Normal Left Ventricular Volume Research Articles

P94 LATE–ONSET POST–INFECTIVE AORTIC PSEUDO–ANEURYSM AFTER BIOPROSTETHIC AORTIC VALVE REPLACEMENT

Abstract A 74 year–old man was admitted three months after SAVR symptomatic for dyspnea. Past medical history: DM type 2, PAD and recent SAVR after diagnosis of severe aortic stenosis, complicated by Stafilococcus Epidermidis blood culture sternal wound dehiscence, requiring Robicsek technique treatment and long–term parenteral antibiotics. He was finally discharged to our cardiac rehab unit. Blood analysis: negative blood culture at admission with negative CPR. Late positivity (after 2 weeks) for a Staphylococcus epidermidis reinfection. EKG: normal atrio–ventricular and intra–ventricular conduction with regular repolarization. TTE: Normal left ventricular volume and ejection fraction with severe aortic regurgitation secondary to suspected partial bioprosthesis detachment. TOE: valvular detachment with a newly–formed pouch located in the mitro–aortic membrane. Bioprosthetic valvular failure (BVF) is a pathological entity arising from a variety of conditions affecting prosthetic heart valves. We present the case of a late–onset partial valvular bioprosthesis detachment associated with a newly–formed pseudoaneurysm due to late infective endocarditis occurred after cardiac surgery, initially manifested with negative cultural findings and suddenly evolved in severe aortic regurgitation. Valvular detachment is an infrequent complication of infective endocarditis. Surgery is the only option capable of restoring a proper anatomy and a correct function of the valvular apparatus. Patient underwent re–do surgery and a new SAVR was needed after confirmation of diagnosis with no residual aortic regurgitation after discharged. BVF is a fearsome and severe condition presenting with a wide spectrum of clinical presentation. Our experience highlights the need of a prompt diagnosis. Late positivity of blood cultures for Stafilococcus Epidermidis probably depend on prolonged antimicrobial therapy after sternal dehiscence treatment which have probably masked laboratoristic finding in early phase (negative CPR and blood cultures). An early intervention is mandatory in order to prevent systemic dissemination or acute decompensation secondary to severe aortic regurgitation. Surgical approach in this case guaranteed a radical treatment with no residual regurgitation or sub–acute microbial infection. 4–weeks parenteral antibiotics during cardiac–rehab efficacy–controlled relapse of CPR and blood–culture (negative before final discharge).

Abstract 12718: ST Segment Elevation Myocardial Infarction Case With a Novel Therapy

History: A 78-year-old man presented with anterior ST-segment elevation. Coronary angiography demonstrated an occluded left anterior descending coronary artery (LAD Figure 1A) with stenosis of the left circumflex (Cx) coronary artery. Procedure: The LAD was crossed with a workhorse wire (Figure 1B). Predilation restored the flow in the LAD and two diagonal branches (Figure 1C). After assessing the lesion with intravascular imaging (Figure 1D), two drug-eluting stents (DES) were deployed with provisional technique (Figure 1E). The diagonal was rewired and dilated with a 2.0 mm balloon (Figure 1F). A 3.5x20 mm DES was deployed covering the proximal LAD lesion (Figure 1G). The Cx ostium appeared pinched, but the diastolic pressure ratio was 0.95, hence no PCI was performed. Given the large MI size, we administered super saturated oxygen (SSO2). A 5F FR5 catheter was inserted into the LM ostium and SSO2 was administered for 1 hour. An excellent final angiographic result was achieved with TIMI 3 flow and well-expanded stents (Figure 1H). Peak creatinine kinase was 5840 U/l. Magnetic resonance imaging on the next day showed small thrombi, prominent microvascular obstruction in the mid LAD territory, and transmural infarction (Figure 1I). Left ventricular ejection fraction of 39% with normal left ventricular volume. The patient was discharged 3 days later on dual antiplatelet therapy and warfarin and referred to cardiac rehabilitation. Conclusion: “Time is muscle”, hence immediate revascularization is essential. Large anterior STEMIs may benefit from SSO2.

