Systolic Time Intervals for Diagnosis of Severe Aortic Stenosis.

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.

Bicuspid aortic valve area in normal heart.

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.

Tricuspid Regurgitation following Lead Extraction: Risk Factors and Clinical Course.

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.

Morphological features of the P-waves at surface electrocardiogram as surrogate to mechanical function of the left atrium following a successful modified maze procedure.

AIMS: Absent left atrium (LA) mechanical contraction may occur following the modified Cox-maze operation, and was found to impose a potential risk for the occurrence of thrombo-embolic stroke. It is unknown whether certain morphological P-wave characteristics can surrogate absent LA mechanical activity. The aim of this study was to evaluate the morphological features of the P-waves on the surface electrocardiogram (ECG) of patients who underwent the maze operation and to relate them to the contractile profile of the LA. METHODS AND RESULTS: Electrocardiogram tracings of 150 consecutive patients that were in sustained sinus rhythm following the maze operation were evaluated. P-waves were scrutinized for morphology, duration, axis, and amplitude. Clinical, surgery-related, and echocardiographic data were collected and analysed. Forty-seven patients (31%) had no evidence of LA contraction at 3 months after surgery (baseline assessment) and on follow-up echocardiography. Multivariate analysis showed that a positive-only P-wave deflection at lead V1 (P = 0.03), a negative-only deflection at aVL, and a P-wave amplitude of ≤ 0.05 mV at the septal-anterior leads (P < 0.001 for both) were associated with absent LA mechanical contraction. In a secondary analysis, a risk score involving the above three parameters was developed for the prediction of stroke occurrence. Patients at the high-risk score group had a 30% survival freedom of stroke compared with 70% for patients at intermediate risk (P < 0.001). CONCLUSION: Absent LA mechanical contraction following the modified maze operation may be accompanied by a distinguished pattern of the P-waves on the surface ECG.

Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair.

Herein we investigated a new strategy for the modulation of cardiac macrophages to a reparative state, at a predetermined time after myocardial infarction (MI), in aim to promote resolution of inflammation and elicit infarct repair. The strategy employed intravenous injections of phosphatidylserine (PS)-presenting liposomes, mimicking the anti-inflammatory effects of apoptotic cells. Following PS-liposome uptake by macrophages in vitro and in vivo, the cells secreted high levels of anti-inflammatory cytokines [transforming growth factor ß (TGFß) and interleukin 10 (IL-10)] and upregulated the expression of the mannose receptor--CD206, concomitant with downregulation of proinflammatory markers, such as tumor necrosis factor α (TNFα) and the surface marker CD86. In a rat model of acute MI, targeting of PS-presenting liposomes to infarct macrophages after injection via the femoral vein was demonstrated by magnetic resonance imaging (MRI). The treatment promoted angiogenesis, the preservation of small scars, and prevented ventricular dilatation and remodeling. This strategy represents a unique and accessible approach for myocardial infarct repair.

MitraClip implantation for high risk patients with severe mitral regurgitation: the Sheba experience.

BACKGROUND: Percutaneous edge-to-edge mitral valve repair using the MitraClip system has evolved as a new tool in the treatment of mitral regurgitation (MR). OBJECTIVES: To present our initial experience with MitraClip implantation in 20 high risk patients at Sheba Medical Center. METHODS: Twenty high surgical risk patients with symptomatic significant MR underwent MitraClip implantation. Clinical and echocardiographic parameters were recorded at baseline and at follow-up. RESULTS: The patients' mean age was 76 years and 65% were male. Coronary artery disease was present in 85% and 45% ent in had previous bypass surgery. Renal failure was present in 65%, atrial fibrillation in 60%, and 30% had an implantable cardioverter defibrillator/cardiac resynchronization therapy device. Mean left ventricular ejection fraction was 36%. Grade III-IV MR was present in all patients with the vast majority suffering from functional MR secondary to ventricular remodeling. New York Heart Association (NYHA) class was III-IV in 90%. Patients were followed for a mean of 231 days. Acute reduction of MR grade to < or = 2 was accomplished in 19 of the 20 patients (95%) with a 30 day mortality of 5%. At follow-up MR was reduced to < or = 2 in 64% of patients, and NYHA class improved in 70% of patients. An additional 2 patients (11%) died during follow-up. CONCLUSIONS: MitraClip implantation is feasible and safe in high risk highly symptomatic patients with significant MR. Acute and mid-term results are comparable to similar high risk patient cohorts in the literature. Continued surveillance and longer follow-up are needed to elucidate which patients are most likely to benefit from the procedure.

Prevalence and clinical predictors of reverse remodeling in patients with dilated cardiomyopathy.

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.

Effects of tricuspid valve regurgitation on clinical and echocardiographic outcome in patients with cardiac resynchronization therapy.

