow-up. RESULTS: The study population included 92,622 patients. There were 2,202 patients (2%) with moderate AS, with a median age of 79 years (interquartile range, 70-85 years), of whom 1,254 (57%) were men. During median follow-up of 5 years (interquartile range, 3-8 years), 19,712 patients (21%) died. The cumulative probability of death at 5 years was higher for patients with moderate AS (46% vs 18%, respectively, log-rank P < .001). Propensity score matching analysis (n = 2,896) that included clinical, laboratory, and echocardiographic predictors of poor survival demonstrated that compared with patients with mild or less AS, those with moderate AS were 17% more likely to die (95% CI, 1.04-1.30; P = .007). Moreover, the model showed that the moderate AS-associated risk was ejection fraction and age dependent, with a more pronounced association among nonoctogenarian patients (P for interaction = .001) and those with reduced ejection fractions (P for interaction = .016). CONCLUSIONS: Moderate AS is independently associated with excess mortality, even when it does not progress to severe AS. The associated risk is more pronounced among patients with reduced ejection fractions and those <80 years of age.


Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis Implantation , Aged , Aged, 80 and over , Aortic Valve/surgery , Big Data , Humans , Male , Retrospective Studies , Risk Factors , Severity of Illness Index , Stroke Volume , Treatment Outcome , Ventricular Function, Left
5.
Cardiol J ; 29(2): 245-251, 2022.
Article in English | MEDLINE | ID: mdl-34708864

ABSTRACT

BACKGROUND: The treatment of choice for severe rheumatic mitral stenosis (MS) is balloon mitral valvuloplasty (BMV). Assessment of MS severity is usually performed by echocardiography. Before performing BMV, invasive hemodynamic assessment is also performed. The effect of anesthesia on the invasive assessment of MS severity has not been studied. The purpose of the present study was to assess changes in invasive hemodynamic measurement of MS severity before and after induction of general anesthesia. METHODS: The medical files of 22 patients who underwent BMV between 2014 and 2020 were reviewed. Medical history, laboratory, echocardiographic and invasive measurements were collected. Anesthesia induction was performed with etomidate or propofol. Pre-procedural echocardiographic measurements of valve area using pressure half time, and continuity correlated well with invasive measurements using the Gorlin formula. RESULTS: After induction of anesthesia the mean mitral valve gradient dropped by 2.4 mmHg (p = 0.153) and calculated mitral valve area (MVA) increased by 0.2 cm2 (p = 0.011). A wide variability in individual response was observed. While a drop in gradient was noted in 14 patients, it increased in 7. Gorlin derived MVA rose in most patients but dropped in 4. Assuming a calculated MVA of 1.5 cm2 and below to define clinically significant MS, 4 patients with pre-induction MVA of 1.5 cm2 or below had calculated MVA above 1.5 cm2 after induction. CONCLUSIONS: The impact of general anesthesia on the hemodynamic assessment of MS is heterogeneous and may lead to misclassification of MS severity.


Subject(s)
Anesthesia , Balloon Valvuloplasty , Mitral Valve Stenosis , Hemodynamics , Humans , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Mitral Valve Stenosis/diagnosis
6.
J Am Heart Assoc ; 10(24): e023603, 2021 12 21.
Article in English | MEDLINE | ID: mdl-34873923

ABSTRACT

Background The association of pulmonary and systemic arterial hypertension is believed to be mediated through hypertensive left heart disease. The purpose of the current study was to investigate whether pulmonary hypertension (PHT) is associated with systemic arterial hypertension among patients with apparently normal left ventricular diastolic function. Methods and Results Consecutive patients who had echocardiographic evaluation between 2007 and 2019 were enrolled. Patients with disease states that are known to be associated with PHT, including diastolic dysfunction, were excluded from the analysis. Estimated right ventricular systolic pressure was extracted for all patients from the echocardiographic reports. PHT was defined as estimated right ventricular systolic pressure >40 mm Hg. Multivariate logistic regression models were applied. Final study population included 25 916 patients with a median age of 59 (interquartile range, 44-69) years, of whom 12 501 (48%) were men and 13 265 (51%) had systemic arterial hypertension. Compared with normotensive patients, hypertensive patients were 3.2 times more likely to have PHT (95% CI, 2.91-3.53; P<0.001). A multivariate model adjusted for clinical and echocardiographic parameters that are known to be associated with PHT demonstrated that hypertensive patients are almost 3 times more likely to have PHT (95% CI, 2.45-3.15; P<0.001). The association was significant in multiple subgroups but was more significant among women compared with men (odds ratio, 3.1 versus 2.4; P for interaction <0.001). Conclusions PHT is associated with systemic arterial hypertension irrespective of left heart disease. The association is more pronounced among women.


