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Bone scintigraphy is a main diagnostic tool in suspected ATTR patients. Almost all literature is based on conventional whole body gamma cameras, and there is very sparse data evaluating the use of dedicated cardiac CZT cameras. The aim of this study was to evaluate the utility of bone scintigraphy in suspected transthyretin cardiac amyloidosis (ATTR-CA) patients on a dedicated cardiac CZT camera. Seventy-three patients with suspected ATTR-CA underwent planar and SPECT Tc-99 m pyrophosphate scintigraphy using dedicated cardiac CZT camera between May and August 2019. Planar D-SPECT image quality was mostly good. Six patients were identified as ATTR-CA positive. Inter-observer agreement based on both Perugini score and on planar D-SPECT H/CL ratio was excellent. ATTR-CA scintigraphy using dedicated cardiac CZT camera was feasible, and yielded planar D-SPECT images with excellent inter-observer agreement.

Introduction Takotsubo cardiomyopathy (TCM) is characterized by transient left ventricle dysfunction. Hypothesis A residual cardiac and endothelial dysfunction is present in patients who recovered from TCM. Methods In this single‐center prospective study, patients with prior TCM were included and followed for 6.4 ± 1.6 years. All underwent comprehensive cardiac function assessment, including tissue Doppler imaging (TDI) and 2‐dimensional strain (2DS) echocardiography at their first visit. The number of circulating endothelial progenitor cells and levels of proangiogenic vascular endothelial growth factor (VEGF) and its receptor (VEGF‐R) were measured. All measurements were compared with healthy controls. Results Forty‐two women (age 58. ±8.6 years, LVEF 58.1 ± 6.1%) comprised the TCM group. Patients post‐TCM had significantly lower early velocities E′ (6 (5.0–8.0) vs. 9 (7.0–11.0) cm/s, p = .001) by TDI and higher E/E′ ratio (p = .002), lower LV global average longitudinal strain (LGS) (−18.9 ± 3.5% vs. −21.7 ± 2.3%, p = .002) and RV LGS (−20.1 ± 3.9% vs. −23.4 ± 2.8%, p = .003) were evident. There was a trend toward a higher VEGF‐R (p = .09) along with decreased VEGF/VEGF‐R ratio representing inadequate VEGF production. In‐hospital mortality was not reported and only two non‐cardiac deaths occurred at long‐term follow‐up. Conclusions Altered TDI and 2DS indices suggest residual biventricular myocardial injury in post‐TCM patients with the apparent LV function recovery. Inappropriate production of VEGF and VEGF‐R were observed, suggesting a possible underlying endothelial dysfunction in these patients.

Aims We evaluated the impact of MitraClip on systolic pulmonary artery pressure (sPAP) and the effects of baseline sPAP on outcomes. Methods and results In a cohort of patients who underwent MitraClip implantation, three groups were defined according to pre‐procedure sPAP levels. Clinical and echocardiographic data were compared. The study included 177 patients: 59 had severe pulmonary hypertension (PHT), 96 had mild to moderate PHT, and 22 had no PHT. In patients with pre‐existing severe PHT, sPAP was reduced from 70.8 ± 9.2 to 56.8 ± 13.7 mmHg (P

The role of percutaneous mitral valve repair (PMVr) in management of high-risk patients with severe mitral regurgitation (MR) and acute decompensated heart failure (ADHF) is undetermined. We screened all patients who underwent PMVr between October 2015 and March 2020. We evaluated immediate, 30-day, and 1-year outcomes in patients who underwent PMVr during hospitalization due to ADHF as compared to elective patients. From a cohort of 237 patients, we identified 46 patients (19.4%) with severe MR of either functional or degenerative etiology who underwent PMVr during index hospitalization due to ADHF, including 17 (37%) critically ill patients. Patients’ mean age was 75.2 ± 9.8 years, 56% were males. There were no differences in background history between ADHF and elective patients. Patients with ADHF were at higher risk for surgery, reflected in higher mean EuroSCORE II, compared with elective patients. After PMVr, we observed higher 30-day mortality rate in ADHF patients as compared to the elective group (10.9% vs. 3.1%, respectively, p = 0.042). One-year mortality rate was similar between the groups (21.7% vs. 17.9%, p = 0.493). Clinical and echocardiographic follow-up showed improvement of NYHA functional class and sPAP reduction in both groups ((54 ± 15 mmHg to 50 ±15 in the elective group (p = 0.02), 58 ± 13 mmHg to 52 ± 12 in the ADHF group (p = 0.02)). PMVr could be an alternative option for treatment of patients with severe MR and ADHF.

Aims: Myocardial abnormalities are common during COVID-19 infection and recovery. We examined left (LV) and right (RV) ventricular longitudinal strain in patients who had recovered from COVID-19 and assessed the correlation with exercise capacity. Methods and results: One hundred and eighty-four consecutive patients with history of COVID-19 disease who had been referred to rest or stress echocardiography because of symptoms, mainly dyspnea and chest pain, were included in the study. These patients were compared to 106 patients with similar age, symptoms, and risk factor profile with no history of COVID-19 disease. Clinical and echocardiographic parameters, including strain imaging, were assessed. The patient’s age was 48 ± 12 years. Twenty-two patients had undergone severe disease. There were no differences in the LV ejection fraction and diastolic function between the groups. However, LV and RV global and free wall strain were significantly lower (in absolute numbers) in patients who had recovered form COVID-19 infection (−20.41 ± 2.32 vs −19.39 ± 3.36, p = 0.001, −23.69 ± 3.44 vs −22.09 ± 4.20, p = 0.001 and −27.24 ± 4.7 vs −25.43 ± 4.93, p = 0.021, respectively). Global Longitudinal Strain (GLS) &lt, −20% was present in only 37% of post COVID-19 patients. Sixty-four patients performed exercise echocardiography. Patients with GLS &lt, −20% had higher exercise capacity with higher peak metabolic equivalent and exercise time compared to patients with GLS ≥ −20% (12.6 ± 2 vs 10 ± 2.5 METss and 8:00 ± 2:08 vs 6:24 ± 2:03 min, p &lt, 0.001 and p = 0.003, respectively). Conclusion: In patients, who had recovered from COVID-19 infection, both LV and RV strain are significantly lower compared to control patients. The exercise capacity of these patients correlates with LV strain values. Rest and stress echocardiography in patients with symptoms after COVID-19 infection may identify patients that need further follow up to avoid long term complications of the disease. These preliminary results warrant further research, to test the natural history of these findings and the need and timing of treatment.