P302 ENDOTHELIALITIS AS A POSSIBLE CAUSE OF MYOCARDIAL INJURY DURING COVID–19 INFECTION

A 53–year–old woman was admitted for chest pain for over two weeks, fever, dry cough, fatigue and myalgia. Chest pain increased in supine position and inspiration. Nasopharyngeal swab was positive for SARS–CoV–2 RT–PCR assay. Admission ECG displayed mild ST–segment elevation (0,5 mm) in inferolateral leads and echocardiogram showed normal left ventricular volume, mildly decreased left ventricular EF (52%) and no regional wall motion abnormalities. Blood tests exhibited elevated values of high–sensitivity troponin I (818 pg/mL), proBNP (19.190 pg/mL), CRP (42 mg/dL), D–Dimer test (1090 ng/mL) and WBC (13000/uL, N 89%, L 7%). IL–6 resulted slightly increased (18 ng/mL). ECG after 24 hours showed T wave inversion in inferolateral leads. Coronary CT angiography revealed normal epicardial arteries. A new echocardiogram, after five days, showed infero–basal hypokinesia, improved global EF (57%) and minimal pericardial effusion. Aspirin and fondaparinoux were started. Myopericarditis was suspected and high dose steroids were administered. After a few days, symptoms improved and ECG, echocardiographic abnormalities and troponin levels were normalized. At 6 weeks follow–up the patient was asymptomatic, ECG and echocardiogram were both normal. Instead cardiac MRI showed signs of endothelial injury: presence of interstitial oedema in the inferoapical and anteroseptal wall (STIR–T2–weighted), without late gadolinium enhancement. We measured blood levels of endothelial dysfunction markers: soluble ICAM–1, VCAM–1 and von Willebrand factor (vWF). They all resulted elevated as compared to a laboratory pool of normal serum (535 ng/ml, 265 ng/ml, and 1659 ng/ml, respectively). Our case was suggestive of myopericarditis related to Sars–Cov–2, but echocardiogram and MRI did not show signs of myocarditis permanent damage. However MRI showed interstitial oedema and hyperemia, typical signs of endothelial injury. Moreover we found high levels of soluble endothelial adhesion molecules, vWF, ICAM–1 and VCAM–1, likely expression of the microcirculatory endothelial dysfunction due to myocardial endothelialitis.In conclusion, our case report suggests that, in COVID–19, acute myocardial injury associated with clinical and investigational signs of myocarditis can be due to myocardial endothelialitis rather than true myocarditis and that an early management with anti–inflammatory drugs (steroids) can be particularly beneficial in patients with unexplained elevated cardiac troponin.

813 The added value of transthoracic three dimensional echocardiography in apical hypertrophic cardiomyopathy

Abstract We present the case of a 73-year-old patient with a recent diagnosis of hypertrophic cardiomyopathy (HCM). He was asymptomatic and has no family history of sudden cardiac death (SCD), syncope or ventricular arrhythmias. An echocardiogram performed at the moment of diagnosis (2020), showed left ventricular (LV) asymmetric apical hypertrophy with maximal wall thickness of 21 mm. Cardiac magnetic resonance (CMR) confirmed LV apical hypertrophy with mid-ventricular obliteration, and late gadolinium enhancement in the apical segments, without wall motion abnormalities present at rest. According to 2014 ESC guidelines, his calculated risk score for sudden cardiac death was low (1.23% at 5 years). On 2021, a comprehensive transthoracic echocardiographic examination including advanced techniques (three-dimensional echo-3DE-, and two-dimensional speckle-tracking-2DSTE) was done as part of his routine follow-up in our cardiomyopathy outpatient clinic. The echo study showed an asymmetric pattern of LV hypertrophy with a maximal wall thickness of 21 mm at the level of the anterolateral apical segment, normal LV volumes (end-diastolic volume 55 mL/m2) and ejection fraction (69%) by 3DE. LV longitudinal strain analysis by 2DSTE showed impaired LV myocardial deformation mainly at the apical LV segments (GLS = −13.6%). There was evidence of dynamic intracavitary obstruction (maximal gradient 32 mmHg at rest and raised to 52 mmHg during Valsalva manoeuvre). 3DE views of the LV (both multi-slice display and 3D rendered image) allowed to avoid foreshortening of the LV apical views, and to appreciate the actual wall motion at the real LV apex. They revealed a LV apical aneurysm which was not detected in the conventional LV-focused apical 2D views (Figure 1A and B). Apical hypertrophic cardiomyopathy (ApHCM) is a variant of HCM that is characteristic of focal thickening of the LV apical myocardium and was reported to have a more benign course than other non-apical forms. However, the presence of LV aneurysm in ApHCM patients is associated with an increased risk for ventricular arrhythmias, sudden cardiac death and thromboembolism. Accordingly, the detection of apical LV aneurysms has significant impact on patient management. Guidelines recommend the use of contrast echocardiography or CMR when the apical region of the LV is suboptimally visualized by conventional 2D echocardiography. However, contrast echocardiography may still be affected by apical foreshortening resulting in suboptimal accuracy, as it is a 2D technique. On the other end, CMR may be contraindicated or not widely available for routine yearly follow-up for all HCM patients requiring regular imaging follow-up. Our clinical case emphasizes the added value of 3DE to increase the sensitivity of transthoracic echocardiography in detecting apical LV aneurysms in patients with apical HCM with important clinical implications for the management of the patient. 813 Figure 1(A) 2D 4chamber-view showing maximal wall thickness in the apical segments (21 mm) with apical obliteration. At a first evaluation, apical aneurism is not easily detected. (B) 4D rendering of the apex showing the apical aneurism.