Subject(s)
Diastole , Hypertension, Pulmonary , Hypertension , Ventricular Function, Left , Adult , Aged , Diastole/physiology , Female , Humans , Hypertension/epidemiology , Hypertension, Pulmonary/epidemiology , Male , Middle Aged , Ventricular Function, Left/physiology
7.
J Invasive Cardiol ; 32(11): 417-421, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32653864

ABSTRACT

BACKGROUND: Percutaneous mitral valve repair is an alternative treatment for high-risk patients with symptomatic mitral regurgitation (MR). Proper patient selection is crucial to ensure that patients will benefit from the procedure while avoiding futile and potentially harmful medical interventions. OBJECTIVES: To assess the reasons for and outcomes of patients who were declined MitraClip (Abbott Vascular) implantation and compare them with patients who underwent the procedure at our medical center. METHODS: We screened 182 patients for percutaneous mitral valve repair with the MitraClip device. Of these, 84 were referred for MitraClip implantation and 75 underwent the procedure. RESULTS: Procedural success was achieved in 64 patients (85%) and was associated with superior survival at 30 months (73%) compared with implanted patients who did not achieve procedural success (41%; P=.02). Ninety-eight patients were turned down for the procedure due to anatomical incompatibility (72%), lack of indication ("too well") (16%), and clinical incompatibility ("too sick") (12%). Among turned down patients, those who were deemed too well had the highest survival rate (85%) at 30 months, patients with anatomical incompatibility had intermediate survival rates (63%), and patients deemed "too sick" had a dismal survival rate of only 25% (P<.01). In fact, the patients who were too well had outcomes that were equivalent to patients who underwent successful MitraClip implantation. CONCLUSIONS: We identified a number of reasons for not performing MitraClip implantation that impact patient survival. The best outcomes were seen in patients who underwent successful MitraClip implantation and in patients who were deemed too well.


Subject(s)
Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency , Cardiac Catheterization , Heart Valve Prosthesis Implantation/adverse effects , Humans , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Mitral Valve Insufficiency/diagnosis , Mitral Valve Insufficiency/surgery , Treatment Outcome
8.
Echocardiography ; 37(3): 439-444, 2020 03.
Article in English | MEDLINE | ID: mdl-32077517

ABSTRACT

INTRODUCTION: Bicuspid aortic valve (BAV) is a common congenital valve abnormality. There are no data in the literature regarding the range of aortic valve area (AVA) in normal functioning BAV. We aimed to evaluate the normal range of BAV area and to compare it to subjects with tricuspid aortic valve (TAV). METHODS: Bicuspid aortic valve subjects were identified from Sheba medical center echocardiographic database and were compared with TAV subjects. Inclusion criteria were normal tissue leaflets appearance and normal functioning valve in the presence of normal echocardiogram. Echocardiographic data, patients hemodynamics, and size were collected. AVA was measured with both planimetry and the continuity equation. RESULTS: Fifty BAV and 50 control subjects were studied (37 men, age 40 ± 13 years). All studies were performed with normal hemodynamics. Fusion between the coronary leaflets was the most common morphology (82%), followed by fusion between the right coronary leaflet with the noncoronary leaflet (18%). The left ventricular outflow tract (LVOT) diameter in BAV group was significantly larger (2.3 ± 0.3 cm vs 2.1 ± 0.2; P < .001). The BAV group presented with a larger AVA planimetry (3.8 ± 0.9 vs 3.3 ± 0.6; P < .001). However, measuring AVA using continuity equation has shown no differences between groups. If using the principles of coefficient of contraction, it seems that measuring AVA by planimetry overestimates the real anatomic AVA. CONCLUSION: This data provide normal values for echocardiographically determined AVA in BAV subjects. This population was characterized by large LVOT diameter and large AVA. The larger AVA measured with the planimetry emphasizes the limitation of this method in BAV population.


