P < 0.2 as per univariate analysis, multivariate analysis indicated that only LGE area was an independent predictor of subsequent LVRR  0.87–2.53; P < 0.001), as indicated by decreasing left ventricular end-systolic volume index over the 1-year follow-up. Kaplan–Meier curves indicated significantly lower cardiac event-free survival rates in patients with LGE at baseline than in patients without (P < 0.01). By contrast, there was no significant difference in prognosis between patients with CVF values above (severe fibrosis) and below (mild fibrosis) the median of 4.9 %. Cox proportional hazard analysis showed that LGE area was an independent predictor of subsequent cardiac events . The degree of myocardial fibrosis estimated by baseline LGE-CMR imaging, but not that estimated by baseline EMB, can predict LVRR and cardiac event-free survival in response to therapy in patients with newly diagnosed IDCM.Endomyocardial biopsy (EMB) and late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging performed at baseline are both used to evaluate the extent of myocardial fibrosis. However, no study has directly compared the effectiveness of these diagnostic tools in the prediction of left ventricular reverse remodeling (LVRR) and prognosis in response to therapy in patients with idiopathic dilated cardiomyopathy (IDCM). Seventy-five patients with newly diagnosed IDCM who were undergoing optimal therapy were assessed at baseline using LGE-CMR imaging and EMB; the former measured LGE area and the latter measured collagen volume fraction (CVF) as possible predictive indices of LVRR and cardiac event-free survival. Among all the baseline primary candidate factors with  Left ventricular (LV) remodeling is a major pathogenic mechanism in the progression of idiopathic dilated cardiomyopathy (IDCM) and is a confirmed predictor of future cardiac events, including severe heart failure (HF) . In someMyocardial fibrosis is a common feature of LV remodeling, and the increased ventricular stiffness associated with excess collagen accumulation can increase the risk of HF in patients with chronic cardiovascular diseases such as hypertension , 8. HistA total of 91 patients with newly diagnosed IDCM and an LV ejection fraction (LVEF) of <45 % on baseline echocardiography were referred to the Kitasato University Hospital between January 2007 and June 2012. Both LGE-CMR imaging and EMB were performed in these patients to determine the etiology of cardiomyopathy and the extent of fibrosis prior to treatment. Exclusion criteria were the presence of significant coronary artery disease , myocarditis, severe valvular heart disease, and/or chronic renal failure (estimated glomerular filtration rate <30 ml/min). Patients whose CMR images were of poor quality were also excluded. Six patients who underwent mitral valvoplasty and/or left ventriculectomy during the follow-up period were excluded from final analyses. Ten patients who were unable to be followed for >6 months were also excluded. A total of 75 patients were finally selected as the study subjects. Therapies for HF were in accordance with current guidelines  and wereRelevant clinical parameters derived from general laboratory analyses, electrocardiography, and echocardiography were recorded at baseline and approximately 1 year later (326 ± 102 days). Baseline data were collected with patients in a clinically stable condition. Transthoracic echocardiography was performed using an APLIO SSA-770A system , and repeated by the same experienced ultrasonographers whenever possible. M-mode images were obtained in the left parasternal long-axis view to measure the dimension of each chamber. LVEF and LV end-systolic volume index (LVESVI) were calculated by the modified Simpson method using biplanar images from apical views.2; field of view, 340 mm × 340 mm; slice thickness, 8 mm; interslice gap, 8 mm; and four slices acquired in the LV short axis over two R–R intervals. The presence of LGE was determined by two experienced and independent observers blinded to patient outcome. The extent of LGE was expressed as “LGE area,” defined as an area showing a signal intensity of ≥5 standard deviations (SDs) above the mean of the remote reference myocardium. LGE area was quantified by semiautomatic planimetry on the short-axis contrast images using Ziostation 2 .All LGE-CMR examinations were performed at baseline using a 1.5-T clinical scanner  with a maximum gradient strength of 33 mT/m and a slew rate of 120 mT/m/s. An eight-channel phased-array coil and vector electrocardiograph (ECG) were used for signal reception and cardiac gating, respectively. ECG-gated two-dimensional LGE images were acquired 10–15 min after the intravenous injection of 0.2 mmol/kg gadolinium using segmented inversion recovery fast gradient-echo sequences with the following parameters: echo time, 4.2 ms; repetition time, 8.0 ms; views per segment, 24; flip angle, 20°; inversion time, 150–220 ms; bandwidth, ±25 kHz; number of excitations, 1; in-plane resolution, 1.5 × 1.7 mmAt least three EMB specimens were obtained at baseline from the posterior wall of the LV chamber. The interval between LGE-CMR imaging and EMB was <3 weeks. When required, tissue sections were stained with Masson’s trichrome to distinguish cardiomyocytes from connective tissue, and labeled with antibodies against CD3, CD68, and tenascin C to exclude infiltrative myocarditis . Serial t tests, whereas binary variables were compared using the Chi-square test with Yates’ correction for continuity when necessary. Correlation between LGE area and CVF were examined using Spearman’s rank-correlation test.Patients were divided into groups by the presence or absence of LGE on baseline LGE-CMR images (LGE+ and LGE− groups) and by the median value of CVF derived from baseline EMB . Continuous variables expressed as mean ± SD were compared between groups using Student’s P < 0.2 as per univariate analysis to estimate the multivariable regression equation. Event-free survival curves were drawn according to the Kaplan–Meier method and compared using the log-rank test. Cardiovascular events, including sudden death, readmission for HF exacerbation, and major ventricular arrhythmias were considered as secondary end points. For the univariate analysis, we included potential covariates that affect HF prognosis, as per earlier reports [P ≤ 0.04 as per univariate analysis were examined using multivariate analysis in a Cox proportional hazard model. All statistical analyses were performed using JMP Pro 9.0.2 . All P values were two-sided, and P < 0.05 was considered statistically significant.The change in LVESVI at 1 year after treatment as revealed by echocardiography was set as a primary end point of this study, considering the contributing factors for LVRR. To predict the extent of LVRR from baseline variables, univariate screening of all baseline clinical and laboratory variables was performed. Then a stepwise backward conditional algorithm was subsequently applied to selected candidates with  reports , 13–18. P = 0.026; Table P = 0.019). In addition, there were no significant differences in the proportion of patients with implantable defibrillation or CRT devices between the LGE+ and LGE− groups  admitted for treatment of IDCM met the inclusion criteria for this study. At baseline, LVEF was 30 ± 7 % while HF was sufficiently compensated in most cases, with 85 % of patients exhibiting New York Heart Association (NYHA) functional class ≤III under standard therapies. Thirty-six patients (48 %) exhibited positive LGE on LGE-CMR images, with a mean LGE area of 6.4 ± 9.9 %. There were no significant differences in clinical parameters between the LGE+ and LGE− groups, including CVF as determined by EMB, plasma B-type natriuretic peptide (BNP) and serum creatinine levels, QRS width, and LVESVI, with the exception of systolic blood pressure, which was higher in the LGE+ group (116 ± 14 mmHg) than in the LGE− group  0.87 − 2.53; P < 0.001) and plasma BNP levels were independent predictors of subsequent LVRR , but there was no significant difference in prognosis between the group with a CVF value above the median (4.9 %) and the group with a CVF value below the median  among the different clinical parameters at baseline included LGE area and systolic blood pressure. Multivariate analysis indicated that out of these primary candidates, only LGE area was an independent predictor of subsequent cardiac events : 11 with HF hospitalization and 2 with major ventricular arrhythmias. Kaplan–Meier curves indicated significantly higher cardiac event-free survival rates in the LGE− group than in the LGE+ group  myocardial scintigraphy is a particularly powerful tool, not only for detecting myocardial abnormalities in the adrenergic nervous system of IDCM patients  but alsoMyocardial fibrosis is associated with both ventricular remodeling leading to HF and a scar-related re-entrant mechanism linked to ventricular arrhythmia. Although it has been established that both LGE and CVF as measured by LGE-CMR imaging and EMB can estimate the extent of fibrosis in myocardial tissue , there wA hallmark of myocardial damage in IDCM patients is myocardial fibrosis. However, the extent of myocardial fibrosis at first presentation and its association with subsequent responses to various therapies have not been examined in requisite detail. The present multivariate analysis clearly demonstrated the prognostic value of LGE area, but not that of CVF, as a predictor of poor LVRR Table  and adveThe findings of this study have important implications for the clinical management of patients with newly diagnosed IDCM. LGE positivity at baseline may signify the need for more aggressive therapies. The ability to estimate the likelihood of LVRR (or risk of poor LVRR) before initiating therapy should influence treatment strategy. LVEF is a major determinant of feasible therapeutic options, including device implantation, but baseline LVEF may be a poor predictor of subsequent LVRR and prognosis in patients with new-onset IDCM . When thThe present study had some limitations. It was a single-center study, so selection bias was a major concern. Because of the low number of cardiac events in our cohort, which comprised a relatively small number of patients, the findings of this observational study should be interpreted with caution. Although LGE-CMR imaging allows for semiqualitative assessment of myocardial structure and function, it is of limited accuracy for the absolute quantification of myocardial fibrosis. Indeed, there is no clear consensus on the optimal intensity threshold to identify fibrosis. Reports have demonstrated the efficacy of LGE patterns such as mid-wall, epicardial, diffuse, and focal enhancement in patients with IDCM , 23. HowIn patients with newly diagnosed IDCM, the degree of myocardial fibrosis detected by LGE-CMR imaging, but not that estimated by EMB, was an independent predictor of LVRR and prognosis in response to optimal medical therapy.