Background: Prior studies have proven the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with reduced left ventricular (LV) function. This study’s aim was to investigate periprocedural inflammatory responses after TAVI. Methods: Patients with severe symptomatic aortic stenosis and reduced LV function who underwent transfemoral TAVI were enrolled. A paired-matched analysis (1:2 ratio) was performed using patients with preserved LV function. Whole white blood cells (WBC) and subpopulation dynamics as well as the neutrophil to lymphocyte ratio (NLR) were evaluated at different times. Results: A total of 156 patients were enrolled, including 52 patients with LVEF &lt, 40% 35.00 [30.00, 39.25] and 104 with LVEF &gt, 50% 55.00 [53.75, 60.0], p &lt, 0.001. Baseline NLR in the reduced LV function group was significantly higher compared to the preserved LV function group, 2.85 [2.07, 4.78] vs. 3.90 [2.67, 5.26], p &lt, 0.04. After a six-month follow-up, the inflammatory profile was found to be similar in the two groups, NLR 2.94 [2.01, 388] vs. 3.30 [2.06, 5.35], p = 0.288. No significant mortality differences between the two groups were observed in the long-term outcome. Conclusions: TAVI for severe symptomatic aortic stenosis, with reduced LV function, was associated with an improvement in the inflammatory profile that may account for some of the observable benefits of the procedure in this subset of patients.

Aims The aim of this study was to examine the prevalence of amyloid transthyretin (ATTR) cardiac amyloidosis in patients 1–2 years after trans‐catheter aortic valve replacement (TAVR) and to assess their clinical and echocardiographic outcome and long‐term survival. Methods and results We enrolled 88 patients, mean age 81 years, 534 (390–711) days after TAVR. Patients underwent a Tc99m‐PYP scintigraphy for the diagnosis of ATTR cardiac amyloidosis. Eleven (12.5%) participants were diagnosed with ATTR cardiac amyloidosis. Eighty eight per cent of patients without amyloidosis were in New York Heart Association Classes 1–2 after TAVR, compared with 64% patients with ATTR cardiac amyloidosis (P = 0.022). There were no differences in left ventricular (LV) ejection fraction (P = 0.69) between patients with and without ATTR cardiac amyloidosis at enrolment. The LV mass index and pulmonary artery pressure were significantly higher in patients with ATTR cardiac amyloidosis (P = 0.046 and P = 0.002, respectively). Global longitudinal strain and myocardial work efficiency were significantly lower in patients with ATTR cardiac amyloidosis (P = 0.031 and P = 0.048, respectively). We assessed changes in echocardiographic data, from the time of TAVR to enrolment, and as expected, there was a significant decrease in aortic valve gradient in both groups. There was a significant reduction in LV mass and LV mass index and improvement in basal segment LV strain in the ATTR cardiac amyloidosis negative group (P = 0.045, P = 0.046 and 0.023, respectively). However, in the ATTR cardiac amyloidosis group the change in LV mass and LV mass index and LV basal strain values was not significant (P = 0.24, P = 0.13 and P = 0.35, respectively). The were no significant changes in other echocardiographic parameters in both groups. The patients were followed for 1150 (1086–1221) days after enrolment. Twenty seven patients had at least one cardiac hospitalization during of follow up, of them seven were with ATTR cardiac amyloidosis and 20 patients without amyloidosis (P = 0.017). Eighteen patients (20%) died during follow up; 12 (14%) patients died due to cardiac causes. There was no difference in all‐cause and cardiac mortality between patients with and without ATTR cardiac amyloidosis (P = 0.6 and P = 0.53, respectively). Conclusions The long‐term survival after TAVR is not significantly affected by the presence of ATTR cardiac amyloidosis. However, the clinical course of these patients and the LV hemodynamic improvement is less favourable. This hypothesis‐generating study suggests screening for ATTR cardiac amyloidosis in patients who underwent TAVR and have limited clinical or echocardiographic improvement, because they may potentially improve with new therapies for ATTR cardiac amyolidosis.

Aims Cardiac amyloidosis typically manifests as heart failure with preserved left ventricular function due to extracellular plaques comprising aggregated TTR. Despite recent success in halting disease progression with a TTR stabilizer and encouraging preliminary findings with TTR silencers, these agents are not targeting preexisting plaques. Herein, we report the development of a novel monoclonal antibody capable of attenuating experimental cardiac amyloidosis. Methods and results We generated an IgG1 monoclonal antibody against aggregated TTR that immunoprecipitated the protein in the sera of patients with wild-type ATTR (wtATTR) and robustly stained cardiac plaques from patients. The antibody was shown to facilitate aggregated-TTR uptake by various myeloid cells and to protect cardiomyocytes from TTR-inducible toxicity. In a novel in vivo model of wtATTR amyloidosis, the antibody enhanced the disappearance of the pyrophosphate signals attesting for a rapid amyloid deposit removal and degradation and also exhibited improved echocardiographic measures of cardiac performance. Importantly, a capture ELISA developed based on the antibody exhibited higher levels of aggregated TTR in the sera of wtATTR amyloidosis patients as compared to control patients with heart failure suggesting a potential applicability in diagnosis and pharmacodynamic guidance of dosing. Conclusion We developed a proprietary antibody targeting aggregated TTR that exhibits beneficial effects in a novel experimental wtATTR model and also possesses a potential diagnostic utility. The antibody could potentially be tested as a disease modifying agent in ATTR amyloidosis.