Subject(s)
Aortic Valve Stenosis , Bicuspid Aortic Valve Disease , Adult , Aorta , Aortic Valve/diagnostic imaging , Echocardiography , Humans , Male , Middle Aged
9.
J Interv Card Electrophysiol ; 58(1): 87-94, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31332607

ABSTRACT

PURPOSE: Response to cardiac resynchronization therapy (CRT) is well-established in patients with typical left bundle branch block (LBBB) but modest or even negative in those with intraventricular conduction delay (IVCD). However, IVCD pattern is heterogeneous, and it is possible that QRS patterns may also respond to CRT. METHODS: Consecutive baseline ECGs of 239 patients implanted between 2007 and 2010 with CRT were analyzed. ECGs were classified into the following three groups: (a) typical LBBB (TLBBB) according to accepted guidelines (n = 67); (b) IVCD with LBBB pattern criteria in V1, 1, and aVL but with QS or rS in V5-V6 which we defined as atypical LBBB (ALBBB) (n = 74); and (c) all other IVCD (OIVCD) patterns (n = 98). Endpoints were 2 years mortality and echocardiographic response, defined as a decrease of ≥ 10% in indexed LVESV or an increase of ≥ 5% in left ventricular ejection fraction at 1 year of follow-up. RESULTS: Baseline clinical characteristics were similar among all the three groups. Rates of echocardiographic response were lower among those with OIVCD compared to those with LBBB and ALBBB (50% vs. 75% and 72%, respectively, p = 0.01 for both comparisons). A multivariable model showed a lower likelihood of echocardiographic response in OIVCD [HR = 0.40; (0.16-0.98)] and a similar likelihood in ALBBBB [HR = 0.98; (0.40-2.40)] compared to TLBBB. Cumulative 2-year survival was 88% in ALBBB, 86% in TLBBB, and 76% in OIVCD (p value = 0.011). CONCLUSION: Patients with ALBBB may have a favorable echocardiographic response to CRT and display similar survival rates to typical LBBB. This subgroup of IVCD should be considered for CRT. Atypical left bundle branch morphology defined as QS or rS in lead V1, broad R waves in lead I, and aVL but with QS or rS in V5-V6 is associated with favorable echocardiographic response to CRT and displays similar survival rates to typical LBBB patients.


Subject(s)
Cardiac Resynchronization Therapy , Heart Failure , Bundle-Branch Block/diagnostic imaging , Bundle-Branch Block/therapy , Electrocardiography , Heart Failure/diagnostic imaging , Heart Failure/therapy , Humans , Stroke Volume , Treatment Outcome , Ventricular Function, Left
10.
Am J Cardiol ; 124(11): 1748-1756, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31629462

ABSTRACT

There is limited organized "real life" data regarding the long-term structural and functional durability of transcatheter aortic valve implants, a topic of major importance. We assessed the 5-year structural and functional integrity outcomes following trans-catheter aortic valve implantation (TAVI) with both self-expandable and balloon-expandable prosthetic valve devices. This study included 450 consecutive patients who underwent TAVI for severe symptomatic aortic stenosis (AS) between September 2008 and December 2011. Data were acquired from a multicenter Israeli registry and the median follow up time was 5.6 years. In 184 patients (40.9%) who survived 5 years, prostheses displayed sustained hemodynamic performance, with average peak and mean aortic valve gradients of 16.2 ± 8.9 and 9.2 ± 6.6 mm Hg, respectively. Late structural valve deterioration was found in 22 (12.3%) patients. Of these, 16 (8.9%) experienced valve deterioration and 6 (3.3%) experienced valve failure. Among the 6 patients with bioprosthetic valve failure, only 3 underwent re-interventions. Bioprosthetic valve dysfunction occurred more frequently in patients with small valves (23 mm) and high peak and mean transvalvular gradients at baseline. In conclusion, a relatively low rate of valve deterioration or failure was noted in our long-term follow-up study after TAVI procedures with both the catheter-based self-expandable and balloon-expandable prosthetic valves.