Graves’ disease (GD) is a common cause of hyperthyroidism resulting in development of thyrotoxic heart disease (THD).to assess cardiovascular disorders and health related quality of life (HRQoL) in patients with THD secondary to GD.All patients diagnosed with THD secondary to GD between January 2011 and December 2013 were eligible for this study. Clinical assessment was performed at baseline and at the follow-up visit after the restoring of euthyroid state. HRQoL was studied with a questionnaire EQ-5D-5L.Follow-up data were available for 61 patients, but only 30 patients with THD secondary to GD were consented to participate in investigation of their HRQoL. The frequency of cardiovascular complications was significantly reduced as compared before and after the antithyroid therapy as follows: resting heart rate (122 vs. 74 bpm), blood pressure: systolic (155 vs. 123 mm Hg), diastolic (83 vs. 66 mm Hg), supraventricular premature contractions (71% vs. 7%), atrial fibrillation (72% vs. 25%), congestive heart failure (69% vs. 20%), thyrotoxic cardiomyopathy (77% vs. 26%), all p<0.01. Anti-TSH receptor antibodies were determined as independent predictor of left ventricular geometry changes, . HRQoL was improved in all domains and self-rated health increased from 43 to 75 units by visual analogue score (p<0.001).Restoring of euthyroid state in patients with GD is associated with significant elimination of cardiovascular disorders and improvement of HRQoL. To our knowledge this is the first study evaluating Ukrainian patients with THD secondary to GD with focus on HRQoL. GD is fyronine T in serumin serum –7. Moreoin serum , 9. THD in serum –12. In gin serum .The administration of antithyroid drugs and beta-blockers is initial treatment of GD resulting in elimination of hyperthyroidism and normalization of cardiovascular parameters as well as HRQoL –16. It iThis prospective study aimed at evaluating HRQoL and cardiovascular changes in patients with THD secondary to GD.The study and consent procedure were approved by the ethical committee at Kyiv City Teaching Endocrinological Center . All patients provided their written informed consent to participate in the study. All patients diagnosed with GD at the Kyiv City Teaching Endocrinological Center between January 2011 and December 2013 were eligible for the study. Among 2,221 individuals with hyperthyroidism, 1,194 patients were diagnosed with GD. Of these, 75 patients were presented with THD and invited to participate in the study. Clinical information and follow-up data were available for 61 patients, but only 30 patients with THD secondary to GD consented to participate in HRQoL part of the study.The inclusion criteria were diagnosis of GD with overt hyperthyroidism and THD. We excluded patients diagnosed with cancer, infectious disease, lung, renal or liver failures, other types of secondary arterial hypertension, history of myocardial infarction or stroke, heart failures NYHA III and IV, congenital heart defects, valvular heart disease.All patients underwent an antithyroid therapy with titration block-regimen by methimazole; metoprolol (beta-blocker), ramipril (angiotensin-converting enzyme (ACE) inhibitor) or telmisartan (angiotensin II receptor blocker) were administrated to treat cardiological complications .i.e. at the time of GD diagnosis and at follow-up when the stable euthyroid state was established. Both assessments included HRQoL evaluation and clinical follow-up with relevant thyroid and cardiovascular examinations.Patients were subjected to prospective evaluation: at baseline, www.euroqol.org EuroQol Group, Netherlands), previously validated in studies of cardiac disorders [HRQoL was evaluated using the Ukrainian printed version of the EQ-5D-5L questionnaire containing visual analogue score (VAS) system , free T3 , TSH < 0.1 mIU/l  accompanied by at least two of following parameters: diffuse goiter, Graves’ ophthalmopathy, increased level of TRAb , TPOAb . The thyroid was evaluated by physical examination, blood testing  by using Cobas E 411 analyzer  and ultrasonography by using Sonoline Sienna equipped with 3.5–7.5 MHz transducers .Diagnosis of GD was established for patients with biochemical evidence of overt hyperthyroidism, Resting heart rate was determined by manual evaluation of the heartbeats per minute (bpm) at the radial artery. Tachycardia was noted if resting heart rate was >100 bpm. THD was confirmed by an experienced cardiologist (IT) in patients with manifestations of supraventricular premature contractions, atrial fibrillation, arterial hypertension, thyrotoxic cardiomyopathy, or congestive heart failure according to available guidelines and recommendations –24. Arte2). Body surface area (BSA) was determined by Mosteller formula [A 12-lead electrocardiography was performed by using electrocardiograph UCARD-200 . Echocardiography was performed on the EnVisor C Ultrasound System  with 2–4 MHz phase transducers using M-mode, two-dimensional imaging and Doppler technique to measure the following parameters of the heart: left ventricular (LV) mass and LV mass index, left atrium dimension, interventricular septum wall thickness, LV posterior wall thickness, LV relative wall thickness, LV end-systolic diameter, LV end-diastolic diameter, LV end-systolic volume and LV end-diastolic volume LV end-diastolic volume, LV end-systolic diameter, LV end-diastolic diameter, LV ejection fraction (LVEF); the pulmonary hypertension was diagnosed if BP in pulmonary artery was > 25 mm Hg as determined by Doppler-echocardiography; geometry of LV was determined by the comparison of LV relative wall thickness and LV mass index in male and female patients as recommended elsewhere [ formula .The Statistica v12.0  software system was used for univariate statistical analyses. The Wilcoxon signed-rank test and Fisher’s (two-tailed) exact test were applied to evaluate the differences in the studied parameters. The level of statistical significance was set to p<0.01 due to multiplicity. A regression analysis was performed using STATA/SE v13 . In the linear regression, correlation of LV geometry changes was tested in the uni- and multivariate analyses with the following factors as age, BMI, systolic blood pressure, TSH, free T3, free T4, TRAb, TPOAb . Results with p<0.05 were considered as statistically significant.2) and BSA (1.80 vs. 1.88 m2), p<0.001.Analyses of the clinical data of the cohort are summarized in 3 (range 12–225 cm3) right lobe and 45 cm3 (range 9–182 cm3) left lobe. A significantly increased thyroid size was also detected after the treatment: 67 cm3 right lobe and 62 cm3 left lobe (p<0.001). At the baseline, Graves’ ophthalmopathy was present in 42 (69%) and in 11 (18%) patients after the antithyroid therapy (p<0.001). The hyperthyroidism was confirmed by low levels of TSH with mean concentration 0.023 mIU/l followed by its significant elevation to 3.6 μIU/ml after the antithyroid therapy (p<0.001). All patients exhibited overt hyperthyroidism followed by restoring of euthyroid state as judged from the thyroid hormones levels before and after the antithyroid therapy, respectively: free T3 (27.4 vs. 5.2 pmol/l), free T4 (81.3 vs. 17.4 pmol/l). These data indicate that decreasing of both free T3 and T4 in serum was supported by TSH elevation > 0.1 mIU/l in 48 (79%) cases after the treatment. Hence, a subclinical hyperthyroidism was diagnosed in remaining 13 (21%) patients without evidence of clinical manifestations.An ultrasonography at baseline detected the diffusely enlarged thyroid in 56 (92%) patients, measuring 49 cmThyroid autoantibodies showed higher concentrations at the diagnosis followed by decreasing of their levels after the antithyroid therapy, respectively: TRAb (104 vs. 27 IU/l), TPOAb (87 vs. 117 kIU/l), p<0.001.2, left atrium dimension from 4 to 3.7 cm, both interventricular and posterior septum wall thickness from 1.2 to 1.1 cm, LV relative wall thickness from 0.6 to 0.5 cm, LV end-systolic diameter from 3.6 to 3.2 cm, LV end-diastolic diameter from 5.2 to 4.7 cm, LV end-systolic volume from 51 to 42 ml, LV end-diastolic volume from 142 to 126 ml (p<0.001).The evaluation of cardiac functions showed significant improvements of the hemodynamics, heart sizes and LV mass after the treatment . The anaFurther analyses of cardiovascular parameters showed higher frequency of cardiac rhythm disorders at the time of diagnosis than in euthyroid patients , respectAll types of LV geometry were detected in study cohort . A conceIn the univariate analysis, TRAb was the only predictor of LV geometry changes, b-coefficient = 0.03 (95% CI 0.00–0.06), p = 0.032. The multivariate regression showed that association of TRAb and LV geometry changes remained statistically significant, b-coefficient = 0.04 (95% CI 0.01–0.07), p = 0.02. These data indicate that decreasing of TRAb levels is associated with LV geometry changes. The other factors did not show statistically significant association in the regression model (data not shown).Analyses of the EQ-5D-5L data showed significant improvements of HRQoL in all domains , Fig. 1.Self-rated health status is presented in In this prospective study we investigated cardiovascular complications and HRQoL associated with hyperthyroidism in cohort of Ukrainian patients diagnosed with GD. Restoring of the euthyroid state was associated with elimination of cardiovascular disorders along with overall improvement of HRQoL.We analyzed cardiovascular symptoms constituting THD secondary to GD in relation to HRQoL. In line with other researchers investigating relations between hyperthyroidism and cardiac disorders, we revealed a significant impact of GD on the development of cardiovascular complications followed by normalization of heart functions at the euthyroid state , 27, 28.We diagnosed arterial hypertension in 95% of patients, predominantly demonstrating high systolic blood pressure, as result of low vascular resistance, elevated resting heart rate and blood volume due to excess of thyroid hormones . MoreoveThe role of euthyroidism restoration is supported by findings from other studies showing the direct effect of hyperthyroid state on the cardiovascular system; in animal studies, the excess of thyroid hormones had a major impact on the cardiomyocytes, whereas beta-adrenergic or angiotensin receptor stimulations played a minor role , 36, 37.The thyroid autoantibodies TRAb and TPOAb were detected in majority of patients and TRAb was determined as the independent predictor of LV geometry changes. It is worth to mention that TRAb plays a role for prognosis of GD, in pathogenesis of Graves’ ophthalmopathy or development of pulmonary hypertension –43. HoweAlthough the response rate for the EQ-5D-5L questionnaire was 49%, our results are consistent with other studies –12, 29. conditions [Similarly to other studies, we showed that elimination of hyperthyroidism was associated with significant reduction of anxiety and depression , 48, 49.nditions –16. The The limitation of the study is a relatively small sample size, which could have a potential impact on the external validity. However, it is important to note that our results were in agreement with findings from the studies evaluating larger cohorts of patients , 31, 50.To summarize, we reported the results of prospective study investigating THD secondary and HRQoL in patients with GD. The data analyses revealed the impact of hyperthyroidism to patients’ health status followed by significant improvement of HRQoL and elimination of cardiovascular complications constituting THD after the normalization of thyroid hormones levels in majority of patients, which are partly overlapping and partly distinguishing from other reported cohorts. To our best knowledge this is the first study from Ukraine evaluating HRQoL by the EQ-5D-5L instrument in patients with THD secondary to GD.


Longitudinal motion of the mitral valve, known as the mitral annular plane of systolic excursion (MAPSE), correlates well with LV systolic function. Similarly, tricuspid annular plane systolic excursion (TAPSE) correlates well with RV systolic function. Echocardiographically, the absolute value of TAPSE was greater than MAPSE, by 54.5% in a recent study of normal subjects and the MAPSE/TAPSE ratio is 0.66±0.14 (1). However, the interventricular systolic relationship has not been accurately defined in the presence of regional wall motion abnormalities. We hypothesised that the interventricular systolic relationship, measured by the ratio of averaged-MAPSE and TAPSE, changes in the presence of acute myocardial infarction with regional wall motion abnormality.Thirty-eight patients underwent CMR at 3T  within 3 days following reperfused ST-elevation MI. Black blood, cine and LGE imaging (16-20 minutes following 0.1 mmol/kg gadolinium DTPA) were performed. Infarct location  was determined by location of LGE in the infarcted area. MAPSE  was measured from the 4-chamber cine. A line was drawn across both the medial and lateral mitral annulus as a reference point in end-diastole . A second reference line was drawn across the same plane on an image taken just after closure of the aortic valve. The longitudinal distance parallel to the left ventricular wall was measured for both medial and lateral walls. Using a similar technique, TAPSE was measured .