Background Calcific aortic stenosis (AS) is a progressive disease, and once moderate AS is present, the likelihood of symptom onset within 5 years is significant. The aim of this study was to determine the incremental value of global longitudinal strain (GLS) and basal longitudinal strain (BLS) at rest and during exercise on outcomes among asymptomatic patients' with moderate and severe AS. Methods Seventy-five patients with isolated, asymptomatic AS and preserved left ventricular function were retrospectively enrolled and underwent symptom-limited exercise echocardiography. Clinical and echocardiographic data, including GLS and BLS at rest and during exercise, were assessed. Occurrence of AS-related cardiovascular events was recorded. Results The mean age was 71 ± 10 years, and 63% were men. The mean aortic valve gradient was 30 ± 11 mm Hg, and the mean aortic valve area was 0.98 ± 0.21 cm2. Resting GLS and BLS were −16.5 ± 4% and −16.9 ± 3.6%, respectively. Exercise stress test results were positive in 27 patients (36%). Mean exercise GLS was −17.8 ± 3.5%, and mean exercise BLS was −17.9 ± 4%. During mean follow-up of 34.5 ± 3.5 months, cardiovascular events were observed in 45 patients. In multivariate analysis, aortic valve mean gradient (HR, 1.073; 95% CI, 1.032–1.115; P Conclusions Reduced exercise BLS is associated with future cardiovascular events in patients' with asymptomatic AS, independently of clinical factors and conventional echocardiographic parameters. Detection of postexercise myocardial dysfunction in patients with asymptomatic AS with preserved left ventricular function can aid in risk assessment of these patients.

Aims We have previously shown that 2-dimentional strain is not a useful tool for ruling out acute coronary syndrome (ACS) in the emergency department (ED). The aim of the present study was to determine whether in patients with suspected ACS, global longitudinal strain (GLS), measured in the ED using 2-dimensional strain imaging, can predict long-term outcome. Methods Long-term (median 7.7 years [IQR 6.7-8.2]) major adverse cardiac events (MACE; cardiac death, ACS, revascularization, hospitalization for heart failure, or atrial fibrillation) and all-cause mortality data were available in 525/605 patients (87%) enrolled in the Two-Dimensional Strain for Diagnosing Chest Pain in the Emergency Room (2DSPER) study. The study prospectively enrolled patients presenting to the ED with chest pain and suspected ACS but without a diagnostic ECG or elevated troponin. GLS was computed using echocardiograms performed within 24 hours of chest pain. MACE of patients with worse GLS (>median GLS) were compared to patients with better GLS (≤ median GLS). Results Median GLS was -18.7%. MACE occurred in 47/261 (18%) of patients with worse GLS as compared with 45/264 (17%) with better GLS, adjusted HR 0.87 (95% CI 0.57-1.33, P = .57). There was no significant difference in all-cause mortality or individual endpoints between groups. GLS did not predict MACE even in patients with optimal 2-dimensional image quality (n = 164, adjusted HR=1.51, 95% CI 0.76-3.0). Conclusions Global longitudinal strain did not predict long-term outcome in patients presenting to the ED with chest pain and suspected ACS, supporting our findings in the 2DSPER study.

Objective Transcatheter aortic valve implantation (TAVI) provokes early injury response, represented in part by dynamic changes in the inflammatory markers. The association of self-expanding valves (SEVs) and balloon-expandable valves (BEVs) with the consequent inflammatory response remains uncertain. Materials and methods Patients with severe symptomatic aortic stenosis who underwent transfemoral TAVI: SEVs or BEVs, from January 2010 to December 2019 were enrolled. Whole white blood cells (WBC) and subpopulation dynamics as well the neutrophil to lymphocyte ratio (NLR) were evaluated. Results Three-hundred seventy consecutive patients (mean age 81.75 ± 6.8 years, 199 women’s) were enrolled. In the entire population, significant kinetic changes in the WBC response (p Conclusion This is the first description of a differential inflammatory response between the two leading delivery systems. SEV appears to trigger a more robust inflammatory response as compared to BEV. Clinical studies are warranted to assess the long term effect of our findings.

Aim Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure (HF) with preserved left ventricular ejection fraction (LVEF), typically presenting as restrictive cardiomyopathy. The potential co-existence of ATTR-CA with systolic heart failure has not been studied. The aim of this study is to describe the prevalence of ATTR-CA and its clinical characteristics in HF patients with reduced LVEF. Methods Patients with an unexplained cause of LV systolic dysfunction were screened for ATTR-CA by a 99mTc-PYP planar scintigraphy. Patients in whom presence of ≥ 2 uptake was confirmed by SPECT imaging were included. Their clinical, laboratory and echocardiographic data were collected. Results Out of 75 patients (mean age 65±12 years, LVEF 35.8±7.9%) included in this study, 7 (9.3%) patients (mean age 75±6 years, LVEF 32.0±8.3%) had ATTR-CA. Patients with ATTR-CA were more symptomatic at diagnosis (NYHA FC 3–4 (86% vs 35% (p = 0.03)) and had a more severe clinical course evident by recurrent hospitalizations for HF, and a need for intravenous diuretic treatment (p = 0.04 and p2 vs. 121.0±39.5 g/m2, p = 0.07) and a larger proportions of ATTR-CA patients had IVS thickness >13 mm (57.1% vs 13.1%, p = 0.02) as compared to HF patients with no ATTR-CA. Conclusion In our study, a meaningful percentage of patients with unexplained LV dysfunction had a co-existing ATTR-CA indicating that the clinical heterogeneity of ATTR-CA is much broader than previously thought.