Subject(s)
Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Bioprosthesis , Heart Valve Prosthesis , Hemodynamics/physiology , Registries , Transcatheter Aortic Valve Replacement/methods , Aged, 80 and over , Aortic Valve/diagnostic imaging , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/physiopathology , Echocardiography , Female , Follow-Up Studies , Humans , Israel , Male , Prosthesis Design , Time Factors
11.
Int J Cardiovasc Imaging ; 35(4): 617-625, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30430326

ABSTRACT

Few data exist regarding the effect of image quality on measurements of two-dimensional longitudinal strain (2DLS). In the 2DLS for Diagnosing Chest Pain in the Emergency Room (2DSPER) multicenter study, 2DLS was not useful for ruling out acute coronary syndromes (ACS) in the emergency department (ED). The aim of this substudy was to determine the effect of 2D image quality on the diagnostic accuracy of 2DLS for ACS. We reviewed apical views used for 2DLS analysis in all 605 patients included in the 2DSPER study. Studies with the best image quality (HighQ, n = 177), were compared to the lower quality group (LowQ, n = 428). Abnormal 2DLS was defined as PSS20% > - 17% (PSS20% being the peak left ventricular systolic strain value identifying the 20% worst strain values). Global longitudinal strain (GLS) and PSS20% were significantly worse in LowQ compared to HighQ patients. LowQ independently predicted abnormal 2DLS (OR 1.9, 95% CI 1.3-2.9, P = 0.003). The sensitivity of PSS20% > - 17% for ACS was 85% for LowQ vs. 73% for HighQ (P = 0.2), specificity 22% vs. 38% (P < 0.0001) and overall accuracy 29% vs. 44% (P = 0.0004). Despite better overall accuracy in the HighQ group there was no significant difference between the receiver operating characteristic curves of either GLS or PSS20% in the two groups and abnormal 2DLS did not predict ACS even in HighQ patients (OR 1.7, 95% CI 0.7-4.3, P = 0.3). LowQ echo is associated with worse 2DLS. Abnormal 2DLS was not clinically useful for excluding ACS in the ED even in patients with optimal 2D image quality.Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01163019.


Subject(s)
Acute Coronary Syndrome/diagnostic imaging , Angina Pectoris/diagnostic imaging , Echocardiography/methods , Myocardial Contraction , Ventricular Function, Left , Acute Coronary Syndrome/physiopathology , Aged , Angina Pectoris/physiopathology , Biomechanical Phenomena , Emergency Service, Hospital , Female , Humans , Israel , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Reproducibility of Results
12.
J Invasive Cardiol ; 30(3): 105-109, 2018 03.
Article in English | MEDLINE | ID: mdl-29493511

ABSTRACT

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is now the treatment of choice for high-surgical risk patients with symptomatic aortic stenosis. Little is known regarding the outcome of TAVR in patients with previous malignancy. METHODS: We investigated 477 patients who underwent TAVR in a tertiary medical center. Subjects were divided into two groups according to malignancy status: no history of malignancy (n = 386) and positive history of malignancy (n = 91). RESULTS: Mean age of the study population was 81 ± 7 years, and 52% were men. No major differences in baseline characteristics were found between groups. All-cause mortality was 24% for both malignancy and non-malignancy groups at a mean follow-up of 851 ± 629 days. Kaplan-Meier survival analysis demonstrated no difference in all-cause mortality between groups. Multivariate Cox regression analysis showed that malignancy status did not affect prognosis regarding overall mortality (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.5-1.4; P=.46). However, cancer therapy administered within 12-months of TAVR was significantly associated with increased total mortality among patients undergoing TAVR (HR, 4.38; 95% CI, 1.14-16.77; P=.03). CONCLUSIONS: Malignancy is a common comorbidity among TAVR candidates. Mere history of malignancy among elderly patients does not adversely affect short-term or long-term outcomes after TAVR; however, history of recent (<1 year) cancer-related treatment increases the risk for long-term mortality after TAVR. Decisions regarding TAVR among oncological patients should be individualized according to their malignancy status and anticipated life expectancy.


Subject(s)
Aortic Valve Stenosis , Neoplasms , Transcatheter Aortic Valve Replacement , Aged , Aged, 80 and over , Aortic Valve/surgery , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/epidemiology , Aortic Valve Stenosis/surgery , Comorbidity , Female , Humans , Israel/epidemiology , Kaplan-Meier Estimate , Male , Neoplasms/diagnosis , Neoplasms/epidemiology , Outcome and Process Assessment, Health Care , Proportional Hazards Models , Retrospective Studies , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/methods , Transcatheter Aortic Valve Replacement/statistics & numerical data
13.
J Control Release ; 257: 21-31, 2017 07 10.
Article in English | MEDLINE | ID: mdl-28065861