Because infiltrative cardiomyopathy and hypertrophic cardiomyopathy (HCM) share clinical and hemodynamic features of left ventricular (LV) hypertrophy and abnormal diastolic function, it is often difficult to distinguish these entities.We investigated the potential role of high-sensitivity cardiac troponin T (hs-cTnT) for differentiation of infiltrative cardiomyopathy from HCM.p < 0.001), whereas brain natriuretic peptide levels did not differ between the two groups. In two age-matched the 2 cohorts , hs-cTnT level, maximum LV wall thickness, posterior wall thickness, peak early (E) transmitral filling velocity, peak early diastolic (Ea) velocity of tissue Doppler imaging at the lateral corner and E/Ea ratios at both the septal and lateral corners were significantly different between the two groups. As for diagnostic accuracy to differentiate the two groups by using receiver operating characteristic analysis, hs-cTnT was the highest value of area under the curve (0.939) and E/Ea  was second highest value (0.914).The study group consisted of 46 consecutive patients with infiltrative cardiomyopathies or HCM in whom sarcomere protein gene mutations were identified at Kochi Medical School Hospital; of these, there were 11 patients with infiltrative cardiomyopathy (cardiac amyloidosis in 8 patients and Fabry disease in 3 patients) and 35 HCM patients. Serum hs-cTnT level was significantly higher in patients who had infiltrative cardiomyopathy than in those who had HCM (0.083 ± 0.057 ng/ml versus 0.027 ± 0.034 ng/ml, Serum hs-cTnT is a helpful diagnostic indicator for accurate differentiation between infiltrative cardiomyopathy and HCM. Infiltrative cardiomyopathies such as cardiac amyloidosis and Fabry disease are difficult to differentiate from hypertrophic cardiomyopathy (HCM) because these cardiomyopathies share clinical and hemodynamic features of left ventricular (LV) hypertrophy and abnormal diastolic function –13. AmylRecently, a new generation of high-sensitivity assays for cardiac troponins has been developed to identify minimal cardiac damage in the setting of acute coronary syndromes , 19. Ele2). Informed consent was obtained from all patients or their parents in accordance with the guidelines of the Ethics Committee on Medical Research of Kochi Medical School.The study group consisted of 46 consecutive patients with infiltrative cardiomyopathies or HCM in whom sarcomere protein gene mutations were identified at Kochi Medical School Hospital; of these, there were 11 patients with infiltrative cardiomyopathy (cardiac amyloidosis in 8 patients and Fabry disease in 3 patients) and 35 HCM patients. In this study, we excluded patients with evidence of coronary artery disease and patients with renal failure (estimated glomerular filtration rate (eGFR) < 30 ml/min per 1.73 mThe diagnosis of amyloidosis was made by biopsy study of an involved organ that demonstrated typical Congo red birefringence when viewed under polarized light. Of the 8 patients with cardiac amyloidosis, 2 had AL amyloidosis and 6 were considered to have senile amyloidosis with transthyretin. The diagnosis of Fabry disease was based on low plasma alfa-galactosidase A activity, family surveys, and tissue confirmation. The diagnosis of HCM was based on echocardiographic demonstration of a hypertrophied, nondilated LV  in the absence of systemic hypertension or other cardiac disease (e.g. aortic stenosis) capable of producing clinically evident hypertrophy at some point of clinical course. In this study, all HCM patients with sarcomere gene mutations in whom serum hs-cTnT was measured were enrolled. Sarcomere gene mutations in our current study were S297X, V593fs, V762D, R945fs and R1138C in cardiac myosin-binding protein C gene, R663C and N562K in cardiac beta-myosin heavy chain gene, D46V in cardiac troponin T gene and R162W in cardiac troponin I gene. These were not found in at least 200 chromosomes from healthy Japanese individuals. There were 7 patients with dilated phase of HCM defined as LV systolic dysfunction of global ejection fraction (EF) < 50 %.Evaluation of patients included medical history, clinical examination, 12-lead electrocardiography, and conventional and Doppler echocardiography. Maximum LV wall thickness was defined as the greatest thickness in any single segment. Left ventricular end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD) were measured from M-mode and 2-D images obtained from parasternal long-axis views. Global EF was determined from apical two- and four-chamber views. Mitral inflow velocities were determined using pulsed-wave Doppler with the sample volume positioned at the tips of the mitral leaflets in the four-chamber view. Peak early (E) and late (A) transmitral filling velocities were measured. Tissue Doppler imaging was performed in the pulse-Doppler mode to allow for a spectral display and recording of mitral annulus velocities at septal and lateral corners. Peak early diastolic (Ea) velocity was measured, and the E/Ea ratio was calculated. LV outflow tract gradient was calculated form continuous-wave Doppler using the simplified Bernoulli equation. LV outflow tract obstruction was defined as the presence of basal LV outflow gradient ≥ 30 mmHg at rest. Right ventricular hypertrophy was defined as thickness of right ventricular free wall > 5 mm.Peripheral venous blood samples were collected for measurements of serum hs-cTnT and plasma brain natriuretic peptide (BNP) at the same time in clinically stable condition. Blood was taken at a random time mainly in our outpatient clinic. Serum hs-cTnT was measured by Elecsys Troponin T - High Sensitive immunoassay . The normal range of this troponin marker in an apparently healthy adult population is less than or equal to 0.014 ng/ml (99 percentile). Plasma BNP was measured using an enzyme immunoassay .t-test or Wilcoxon rank sum test was used, and a chi-square test or Fisher’s exact test was used for analysis of categorical variables. The diagnostic accuracies of parameters including biomarkers and echocardiographic indices were compared by receiver operating characteristic (ROC) analysis. Age, New York Heart Association functional class, eGFR, E/Ea , and hs-cTnT were included in a multivariate logistic regression model to identify independent correlations of the differentiation between the two types of cardiomyopathies. Statistical analysis was performed using SPSS (version 14.0 J) statistical software .All data are expressed as mean ± SD or frequency (percentage). Differences between clinical variables of the infiltrative cardiomyopathy group and HCM group were examined with univariate analysis. For analysis of continuous variables, a Clinical characteristics of the patients in the present study are summarized in Table p = 0.047) and E/Ea  (p = 0.028). When the cut-off levels were defined as hs-cTnT of 0.035 ng/ml and E/Ea  of 11, combined measurements of these parameters resulted in 100 % sensitivity and 95 % specificity for the diagnosis of infiltrative cardiomyopathy  was second highest in area under the curve values in ROC curves to differentiate the two groups. This may result from the findings that amyloid deposition in cardiac amyloidosis is diffuse, whereas LV hypertrophy is usually asymmetric and predominantly septal in HCM.There are several limitations to be acknowledged in the present study. First, the number of subjects was small and some of the statistical analyses might have been affected. We need to have more data on hs-cTnT levels in various clinical severities in each disease entity. A diagnostic challenge remains in patients with infiltrative cardiomyopathies who have relatively mild abnormalities on echocardiography. Second, due to the retrospective design of the study, it is possible that there is a selection bias, although the study population consisted of consecutive patients with cardiomyopathies. Third, we could not distinguish between cardiac amyloidosis and cardiac involvement of Fabry disease within infiltrative cardiomyopathies by using hs-cTnT measurements. This biomarker has not been fully evaluated in Fabry disease.Measurement of serum hs-cTnT enables accurate discrimination between infiltrative cardiomyopathy and HCM. The combination of this biomarker and conventional echocardiographic parameters helps to differentiate these cardiomyopathies.