Patients with severe mitral regurgitation (MR) after myocardial infarction (MI) have an increased risk of mortality. Transcatheter mitral valve repair may therefore be a suitable therapy. However, data on clinical outcomes of patients in an acute setting are scarce, especially those with reduced left ventricle (LV) dysfunction. We conducted a multinational, collaborative data analysis from 21 centers for patients who were, within 90 days of acute MI, treated with MitraClip due to severe MR. The cohort was divided according to median left ventricle ejection fraction (LVEF)—35%. Included in the study were 105 patients. The mean age was 71 ± 10 years. Patients in the LVEF &lt, 35% group were younger but with comparable Euroscore II, multivessel coronary artery disease, prior MI and coronary artery bypass graft surgery. Procedure time was comparable and acute success rate was high in both groups (94% vs. 90%, p = 0.728). MR grade was significantly reduced in both groups along with an immediate reduction in left atrial V-wave, pulmonary artery pressure and improvement in New York Heart Association (NYHA) class. In-hospital and 1-year mortality rates were not significantly different between the two groups (11% vs. 7%, p = 0.51 and 19% vs. 12%, p = 0.49) and neither was the 3-month re-hospitalization rate. In conclusion, MitraClip intervention in patients with acute severe functional mitral regurgitation (FMR) due to a recent MI in an acute setting is safe and feasible. Even patients with severe LV dysfunction may benefit from transcatheter mitral valve intervention and should not be excluded.

BACKGROUND Transcatheter aortic valve implantation related thrombocytopenia (TAVI-rTP) is an inevitable phenomenon. However, no study has been performed on TAVI-rTP in the current setting of extended clinical indications combined with technology improvements. METHODS Patients with severe symptomatic aortic stenosis who underwent transfemoral TAVI, from January 2016 to December 2019 were enrolled. RESULTS Two-hundred and one consecutive patients (mean age 81.1 ± 7.1 years, 96 men) enrolled. Platelet count was recorded before and after aortic valve implantation. Dropped platelet count (DPC) occurred in all but 11 patients who were included. Two groups were created: DPC

Introduction Severe aortic stenosis (AS) is the most common valvular heart disease in the western world. Various factors are related to severe AS prognosis, including chronic kidney disease. The aim of this study was to evaluate the prognostic value of urea level in patients with severe AS. Methods We prospectively enrolled 142 patients (79.1±9.4 years, 88 women) with severe AS (mean valve area 0.67± 0.17 cm2). Clinical assessment, blood tests and echocardiography were performed at enrollment and follow up. The patient population was divided into low and high urea level groups, according to the median urea level at enrollment (72 patients, mean urea 35.5±6.2 mg/dL and 70 patients, mean urea 61.1±17.8 mg/dL, respectively). Hundred and twelve patients (79%) underwent aortic valve intervention. The primary endpoint was all-cause and cardiovascular mortality. Outcomes During follow-up of 37±19.5 months, 56 (37.1%) patients died, 39 due to cardiovascular causes. In univariate analysis, age, urea level, creatinine, New York Heart Association (NYHA) class and aortic valve intervention were associated with all-cause mortality. However, in multivariate analysis only aortic valve intervention and blood urea were independent predictors of all-cause mortality (HR 0.494; 95% CI 0.226-0.918, P = 0.026 and HR 1.015; 95% CI 1.003-1.029, P = 0.046 respectively). Urea level, NYHA class and age were also significant predictors of cardiovascular mortality. Whereas, in multivariate analysis, only urea level predicted cardiovascular mortality in these patients (HR 1.017; CI 1.003-1.031 P = 0.019). Conclusions Blood urea, a generally readily available and routinely determined marker of renal function, is an independent prognostic factor in patients with severe AS.

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

Background MicroRNAs are short non-coding RNAs that regulate gene expression. The aim of this study was to gain an understanding of the possible role of the miR-106b~ 25 microRNA cluster in regulating atherosclerosis in mice. Methods MiR-106b~ 25 knockout mice were outcrossed into Apolipoprotein E (ApoE) knockout background to generate double knockout mice. At 36 weeks of age, lesion size was evaluated in the aortic sinus by oil-red-O staining. Results Lesion size was 2-fold smaller in double KO mice in comparison to ApoE KO mice. In addition, collagen staining showed a trend towards a stable plaque phenotype in the double KO mice. Lipid profiling of plasma samples of double KO and ApoE KO mice using FPLC revealed over 2-fold decrease in Very low density lipoprotein (VLDL) cholesterol content and a 50% decrease in low density lipoprotein (LDL) cholesterol content in double KO mice. By using target prediction software, we have identified several possible targets for the miR-106b~ 25 cluster including the VLDL and LDL receptors. We found that upon feeding miR-106b~ 25 KO mice with high fat diet, the expression of LDL and VLDL receptors was higher than in the wild-type mice, suggesting the miR-106b~ 25 cluster regulates atherosclerosis by influencing clearance of VLDL and LDL from the plasma. Conclusions We identified the miR-106b~ 25 cluster as a novel regulator of atherosclerosis in ApoE KO mice, presumably by regulating plasma cholesterol levels.