ABSTRACT

Uncontrolled activation of pro-inflammatory macrophages after myocardial infarction (MI) accelerates adverse left ventricular (LV) remodeling and dysfunction. Hemin, an iron-containing porphyrin, activates heme oxygenase-1 (HO-1), an enzyme with anti-inflammatory and cytoprotective properties. We sought to determine the effects of hemin formulated in a macrophage-targeted lipid-based carrier (denoted HA-LP) on LV remodeling and function after MI. Hemin encapsulation efficiency was ~100% at therapeutic dose levels. In vitro, hemin/HA-LP abolished TNF-α secretion from macrophages, whereas the same doses of free hemin and drug free HA-LP had no effect. Hemin/HA-LP polarized peritoneal and splenic macrophages toward M2 anti-inflammatory phenotype. We next induced MI in mice and allocated them to IV treatment with hemin/HA-LP (10mg/kg), drug free HA-LP, free hemin (10mg/kg) or saline, one day after MI. Active in vivo targeting to infarct macrophages was confirmed with HA-LP doped with PE-rhodamine. LV remodeling and function were assessed by echocardiography before, 7, and 30days after treatment. Significantly, hemin/HA-LP effectively and specifically targets infarct macrophages, switches infarct macrophages toward M2 anti-inflammatory phenotype, improves angiogenesis, reduces scar expansion and improves infarct-related regional function. In conclusion, macrophage-targeted lipid-based drug carriers with hemin switch macrophages into an anti-inflammatory phenotype, and improve infarct healing and repair. Our approach presents a novel strategy to modulate inflammation and improve infarct repair.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Drug Delivery Systems , Hemin/therapeutic use , Macrophages/drug effects , Myocardial Infarction/drug therapy , Ventricular Remodeling/drug effects , Animals , Anti-Inflammatory Agents/administration & dosage , Drug Carriers/chemistry , Female , Heart/drug effects , Heart/physiopathology , Hemin/administration & dosage , Lipids/chemistry , Macrophages/immunology , Macrophages/pathology , Mice , Mice, Inbred BALB C , Myocardial Infarction/immunology , Myocardial Infarction/physiopathology
14.
Eur Heart J Cardiovasc Imaging ; 18(9): 1016-1024, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-27566720

ABSTRACT

AIMS: Left ventricular (LV) two-dimensional longitudinal strain (2DLS) analysis by echocardiography has been suggested as a useful tool for the detection of acute coronary syndromes (ACS). Our aim was to determine whether 2DLS analysis could assist in triage of patients with chest pain (CP) in the emergency department (ED). METHODS AND RESULTS: We prospectively enrolled patients presenting to the ED with CP and suspected ACS but without a diagnostic ECG or elevated troponin. An echocardiogram was performed within 24 h of CP. For each patient, a histogram of LV myocardial peak systolic strain (PSS) was generated and the value identifying the 20% worst strain values (PSS20%) was determined. A predefined value of greater than -17% was considered abnormal. 2DLS analysis was available for 605 patients (mean age 58 ± 9 years, 70% males), of which 74 (12.2%) had ACS. During a 6-month follow-up, MACE occurred in 4 (5.8%) patients with and in 3 (0.6%) without ACS. An abnormal PSS20% was present in 60/74 patients with ACS (sensitivity 81%, negative predictive value 91%), but also in 391/531 patients without ACS (specificity 26%, positive predictive value 13%). Similar results were found for global longitudinal strain (GLS). Receiver-operating characteristic curves showed an area under curve of 0.59 for PSS20% and 0.6 for GLS (P= 0.3). Independent predictors of abnormal 2DLS were male gender, body mass index, heart rate, and mean tissue Doppler e', but not ACS. CONCLUSION: In this large multicentre prospective study, 2DLS was not a useful tool to rule out ACS in the ED. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov. UNIQUE IDENTIFIER: NCT01163019.


Subject(s)
Acute Coronary Syndrome/diagnostic imaging , Chest Pain/diagnostic imaging , Echocardiography , Symptom Assessment/methods , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/mortality , Aged , Chest Pain/diagnosis , Chest Pain/mortality , Cohort Studies , Diagnosis, Differential , Emergency Service, Hospital , Female , Follow-Up Studies , Humans , Israel , Male , Middle Aged , Odds Ratio , Prospective Studies , ROC Curve , Risk Assessment , Severity of Illness Index , Survival Rate
15.
Isr Med Assoc J ; 18(1): 18-22, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26964274