Advances in mechanical circulatory support have significantly expanded the treatment options for patients with heart failure, whether acute or chronic. There are numerous devices available that offer patients short-, intermediate-, and long-term duration of support depending on their clinical needs and cardiac recovery. Each device has its own technical considerations and the decision which device to use depends on several factors, including what is available, the degree of support required, and expected duration of support. Additional issues that need to be considered in choosing level of support include right heart function, respiratory failure, and multi-organ derangements. A widespread availability of short-term ventricular assist devices and timely institution for effective hemodynamic support will translate into improved patient outcomes whether that is successful transfer to a tertiary care facility or recovery of inherent cardiac function. Implantable ventricular assist devices have and will continue to evolve into smaller and more durable devices, and the future for patients with advanced heart failure looks ever-more promising. The limited efficacy of medical therapy to treat end-stage heart failure (ESHF), shortage of available donor hearts, and the increasing number of patients who do not qualify for transplant candidacy despite worsening heart failure have all fueled the evolution of mechanical circulatory support. Currently, long-term implantable left ventricular assist devices (LVAD) have significantly expanded treatment options for patients with ESHF as a bridge-to-decision, recovery, transplant, or destination therapy (DT) . MirroriThe immediate goal for patients in cardiogenic shock is the re-establishment of normal hemodynamics and restoring vital organ perfusion. Cardiogenic shock can occur as a result of myocardial ischemia, valvular heart disease, myocardial disorders , or mechanical complications of myocardial infarction. Ideally, left ventricular support in this setting should be easy to institute, able to rapidly stabilize the patient, able to be transported with the patient, and allow adequate duration of support to address organ derangements and evaluation of neurologic status. A common approach in these patients is conservative, stepwise escalation of support before committing the patient to a more effective mechanical circulatory support (MCS), ie, maximal inotropes, followed by intra-aortic balloon pump, then followed by consideration of VAD therapy. This approach arguably poses a significant delay in reversing malperfusion in these critically ill patients.Percutaneously implanted devices include the Impella 2.5 and 5.0 , TandemHeart , and extracorporeal membrane oxygenation (ECMO). The Impella, a microaxial flow pump, is inserted through a 13-French catheter in the femoral artery and placed across the aortic valve. The Impella 2.5 has been successfully used for left ventricular support during high-risk coronary intervention and for patients with myocardial infarction and cardiogenic shock (The TandemHeart is another percutaneously placed VAD. The inflow cannula 17 French) is placed into the femoral vein and advanced into the left atrium under fluoroscopic guidance by a transseptal puncture. The outflow cannula (15 of 17 French) is inserted into the femoral artery. This pump has been successfully used for high-risk coronary intervention, post-cardiotomy heart failure, bridge-to-bridge (BTB), and bridge-to-transplant (BTT) 7 French . A majorThere is considerable experience with ECMO utilized for the treatment of cardiogenic shock. The major addition to the ECMO circuit is an oxygenator and it is the device of choice when patients have both cardiac and respiratory failure. Cannulation depends on the clinical situation; central cannulation is used in the post-cardiotomy setting and percutaneous cannulation through the femoral, subclavian, or neck vessels is more commonly used for cardiogenic shock. ECMO can provide full cardiopulmonary support, but disadvantages of this device strategy include bleeding because of the strict need for intense anticoagulation, limb ischemia when peripheral cannulation is employed, incomplete left ventricular decompression, and difficulty during patient transportation if the circuit is not compact and simplified. This type of support can be used as bridge-to-recovery (BTR), BTB, or BTT.The Biomedicus Bio-pump  is a centrifugal pump that has been in use since the 1980s. One major advantage of this pump is its widespread availability in most centers that perform cardiac surgery. It is easy to implant and transport patients on this system. However, this pump is prone to fibrin formation in the circuit, and other types of circulatory devices have emerged.The Abiomed BVS5000 is a pneumatically-driven assist device which consists of a filling chamber (fills passively) and blood returns to the patient via a pumping chamber. Pulsatile flow is not usually in concert with native cardiac contraction and can produce flows up to 6 L/min. The pump head requires exchange every week even with adequate anticoagulation. This device can similarly be used as support until weaning, and as a bridge to longer-term implantable VAD, or BTT.A newer external VADs based on improved centrifugal technology is the CentriMag . Patients with CentriMag can be supported until weaning, as a bridge to a longer-term implantable VAD, or transplant . AnticoaAs previously discussed, LVAD selection mainly depends on the indication for mechanical circulatory support. In the United States, long-term, implantable ventricular assist devices have been approved for clinical use on two indications, either as BTT or DT. This section focuses on long-term implantable devices, which have received FDA approval for these clinical scenarios.The clinical indications for use of implantable ventricular assist devices as BTT mainly parallel the eligibility criteria for cardiac transplantation, but its primary therapeutic aim is reducing transplant wait list mortality. Various VADs based on pulsatile pump technology were approved for BTT; these included both paracorporeal pumps such as the Thoratec PVAD  and the Berlin Heart Excor , and implantable devices such as the HeartMate XVE and Novacor VAD . More recently, The HeartMate II, an axial flow pump, has proven to be effective in improving functional status, quality of life, and survival in those who clinically deteriorated while awaiting transplantation . The thiOn the other hand, the majority of patients with advanced ESHF simply do not become eligible for heart transplantation due to the limited number of suitable donor hearts. The HeartMate XVE was the first device FDA approved based largely on the results of the REMATCH trial in which transplant-ineligible patients were randomized to either optimal medical management or LVAD therapy . At 1 anLVAD technology has evolved from large, pulsatile pumps into smaller, continuous-flow pumps. The HeartMate 2 has proven to be significantly more durable than the HeartMate XVE, and survival and quality of life were significantly improved in those supported on the new axial flow pumps . CurrentA unique device, which is also FDA approved for BTT, is the pneumatic total artificial heart Cardiowest TAH . Indications for TAH implantation differ from those of most VADs. This pump is mainly for patients with severe cardiogenic shock resulting in profound multiple organ derangements, extensive myocardial infarction resulting in biventricular failure, left ventricular failure with extensive intraventricular thrombi, or select cases of primary graft failure or rejection following transplantation.As discussed earlier, these implantable devices, which are currently FDA approved for long-term VAD support for either BTT or DT, are typically implanted in patients with chronic heart failure after a thorough evaluation process. However, in patients that are transferred on the aforementioned temporary support instituted for cardiogenic shock or post cardiac surgery, the evaluation process is quite different and their treatment pathway is dependent on several factors . Upon arPatient presentation and acuity of illness dictate the appropriateness of which device is selected for support. Temporary devices can serve as a bridge in order to stabilize patients and facilitate a work-up for candidacy for long-term implantable devices. This field continues to evolve as do the indications for their use


Aim. Our aim was to assess the prevalence of subclinical diabetic cardiomyopathy, occurring among diabetic patients without hypertension or coronary artery disease (CAD). Methods. 656 asymptomatic patients with type 2 diabetes for 14 ± 8 years  and at least one cardiovascular risk factor had a cardiac echography at rest, a stress cardiac scintigraphy to screen for silent myocardial ischemia (SMI), and, in case of SMI, a coronary angiography to screen for silent CAD. Results. SMI was diagnosed in 206 patients, and 71 of them had CAD. In the 157 patients without hypertension or CAD, left ventricular hypertrophy (LVH: 24.1%) was the most frequent abnormality, followed by left ventricular dilation (8.6%), hypokinesia (5.3%), and systolic dysfunction (3.8%). SMI was independently associated with hypokinesia  and systolic dysfunction , while HbA1c  and body mass index  were associated with systolic dysfunction. LVH was more prevalent among hypertensive patients and hypokinesia in the patients with CAD. Conclusion. In asymptomatic type 2 diabetic patients, diabetic cardiomyopathy is highly prevalent and is predominantly characterized by LVH. SMI, obesity, and poor glycemic control contribute to structural and functional LV abnormalities. Myocardial impairment in diabetes mellitus is due to multiple pathophysiological pathways involving myocardial ischemia and/or coronary artery disease (CAD) and hypertension, which are usual in type 2 diabetes. When thosefactors are excluded, myocardial impairment is considered to be specific to diabetes, defining diabetic cardiomyopathy . CardiacHere, we report the prevalence of LV mass and function abnormalities on echocardiography and their determinants in a retrospective series of 656 asymptomatic diabetic patients referred for cardiac and vascular complications screening. Patients were then sorted out according to the presence of hypertension and silent CAD and data on the group without CAD and without hypertension were analysed in order to characterize the determinants of diabetic cardiomyopathy in the absence of confounding factors.We collected the data of type 2 diabetic inpatients of the Department of Endocrinology-Diabetology-Nutrition, Jean Verdier Hospital , between 1991 and 2008. Criteria for inclusion in this study were normal 12-lead resting ECG and the presence of at least one of the following additional cardiovascular risk factors: dyslipidemia , hypertension (blood pressure ≥ 140/90 mmHg or antihypertensive treatment), smoking, microalbuminuria , family history of premature CAD (before the age of 60 in first-degree relatives), proximal peripheral , or carotid  occlusive arterial disease detected by ultrasound examination. Criteria for noninclusion were history of myocardial infarction or angina pectoris, congenital heart disease, known cardiomyopathy or valve diseases, and ECG ischemic abnormalities. Diabetic retinopathy was diagnosed if at least one microaneurysm or hemorrhage was found on eye fundus examination. The diagnosis of peripheral neuropathy was based on the presence of any two or more of the following: neuropathic symptoms, decreased distal sensation, or decreased or absent ankle reflexes. Each patient enrolled in this study gave oral informed consent in accordance with the European directives.Rest cardiac transthoracic echocardiography was performed on Acuson XP128 before 2004 and Sequoia C512  after 2004. Two-dimensional images were acquired on parasternal and apical views, time-motion images were acquired on one parasternal view, and pulsed-wave Doppler was used with a sample volume of 2 mm and a sweep speed of 100 mm/s. Measurements and calculations were done according tothe recommendations of the American Society of Echocardiography . PatientEach patient underwent a thallium-201 myocardial scintigraphy after an ECG stress test and/or a pharmacological stress test (dipyridamole injection). The ECG stress test protocol was previously reported ). Multivariate analysis showed that the three parameters were independently associated with systolic dysfunction: BMI  and peripheral occlusive arterial disease  were independently associated with hypokinesia.Hypokinesia was associated with SMI (OR 10.8 [2.4–48.9]), with a trend for an association with peripheral occlusive arterial disease and lipid-lowering treatment. Multivariate analysis showed that SMI  was associated only with systolic dysfunction. This is consistent with the role of obesity which affected most of these patients and which has been shown to induce structural and myocardial disorders independently of diabetes –25. OnlyThe data collected in this paper concern a cohort that was established since the 1990s, implying that only conventional measurements were complete for the whole population. For example, the Teicholz method was the only available method to determine ejection fraction for some patients, especially before year 2000, although it is not recommended any more. Furthermore, complete diastolic parameters including tissue Doppler imaging measurements are lacking. At the present time, myocardial function examination needs the regional myocardial function assessment. The low prevalence of LV dilation, systolic dysfunction, or focal hypokinesia may have also weakened the statistical analysis. We have only explored inpatients with at least one risk factor in addition to diabetes; therefore, the results are not necessarily generalizable to the diabetic population. Only patients with an abnormal myocardial scintiscan underwent a coronary angiography, and some false negative results might have prevented us from diagnosing asymptomatic CAD. However, it appears unethical to perform a coronary angiography in asymptomatic patients without myocardial ischemia.This carefully designed study included a large population of asymptomatic type 2 diabetic patients without hypertension and CAD and shows that cardiomyopathy is highly prevalent and predominantly characterized by LVH. The mechanisms involved in LV hypertrophy need further clarification. Higher HbA1c levels were only associated with systolic dysfunction, while SMI was linked to systolic dysfunction and hypokinesia suggesting a role played by microvascular impairment. Overweight is likely to play a role in myocardial systolic disorders.Further large studies using conventional parameters with diastolic parameters as defined by the most recent recommendation  and subc