AIMS: The severity of tricuspid regurgitation (TR) is a predictor of outcome among heart failure patients. The interaction between cardiac resynchronization therapy (CRT) and TR has not been described. In this study, we examined the effect of pre-implant TR, and worsened TR post-implant, on response to CRT and overall survival. METHODS AND RESULTS: We included all patients with successfully implanted CRT systems between 2007 and 2010. Patients were divided into two groups pre-implant: (Gp 1) no-or-mild TR; and (Gp 2) moderate-or-severe TR. Post-implant, patients were divided into two groups: (Gp A) improved or stable TR; and (Gp B) worsened TR. The clinical and echocardiographic outcome of all patients was assessed. The study included 193 patients. Thirty-five subjects (18%) had moderate or severe TR pre-implant (Gp 2). Baseline echo parameters and 6 min walk distance were worse in Gp 2 compared with Gp 1 (mild or no TR). There was no significant difference in clinical response to CRT between the two groups. However, Gp 2 had a significantly lower echocardiographic response (35 vs. 60%, P = 0.01) and higher mortality over 3 years (OR = 6.70, 95% CI = 1.8-24.5, P = 0.004). Post-implant, 25 patients (13%) developed worsened TR (Gp B), not associated with deterioration in right ventricle function or elevation in pulmonary artery pressure. Worsened TR predicted a reduced clinical response to CRT (42 vs. 70%, P = 0.006), when compared with Gp A. CONCLUSIONS: The presence of baseline moderate or severe TR is associated with increased mortality but does not predict clinical or echocardiographic response to CRT. Patients with worsened TR following CRT are less likely to clinically respond to CRT. Pacing leads passing through the tricuspid valve may worsen TR. It is conceivable that avoidance of lead-induced TR by alternative implantation techniques could improve the response rate to CRT.

Mitral valve repair: isolated posterior compared to anterior or bileaflet pathology.

OBJECTIVES: The results of mitral valve (MV) repair for anterior leaflet pathology (ALP) are considered less favorable than those for posterior leaflet pathology (PLP). We compared clinical and echocardiography outcomes of PLP repair with ALP and/or bileaflet pathology (BLP) repair. METHODS: Between 2004 and 2011, 407 patients underwent MV repair due to degenerative MV: 276 patients (68%) had PLP and 131 (32%) had ALP/BLP. Mean age was 59 ± 12 and 56 ± 15 years in PLP and ALP/BLP groups, respectively (p = 0.03). Patient characteristics and co-morbidities were similar between groups. Valve repair techniques included leaflet resection (61% and 24%), annuloplasty (99% and 97%), and artificial chordea (46% and 67%), in the PLP and ALP/BLP groups, respectively. RESULTS: There was one (0.4%) in-hospital death in the PLP group, and none in the ALP/BLP group. Early complication rate was similar between groups. Completed clinical and late echocardiography follow-up was 95% (29 ± 22 months, 1 to 87). Freedom from reoperation was 98% (270/276) and 98% (129/131), and there were three (1%) and three (2%) late deaths, in the PLP and ALP/BLP groups, respectively (NS). Late echocardiography revealed that 89% and 94% of patients (PLP and ALP/BLP groups, respectively) were free from moderate or severe mitral regurgitation (MR) (p = 0.13). All other late valve-related complications were similar between groups. CONCLUSIONS: Anterior and bileaflet MV disease can be repaired with early and mid-term results similar to those of posterior MV disease. All patients with severe MR due to anterior or posterior pathology should be considered equally for early valve repair.

Pseudo-discordance mimicking low-flow low-gradient aortic stenosis in transcatheter aortic valve replacement patients with severe symptomatic aortic stenosis.

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.

Brachial artery endothelial function predicts platelet function in control subjects and in patients with acute myocardial infarction.

Platelet activation occurs in an endothelium-dependent flow-mediated dilation (FMD) impairment environment. The aim of this study was to explore the association between platelet reactivity and brachial artery FMD in individuals without established cardiovascular disease (controls) and acute myocardial infarction (AMI) patients. We prospectively assessed brachial artery FMD in 151 consecutive subjects, 104 (69%) controls, and 47 (31%) AMI patients; 115 (76%) men, mean age 53 ± 11 years. Following overnight fasting and discontinuation of all medications for ≥ 12 h, percent change in brachial artery FMD (%FMD) and endothelium-independent, nitroglycerin-mediated vasodilation (%NTG) were assessed. Platelet aggregation was assessed by conventional aggregometry, and platelet adhesion and aggregation under flow conditions by cone-and-plate(let) technology (Impact-R). Smoking, diabetes, and hypertension were more common in AMI compared to control subjects (p < 0.01 for all). Furthermore, aspirin, clopidogrel, beta-blockers, angiotensin-converting enzyme inhibitors, and statin administration were more common in AMI compared to controls (p < 0.01 for all). %FMD but not %NTG was significantly lower in AMI patients compared to controls (10.2 ± 4.2% vs. 15.4 ± 4.4%; p < 0.001 and 17.2 ± 3.9% vs. 18.0 ± 3.7%, p = 0.803, respectively). %FMD was significantly and inversely associated with all platelet functions tests (p < 0.001) in all study participants. In a multivariate logistic regression (unadjusted and adjusted for age, gender, smoking status, diabetes mellitus, hypertension, hypercholesterolemia, overweight, family history, and concomitant medications), %FMD remained the best predictor of platelet function, irrespective of group allocation (AMI patients or controls). In conclusion, FMD is inversely correlated to platelet reactivity in both controls and AMI patients.