ABSTRACT

BACKGROUND: Transvenous lead extraction can lead to tricuspid valve damage. OBJECTIVES: To assess the incidence, risk factors and clinical outcome of tricuspid regurgitation (TR) following lead extraction. METHODS: We prospectively collected data on patients who underwent lead extraction at the Sheba Medical Center prior to laser use (i.e., before 2012). Echocardiography results before and following the procedure were used to confirm TR worsening, defined as an echocardiographic increase of at least one TR grade. Various clinical and echocardiographic parameters were analyzed as risk factors for TR. Clinical and echocardiographic follow-up was conducted to assess the clinical significance outcome of extraction-induced TR. RESULTS: Of 152 patients who underwent lead extraction without laser before 2012, 86 (56%) (192 electrodes) had echocardiography results before and within one week following the procedure. New or worsening TR was discovered in 13 patients (15%). Use of mechanical tools and younger age at extraction were found on multivariate analysis to be factors for TR development (P = 0.04 and P = 0.03 respectively). Average follow-up was 22.25 ± 21.34 months (range 8-93). There were no significant differences in the incidence of right-sided heart failure (50% vs. 23%, P = 0.192) or hospitalizations due to heart failure exacerbations (37.5% vs. 11%, P = 0.110). No patient required tricuspid valve repair or replacement. Death rates were similar in the TR and non-TR groups (20% vs. 33%). CONCLUSIONS: TR following lead extraction is not uncommon but does not seem to affect survival or outcomes such as need for valve surgery. Its long-term effects remain to be determined.


Subject(s)
Device Removal/adverse effects , Electrodes, Implanted/adverse effects , Heart Failure/epidemiology , Pacemaker, Artificial , Tricuspid Valve Insufficiency/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Echocardiography , Female , Follow-Up Studies , Heart Failure/etiology , Humans , Incidence , Male , Middle Aged , Multivariate Analysis , Prospective Studies , Risk Factors , Tricuspid Valve Insufficiency/etiology
16.
Ann Thorac Surg ; 102(1): 118-22, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27016426

ABSTRACT

BACKGROUND: Aortic valve replacement, particularly in elderly patients with small aortic annulus, could lead to patient-prosthesis mismatch. Sutureless bioprosthesis could be an ideal solution for these patients. We compared results of aortic valve replacement with sutureless versus stented bioprosthetic valves. METHODS: Of the 63 patients undergoing aortic valve replacement with sutureless bioprosthesis between 2011 and 2014 in our department, 22 (20 women, 77 ± 6 years) had a small annulus less than 21 mm (sutureless group). They were matched for sex, age, body surface area, and left ventricular ejection fraction with 22 patients (20 women, 79 ± 6 years) undergoing stented bioprosthesis valve replacement (stented group). Body mass index and body surface area were 28 ± 5 kg/m(2) and 28 ± 3 kg/m(2) (p = 0.9), 1.6 ± 0.2 m(2) and 1.6 ± 0.1 m(2) (p = 0.9), in the sutureless and stented groups, respectively. Logistic EuroSCOREs were similar between groups. RESULTS: Postoperative peak transvalvular gradient was lower in the sutureless group (15 ± 7 mm Hg versus 20 ± 11 mm Hg; p = 0.02). The indexed effective orifice area was greater in the sutureless group (1.12 ± 0.2 cm(2)/m(2) versus 0.82 ± 0.1 cm(2)/m(2); p < 0.05). Aortic cross-clamp and cardiopulmonary bypass times were 47 ± 21 and 67 ± 15 minutes, respectively (p < 0.05) in the sutureless group versus 70 ± 22 and 85 ± 21 minutes, respectively (p = 0.02) in the stented group. Intensive care unit stay, hospitalization, and major complications were not significantly different between groups. At follow-up, regression of left ventricular hypertrophy was better in the sutureless group (93 ± 21 g/m(2) versus 106 ± 14 g/m(2); p = 0.02). CONCLUSIONS: Sutureless bioprosthetic valves demonstrate improved hemodynamic performance compared with stented valves in elderly patients with small aortic annulus, providing better regression of left ventricular hypertrophy and decreased rates of patient-prosthesis mismatch. Aortic cross-clamp and cardiopulmonary bypass times are also decreased.