Introduction Aortic Stenosis (AS) is the most common valvular heart disease in the Western world. Transcatheter aortic valve implantation (TAVI) is an alternative to surgical valve replacement in medium and high-risk patients. One of the most common complications after TAVI is conduction system disturbances including bundle branch block, complete heart block and need for permanent pacemaker implantation. Transthyretin cardiac amyloidosis (TTR–CA) is an increasingly recognized cause of heart failure that almost exclusively affects older adults. Diagnosis of TTR-CA in patients undergoing valvular intervention is relevant to understand their clinical outcomes and to discuss specific management. Objectives Occult amyloid may account for the frequent need for pacemakers among TAVR patients. We aimed to assess the correlation between intervention induced conduction abnormalities and the need for a pacemaker insertion and the presence of TTR-CA. Methods The study population included patients who had aortic valve intervention between 2011–2018. The patients underwent Tc99m-PYP scan using SPECT technology which has been shown to be valid for the diagnosis of TTR-CA. We examined the rate of conduction disorders and the need for a permanent pacemaker from patient files at the time of hospitalization and during a 24-month follow-up. Results The study population included 86 patients, mean age 78±6 years, 55% women. Twenty-nine (33%) of the participants were diagnosed as positive (VAS 2 and 3) for transthyretin cardiac amyloidosis. There were no differences in baseline characteristics with regard to age, gender, risk factors, hemoglobin and renal function between patients positive and negative for TTR CA. Conduction disorders were seen in 35 (40%) patients. Patients with TTR CA had a statistically higher prevalence of conduction disorders. Forty-two percent of TTR CA positive patients underwent peri-procedural permanent pacemaker implantation compared to 28% peri-procedural pacemaker implantations in the negative group (p=0.043). Development of a new left bundle branch block during the follow-up period was observed in 14.1% of all patients. There was a statistically significant higher rate in the positive group compared to TTR CA negative group (39.1% vs 10.9% p=0.03). Conclusions We observed a high prevalence of occult TTR-CA in older adults with aortic stenosis who underwent TAVI. We also found a high prevalence of conduction abnormalities following TAVI in patients with TTR CA. These findings suggest a need for more careful observation for possible conduction abnormalities and requirement for pacemaker insertion in these patients. Acknowledgement/Funding None

Background We previously demonstrated that elevated levels of antiendothelial cell antibodies are associated with improved survival of patients undergoing coronary angiography. However, renal insufficiency, which is associated with decreased survival, leads to increased level of the antiendothelial cell antibodies. The purpose of this study was to evaluate the correlation of the levels of these antibodies with survival in patients with normal versus reduced renal function. Patients and methods This was a single center prospective study. Eight hundred thirty eight consecutive patients undergoing coronary angiography with detectable antibody levels were enrolled. The levels of antiendothelial antibodies were determined by ELISA and measured in optical density units. Renal insufficiency was defined as adjusted GFR Results Of total 838 patients, 481 (57%) had normal and 357 (42.6%) had reduced renal function. Total mortality was 13.6%, being significantly higher in patients with reduced (23.2%) versus normal (6.4%) renal function (p Conclusions Renal insufficiency leads to mild decrease in the antiendothelial cell antibodies' levels. Higher levels of antiendothelial cell antibodies are associated with improved survival in patients undergoing coronary angiography. This association is significant in patients with normal but not reduced renal function. Thus, the effect of the higher levels of these antibodies on survival cannot be explained by its association with renal dysfunction.

Background Aortic Stenosis (AS) is the most common valvular heart disease in the Western world. Wild-type transthyretin amyloid (wtATTR) affects the heart, causing restrictive cardiomyopathy. Deposits can be found in up to 25% of individuals >85 years of age at autopsy. Recently several reports showed a relatively high prevalence of transthyretin cardiac amyloidosis (TTR-CA) in patients with AS. Objectives The aim of this study was to examine the clinical effects of TTR-CA in patients who have undergone aortic valve replacement therapy and evaluate the outcome of the intervention. Methods We recruited patients who underwent surgical (AVR) or percutaneous (TAVI) aortic valve intervention between 2011 and 2018. The patients underwent a Tc99m-PYP scan using SPECT technology which has been shown to be valid for the diagnosis of TTR-CA. We reviewed patient files before (time point 1) and after intervention (time point 2) and at 2 years (time point 3) follow up, and collected data on hospitalizations, laboratory, and echocardiography. Results The study included 86 patients, mean age 78±6 years, 55% women. Twenty-nine (33%) participants were diagnosed as positive (VAS 2 and 3) for transthyretin cardiac amyloidosis.There were no differences in baseline characteristics between patients with and without TTR-CA in cardiovascular risk factors and co-morbidities, laboratory parameters and nutritional status. There were no differences in baseline echocardiographic parameters including valve gradients and left ventricular hypertrophy. However, the patients with TTR CA had more advanced diastolic dysfunction compared to patients without TTR CA (P=0.03) and higher pulmonary artery pressure (44±14.75mmhg vs 30.5±11.38mmhg, p=0.06). Before the intervention, patients with transthyretin cardiac amyloidosis had 3.26 times more hospitalizations due to heart failure as compared to patients in the negative group (p=0.01). After the intervention, diastolic function remained more severely affected in the positive group at all follow-up points compared to the negative group (p=0.05). Similar observations were seen in the measurements of pulmonary arterial pressure (p=0.019 at time 2 and p=0.015 at time 3). Consistent with the echocardiographic findings, patients with transthyretin cardiac amyloidosis had 2.84 times more hospitalizations after intervention for heart failure than patients in the negative group (p=0.02). Conclusions Co-existence of transthyretin cardiac amyloidosis and aortic stenosis in the older population is associated with a more severe clinical presentation and with more advanced clinical and echocardiographic signs of heart failure. Improvement after valvular intervention might be limited in terms of symptoms and hospitalizations in this subgroup. Acknowledgement/Funding None