Prognostic Significance of Nonischemic Myocardial Fibrosis in Patients With Normal LV Volumes and Ejection-Fraction

ObjectivesThis study aims to investigate the prognostic significance of late gadolinium enhancement (LGE) in patients without coronary artery disease and with normal range left ventricular (LV) volumes and ejection fraction. BackgroundNonischemic patterns of LGE with normal LV volumes and ejection fraction are increasingly detected on cardiovascular magnetic resonance, but their prognostic significance, and consequently management, is uncertain. MethodsPatients with midwall/subepicardial LGE and normal LV volumes, wall thickness, and ejection fraction on cardiovascular magnetic resonance were enrolled and compared to a control group without LGE. The primary outcome was actual or aborted sudden cardiac death (SCD). ResultsOf 748 patients enrolled, 401 had LGE and 347 did not. The median age was 50 years (interquartile range: 38-61 years), LV ejection fraction 66% (interquartile range: 62%-70%), and 287 (38%) were women. Scan indications included chest pain (40%), palpitation (33%) and breathlessness (13%). No patient experienced SCD and only 1 LGE+ patient (0.13%) had an aborted SCD in the 11th follow-up year. Over a median of 4.3 years, 30 patients (4.0%) died. All-cause mortality was similar for LGE+/- patients (3.7% vs 4.3%; P = 0.71) and was associated with age (HR: 2.04 per 10 years; 95% CI: 1.46-2.79; P < 0.001). Twenty-one LGE+ and 4 LGE- patients had an unplanned cardiovascular hospital admission (HR: 7.22; 95% CI: 4.26-21.17; P < 0.0001). ConclusionsThere was a low SCD risk during long-term follow-up in patients with LGE but otherwise normal LV volumes and ejection fraction. Mortality was driven by age and not LGE presence, location, or extent, although the latter was associated with greater cardiovascular hospitalization for suspected myocarditis and symptomatic ventricular tachycardia.

A multicenter study of three-dimensional echocardiographic evaluation of normal pediatric left ventricular volumes and function.

Three-dimensional echocardiography (3DE) evaluation of left ventricular (LV) volume and function in pediatrics compares favorably with cardiac magnetic resonance imaging. The aim of this study was to establish from a multicenter, normal pediatric z-score values of 3DE left ventricular volumes and function. Six hundred and ninety-eight healthy children (ages 0-18years) were recruited from five centers. LV 3DE was acquired from the 4-chamber view. A vendor-independent software analyzed end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) using semi-automated quantification. Body surface area (BSA)-based z-scores were generated. Intraobserver and interobserver variability were calculated using intraclass correlation (ICC) and repeatability coefficient (RC). Z-scores were generated for ESV, EDV, and SV. The ICC for intraobserver variability for EDV, ESV, and SV was 0.99, 0.99, and 0.99, respectively. The ICC for interobserver variability for EDV, ESV, and SV was 0.98, 0.94, and 0.98, respectively. The RC for intraobserver and interobserver variability for LV EF was 4.39% (95% CI: 3.01, 5.59) and interobserver was 7.08% (95%CI: 5.51, 8.42). We report pediatric z-scores for normal LV volumes using the semi-automated method from five centers, enhancing its generalizability. 3DE evaluation of LV volumes and EF in pediatric patients is highly reproducible.

Fully penetrant genetic mutation results in wide familial variability: a cardiac magnetic resonance focused report

Abstract Dilated cardiomyopathy (DCM) is a myocardial disorder characterized by ventricular dilation (LV or biventricular) and systolic dysfunction, with a broad etiological spectrum, comprising numerous genetic and non-genetic causes. Cardiac magnetic resonance (CMR) has become an important tool in guiding the etiological diagnosis in DCM. We present the case of a 37-years old man admitted to our department in order to investigate the diagnosis of DCM using CMR. Cine imaging showed mild left ventricular (LV) dilatation and moderate systolic (LV ejection fraction = 42%) dysfunction, but also apical hypertrabeculation meeting the criteria for non-compaction and late gadolinium enhancement (LGE) images revealed mid-wall fibrosis in the basal and midventricular segments of the inferior interventricular septum (IVS) – typical of non-ischemic DCM. Complete family history revealed the diagnosis of DCM in the mother of the patient and in the maternal grandfather, who had died at 87. After genetic testing of the index patient showed a pathogenic mutation in the TTN (titin) gene (c.79273A&gt;T), cascade genetic testing followed, for his mother, sister, uncle and two cousins who all came back positive for the same mutation. CMR examination of the mother done 6 years prior demonstrated severe LV dilatation and systolic dysfunction (LV ejection fraction = 23%), LV non-compaction and mid-wall IVS fibrosis. CMR examination was performed for the other members of the family and discovered pathological findings in the uncle (normal LV volume and function, but focal mid-wall fibrosis in the inferior IVS) and the male cousin (LV non-compaction), while the female cousin had a normal exam. Using CMR and genetic testing, this case report proves the phenotypic heterogenicity of a completely penetrant titin mutation in the same family. Moreover, CMR is shown to be essential in DCM evaluation, having the ability to guide etiologic diagnosis and to detect alterations such as fibrosis and non-compaction in the absence of LV dilation or dysfunction.

Children With Acute Myocarditis Often Have Persistent Subclinical Changes as Revealed by Cardiac Magnetic Resonance.