Subject(s)
Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Bioprosthesis , Heart Valve Prosthesis , Postoperative Complications/epidemiology , Aged , Aortic Valve/diagnostic imaging , Aortic Valve Stenosis/diagnosis , Echocardiography , Female , Follow-Up Studies , Humans , Incidence , Israel/epidemiology , Male , Prosthesis Design , Retrospective Studies , Survival Rate/trends , Treatment Outcome
17.
Int J Cardiol ; 203: 381-95, 2016 Jan 15.
Article in English | MEDLINE | ID: mdl-26539962

ABSTRACT

BACKGROUND: Inflammation has been implicated in the initiation, progression and manifestation of hypertensive heart disease. We sought to determine the role of monocytes/macrophages in hypertension and pressure overload induced left ventricular (LV) remodeling. METHODS AND RESULTS: We used two models of LV hypertrophy (LVH). First, to induce hypertension and LVH, we fed Sabra salt-sensitive rats with a high-salt diet. The number of macrophages increased in the hypertensive hearts, peaking at 10 weeks after a high-salt diet. Surprisingly, macrophage depletion, by IV clodronate (CL) liposomes, inhibited the development of hypertension. Moreover, macrophage depletion reduced LVH by 17% (p<0.05), and reduced cardiac fibrosis by 75%, compared with controls (p=0.001). Second, to determine the role of macrophages in the development and progression of LVH, independent of high-salt diet, we depleted macrophages in mice subjected to transverse aortic constriction and pressure overload. Significantly, macrophage depletion, for 3 weeks, attenuated LVH: a 12% decrease in diastolic and 20% in systolic wall thickness (p<0.05), and a 13% in LV mass (p=0.04), compared with controls. Additionally, macrophage depletion reduced cardiac fibrosis by 80% (p=0.006). Finally, macrophage depletion down-regulated the expression of genes associated with cardiac remodeling and fibrosis: transforming growth factor beta-1 (by 80%) collagen type III alpha-1 (by 71%) and atrial natriuretic factor (by 86%). CONCLUSIONS: Macrophages mediate the development of hypertension, LVH, adverse cardiac remodeling, and fibrosis. Macrophages, therefore, should be considered as a therapeutic target to reduce the adverse consequences of hypertensive heart disease.


Subject(s)
Blood Pressure , Hypertrophy, Left Ventricular/pathology , Macrophages/pathology , Myocardium/pathology , Ventricular Function, Left/physiology , Ventricular Remodeling/physiology , Animals , Disease Models, Animal , Disease Progression , Hypertrophy, Left Ventricular/physiopathology , Macrophages/metabolism , Male , Rats , Rats, Inbred SHR
18.
J Cardiovasc Med (Hagerstown) ; 16(4): 261-6, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25004001

ABSTRACT

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is thought to change the characteristics and outcome of patients with aortic stenosis undergoing surgical aortic valve replacement (SAVR). We investigated the difference in clinical characteristics and outcomes of SAVR patients in the TAVI era. METHODS: Two cohorts of consecutive patients undergoing isolated SAVR for severe tricuspid aortic stenosis, in 4 years before (period-1) and 4 years after (period-2) the introduction of TAVI were analysed. Primary endpoint of 1-year mortality by Cox proportional hazard models was analysed. Secondary endpoints included 1-year, 30-day mortality and adverse perioperative events. RESULTS: The study consisted of 207 patients in period-1 and 200 in period-2. Mean age was 74.9 ±â€Š9.6 and 73.5 ±â€Š9.4 years in periods 1 and 2, respectively. Mean EuroSCORE was 11.5 ±â€Š10.3 during period-1 vs. 8.4 ±â€Š7.2 during period-2 (P = 0.001). One-year mortality decreased from 15.5 to 7.5% (P = 0.013). Composite of major adverse perioperative complications dropped from 12.6 to 6% (P = 0.027). EuroSCORE was an independent predictor of 30-day and 1-year mortality in period-1 (P < 0.005 for both) and not in period-2. Chronic pulmonary disease and preoperative atrial fibrillation were also independent predictors of 1-year mortality in period-1 only, although lower haemoglobin predicted mortality in both periods. CONCLUSION: We show a dramatic decrease in 1-year mortality and adverse perioperative events in patients undergoing SAVR for severe aortic stenosis during recent years. This change is likely related to selection of lower-risk patients for AVR in the TAVI era.