Right ventricle (RV) dysfunction and hypotension can be induced by high levels of positive end-expiratory pressure (PEEP). We sought to determine in an animal model if a novel ultrasound analysis technique: speckle tracking echocardiography (STE), could determine deterioration in RV function induced by PEEP and to compare this to a conventional method of RV analysis: fractional area change (FAC). STE is a sensitive, angle-independent method for describing cardiac deformation (‘strain’) and is particularly useful in analyzing RV function as has been shown in pulmonary hypertension cohorts.20). Intracardiac echocardiography was used to image the RV as transthoracic and transesophageal echocardiography did not give sufficient image quality or flexibility. Off-line STE analysis was performed using Syngo Velocity Vector Imaging . STE systolic parameters are RV free wall strain (RVfwS) and strain rate (RVfwSR) and the diastolic parameter RV free wall strain rate early relaxation (RVfwSRe)Ten pigs, 40-90 kg, anaesthetized, fully mechanically ventilated at 6 ml/kg were subject to step-wise escalating levels of PEEP at two-minute intervals  and FAC. Significant hypotension  occurred at approximately PEEP 15 cmHSTE is a sensitive method for determining RV dysfunction induced by PEEP and deteriorated ahead of a conventional assessment method: FAC. RVfwS decreased to greater extent compared to baseline than FAC, earlier in the PEEP escalation process and showed a significant decrease before there was a clinical relevant decrease in mean arterial blood pressure. Studies in ICU patients using transthoracic echocardiography are warranted to further investigate the most sensitive echocardiography method for detecting RV dysfunction induced by mechanical ventilation. Right ventricle (RV) failure in the critically ill is an independent risk factor for mortality in patients with acute lung injury and acute respiratory distress syndrome (ARDS) ,2. It caPositive end expiratory pressure (PEEP) is an integral component of mechanical ventilation in critically ill patients suffering from acute lung injury and ARDS, yet can have negative consequences on cardiac haemodynamics . ‘Open-lThe aim of this study was to perform a step-wise PEEP escalation maneuver in anesthetized, fully mechanically ventilated pigs and to assess their RV function with STE and a conventional echocardiography measure of RV function analysis: FAC. We sought to 1) Determine if STE could describe changes in RV function induced by escalating levels of PEEP; 2) To compare RVfwS to a conventional measure of RV function assessment: FAC; and 3) Determine if RVfwS or FAC deterioration occurred prior to PEEP induced hypotension .2O. Anesthesia was maintained with inhaled isoflurane 1.0-3.0%. The pigs were placed in a supine position during the entire experiment.All animal experiments and protocols were approved and carried out according to the guidelines of the Animal Care and Use Committee of the Mayo Clinic . In 10 Yorkshire female swine weighing median 45 kg (41.5 to 60.5 interquartile range [IQR]), after overnight fasting, anesthesia was induced with Telazol (5 mg/kg intramuscularly) and Xylazine (2.0 mg/kg intramuscularly). The animals were intubated with a 7 mm internal diameter endotracheal tube, mechanically ventilated by a Datex-Ohmeda 7100 ventilator  with volume control mode at tidal volumes of 6 ml/kg, fraction of inspired oxygen (FiO2) started at 0.4 aiming for saturations greater than 92%, inspiratory/expiratory ratio of 1:2, end-inspiratory pause of 10%, respiratory rate of 16 breaths per minute and initial PEEP of 0 cmHPercutaneous access was achieved through the femoral artery and both femoral veins for monitoring of arterial pressures (9 F sheath), pulmonary artery pressures  and for the intracardiac echocardiography (ICE) catheter respectively. Correct positioning of the pulmonary artery catheter in the pulmonary artery was confirmed with fluoroscopy  inserted into the right atrium. Imaging was performed by A.B. (who is appropriately trained in this method) and was optimized for maximal frame rate to enable accurate speckle tracking and focused on the RV free wall in the long axis ensuring the tricuspid annulus was visible throughout the cardiac cycle . A single best cardiac cycle was chosen to determine FAC by manually tracing the RV endocardium at end-diastole and end-systole: FAC = ([end diastolic area – end systolic area]/end-diastolic area) x 100. One to three beat cardiac cycles were chosen for STE analysis. The endocardium was traced manually at end-systole from the medial to lateral annulus with approximately 7–15 points. RV function values are an average of the three free wall segments. Systolic function parameters are measures of deformation or strain: RVfwS and RVfwSR (change in strain/time) and these are negative values: the more negative the value the better the function. Diastolic function is determined by a positive value: RV free wall strain rate early relaxation (RVfwSRe): the speed that deformation returns to the end-diastolic value. Strain and strain rate curves were chosen based on appropriate tracking as well as assessing displacement, velocity, strain and strain rate curves for appropriate motion, smoothness and segment correlation. The same cardiac cycle was chosen for strain and strain rate values. See Figure 2O was used as the reference value and 2 standard deviations was added to this to obtain the 95th percentile value. We then assessed the TTP delay at the highest PEEP level that was reached for each pig. Dyssynchrony was considered if the TTP delay was above the PEEP 0 cmH2O 95th percentile value.To assess for synchrony of RV free wall segment contraction we used a method proposed by Yu et al.  to assesStatistical analysis was performed with JMP version 10 . Continuous variables are expressed as mean +/− standard deviation (SD) or median with IQR. Repeated measure analysis at various PEEP levels was done with the one-way ANOVA. If a significant difference was found, post-hoc comparisons between the individual PEEP levels was done using Tukey HSD test with Bonferroni correction for p-value. All probability values are 2-sided and a value of ≤0.05 was considered significant, except for multiple comparisons between the different PEEP levels where, according to Bonferroni correction, p < 0.002 was considered significant.2O and higher vs baseline PEEP 0 cmH2O  between the earliest contracting segment vs the latest contracting segment.Analysis of the individual RV free wall segments showed a similar trend of deterioration across segments with escalating PEEP levels  were respectively: RVfwS −1 (±0.5) and −0.6 (±0.6); RVfwSR −0.1 (±0.1) and −0.1 (±0.1); RVfwSRe 0.1 (±0.1) and 0.1 (±0.1).2O. FAC only showed a significant deterioration at PEEP level of 20 cmH2O. However STE values of systolic function (RVfwS and RVfwSR) and diastolic function (RVfwSRe) showed significant deterioration earlier in the PEEP escalation process: at PEEP 10 cmH2O. No significant difference was seen between either systolic or diastolic parameters at higher PEEP levels suggesting a plateau effect in the degree of RV functional deterioration. Our findings suggest that RV dysfunction induced by PEEP may be identified earlier and with increased sensitivity with STE than by FAC. The effect of PEEP on RV strain has been demonstrated in a study in critically ill patients undergoing a recruitment maneuver [Our study demonstrates a clear trend of reduction in RV function with escalating PEEP levels assessed with a conventional echocardiography method, FAC, and with Speckle Tracking Echocardiography (STE), a novel echocardiography technique. Both RV systolic function parameters measured by STE (RVfwS and RVfwSR) and the diastolic function parameter (RVfwSRe) reduced with elevated PEEP levels. A drop of 20 mmHg in the MAP was considered a clinically relevant end-point and this occurred at approximately PEEP 15cmHmaneuver  indicatiEchocardiography is an important means of recognizing RV dysfunction induced by mechanical ventilation . SonograUnlike the LV, which contracts in all planes  the RV PEEP is an integral part of mechanical ventilation particularly in the critically ill patient with acute lung injury or ARDS. Counteracting alveolar cycling, collapse, derecruitment and to maintain functional residual capacity PEEP aims to reduce hypoxaemia and ventilator-induced lung injury . High leSTE, as with conventional echocardiography, is limited by adequate image quality. We utilized ICE in order to maximize the imaging quality of the RV free wall as neither transthoracic or transoesophageal echocardiography could reliably be performed to provide sufficient image quality of the RV free wall for STE analysis. This relates to the mediastinal anatomy of the pig model. The use of STE with ICE has not been validated, however STE analysis is angle-independent, was feasible and each pig acted as its own control. The ultrasound equipment is comparable and the only difference is the transducer. Our data should be translatable to echocardiography images acquire by other transducers. However, the need to use ICE prevented many of the standard echocardiography measures of RV function such as TAPSE and Sm by Tissue Doppler Imaging as these values are angle dependent and require apical imaging. FAC was the most plausible method to assess RV function as recommended by ASE guidelines . TachycaRV dysfunction in the critically ill is known to be associated with poor outcomes and can be induced by mechanical ventilation and PEEP therapy. Speckle tracking echocardiography is a quantifiable, sensitive and feasible angle-independent method for detecting RV dysfunction induced by escalating PEEP levels, and may display dysfunction ahead of conventional echocardiographic methods of assessment. The STE software is available on most current high-end machines, and is becoming increasingly available in intensive care units world-wide. Further studies in the ICU population, particularly with acute lung injury and ARDS, using transthoracic imaging are warranted.


Recent studies have reported significant T1 differences in fibrotic and normal tissue, but whole-heart T1-mapping is rarely performed in clinical practice, due to the associated time-consuming data acquisition; this can lead to sampling error when the fibrotic process is not homogenous. Signal acquisition over multiple heart beats can also be problematic, due to the potential for motion artifacts. In this study, we present a rapid whole-heart T1-mapping in a single breath-hold of, e.g., 6 heartbeats .T1-mapping, we modified a turboFLASH pulse sequence to acquire multiple T1-weighted (T1w) images, with increasing sequential time delays (TD), after a non-selective saturation pulse. Whole-heart T1-mapping was performed using a 1.5T MRI scanner . Within three heart beats, we acquired 9 T1w images at different levels, with increasing sequential time delays TD=200 , 397  and 594 ms  after a non-selective saturation pulse  images are acquired, in order to correct for the B1- and the unknown equilibrium magnetization, and normalize the signal. Post-contrast T1 maps were acquired 37 minutes after contrast injection (0.15mmol/kg of gadolinium-DTPA). Using the Bloch equation, T1 is obtained from the normalized signal, Snorm (=ST1w/SPDw), and TD: T1 = -TD/ln(1-Snorm).To achieve rapid whole-heart T1 values of slice 3-8 were 1421±158ms and ECV values (assuming hematocrit of 0.4) were 0.24±0.05. Although there is no focal LGE, this patient shows a higher pre-contrast T1 than in normal controls (T1 of ~1s at 1.5T), suggesting a higher degree of diffuse myocardial fibrosis.Figure 1-mapping methods are very time-consuming for routine clinical application, this whole-heart T1-mapping method can be performed well in patients with cardiac disease-related problems, including arrhythmia or difficulty with breath-holding, due to its short acquisition time of, e.g., 6 heartbeats. Better characterizing whole-heart fibrosis may allow for more accurate and earlier diagnosis. Further studies are warranted.While conventional TNone.


Reduction of post-contrast T1 in remote normal myocardium was recently reported in patients with AMI, indicating that extracellular matrix expansion occurs in remote myocardium early after MI. Such extracellular matrix expansion observed in non-infarcted myocardium without edema seems to be one of key factors causing LV remodeling after MI. However, since the previous study only determined post-contrast T1, alteration of extracellular volume fraction (ECV) in remote myocardium early after MI is not investigated quantitatively. Consequently, we sought to quantify ECV in remote normal myocardium in AMI patients using T1 mapping before and after gadolinium contrast with hematocrit and heart-rate corrections, and investigate the association between ECV expansion in remote normal myocardium and extents of infarction and area at risk.Sixteen reperfused AMI patients , age- and sex-matched 16 OMI patients (4.1 ± 5.7years after onset) and age- and sex-matched 16 control subjects with normal CMR findings who underwent CMR including cine, T2WI (for AMI patients only), LGE and T1 mapping were retrospectively studied. T1 mapping was performed using a modified Look-Locker inversion recovery sequence. ECV was determined according to myocardial and blood T1 values measured before and after administration of gadolinium contrast and hematocrit measures. T1 values were corrected for heart rate. Risk size and infarct size was determined on T2WI and LGE images, respectively, in AMI patients. Age-related changes in T1 and ECV were also corrected using a least square fitted line obtained in control subjects.Both ECV and native T1 were strongly associated with age in control subjects . Age-corrected remote myocardial ECV was significantly larger in AMI patients (28.8 ± 2.4%) than in normal subjects , whereas age-corrected native remote myocardial T1 was significantly longer in AMI patients (1349 ± 47 ms) than in control subjects . However, no significant difference was observed between AMI and OMI patients both in ECV and native T1 in remote myocardium  (Figure ECV expansion up to 30% in remote normal myocardium occurs early after AMI onset and persists in chronic state. ECV expansion in remote normal myocardium is correlated with the extent of risk area in AMI patients.I have no conflict of interest.