Prevascularization of cardiac patch on the omentum improves its therapeutic outcome.

The recent progress made in the bioengineering of cardiac patches offers a new therapeutic modality for regenerating the myocardium after myocardial infarction (MI). We present here a strategy for the engineering of a cardiac patch with mature vasculature by heterotopic transplantation onto the omentum. The patch was constructed by seeding neonatal cardiac cells with a mixture of prosurvival and angiogenic factors into an alginate scaffold capable of factor binding and sustained release. After 48 h in culture, the patch was vascularized for 7 days on the omentum, then explanted and transplanted onto infarcted rat hearts, 7 days after MI induction. When evaluated 28 days later, the vascularized cardiac patch showed structural and electrical integration into host myocardium. Moreover, the vascularized patch induced thicker scars, prevented further dilatation of the chamber and ventricular dysfunction. Thus, our study provides evidence that grafting prevascularized cardiac patch into infarct can improve cardiac function after MI.

The Association of Moderate Aortic Stenosis with Poor Survival Is Modified by Age and Left Ventricular Function: Insights from SHEBAHEART Big Data.

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.

The Association of Severe Tricuspid Regurgitation with Poor Survival Is Modified by Right Ventricular Pressure and Function: Insights from SHEBAHEART Big Data.

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.

Influence of anesthesia on hemodynamic assessment of mitral stenosis severity.

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.

The effects of anodal stimulation on electrocardiogram, left ventricular dyssynchrony, and acute haemodynamics in patients with biventricular pacemakers.

AIMS: Anodal stimulation (ANS) is a recognized phenomenon among patients with cardiac resynchronization therapy (CRT); this is noted during left ventricular (LV) pacing by the LV tip to right ventricular (RV) ring configuration. Its incidence varies according to the implanted hardware. We aim at evaluating the incidence of ANS and its acute haemodynamic effects among CRT patients. METHODS AND RESULTS: We screened all our patients who previously had an implanted CRT-P/D devices for ANS. After excluding all non-eligible devices, the initial screening was done by evaluating the programmer electrocardiogram (ECG) during device interrogation while pacing LV only from LV tip to RV ring. Those with ANS underwent screening by 12-lead ECG during biventricular pacing with VV interval programmed to 0. Patients with electrocardiographic evidence of ANS underwent detailed echocardiography. We screened 224 patients, 187 patients were excluded due to various causes. Thirty-seven subjects were analysed for this study. Anodal stimulation was found in 29 patients (78.4%) by primary screening. Twelve patients (41.4%) showed electrocardiographic evidence of ANS by 12-lead ECG. The ANS threshold was significantly higher than true bipolar LV threshold (4.5±1.7 vs. 1.1±0.3 V, respectively, P=<0.0001). Ten patients, with ECG evidence of ANS, underwent detailed echocardiography during biventricular pacing with and without ANS. Overall, there were no significant differences in the haemodynamic, echocardiographic, or resynchronization effects with and without ANS, two patients showed significant reduction in LV function with ANS. CONCLUSION: Anodal stimulation is a common phenomenon among CRT patients. In many cases ANS is seen with LV pacing only, while these changes may not be seen by ECG during biventricular pacing. Echocardiography did not show any significant acute haemodynamic benefit during ANS, and some patients may even deteriorate.

LQT5 masquerading as LQT2: a dominant negative effect of KCNE1-D85N rare polymorphism on KCNH2 current.