Many children presenting with myocarditis may not fully recover and have long-term complications, including dilated cardiomyopathy. Magnetic resonance imaging (MRI) has a potential for early detection of persistent changes with long-term implications, but is not performed routinely in the monitoring of myocarditis. To monitor adolescents who present with acute myocarditis using MRI and routine diagnostic tests over the short- to mid-term. Prospective. Eighteen consecutive adolescents (median age 15.5, interquartile range 14.8-16.9 years, 78% male) with acute myocarditis. A 3T scanner including cine steady-state free precession (SSFP), dark-blood T2 -weighted (T2 W) images, and late gadolinium enhancement (LGE). The diagnosis of acute myocarditis was based on clinical symptoms and signs and MRI criteria (cine, T2 -W images, LGE). Follow-up MRI was performed after median 7 months (range 6-9 months). Other routine diagnostic tests included electrocardiogram (ECG), high-sensitivity troponin levels, transthoracic echocardiography, and Holter monitoring. Fisher's exact test, Wilcoxon test for paired samples, Mann-Whitney test for independent samples, Kruskal-Wallis test. At baseline, 17 patients (94%) had elevated troponin levels and/or ST-T changes on resting ECG; ECG showed depressed left ventricular ejection fraction (LVEF<50%) in four patients (22%). At follow-up there was a complete recovery in 16 patients (89%) observed with routinely performed tests, with two cases of persistent ventricular arrhythmia. Despite normal left ventricular volume and LVEF, MRI disclosed ongoing active inflammation in five patients (28%), healed myocarditis with persistent scars in eight patients (44%), and complete resolution of initially observed changes in five patients (28%). In children with acute myocarditis, despite normalization of other routinely assessed parameters (including LVEF), there is a high prevalence of persistent MRI changes showing ongoing disease or remnant scars at follow-up. MRI may allow early detection and prevention of long-term complications of myocarditis in the follow-up care of children with acute myocarditis. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020. J. Magn. Reson. Imaging 2020;52:488-496.

Transthyretin cardiac amyloidosis in continental Western Europe: an insight through the Transthyretin Amyloidosis Outcomes Survey (THAOS).

AimsTransthyretin amyloidosis (ATTR amyloidosis) is a heterogeneous disorder with cardiac, neurologic, and mixed phenotypes. We describe the phenotypic and genotypic profiles of this disease in continental Western Europe as it appears from the Transthyretin Amyloidosis Survey (THAOS).Methods and resultsTHAOS is an ongoing, worldwide, longitudinal, observational survey established to study differences in presentation, diagnosis, and natural history in ATTR amyloidosis subjects. At data cut-off, 1411 symptomatic subjects from nine continental Western European countries were enrolled in THAOS [1286 hereditary (ATTRm) amyloidosis; 125 wild-type ATTR (ATTRwt) amyloidosis]. Genotypes and phenotypes varied notably by country. Four mutations (Val122Ile, Leu111Met, Thr60Ala, and Ile68Leu), and ATTRwt, were associated with a mainly cardiac phenotype showing symmetric left ventricular (LV) hypertrophy, normal diastolic LV dimensions and volume, and mildly depressed LV ejection fraction (LVEF). Morphologic and functional abnormalities on echocardiogram were significantly more severe in subjects with cardiac (n‘= 210), compared with a mixed (n = 298), phenotype: higher median (Q1–Q3) interventricular septal thickness [18 (16–21) vs. 16 (13–20) mm; P = 0.0006]; and more frequent incidence of LVEF <50% (38.1 vs. 17.5%; P = 0.0008). Subjects with cardiac mutations or ATTRwt (or cardiac or mixed phenotype) had a lower survival rate than subjects in other genotype (or the neurologic phenotype) categories (P < 0.0001, for both).ConclusionATTR amyloidosis genotypes and phenotypes are highly heterogeneous in continental Western Europe. A geographic map of the different disease profiles and awareness that a subset of subjects have a dominant cardiac phenotype, mimicking hypertrophic cardiomyopathy, at presentation can facilitate the clinical recognition of this underdiagnosed disease.Trial registrationClinicalTrials.gov: NCT00628745.

Reverse, stationary and progressive left ventricular dilatation in dilated and nondilated ventricles on admission following first anterior STEMI

The relationship between admission left ventricular (LV) volumes, regional contractility and persistent ST elevation in first anterior ST elevation myocardial infarction (STEMI) with evolution of LV volumes at 12 months remains inconclusive. Thus possible differences among patients with reverse dilatation (RD), stationary dilatation (SD) or progressive dilatation (PD) at 12 months based on left ventricle end-systolic volume (LVESV) index changes were investigated. ECG and echocardiographic features of 394 1-year survivors of anterior STEMI were analyzed at admission, 6 and 12 months in those with RD (≥15% reduction of LVESV index, at 12 months n=141), SD (<15% reduction or increase, n=123) or PD (≥15% increase, n=130). Long-term outcome was also evaluated. Admission LVESV values in tertiles and incidence of moderate-severe mitral regurgitation were similar in three groups. In patients with RD, LVESV decreased at 6 months (P<0.001) and further at 12 months (P=0.003), whereas in PD, it increased at 6 months (P<0.001) and further at 12 months (P=0.016). Contractility score in PD was higher on admission (P=0.050) than in the other groups, but it involved the same segments. At 12 months, it improved in each of the six most affected in RD (P<0.001) and SD (P=0.025-0.001) but not in PD group (P=0.452-1.00). Persistent ST elevation at 24 h and peak troponin I were the only independent predictors for RD (odds ratio: 0.900, 95% confidence interval: 0.840-0.905, P=0.003; 0.996, 0.986-0.994, P<0.001) and PD (1.143, 1.001-1.304, P=0.048; 1.004, 1.002-1.006, P<0.001), respectively. During an 8-year follow-up, 77 (19.5%) patients died and although the total mortality was comparable in the three groups, cardiac death or hospitalization for heart failure was higher in the PD (16/130, 14%) than in the other two groups (14/250, 5.6%, P=0.014). Admission normal or enlarged LV volumes may evolve towards RD, SD or PD at 12 months following first anterior STEMI mainly depending in part on infarct size. Importantly, relevant changes occur at not only 6 months but also between 6 and 12 months.