Congenital heart defects affect 8 out of every 1,000 newborns. Although many do not require immediate treatment, most cases will require a surgical or catheter based intervention during their lifetime. Complex cases can involve multiple anomalies. These unique and complex procedures require comprehensive pre-intervention or surgical planning. A state of the art method for creating patient-specific compliant models of heart anatomy from medical image data is investigated. A case study is explored to assess the feasibility of this modeling method.This case study includes a patient with complx congenital heart disease consistenting of L-Transposition of the Great Arteries, subpulmonic stenosis, ventricular septal defect complicated by straddling tricusipid valve, and hypoplastic right ventricle. The uncorrected anatomy is being evaluated for surgical palliation. A cardiac magnetic resonance study and magnetic resonance angiography was obtained (Siemens Avanto 1.5T). Turbospin echo and gradient echo were used for anatomic definition. Following administration of gadolinium, volumetric acquisition of the chest was performed. The Mimics Innovation Suite software is then used to obtain virtual 3D reconstructed models of the heart, showcasing the defects, and to prepare them for 3D printing. Figure Flexible 3D printing with the HeartPrint flex material process was successful for representing patient-specific anomalies. Transparency and the ability to cut/bend the model were important features to include in the model for clinical inspection and assessment. All were achieved. The model was sectioned prior to printing to provide the most optimal viewing plane of the anomalies. Complex congenital heart disease presents unique challenges to cardiac imagers, interventional cardiologists, and cardiac surgeons. The relationship of the ventricular septal defect, size of the systemic ventricle, and presence straddling tricuspid valve tissue were important to understand. In this case the model provided accurate anatomical definition of complex cardiovascular structures. This allowed for a more complete assessment for various surgical options. The presence of hypoplastic right ventricle when viewed by the 3D model confirmed the findings of our 2D studies and moved us away from a two ventricle repair and towards a Glenn shunt and Fontan palliation.The HeartPrint process proved capable for timely providing clinicians with an accurate patient-specific model to aid in the pre-surgical planning for treatment of complex congenital heart defects. The use of 3D printing patient-specific models can be a powerful supplement to traditional imaging-only planning for complex congenital heart cases.


In adults with heart failure, central sleep apnea (CSA), often manifested as Cheyne–Stokes respiration, is common, and has been associated with adverse outcome. Heart failure in children is commonly caused by dilated cardiomyopathy (DCM). It is unknown whether children with heart failure secondary to DCM have CSA, and whether CSA is related to the severity of heart failure. In this prospective observational study, 37 patients (<18 year) with heart failure secondary to DCM were included. They underwent polysomnography, clinical and laboratory evaluation and echocardiographic assessment. After a median follow-up time of 2 years, eight patients underwent heart transplantation. CSA (apnea–hypopnea index [AHI] ≥1) was found in 19 % of the patients. AHI ranged from 1.2 to 4.5/h. The occurrence of CSA was not related to the severity of heart failure. Three older patients showed a breathing pattern mimicking Cheyne–Stokes respiration, two of whom required heart transplantation. CSA was found in 19 % of the children with heart failure secondary to DCM. No relation was found with the severity of heart failure. In a small subset of children with severe DCM, a pattern mimicking Cheyne–Stokes respiration was registered. In adults with heart failure, central sleep apnea (CSA) is highly prevalent –4. CheynDilated cardiomyopathy (DCM) in children is a severe cardiac disorder resulting in heart failure. To the best of our knowledge, so far, no study has been published that has investigated whether CSA occurs in children with heart failure. According to the prevalence in adults, we speculated that CSA occurs in children with heart failure and may also be related to the severity of heart failure. Therefore, we conducted a prospective study to determine the prevalence of CSA and its clinical relevance in children with heart failure secondary to DCM.Between October 2010 and October 2013, children <18 year) with DCM were asked to participate in a nationwide prospective follow-up study. DCM was defined as a left ventricle end-diastolic dimension (LVEDD) >95th percentile for body surface area and a shortening fraction (SF) ≤25 %. DCM was of idiopathic origin or secondary to other causes. Patients with DCM secondary to neuromuscular diseases were excluded, because sleep-disordered breathing can be present as result of muscular weakness [ year witAs part of the follow-up study, an overnight polysomnography was planned. Furthermore, a detailed clinical evaluation, including echocardiography, NT-pro BNP measurement and clinical assessment using the New York University Pediatric Heart Failure Index , was per2) and heart rate using an infant or pediatric oxygen sensor  on a fingertip. Caregivers were instructed to apply all sensors and to start the measurement at bedtime and to end the measurement the next morning. In hospital, measurements were performed using BrainRT Shell +  and analyzed using BrainRT Shell + . Oronasal flow was measured with a thermal sensor. Breathing effort was measured through respiratory elastic belts at abdominal and chest level, heart rate using three electrocardiogram leads and SaO2 using an infant or pediatric oxygen sensor on a fingertip  applied to a pulse oxymeter . Recordings of both devices were analyzed using the same methods as described below.Patients underwent overnight polysomnography either at home or in hospital. Measurements at home were done with the Embletta Portable Diagnostic System and analyzed using Somnologica for Embletta Software 3.3 ENU . Embletta is a multichannel test that continuously measures respiration by a pressure transducer attached to a nasal cannula , breathing effort through respiratory elastic belts at abdominal and chest level (X act), and oxygen saturation  showed a technical failure. Measurements were excluded if either the impedance or the SaO2 was missing, because the purpose of the study was to detect central apneas. Mean pulse rate and mean respiratory rate were labeled as, respectively, tachycardia and tachypnea if they were >90th percentile for age [Due to the absence of electroencephalography, arousals were not recorded and therefore not used in the criteria. In some patients, one of the channels  the event lasted ≥20 s; (2) the event lasted for at least 2 breaths and was accompanied by an oxygen desaturation of ≥3 %. A central apnea following a sigh was scored only if it caused a desaturation ≥3 %. Hypopnea was defined as a reduction of ≥30 % of the pre-events baseline flow, lasted for at least 2 breaths and was accompanied by a desaturation of ≥3 %.One observer (SvdB), blinded to the clinical characteristics of the patients, scored the sleep studies. All respiratory events were scored according to the American Academy of Sleep Medicine (AASM) criteria . An apneapnea–hypopnea index (AHI) as the number of central apneas and hypopneas per hour of sleep. An AHI of ≥1 was defined as abnormal [Periodic breathing was scored if ≥3 episodes of central apnea lasted >3 s separated by no more than 20 s of normal breathing.We calculated the abnormal –17. PeriU test. Relationships between two non-normally distributed continuous variables were assessed using Spearman’s correlation. Statistical significance was defined as p < 0.05.All continuous variables are displayed as median (IQR), because of the low sample size in this study. Categorical variables are displayed as numbers and percentages. Difference between the median of two independent groups were assessed using the Mann–Whitney During the 3 years of the follow-up study, 58 of 79 eligible patients were willing to undergo polysomnography. Of these 58, eight patients were not measured, because they died or received a heart transplantation shortly after inclusion and before the polysomnography was performed; and in 13 patients the measurement failed, due to a lack of patient cooperation. As a result, 37 measurements were available.The median age of the patients was 11.1 years. The median time since diagnosis of DCM was 3.6 years (range 0–15.6 years). Almost all patients (97 %) took angiotensin-converting enzyme inhibitors, 81 % took β-blockers and 70 % took diuretics as medical treatment for heart failure. The median LVEDD z-score was +4.7 and SF 19.4 %. (Table n = 21 not willing to undergo polysomnography and n = 13 measurement failure) were significantly younger  than the study group. LV dilation and function was not significantly different between groups .The 34 patients in whom polysomnography was not performed (Thirty-three patients (89 %) were measured at home with the ambulatory device, whereas four patients were measured in hospital. The median recording time was 513 min. Five recordings were shorter than 360 min (range 211–352). As we studied the prevalence of sleep-disordered breathing, we included these measurements in the analysis.p = 0.01). Three patients were younger than one year of age; all had an abnormal AHI (≥1)  had AHI ≥1 range 1.2–4.5). These children were significantly younger than children with AHI <1  had a typical crescendo–decrescendo cycling pattern in breathing amplitude with apneas and hypopneas with a maximal episode duration of 58 min , and not with the time since DCM diagnosis. During follow-up , eight patients underwent heart transplantation, no deaths occurred. The patients who underwent heart transplantation had more heart failure symptoms and worse LV function than those who survived without transplantation. AHI was not different between groups , while reports in adults showed a prevalence of CSA around 35–40 % 9 %, whil, 4. CSA Cheyne–Stokes respiration is a typical breathing abnormality, which is seen in adults with heart failure and associated with higher mortality rates . In the 2 below the apneic threshold. The amount of fluid that shifted from the legs was directly related to the amount of leg edema and sitting time, and inversely related to physical activity [There may be several explanations why CSA in children with heart failure is less prevalent than in adults. One of the pathophysiological concepts of CSA is that the nocturnal fluid shift from legs to lungs stimulates pulmonary irritant chemoreceptors by pulmonary congestion, leading to hyperventilation and subsequently to a drop in PaCOactivity . Leg edeactivity . In cont2. One of the mechanisms that results in a drop in PaCO2, leading to a central apnea, is hyperventilation initiated by an arousal [2 has been observed, and the sensitivity to CO2 has been positively correlated to the AHI [2 exist and contribute to the occurrence of CSA. Interestingly, Cheyne–Stokes breathing pattern in our study was observed in the oldest children with severe heart failure. One may speculate that it occurs in those with severe heart failure and most resembling adults.Another factor to take into consideration may be a difference in regulation of respiration in response to CO arousal . Since t arousal , 24, chi the AHI . In chilIn our study, we reported the NYU PHFI to grade the severity of heart failure. We could not detect a correlation between NYU PHFI, LV function and dilation and the presence of CSA. The Cheyne–Stokes breathing pattern in two of eight children receiving a heart transplantation indicates that there might be a relation between the severity of heart failure and CSA, which needs further exploration.This study has several limitations, which may have led to an underestimation or overestimation of the prevalence of CSA. Firstly, we recognize that we were unable to measure a substantial number of patients due to technical and practical problems. Although we used ambulatory devices, several parents and children were not willing to agree to undergo polysomnography. And probably, the use of ambulatory devices negatively influenced the success rate of the measurements. The children who were not measured were significantly younger, and their LV function was similar to children who were measured. Since the midterm prognosis of heart failure in young children is better than in older children , and we In the present study, only a relatively small patient group remained for final analysis. In order to increase the number of eligible patients in future research, we suggest to use in-hospital measurements on all newly diagnosed patients, since almost 80 % of the patients with DCM need hospital admission at diagnosis . The useIn conclusion, in this first prospective study to investigate the prevalence of central sleep apnea in children with moderate-to-severe heart failure, we found CSA in 19 % of the patients. In a small subset of older children with signs of severe heart failure, a Cheyne–Stokes respiration pattern was noticed, similar to that has been observed in adults. For the whole study group, no relation was found with the severity of heart failure.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