AIMS: KCNE1 encodes an auxiliary subunit of cardiac potassium channels. Loss-of-function variations in this gene have been associated with the LQT5 form of the long QT syndrome (LQTS), secondary to reduction of I(Ks) current. We present a case in which a D85N rare polymorphism in KCNE1 is associated with an LQT2 phenotype. METHODS AND RESULTS: An 11-year old competitive athlete presented with mild bradycardia and a QTc interval of 470 ms. An LQT2 phenotype, consisting of low-voltage bifid T waves, was evident in the right precordial electrocardiogram leads. During the tachycardia phase following adenosine, QTc increased to 620 ms. Genetic analysis revealed a rare heterozygous polymorphism in KCNE1 predicting the substitution of asparagine for aspartic acid at position 85 of minK (D85N). Patch clamp experiments showed that KCNE1-D85N, when co-expressed with KCNH2 in TSA201 cells, significantly reduced I(Kr). Homozygous co-expression of the mutant with KCNH2 reduced I(Kr) tail current by 85%, whereas heterozygous co-expression reduced the current by 52%, demonstrating for the first time a dominant-negative effect of D85N to reduce I(Kr). Co-expression of the mutant with KCNQ1, either homozygously or heterozygously, produced no change in I(Ks). CONCLUSIONS: Our results suggest that a rare polymorphism KCNE1-D85N underlies the development of an LQT2 phenotype in this young athlete by interacting with KCNH2 to cause a dominant-negative effect to reduce I(Kr). Our data provide further evidence in support of the promiscuity of potassium channel ß subunits in modulating the function of multiple potassium channels leading to a diversity of clinical phenotypes.

Pulmonary Hypertension Is Associated With Systemic Arterial Hypertension Among Patients With Normal Left Ventricular Diastolic Function.

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.

Pulse pressure is a predictor of vascular endothelial function in middle-aged subjects with no apparent heart disease.

Elevated pulse pressure (PP) is increasingly being recognized as a cardiovascular risk factor. To investigate whether PP is associated with endothelial function in subjects with no apparent heart disease we prospectively assessed brachial flow-mediated dilation (FMD) in 525 consecutive subjects with no apparent heart disease [323 (61%) men, mean age 52 +/- 11 years, mean body mass index (BMI) 26 +/- 4 kg/m(2)]. Following an overnight fast and discontinuation of all medications for >/= 12 hours, the FMD and endothelium-independent, nitroglycerin-mediated vasodilation (NTG) were assessed using high-resolution linear array ultrasound. Univariate linear analysis revealed a significant inverse association between FMD and PP (r = -0.65, p < 0.01), systolic blood pressure (r = -0.52, p < 0.01) and age (r = -0.21, p < 0.05). Multivariate analysis showed that PP was the strongest independent predictor of FMD. We therefore divided the study population into two groups: group A (n = 290) the median PP of 50 mmHg. Male sex, hypertension, diabetes, BMI, heart rate, and the use of aspirin, long-acting nitrates, calcium channel blockers, angiotensin-converting enzyme inhibitors and beta blockers were significantly more common in Group B compared with Group A. FMD but not NTG was significantly greater in patients with PP the median PP (14.9 +/- 7.9% vs 10.8 +/- 8.8%, p < 0.001 and 16.1 +/- 9.6% vs 14.8 +/- 8.4%, p = 0.38; respectively). Thus, PP is inversely associated with brachial FMD in middle-aged subjects with no apparent heart disease, suggesting a potential mechanism whereby elevated PP contributes to cardiovascular disease. Long-term follow-up is warranted to elucidate the incidence of coronary artery disease in both study groups.

Percutaneous implantation of the self-expandable CoreValve for high risk patients with severe aortic valve stenosis: early Israeli experience.

BACKGROUND: The prevalence of aortic stenosis increases with advancing age. Once symptoms occur the prognosis in patients with severe aortic stenosis is poor. The current and recommended treatment of choice for these patients is surgical aortic valve replacement. However, many patients, mainly the very elderly and those with major comorbidities, are considered to be at high surgical risk and are therefore denied treatment. Recently, a transcatheter alternative to surgical AVR has emerged. OBJECTIVES: To describe the first year experience and 30 day outcome of transcatheter aortic self-expandable CoreValve implantation in Israel. METHODS: Transcatheter aortic valve implantation using the CoreValve system has been performed in Israel since September 2008. In the following year 55 patients underwent CoreValve TAVI in four Israeli centers. RESULTS: Patients' mean age was 81.7 +/- 7.1 years; there were 35 females and 20 males. The mean valve area by echocardiogram was 0.63 +/- 0.16 cm2. The calculated mean logistic Euroscore was 19.3 +/- 8%. Following TAVI, mean transvalvular gradient decreased from baseline levels of 51 +/- 13 to 9 +/- 3 mmHg. The rate of procedural success was 98%. One patient died on the first day post-procedure (1.8%) and all-cause 30 day mortality was 5.5% (3 of 55 patients). One patient had a significant post-procedural aortic regurgitation of > grade 2. Symptomatic improvement was evident in most patients, with reduction in functional capacity grade from 3.2 +/- 0.6 at baseline to 1.4 +/- 0.7. The most common post-procedural complication was complete heart block, which necessitated permanent pacemaker implantation in 37% of patients. CONCLUSIONS: The Israeli first year experience of transcatheter aortic valve implantation using the CoreValve self-expandable system demonstrates an effective and safe procedure for the treatment of severe aortic stenosis in patients at high surgical risk.