3D echocardiographic reference ranges for normal left ventricular volumes and strain: results from the EACVI NORRE study.

To obtain the normal ranges for 3D echocardiography (3DE) measurement of left ventricular (LV) volumes, function, and strain from a large group of healthy volunteers. A total of 440 (mean age: 45 ± 13 years) out of the 734 healthy subjects enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study had good-quality 3DE data sets that have been analysed with a vendor-independent software package allowing homogeneous measurements regardless of the echocardiographic machine used to acquire the data sets. Upper limits of LV end-diastolic and end-systolic volumes were larger in men (97 and 42 mL/m2) than in women (82 and 35 mL/m2; P < 0.0001). Conversely, lower limits of LV ejection fraction were higher in women than in men (51% vs. 50%; P < 0.01). Similarly, all strain components were higher in women than in men. Lower range was -18.6% in men and -19.5% in women for 3D longitudinal strain, -27.0% and -27.6% for 3D circumferential strain, -33.2% and -34.4% for 3D tangential strain and 38.8% and 40.7% for 3D radial strain, respectively. LV volumes decreased with age in both genders (P < 0.0001), whereas LV ejection fraction increased with age only in men. Among 3DE LV strain components, the only one, which did not change with age was longitudinal strain. The NORRE study provides applicable 3D echocardiographic reference ranges for LV function assessment. Our data highlight the importance of age- and gender-specific reference values for both LV volumes and strain.

39. Speckle tracking echocardiography in patients with severe aortic stenosis and preserved ejection fraction undergoing aortic valve replacement

Aim To evaluate myocardial strain by 2-dimensional speckle-tracking Echocardiography (2D-STE) in patients with severe aortic stenosis (AS) and preserved left ventricular (LV) ejection fraction (EF), before and after aortic valve replacement (AVR). Introduction Severe AS is characterized by chronic increase in the LV pressure and LV hypertrophy which lead to changes in the LV geometry. Impairment of the LV function in severe AS occurs despite of normal LV volumes and EF. Strain analysis by (2D-STE) can detect early and subtle changes of the LV function and can help in referring patients for earlier AVR to obtain better outcome. Methods 15 selected patients with severe AS (aortic valve area 2 ) and normal EF referred for surgical AVR (SAVR) or transcutaneous aortic valve implantation (TAVI). All patients had 2D transthoracic echocardiography and 2D-STE to assess both longitudinal and circumferential strain before and after AVR. Results the entire study cohort showed significant improvement in myocardial strain values. Global longitudinal strain (GLS −15.3 vs. −18.5) mean change of 2.1% and p value = 0.02 and global circumferential strain (GCS −28.9 vs. −31.9), mean change of 2.9% and p value = 0.036. Conclusions following AVR a significant improvement in LV myocardial strain both longitudinal and circumferential occurred. Strain analysis by 2D-STE can detect early and subtle changes in LV systolic function and might play a role in early intervention for severe AS with preserved ejection fraction.

Saxagliptin Preserves Cardiomyocyte Function and Morphology in Aortic-Banded Mini-Swine

Impaired cGMP-PKG signaling may contribute to cardiomyocyte remodeling and cardiac dysfunction in heart failure with preserved ejection fraction (HFpEF) patients. The purpose of this study was to assess cardiomyocyte function and morphology in aortic-banded mini-swine displaying a HFpEF phenotype following manipulation of cGMP signaling via two mechanisms: 1) driving cGMP synthesis with the DPP4 inhibitor saxagliptin; and 2) preventing cGMP catabolism via the PDE5 inhibitor tadalafil. We hypothesized that preserving cGMP-PKG signaling would prevent cardiomyocyte dysfunction and remodeling. Contractile function was measured in enzymatically isolated cardiomyocytes electrically stimulated at three frequencies (0.25, 0.5, 1.0 Hz)from four groups: control (CON), aortic-banded (AB), AB saxagliptin-treated (AB-SAX), and AB tadalafil-treated (AB-TAD). Increased cGMP activity was only observed in AB-TAD animals, however, neither drug treatment increased PKG activity. A significant pacing-induced decrease in diastolic sarcomere length was observed in the AB and AB-TAD groups compared to CON. This finding, indicative of impaired diastolic relaxation, was prevented by saxagliptin treatment. Shortening amplitude decreased in AB cardiomyocytes with increasing pacing frequency, revealing a negative shortening-frequency relationship that was attenuated by both drug treatments. Length:width ratio was decreased in AB and AB-TAD animals with commensurate decreases in left ventricular (LV) end diastolic and end systolic volumes. Normal cardiomyocyte size and LV volumes were preserved in the AB-SAX group. Interestingly, all AB groups exhibited similar gross hypertrophic remodeling (heart weight:body weight ratio) despite differences in cardiomyocyte morphology. In conclusion, saxagliptin appears superior for preserving normal cardiomyocyte morphology and overall function versus tadalafil, independent of changes in cGMP-PKG activity.