To better understand the different risk-stratifying approaches, we evaluated 123I-mIBG scintigraphy, conventional and strain echocardiography and biomarker  assessment in 59 breast cancer survivors 1 year after anthracycline treatment. Interobserver and intermethod variability was calculated on planar and SPECT 123I-mIBG scintigraphy, using the heart/mediastinum (H/M) ratio and washout (WO). Pearson’s r and multivariate analyses were performed to identify correlations and independent predictors of 123I-mIBG scintigraphy results.We performed 123I-mIBG parameters. Significant correlations were observed between 123I-mIBG parameters and several conventional echo parameters, global longitudinal and radial strain (GLS and GRS) and galectin-3. The highest Pearson’s r was observed between delayed H/M ratio and GRS . Multivariate analysis showed that GRS was the only independent predictor of the delayed WH H/M ratio (p = 0.023).Delayed planar anterior whole-heart ROI (WH) H/M ratios and WO were the most robust 123I-mIBG parameter. It correlates with several conventional echocardiographic parameters, GLS, GRS and galectin-3. Of these, only GRS predicts the H/M ratio.The delayed planar H/M ratio is the most robust  Anthracyclines are widely used for (neo)adjuvant treatment of breast cancer , 27. ThiMeta-iodobenzylguanidine (mIBG) is an analogue of the sympathetic neurotransmitter NE. Labelling of mIBG with 123I allows for scintigraphic assessment of sympathetic activity and may provide a measure for early detection of AIC [123I-mIBG uptake are the measurement of the heart/mediastinum (H/M) ratio and washout (WO). Increased sympathetic cardiac activity is characterized by a decreased H/M ratio and an increased myocardial washout of 123I-mIBG.The pathophysiology of AIC is complex and not yet fully understood. Recent research has focused on the topoisomerase-IIβ enzyme as the core defect mechanism, which is believed to induce cell death upon the formation of a complex with the anthracycline doxorubicin , 38. Thin of AIC . The mosOther novel methods that may detect AIC in an early stage include 2D strain (rate) imaging with echocardiography and blood biomarkers. 2D strain (rate) imaging measures the relative deformation (i.e. stretch) of cardiac tissue in three different axes . Since s123I-mIBG scintigraphy, 2D strain (rate) imaging and blood biomarkers reflect different aspects of the same pathophysiological mechanism, they most likely show some interrelationship. However, knowledge on this possible correlation is still lacking. Therefore, the aim of the current study was to study the relation between 123I-mIBG scintigraphy, echocardiographic (strain) imaging and a selection of the most promising biomarkers. We aimed to study this in a homogenous group of breast cancer survivors 1 year after a potentially cardiotoxic chemotherapeutic regimen, containing anthracyclines.As 123I-mIBG accumulating tumour.All adult female patients presented between October 2010 and May 2012 with breast cancer and at least 1 year after completion of (neo)adjuvant treatment with docetaxel, doxorubicin (i.e. anthracycline) and cyclophosphamide (TAC) were asked to participate in the study. Exclusion criteria consisted of major heart disease  at the time of breast cancer diagnosis, renal failure at the time of cardiac evaluation, evidence of breast cancer recurrence or metastatic disease, pregnancy or breast feeding, participation in a research protocol with ionizing radiation 1 year prior to inclusion, diabetes mellitus, Parkinson’s disease or an A detailed medical history and physical examination were obtained in all patients, with special attention to risk factors and signs and symptoms of cardiac disease. Current medication use was noted. A standard 12-lead electrocardiogram was performed and analysed for signs of cardiac disease and rhythm disturbances. The study was approved by the medical ethics committee of the Radboud University Medical Center , and informed consent was obtained from all patients.123I-mIBG uptake was interrupted for at least 5 half-lives after consultation of the attending physician. Thyroid 123I uptake was blocked by oral administration of 400 mg potassium perchlorate 1 h before intravenous injection of 185 MBq123I-mIBG . Patients rested for 30 min prior to injection.Patient medication interfering with 123I-mIBG images were acquired in anterior and posterior view 15 min (‘early’) and 4 h (‘delayed’) after injection. Imaging was performed during 10 min using a 20 % energy window centred on the 159-keV photopeak of 123I, and acquired with a medium energy collimator and stored in a 128 × 128 matrix. No scatter correction was applied. Subsequently, a single-photon emission computed tomography (SPECT) of the thorax was performed 35 and 260 min post-injection, obtaining 32 frames of 60 s/frame, on a dual-head detector system, using a rotation of 180°.Planar On the anterior planar images, 10–20 pixel regions of interest (ROI) were drawn over the upper mediastinum by two observers (BB and ASL)  myocardial WO was defined as described by Veltman .This was done for both the anterior images and the geometric mean method, using both the WH and Sm ROI delineation method. WO is expressed as a percentage.For SPECT image interpretation, tomographic slices were reconstructed in short axis, horizontal axis and vertical long axis planes. Early and delayed images were identically aligned so that simultaneous analysis of the image planes was allowed. Mediastinal, WH and LV (i.e. including or excluding the cavum) voxels of interest (VOIs) were visually drawn using Inveon Research Workplace 4.1 . The mediastinal VOI had a fixed spherical shape of 20 voxels, and care was taken to exclude thyroid tissue. H/M ratios and WO were calculated with mean voxel count as described above.123I-mIBG values. The parameters on conventional echocardiography that were studied included the internal dimensions of the left ventricle at end-diastole (LVIDd) and end-systole (LVIDs), the posterior and septal wall thickness at end-diastole , left ventricular mass (LVM), left ventricular volume at end-diastole (LVEDV) and end-systole (LVESV), left atrial end-diastolic volume (LAEDV), left ventricular ejection fraction (LVEF), early (E) and late (A) diastolic transmitral peak flow velocity (E/A ratio), the systolic to diastolic pulmonary vein peak flow velocity (PV S/D ratio) and early diastolic transmitral peak flow velocity (E) to early diastolic annular velocity (e′) ratio (E/e′ ratio). Measurements of LVEDV, LVESV, LVM and LAEDV were indexed by body surface area (BSA).Methods on the measurement of conventional and strain echocardiography parameters and biomarkers have been described extensively elsewhere , 34. TheThe biomarkers we studied were NT-proBNP, TNF-α, galectin-3, IL-6, troponin I, ST-2 and sFlt-1. Biochemical risk factors for cardiovascular disease  were also determined.123I-mIBG and echocardiographic values are expressed as mean ± SD. Biochemical values are expressed as median with interquartile range.Patient age and time after treatment are expressed in years or months with range. Other patient characteristics are expressed in numbers of total and percentage. Lin’s concordance correlation coefficients (LCCs) with 95 % confidence intervals are calculated for interobserver variability and depict the correlation of measurements of two different observers. For clinically relevant agreement, the following criteria are used: LCC values <0.90, 0.90–0.95, 0.95–0.99 and >0.99 were considered to indicate poor, moderate, substantial and almost perfect agreement, respectively . The coer. Correlations with a one-tail p < 0.1 were included in multivariate regression analysis, which was performed in a forward stepwise fashion. Significance was set at p < 0.05. All statistical analyses were performed with SPSS for Windows, version 20.0.Correlations of the various studied methods are expressed in Pearson’s 2), except one who received 250 mg/m2. None of the patients had a history of major cardiac events , nor did any of them indicate chest pain or express heart failure signs/symptoms. One patient presented with a known left bundle branch block. Other patient characteristics, including risk factors and medication use, are displayed in Table Fifty-nine breast cancer survivors were included in the study. All patients had received a full dose of anthracyclines  and WO was almost perfect (LCC 0.99). Mean differences were very small Fig. .Fig. 4IRr of 0.33 (p < 0.05) for the early images, r = 0.35 (p < 0.05) for the late images and r = 0.76 (p < 0.001) for WO.The WH method is the only method used for both planar and SPECT images. Therefore, correlation between SPECT and planar H/M ratio was calculated specifically for that method. We observed a Pearson’s Although additional data on conventional echocardiographic and strain (rate) imaging and biomarkers are described in earlier work, , 34 for r 0.36, p = 0.01), the least significant for E/A ratio . LVEDV/BSA, LVESV/BSA, IVSd, LVM/BSA, GLS and galectin-3 showed an inverse correlation, while E/A ratio and GRS showed a direct correlation.Significant correlations between the delayed planar WH H/M ratios and LVEDV/BSA, LVESV/BSA, IVSd, LVM/BSA, E/A ratio , GLS, GRS (strain echocardiography) and galectin-3 (biomarker) were identified Table . The mosβ = 0.36, p = 0.023).Since delayed anterior WH H/M ratio seems to be the most robust measurement in our population, we aimed to identify by which parameters it was influenced. Multivariate analysis showed that GRS was the only independent predictor of the WH H/M ratio , yielding a positive strain value during systole. In AIC, functioning myocytes are replaced by non-contracting fibrotic cells , which lOf the studied biomarkers, only the novel blood biomarker galectin-3 showed a significant correlation with the WH H/M ratio. Galectin-3 is a protein expressed by macrophages and believed to be a mediator of the profibrotic pathway, stimulating cardiac fibroblasts to proliferate and deposit collagen . GalectiConventional echocardiographic parameters that correlated with the WH H/M ratio included LVEDV/BSA, LVESV/BSA, IVSd, LVM/BSA and E/A ratio. The correlation of the WH H/M ratio and LVEDV, LVESV, IVSd and LVM displayed an inverse nature, which means that both cardiac volumes and cardiac wall diameters increase as the WH H/M ratio drops. This is an interesting finding, since typical AIC in adults presents as a dilated cardiomyopathy, featuring increased ventricle sizes and thin walls . A possiThe main limitation of the current study is the lack of baseline and follow-up measurements, so we could not assess the change in parameters over time. However, the aim of the study was not to detect a change in certain parameters, nor to predict AIC, but to assess the interrelationship of different interesting parameters in the pathophysiological process of AIC.123I-mIBG parameters. Furthermore, we focused on a homogenous group of breast carcinoma survivors with potential AIC damage, which is a patient group that has not yet been studied properly.Although the correlations of certain parameters have been studied, for example strain (rate) imaging and troponin or conventional echocardiography and strain (rate) imaging, they have not been studied for their correlation with With the current study we have identified the relationship of the WH H/M ratio with 2D strain imaging, biomarkers and conventional echocardiography 1 year after anthracycline-based chemotherapy. This sheds some light on the complex pathophysiology of AIC, enabling future studies to identify appropriate parameters for the detection of AIC.123I-mIBG parameter. It is correlated with several conventional echocardiographic parameters, GLS, GRS and galectin-3. Of these, only GRS is an independent predictor of the WH H/M ratio. Future studies should concentrate on a combination of 123I-mIBG scintigraphy, MUGA, echocardiographic strain, CMR and biomarkers, preferably in a prospective multicentre trial with long-term follow-up in breast cancer survivors.Delayed planar WH H/M ratio is the most robust