Background Coronary artery disease (CAD) is the leading cause of diastolic dysfunction. Diastolic dysfunction is associated with adverse outcomes. Renal insufficiency is also associated with adverse outcomes in CAD patients. The interaction between diastolic dysfunction and renal insufficiency is not completely elucidated. Aims We evaluated the prognostic value of diastolic function assessed by echocardiography in patients with and without renal failure undergoing coronary angiography. Patients and methods An observational prospective study of 547 consecutive patients undergoing coronary angiography. The median follow up was 30 months. Significant diastolic dysfunction was defined as elevated LV filling pressure with e/e'>12. Renal insufficiency was defined as adjusted GFR Results Significant diastolic dysfunction and renal insufficiency had additive effect on mortality (Table 1). A significant association was observed between diastolic dysfunction and mortality in patients with and without renal insufficiency (p Table 1. Patients divided into 4 groups according to the presence of the significant diastolic dysfunction and renal insufficiency Patients' group N (%) Mortality Normal LV filling pressure / Normal renal function 230 (42.0%) 4.8% Elevated LV filling pressure / Normal renal function 58 (10.6%) 15.5% Normal LV filling pressure / Renal insufficiency 138 (25.2%) 15.9% Elevated LV filling pressure / Renal insufficiency 121 (22.1%) 38.8% P Fugure 1 Conclusions In patients undergoing coronary angiography, significant diastolic dysfunction with elevated filling pressure is associated with mortality in patients both with and without renal insufficiency. Both significant diastolic dysfunction and renal insufficiency are independent predictors of mortality.

Severe aortic valve stenosis (AS) accounts for considerable morbidity and death, especially in older patients. There is increasing evidence to suggest a role for immune modulating cells in aortic valve (AV) degeneration. Regulatory T cells (Tregs) tune down inflammation. We aimed to study the levels of circulating Tregs in patients with AS and to assess their association with disease progression.The number of Tregs (CD4+CD25+Foxp3+) was determined by flow cytometry in 229 patients with AS and a control group of 69 patients. Tregs were significantly higher in patients with AS compared to the control group (1.64± .61% vs 1.13±0.97%, p=0.04). In the logistic regression analysis, adjusted for baseline characteristics, only the hemoglobin level and Treg percent correlated with the presence of AS (OR 0.642 95% CI 0.512-0.805, p0.001 and OR 1.411, 95% CI 1.080-1.844, p=0.011, respectively). One hundred patients underwent 2 echocardiographic studies during follow-up. The median decrease in AV area (AVA) was 0.1cm(2)/year. A borderline association was observed between Tregs and AVA progression (r=0.19, p=0.054). In a subgroup of 68 patients with severe AS, the association between Tregs and AVA progression was significant (r=0.374, p=0.0017). In addition, a drop in Treg levels was observed 3-6months after AV-intervention (1.86±1.6% vs 1.04±1.8%, p=0.0005).Circulating Tregs are elevated in patients with AS. The levels of Tregs are higher in patients with severe AS and accelerated progression of valve narrowing. These results may help to identify AS patients with accelerated disease progression and possibly in need for earlier intervention.

An 84-year-old male patient with ischemic heart disease was referred to transesophageal echocardiography evaluation of mitral regurgitation. He previously underwent multiple percutaneous coronary interventions (PCI) in another hospital, the last intervention 3 years ago. Flail anterior leaflet of

Background Shortness of breath (SOB) is common among healthy women with normal pregnancies. However, when no overt cardiac or extra cardiac etiology is found, a subtle cardiac source must be excluded. Hypothesis Pregnancy may induce or unmask myocardial dysfunction that may cause SOB. Methods Healthy pregnant women with significant SOB were recruited for this study. We performed a comprehensive echocardiographic assessment including tissue Doppler imaging (TDI) and 2- dimensional strain imaging (2DS). The echocardiographic data obtained were compared with that of a control group of pregnant women without SOB. Results Thirty pregnant women with SOB were enrolled in the study (age, 31.8 ± 4.9 years, and gestation, 38.2 ± 2.8 weeks) for whom no overt etiology for SOB was detected. Patients with SOB compared with controls had thicker hearts (septum: 10.1 ± 1.1 vs 8.9 ± 0.9 mm; P

Objectives: The aim of this study was to evaluate the relationship between valvular resistance and stroke volume (SV) and to assess SV adequacy to afterload in patients with severe aortic stenosis (AS) and normal left ventricular ejection fraction (LVEF). Methods: We assessed clinical characteristics and echocardiographic parameters in 44 patients with isolated severe AS and preserved LVEF. LV end-diastolic pressure (LVEDP) and LV mean diastolic pressure (LVMDP) were measured by cardiac catheterization. SV values were plotted in relation to valvular resistance. Patients were divided into 2 groups, with an SV that was higher (group 1) or lower (group 2) than the SV calculated by a regression equation using valvular resistance as the dependent variable. Results: At the same degree of valvular stenosis, the patients in group 1 exhibited better contractility as assessed by global longitudinal strain (p < 0.05), higher peak (p < 0.01) and mean gradient (p < 0.05), indexed SV (p < 0.001) and transvalvular flow (p = 0.01) than the patients in group 2, who had a higher heart rate (HR, p < 0.05), shorter ejection time (ET, p < 0.05) and more elevated LVEDP (p < 0.05) and LVMDP (p < 0.05). Conclusion: The presence of inappropriately decreased SV relative to afterload in patients with severe AS and normal LVEF was associated with lower contractility, higher HR, shorter ET and elevated LV diastolic pressure, which suggest failed hemodynamic adaptation to afterload.