Normal Range of Left Ventricular Strain, Dimensions and Ejection Fraction Using Three-dimensional Speckle-Tracking Echocardiography in Neonates.

Aims:Three-dimensional speckle-tracking echocardiography (3D-STE) is a promising new technique to evaluate left ventricular (LV) mechanics. The feasibility and normal values of LV strain using 3D-STE have recently been established in adults and children. Unfortunately, no data are available in neonates. The aims of this study were to evaluate the feasibility and establish normal values of 3D LV volumes, ejection fraction (EF), and the 4 normal strains in healthy neonates.Materials and Methods:Of 50 consecutive newborns who were delivered at our hospital or returned to their first newborn follow-up within the first 3 weeks of life, 38 babies underwent full echocardiographic evaluation, including the acquisition of at least 3 full volume data sets from the apical window, while naturally sleeping. Data sets were analyzed offline. Global LV longitudinal, circumferential, and radial strain, as well as 3D LV volumes and EF, were measured using 3D-STE.Results:Of the 50 newborns, 2 patients were excluded because of significant intra-cardiac shunts, and in another 10 subjects, parents did not give consent. At least one data set was adequate for analysis in all the remaining subjects. Mean indexed LV diastolic, systolic volumes, and EF were 24.7 ± 3.6 ml/m2, 9.2 ± 1.3 ml/m2, and 63% ± 3.7%, respectively. Normal global longitudinal, circumferential, radial, and tangential 4D strain were −20.9% ± 2.8%, −32.4% ± 3.1%, 44.3% ± 3.4%, and −39.7% ± 3.4%, respectively.Conclusions:3D-STE is feasible in newborns without the needed for sedation. Reference values of normal, regional, and global LV 4D strain and volumes were obtained.

Surgical Strategy for Severe Aortic Hypoplasia and Aortic Stenosis With Ventricular Septal Defect and Normal Left Ventricle

At our institution, the strategy for patients with bicuspid aortic valve, aortic valve stenosis (<5 mm), and aortic hypoplasia [hypoplastic aortic arch, coarctation of the aorta (CoA), or interrupted aortic arch (IAA)] with ventricular septal defects (VSDs) as well as normal left ventricular (LV) volume and mitral valve size consists of two parts. The Norwood operation is applied as the first palliation for this group of patients. Second, the decision whether the patients are to undergo the Rastelli operation or a univentricular repair is made depending on the size of the right ventricle after the Norwood operation. This study aimed to examine whether the aforementioned surgical strategy for this group of patients is adequate or not. Seven patients undergoing the Norwood operation as the first palliation for bicuspid aortic valve, aortic valve stenosis (<5 mm), and aortic hypoplasia with VSDs as well as normal LV volume and mitral valve size between February 2005 and March 2010 at Kitasato University Hospital and the Gunma Children's Medical Center were reviewed. Postoperative serum B-type natriuretic peptide (BNP) and central venous pressure (CVP) were measured in the patients undergoing the staged Norwood-Rastelli operation to assess whether the authors' right ventricular end-diastolic volume index (RVEDVI) cutoff (80 % of normal) is adequate. At this writing, all seven patients are alive after a mean follow-up period of 58.8 ± 17.8 months. They all had aortic valve stenosis of <5 mm and a bicuspid aortic valve. Four patients had a diagnosis of CoA with VSD, and three patients had IAA with VSD. Six patients underwent biventricular repair, and one patient had univentricular repair due to the small RVEDVI (74 % of normal). The patients with 80-90 % of normal RVEDVI had higher BNP and higher CVP than those with more than 90 % of normal RVEDVI after the Rastelli operation, whereas the patient undergoing the Fontan operation had a low BNP level. In conclusion, the described strategy for patients with severe aortic hypoplasia and aortic stenosis with VSD as well as normal LV and mitral valve size is reasonable.