Clinical outcome after acute ST-elevation myocardial infarction (STEMI) has been shown to be predictable by myocardial salvage index (MSI) and microvascular obstruction as determined by cardiac magnetic resonance imaging (CMR). In the setting of non-ST-elevation myocardial infarction (NSTEMI) prognostic significance is less well investigated. Due to comparable incidence of major adverse cardiovascular events (MACE) in the setting of STEMI and NSTEMI the importance of risk stratification in NSTEMI patients is obvious. Aim of the present study was to evaluate CMR parameters with prognostic value for NSTEMI patients.In 60 patients presenting with NSTEMI, functional and volumetric analyses assessed by standard steady-state free-precession sequences, a T2-weighted black-blood fat-saturated spin-echo sequence for visualization of myocardial edema and late gadolinium enhancement imaging for quantification of infarct size was performed by CMR after acute coronary revascularization within 72 hours of symptom onset. For CMR measurements a 1.5 T whole-body scanner with a 32-channel phased-array surface coil was used. Major acute cardiovascular events defined as death and acute coronary syndrome were investigated for a follow-up period of three years after index event.Median follow-up time was 34 ± 11 months after index event. In sum, 15 major adverse cardiovascular events occurred during the entire follow-up period. Mean CMR derived infarct size determined by LGE was 18.4 ± 13.5 % of LV mass, mean MSI was 34.2 ± 30.4 %. The mean area of microvascular obstruction was 1.0 ± 2.2 % of LV mass. When comparing survivals using the Log rank test, severely impaired left ventricular ejection fraction (LVEF ≤ 40%) was the only significant variable . Infarct size, microvascular obstruction and MSI did not differ significantly.Among patients presenting with NSTEMI there is substantial heterogeneity concerning the risk of major adverse cardiovascular events. In our cohort severely impaired left ventricular ejection fraction was the only predictor for adverse event yielding a hazard ratio of 3.9. To date prognostic significance of MSI and microvascular obstruction was mainly evaluated in STEMI patients but in terms of NSTEMI CMR parameters for prediction of MACE remain unsettled. Based on our results further studies are warranted to assess the prognostic value of CMR-derived parameters in the heterogenic group of NSTEMI patients.None.


This, we hypothesized, would enhance the characterization of fiber architecture in the left ventricle (LV), allow myofiber organization in the right ventricle (RV) to be characterized in vivo, and further elucidate microstructural differences in the heart between systole and diastole.Diffusion Tensor MRI (DTI) tractography of the human heart coverage ,2. The a2, resolution 2.8 × 2.8 × 8 mm3, 8 averages and multiple breath-holds. The entire LV and RV were covered in 13 contiguous short-axis slices. Images were acquired in the systolic and diastolic sweet spots [th order Runge-Kutta method. The impact of cumulative image averages (1-8) on the reliability of the fractional anisotropy (FA) and fiber helix angle (HA) indices was assessed.DTI was performed on a clinical 3T scanner  using a fat-suppressed, zone-selected, diffusion-encoded stimulated echo sequence with 10 diffusion encoding directions, TE/TR 33/80 ms, GRAPPA rate 2, b-value 500 s/mmet spots . Tractog. In contrast, fibers in the midwall of the LV were circumferential, forming a distinct band between the subendocardial and subepicardial fibers . Figure .A composite view of the anterior thorax and heart is shown in Figure Figure . In conts Figure . Figure e Figure .in vivo, without slice gaps, and allows both the LV and the RV to be characterized. A minimum of 5 averages at each slice location is required for accurate quantification. The ability to characterize fiber architecture in the LV and RV in vivo has the potential to provide new insights into a range of diseases affecting both the pulmonary venous and arterial circulations.DTI-tractography of the entire human heart can be performed R01 HL093038 (D.E.S.), R01HL112831 (D.E.S.), P41RR14075 (Martinos Center).


Diastolic dysfunction is common in geriatric heart failure. A reliable parameter to predict myocardium stiffness and relaxation under similar end-diastolic pressure is being developed. We propose a material and mathematical model for calculating myocardium stiffness based on the concept of linear correlation between We enrolled 919 patients (male: Our material and geometric mathematical model successfully described the stiffer myocardium in aging hearts with higher intraventricular pressure. Additional studies that compare individual differences, especially in health status, are needed to validate its application for detecting diastolic heart failure. Heart failure is increasingly prevalent among older adults It remains uncertain whether current available invasive and noninvasive diagnostic tools can accurately predict myocardium stiffness. The time constant of relaxation  using a 3.5-MHz multiphase-array probe. The chamber dimensions and LV mass were measured using the two-dimensionally guided M-mode method, and the LV ejection fraction (LVEF) was measured with the two-dimensional M mode . IntraveTo measure the circumferential strain, 20 patients were randomly selected from the hy (STE) . Short-at test for normally distributed values. Significant factors in univariate analysis were entered into multivariate analysis. Multivariate logistic regression analysis was used to identify the independent significance of E in patients with diastolic dysfunction. A Pearson's partial correlation coefficient (r) between E and SPSS 18.0  was used for data management and statistical analyses. Data are means ± standard deviation (SD). Continuous variables were compared using Student's a and b, respectively. The quantity r denotes the radius at an arbitrary position between a and bIn this section, a mathematical model for computing the myocardium stiffness of the left ventricle is presented. The left ventricle is assumed to be made of elastic, isotropic, and homogeneous tissue that will completely recover its native form when the forces are removed. To capture LV wall dynamics, a thick-walled cylindrical pressure vessel was used . The cylr−θ plane), For simplification, the strain normal to the cross-sectional plane   than didTo establish a model for predicting the stiffness characteristics of myocardium, we used the M-mode and 2-D echocardiographic volumetric parameters, intraventricular filling pressure, and STE from all clinical patients and the 2 cohorts. The feasibility of this model was validated. Despite a slight but significant  . Howeverd group) . Multivaased 45,00 Pa. Cat hearts.  and S3To simulate the human heart, we created a model to obtain the circumferential strain. In addition to the radial strain, the circumferential strain of the actual myocardial contraction was measured using STE Besides a grossly attenuated E, the model reflected a similar trend of geometric and pressure change, regardless of whether the circumferential strain was considered . Thus, iLV hypertrophy was more prevalent in the elderly than in the younger and middle-aged patients; it led to poor compliance and to difficulty in shape changing; thus, it impaired diastolic function. Although the association between a thicker wall and higher intraventricular pressure has been frequently reported, a suitable model to illustrate it in patients of various ages is lacking. Our mathematical model depicted positive associations between IVSd and E, along with the increasing  . It alsoIn addition, by inputting the representative E  E (Young's modulus), the tensile elasticity of the myocardium, can be used clinically to describe myocardial relaxation and to noninvasively detect early diastolic dysfunction; (2) aging myocardium becomes thicker, stiffer, and less expandable, which agrees with previous clinical findings. Even under the same intraventricular filling pressure, E was significantly higher in elderly patients (The criteria for diagnosing diastolic dysfunction and diastolic heart failure remain imprecise Researchers have discovered a continuous loss of myocytes surrounded by the adipose and fibrotic tissue deposited in the extracellular matrix (ECM) in the aging process In Yang et al. In our study, the left ventricle considered as a pressurized thick-walled cylinder is assumed to be made of one type of elastic, isotropic, and homogeneous tissue that will be completely restored its native form when the forces are removed. We restricted the equations (stress-strain relations) to the case of plane elasticity. Strains in the radial direction and in the circumferential direction can be taken into account when determining the stiffness of myocardium. The radial and circumferential strains measured from experiments were directly used to calculate the Young's modulus (E), which is currently regarded as a practical indicator for evaluating cardiac diastolic dysfunction. Also, in our mathematical model, the pressure, elastic modulus, and left ventricle dimensions are mutually influenced. We found that when using the same intraventricular filling pressure to compare the elderly and younger patients, the former had a tendency to have a higher E value.  Because STE is an emerging technique, with angle- and load-independent characteristics, for evaluating subtle myocardial dysfunction The present study clearly showed that E was significantly higher in the elderly cohort than in the younger cohort, even under the same intraventricular pressure. E, which has never been used to describe the diastolic function using clinical data, has the potential to detect early diastolic dysfunction with high sensitivity. This will help us understand changes in myocardial stiffness with aging; therefore, we should be able to detect occult diastolic dysfunction in the early stage of systemic chronic diseases like hypertension disorder diabetes mellitus.x−y plane, This study has several limitations. First, the main hypothesis was based on the linear correlation between the Although a mathematical model has limitations, it enables us to illustrate the quantitative relationships between structural and functional changes. because diastolic and systolic heart failure share similar poor outcomes In conclusion, this is the first report to document using a mathematical model to delineate diastolic dysfunction in the aging human heart. The vulnerability of the elderly to higher pressure may contribute to their developing earlier signals for heart failure. E is useful for the early and noninvasive detection of diastolic dysfunction.Table S1After excluding patients with hypertension, diabetes mellitus, and coronary artery disease, the correlation between E and diastolic dysfunction remained significant in the healthy elders.(DOC)Click here for additional data file.Table S2Multivariate analysis on the relationship between E and echocardiographic intraventricular pressure in younger patients.(DOCX)Click here for additional data file.Table S3Multivariate analysis on the relationship between E and echocardiographic intraventricular pressure in older patients.(DOCX)Click here for additional data file.