Background— Recent studies suggest that angiogenic imbalance during pregnancy may lead to acute peripartum cardiomyopathy (PPCM). We propose that angiogenic imbalance and residual cardiac dysfunction may exist even after recovery from PPCM. Methods and Results— Twenty-nine women at least 12 months after presentation with PPCM, who exhibited recovery of left ventricular (LV) ejection fraction (≥50%), were included in the study (mean age 35±6 years, LV ejection fraction 61.0±3.9%). The number of circulating endothelial progenitor cells (EPCs) and plasma levels of proangiogenic vascular endothelial growth factor and of soluble vascular endothelial growth factor receptor Flt1 (sFlt1) were measured. All patients underwent comprehensive cardiac function assessment, including tissue Doppler imaging and 2-dimensional (2D) strain echocardiography. All measurements were compared with healthy controls. Patients with a history of PPCM have significantly higher sFlt1 concentrations (median [25th–75th percentile]; 149.57, [63.14–177.89] versus 20.29, [15.00–53.89] pg/mL, P P =0.012) compared with controls, with a trend toward lower concentration of circulating CD34 + /KDR + levels. In addition, patients with PPCM had lower early velocities E′ septal (9.9±2.1 versus 11.0±1.5 cm/s, P =0.02), with a significantly lower systolic velocity S′ septal (7.6±1.2 versus 8.5±1.2 cm/s, P =0.003) by tissue Doppler imaging. Significantly lower LV global longitudinal (−19.1±3.3 versus −22.7±2.2%, P P =0.02) were present in patients with PPCM compared with controls. Conclusions— Higher concentration of sFlt1 with concomitant decreased circulating endothelial progenitor cell levels along with inappropriate attenuated vascular endothelial growth factor levels may imply an angiogenic imbalance that exists even after recovery and may thus predispose to PPCM. In addition, tissue Doppler imaging and 2D strain were able to identify residual myocardial injury in post-PPCM women with apparent recovery of LV systolic function. Both angiogenic imbalance and residual myocardial injury may play an important role in the recurrence of LV dysfunction during subsequent pregnancies.

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 . Unique identifier NCT01163019.

A 56-year-old male presented with new onset of congestive heart failure symptoms and a continuous murmur. Transthoracic and transesophageal echocardiography showed severely reduced left ventricle function and shunt flow from an aneurysm in the non-coronary cusp of the aortic valve to the right atrium. The patient underwent surgery with 3 coronary artery bypass grafts and direct closure of the fistula with no residual flow

Background Aortic stenosis (AS) is the most common valvular disease. Endothelial progenitor cells (EPCs) have a role in the repair of endothelial surfaces after injury. Reduced numbers of EPCs are associated with endothelial dysfunction and adverse clinical events, suggesting that endothelial injury in the absence of sufficient repair by circulating EPCs promotes the progression of vascular and possibly valvular disorders. The aim of this study was to assess EPC number in patients with AS and to study the predictive value of their circulating levels on prognosis. Methods The number of EPCs was determined by flow cytometry in 241 patients with AS and a control group of 73 pts. Thirty-eight, 52 and 151 patients had mild, moderate and severe AS, respectively. We evaluated the association between baseline levels of EPCs and death from cardiovascular causes during follow up. Results EPC level was significantly higher in patients with AS compared to the control group (p = 0.017). Two hundred and three patients with moderate and severe AS were followed for a median of 20 months. One hundred and twenty patients underwent an intervention. Thirty four patients died during follow up, 20 patients died due to cardiac causes. Advanced age, the presence of coronary artery disease, AS severity index (combination of high NYHA class, smaller aortic valve area and elevated pulmonary artery pressure) and a low EPC number were predictors of cardiac death in the univariate analysis. Multivariate logistic regression model identified low EPCs number and AS severity index as associated with cardiac death during follow up (p = 0.026 and p = 0.037, respectively). Conclusions EPC number is increased in patients with AS. However, in patients with moderate or severe AS a relatively low number of EPCs is associated with cardiac death at follow up. These results may help to identify AS patients at increased cardiovascular risk.

Aims. Hemochromatosis is a condition in which iron loading impairs the function of many organs, including the heart. Congestive heart failure with left ventricular dilatation is commonly found in patients with hemochromatosis. Two missense mutations (C282Y and H63D) have been shown to be responsible for the majority of cases of hemochromatosis. Methods and results. We examined 156 patients with congestive heart failure due to dilated cardiomyopathy. Details were recorded of clinical and echocardiographic parameters. DNA was extracted from peripheral blood and checked for the presence of the C282Y and H63D mutations by a commercially available single nucleotide primer extension assay. A control group of 98 healthy blood donors was also checked for the presence of these mutations. Of the 157 patients, 42 (26.75%) had at least one mutation. Five (3.65%) were homozygotic for the H63D mutation and 37 (23.6%) were heterozygotic for the H63D mutation. The C282Y mutation was not present. In a control population of 98 healthy blood donors, 27 (27.6%) were heterozygous for the H63D population and none had the C282Y mutation (no significant difference between the patients with cardiomyopathy and the healthy blood donors, χ2 test 0.754). There was a non-significant trend to a difference in the prevalence of homozygotic H63D between the cardiomyopathy patients and the healthy blood donors (3.18% vs. 0%, P=0.076, χ2 test). There was no statistically significant difference between the cardiomyopathy patients with and without the mutations in terms of age, gender, hemoglobin, iron, transferrin, ferritin, presence of diabetes mellitus, hypertension and previous coronary artery bypass grafting. Conclusion. In our population of patients with dilated cardiomyopathy, there was no evidence for hemochromatosis being an important etiology.

Evaluation of: Damani S, Bacconi A, Libiger O et al. Characterization of circulating endothelial cells in acute myocardial infarction. Sci. Transl. Med. 4(126), 126ra33 (2012).Acute coronary syndromes are the most common cause of death in the Western world. Plaque rupture is most commonly associated with acute coronary events, although they primarily involve a complex interplay of numerous initiating and perpetuating factors. The identification of coronary atherosclerotic plaques that are prone to rupture and can lead to acute coronary events is being intensely studied. Circulating endothelial cells (CECs) have been detected in association with endothelial injury and may reflect damage to the vascular tree. In this article, the authors evaluate a recent publication investigating CECs using an automated and clinically feasible CEC three-channel fluorescence microscopy assay.