Prognostic Implications of Left Ventricular Dilation in Patients With Nonischemic Heart Failure: Interactions With Restrictive Filling Pattern and Mitral Regurgitation

The aim of this study was to evaluate whether small left ventricular (LV) volumes increase the negative prognostic impact of a restrictive filling pattern (RFP) and that of mitral regurgitation (MR) in patients with nonischemic heart failure (HF). The Meta-analysis Research Group in Echocardiography (MeRGE) is a meta-analysis that collated individual patient data from several prospective echocardiography outcome studies. This analysis was restricted to 10 studies and 601 patients with nonischemic HF. The role of MR was tested in a subgroup of 252 patients. A total of 106 deaths occurred during a median follow-up of 32 months. At multivariate analysis, RFP (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.54-11.23; P=.005) and New York Heart Association class III or IV (HR, 2.15; 95% CI, 1.33-3.47; P=.001) were the independent predictors of poor prognosis, and there was no statistically significant interaction between LV dilation and RFP. Moderate/severe MR was associated with poorer outcome in the group of patients with normal volumes, whereas it was not a significant predictor of mortality in patients with any degree of LV dilation. In patients with nonischemic HF, RFP is the most important indicator of poor prognosis, irrespective of the degree of LV dilation. Normal LV volumes increase the negative prognostic impact of moderate to severe MR.

Left Ventricular Volumes, Mass and Function Normalized to the Body Surface Area, Age and Gender From CMR in a Large Cohort of Well-Treated Thalassemia Major Patients without Myocardial Iron Overload

Abstract 1090Introduction. Cardiovascular Magnetic Resonance (CMR) allows an accurate and reproducible quantification of left ventricular (LV) parameters. In Thalassemia major (TM) patients different “normal” LV values have been reported due to chronic anemia and eventually pre-existing iron burdens. Moreover, in this population it is unknown the influence of sex and age on LV parameters and no ranges of normal have been reported using MASS® software. The aim of this study was to establish the ranges for normal LV volumes, mass and ejection fraction normalized to the influence of body surface area (BSA), age and sex from CMR in a large cohort of well-treated TM patients without myocardial iron overload.Methods. Among the 923 TM patients who underwent CMR within the MIOT network for the assessment of cardiac iron overload, function and fibrosis, we selected 142 patients with no known risk factors or history of cardiac disease, normal electrocardiogram, no myocardial fibrosis and no myocardial iron overload (all the cardiac segments with a normal T2* value). All patients had been regularly transfused and chelated since early childhood. Moreover, we studied 71 healthy subjects matched for age and sex. LV function parameters were quantitatively evaluated in a standard way by SSFP cine images using MASS® software. LV end-diastolic volume, end-systolic volume, stroke volume, and mass were normalized to BSA (EDVI, ESVI, SVI, massI).Results. The table shows the comparison of the CMR parameters with differentiation for sex and age in TM patients and healthy subjects and the cut-off of normality defined as mean – or + 2 standard deviation (SD). TM patients showed significantly lower BSA than the controls (P<0.0001). Significantly higher EDVI and SVI were found only for males < 14 years and > 30 years. Significantly higher LVEF were found only for males < 14 years. In TM patients all LV volumes indexes were significantly larger in males than in females (P<0.0001 in all cases). The EF was not different between the sexes. In males the ESVI and the EF were significant different among the age groups (P=0.006 and P=0.001, respectively). In females no significant differences were detected among the age groups.<1414–2020–3030–40>=40TMHPTMHPTMHPTMHPTMHPMalesN=7N=7N=6N=6N=25N=15N=23N=11N=6N=5EDVI (ml/m2)94 ± 18 (130)75 ± 110.03496 ± 20 (136)91 ± 200.715103 ± 17 (137)101 ± 130.68692 ± 15 (122)80 ± 110.02294 ± 9 (112)75 ± 110.013ESVI (ml/m2)31 ± 6 (43)24 ± 60.05838 ± 8 (54)35 ± 140.67038 ± 8 (54)39 ± 90.67632 ± 6 (44)29 ± 60.16029 ± 6 (41)28 ± 100.816SVI (ml/m2)63 ± 14 (91)51 ± 70.05057 ± 12 (81)56 ± 80.86865 ± 10 (85)62 ± 90.43359 ± 10 (79)51 ± 100.02764 ± 8 (80)47 ± 80.007Mass I (g/m2)57 ± 7 (71)68 ± 50.00757 ± 13 (83)71 ± 70.04366 ± 12 (90)77 ± 120.00662 ± 12 (86)66 ± 100.18468 ± 16 (100)74 ± 110.536EF (%)66 ± 4 (58)54 ± 6<0.000160 ± 2 (56)66 ± 140.32263 ± 3 (57)62 ± 60.52065 ± 3 (59)65 ± 80.97268 ± 6 (56)62 ± 90.234FemalesN=2N=2N=8N=6N=24N=6N=33N=8N=8N=5EDVI (ml/m2)63 ± 8 (79)62 ± 40.95181 ± 8 (97)80 ± 90.86683 ± 16 (115)78 ± 90.49977 ± 11 (99)79 ± 100.66982 ± 19 (120)77 ± 160.614ESVI (ml/m2)23 ± 1 (25)22 ± 80.82330 ± 6 (42)31 ± 30.78930 ± 8 (46)30 ± 40.88326 ± 6 (38)29 ± 70.21628 ± 8 (44)28 ± 120.974SVI (ml/m2)40 ± 7 (54)41 ± 40.91949 ± 3 (55)49 ± 60.89253 ± 9 (71)48 ± 60.23451 ± 6 (63)50 ± 80.91554 ± 11 (76)49 ± 60.394Mass I (g/m2)34 ± 3 (40)59 ± 190.29647 ± 8 (63)56 ± 60.04053 ± 9 (71)54 ± 120.89352 ± 9 (70)55 ± 130.46551 ± 12 (75)56 ± 50.344EF (%)63 ± 3 (57)46 ± 170.38863 ± 4 (55)62 ± 40.69465 ± 5 (55)62 ± 30.13766 ± 5 (56)63 ± 70.27166 ± 4 (58)63 ± 70.254Conclusions. In a large cohort of well-treated TM patients significant differences in LV parameters compared to controls were limited to males < 14 years and > 30 years. Due to the influence of BSA, sex and age, appropriate “normal” reference ranges normalized these variables should be used to avoid misdiagnosis of cardiomiopathy in TM patients. Disclosures:No relevant conflicts of interest to declare.