Subject(s)
Aortic Valve Stenosis/mortality , Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Transcatheter Aortic Valve Replacement/mortality , Transcatheter Aortic Valve Replacement/methods , Aged , Aged, 80 and over , Aortic Valve/pathology , Atrial Fibrillation/epidemiology , Chronic Disease , Comorbidity , Female , Follow-Up Studies , Hemoglobins/analysis , Humans , Lung Diseases/epidemiology , Male , Prognosis , Proportional Hazards Models , Risk Factors , Survival Rate/trends , Time Factors , Transcatheter Aortic Valve Replacement/adverse effects , Treatment Outcome
19.
Isr Med Assoc J ; 16(7): 405-11, 2014 Jul.
Article in English | MEDLINE | ID: mdl-25167684

ABSTRACT

BACKGROUND: Contemporary therapiesimprove prognosis and may restore left ventricular (LV) sizeand function. OBJECTIVES: To examine the prevalence, clinical features and therapies associated with reverse remodeling (RR) in dilated cardiomyopathy (DCM). METHODS: The study group comprised 188 DCM patients who had undergone two echo examinations at least 6 months apart. RR was defined as increased LV ejection fraction (LVEF) by > or = 10% concomitant with > or = 10% decreased LV end-diastolic dimension. RESULTS: RR occurred in 50 patients (26%) and was associated with significantly reduced end-systolic dimension, left atrial size, grade of mitral regurgitation, and pulmonary artery pressure. NYHA class improved in the SRR group. RR was less common in familial DCM and a long-standing disease and was more prevalent in patients with prior exposure to chemotherapy. Recent-onset disease, Iower initial LVEF and normal electrocardiogram were identified as independent predictors of RR. Beta-blocker dose wasrelated to improved LVEF but not to RR. Over a mean follow-up of 23 months, 16 patients (12%) from the 'no-RR' group died or underwent heart transplantation compared to none from the RR group (P < 0.01). CONCLUSIONS: Contemporary therapies led to an an improvement in the condition of a considerable number of DCM patients. A period of close observation while optimizing medical therapy should be considered before deciding on invasive procedures.


Subject(s)
Cardiomyopathy, Dilated/physiopathology , Cardiomyopathy, Dilated/therapy , Ventricular Remodeling , Cardiomyopathy, Dilated/diagnostic imaging , Disease Progression , Echocardiography, Doppler , Electrocardiography , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prevalence , Prognosis , Remission Induction , Remission, Spontaneous , Risk Factors , Treatment Outcome
20.
Am J Cardiol ; 114(3): 449-55, 2014 Aug 01.
Article in English | MEDLINE | ID: mdl-24948491

ABSTRACT

The aim of the present study was to evaluate whether assessment of stroke volume index (SVI) can be used to improve risk stratification among patients with low-gradient severe aortic stenosis and preserved ejection fraction (EF). Study population comprised 409 patients with aortic valve area ≤1.00 cm(2), mean gradient <40 mm Hg, and a normal EF (≥50%) who were followed up in a tertiary referral center from 2004 to 2012. Echocardiographic parameters and clinical data were collected. Multivariate Cox proportional hazards regression modeling was used to evaluate the association between SVI and the risk of all-cause mortality. Mean age of study patients was 78 ± 11 years, and 42% were men. The mean SVI was 39 ± 7 ml/m(2) (tertile 1 = 32 ± 4 ml/m(2); tertile 2 = 39 ± 1 ml/m(2); tertile 3 = 47 ± 4 ml/m(2)). Multivariate analysis showed that the SVI was the most powerful echocardiographic parameter associated with long-term outcome: each 5 ml/m(2) reduction in SVI was associated with a 20% increase in adjusted mortality risk (p = 0.01). Consistently, Kaplan-Meier analysis showed that the cumulative probability of survival during 3 years of follow-up was 60%, 72%, and 73% among patients in the low-, intermediate-, and high-SVI groups, respectively (p = 0.012). Our findings suggest that in patients with low-gradient severe aortic stenosis and preserved EF, there is a graded inverse relation between SVI and the risk of long-term mortality.


Subject(s)
Aortic Valve Stenosis/physiopathology , Heart Ventricles/diagnostic imaging , Risk Assessment/methods , Stroke Volume/physiology , Ventricular Function, Left/physiology , Aged , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/mortality , Cause of Death/trends , Echocardiography, Doppler , Female , Follow-Up Studies , Heart Ventricles/physiopathology , Humans , Israel/epidemiology , Male , Prognosis , Retrospective Studies , Risk Factors , Survival Rate/trends , Time Factors
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