Objective Hemodynamic forces are potential determinants of aortic atherosclerosis. Aortic regurgitation (AR) alters the flow pattern in the aorta. However, the association between AR and aortic atherosclerosis is not well known. Methods We assessed the presence, extent and distribution of atherosclerotic lesions in the aorta of 42 patients with chronic AR and compared them to 40 patients with similar risk factor profile for atherosclerosis and no valvular disease. Results There was no difference in the extent of atheroma in the ascending aorta and aortic arch between patients with and without AR. Descending aortic atheroma was evident in 25 patients with AR (60%) and 12 patients without AR (30%, p =0.01). AR was found to be the only predicting factor for the presence of aortic atherosclerosis in the descending aorta (odds ratio 4.1; 95% CI 1.2–14.3, p =0.03). Conclusions There is an increased prevalence of descending aortic atherosclerosis in patients with significant AR.

Transcatheter aortic valve implantation (TAVI) is a relatively novel procedure first performed in 2002 and has undergone rapid development since then. Its main indication is treatment of severe symptomatic aortic valve stenosis. Initially, the procedure was indicated for very sick patients who were not eligible for surgical aortic valve replacement. However, rapid development of the technology and operator skill required for TAVI allowed widening of the indications for its use. Currently, there is evidence that TAVI could be better than the surgical intervention in a broad population and not only in the most sick. This paper reviews the medical literature regarding TAVI, including the relevant medical equipment, different modes of its deployment, main complications of the procedure, main indications and contraindications, and the outcome of the patients who undergo it.

Background Speckle-tracking imaging is a novel method for assessing left ventricular (LV) function and ischemic changes. The aim of this study was to assess the predictive value of two-dimensional longitudinal strain in the detection of longitudinal LV dysfunction and the identification of coronary artery disease (CAD) in patients hospitalized with angina. Methods Two-dimensional strain software was extended to allow the analysis of numerous longitudinal strain traces in the entire left ventricle and generate a histogram of peak systolic strain (PSS) values for the left ventricle and for each coronary territory. In each histogram, the value of the 10% worst strain values (PSS 10% ) was determined. Global strain, segmental PSS, and PSS 10% were analyzed in 97 patients hospitalized with angina and had normal LV function, who underwent coronary angiography, and 51 patients with low probability of CAD. Echocardiography was performed 2.9 ± 2 days after admission. Results Sixty-nine patients had significant CAD on coronary angiography. Significant differences were observed in all strain parameters between patients with and without CAD. PSS 10% showed the best accuracy in detecting CAD, with an area under the receiver operating characteristic curve of 0.85. The areas under the curve for global strain and segmental PSS were 0.80 and 0.76, respectively. The optimal cutoff for PSS 10% was −13.9%, with sensitivity and specificity of 86% and 75%, respectively. PSS 10% was better than segmental PSS in the detection of CAD in each coronary territory. Conclusions In patients hospitalized with angina who have significant CAD on coronary angiography, longitudinal systolic function is impaired. Histogram analysis improved the accuracy of longitudinal strain analysis in detecting global and regional impaired function.

The aim of this study was to compare the diagnostic value and safety of sublingual isosorbid dinitrate (ISDN) with intravenous isoproterenol (ISOP) during head-up tilt table testing (HUTT) in pediatric patients with suspected neurocardiogenic syncope.One hundred thirty-six consecutive pediatric patients complaining of presyncope or syncope were submitted to HUTT for the first time. Those who did not develop syncope or presyncope during passive HUTT for 20 minutes underwent repeated HUTT with either 1.25 to 2.5 mg sublingual ISDN or intravenous ISOP (1-3 mug/min) for 20 minutes. There were 54 boys and 82 girls, aged 10 to 18 years with an average of 15.5 +/- 2.4 years and a median of 16 years. Among the patients with cardioinhibition or mixed responses, the severity of the bradyarrhythmia was scored 1 to 3 (restoration of effective rhythm within 10 seconds, 10-20 seconds, and20 seconds while back to supine position, respectively).During the passive period, 24 (17.6%) of 136 patients had a positive response to HUTT. Syncope was observed in another 44 patients during either ISDN or ISOP period (14/58 [24.1%] and 30/54 [55.5%] with ISDN vs ISOP, respectively, P.05). The time to symptoms was shorter with both ISDN and ISOP compared with passive period (6.5 +/- 2.9, 6.3 +/- 5.9, and 10.3 +/- 4.4, minutes, respectively, P.05). The severity score for cardioinhibition response was significantly higher with ISDN compared with the passive period and ISOP (2 +/- 0.8, 1.25 +/- 0.45, and 1.26 +/- 0.45, respectively, P.01).Sublingual ISDN is less sensitive and less safe compared to intravenous ISOP in assessing pediatric age patients with suspected neurocardiogenic syncope and with a negative result in tilt test without provocation. The simplicity of ISDN use should be weighed against the risk of longer symptoms with ISDN.

Nonalcoholic fatty liver disease (NAFLD) is linked to the metabolic syndrome. The aim of the present study is to determine the effect of the metabolic syndrome on left ventricular (LV) geometry and function using as a model patients with NAFLD. Thirty-eight patients with NAFLD, less than 55 years of age and with a normal exercise test, were compared with an age and sex-matched control group. Patients with diabetes mellitus, hypertension, and body mass index>40 were excluded. A complete echocardiographic study including tissue Doppler imaging (TDI) was performed. The following parameters were assessed by echo Doppler: peak velocities of early (E) and late (A) diastolic filling, E/A ratio, flow propagation velocity (Vp). Using TDI early diastolic velocity (E'), and systolic velocity (S') of mitral annulus were obtained. The patients with NAFLD had a significantly higher body mass index (31.4+/-5 vs. 26.4+/-4 kg/m, P=0.01), higher glucose (100.6+/-13 vs. 83.0+/-10 mg/dL, P=0.01), and triglyceride levels (126.5+/-44 vs. 206.5+/-67 mg/dL, P

The Case: A 31-year-old woman, an immigrant from Ethiopia, was admitted to hospital with a 2-week history of general weakness, cough and fever. She denied recent dental treatment or intravenous drug use and had not undergone any invasive procedures. She had a temperature of 38.8° C, with a pulse of