Left Atrial Remodeling and Response to Valsartan in the Prevention of Recurrent Atrial Fibrillation

Background— Left atrial (LA) dilation precedes or appears early after the onset of atrial fibrillation (AF) and factors in perpetuating the arrhythmia. Angiotensin receptor blockers were proposed for reversing LA remodeling. We evaluated the effect of valsartan on LA remodeling in patients with a recent episode of AF and the effect of LA size on AF recurrence (AFr). Methods and Results— LA and left ventricular (LV) echocardiographic variables were measured at baseline and 6 and 12 months in 340 patients from GISSI-AF, a trial testing valsartan prevention of AFr. Reversal of remodeling was considered as a decrease in LA size over 12 months. Changes in patients with and without recurrence and the relationship to duration of AFr were analyzed. Patients were 68.4±8.8 years old, with history of hypertension (85.3%) and cardioversion in the previous 2 weeks (87.4%) or ≥2 AFr in the previous 6 months (40.4%). Baseline LA maximal volume (LAVmax) was severely increased (&gt;40 mL/m 2 ); LV dimensions and function were relatively normal. Over 12 months, 54.4% of patients had AFr. LAVmax was unchanged by rhythm, time, or randomized treatment. Higher baseline LAVmax and lower LA emptying fraction were linearly related to increasing AFr duration during follow-up. Conclusions— GISSI-AF patients in sinus rhythm and history of AF showed severely increased LAVmax with mostly normal LV volume, mass, and systolic and diastolic function. Valsartan for 1 year did not reverse LA remodeling or prevent AFr. Half of the patients without AFr had severe LA dilation; therefore, mechanisms other than structural remodeling triggered recurrence. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00376272.

Cardiac Structure and Function in Persons 85 Years of Age

Individuals aged >85 years constitute the world's most rapidly growing age group. Despite the rapid growth of this population and its high incidence of cardiovascular morbidity, normative data concerning cardiac structure and function are limited. The objective of this study was to define cardiac structure and function in an age-homogenous, community-dwelling population of subjects born in 1920 and 1921. Subjects were recruited from the Jerusalem Longitudinal Cohort Study. Echocardiography was performed using a portable echocardiograph at the subject's place of residence. Standard echocardiographic assessment of cardiac structure and function was performed. Four hundred fifty subjects (219 men, 231 women) were enrolled in the study. The cohort exhibited large left atrial volumes (64.6 ± 26 ml) and high left ventricular (LV) mass indexes (122 ± 36 g/m(2)) with normal LV volumes. Ejection fractions were preserved (55.3 ± 10.2%), but tissue Doppler s-wave velocities (lateral 7.8 ± 2.1 cm/s, septal 6.7 ± 1.9 cm/s) were reduced. Reduced tissue Doppler e waves (lateral 7.3 ± 2.2 cm/s, septal 6.2 ± 2 cm/s) and elevated E/e' ratios (12.2 ± 4.9) indicated significantly impaired diastolic function. In conclusion, the findings of this study demonstrate a high prevalence of left atrial enlargement, elevated LV mass, evidence of LV systolic dysfunction with preserved ejection fractions, and significant LV diastolic dysfunction in a community-dwelling cohort of 85-year-olds. The finding of elevated E/e' ratios in a subset free of known cardiovascular disease should be considered when clinical assessment of LV diastolic dysfunction in this age group is performed.

Left Ventricular Volumes, Mass and Function normalized to the body surface area, age and gender from CMR in a large cohort of well-treated Thalassemia Major patients without myocardial iron overload

Cardiovascular Magnetic Resonance (CMR) allows an accurate and reproducible quantification of left ventricular (LV) parameters. In Thalassemia major (TM) patients have been reported different “normal” LV values due to chronic anemia and eventually pre-existing iron burdens. Moreover, in this population it is unknown the influence of sex and age on LV parameters and no ranges of normal have been reported using MASS® software. The aim of this study was to establish the ranges for normal LV volumes, mass and ejection fraction normalized to the influence of body surface area(BSA), age and sex from CMR in a large cohort of well-treated TM patients without myocardial iron overload.