ATP) channels may contribute to endothelial protection. Therefore, the present study was carried out to investigate the hypothesis that natakalim, a novel KATP channel opener, ameliorates post-infarction left ventricular remodeling and failure by correcting endothelial dysfunction. The effects of myocardial infarction were assessed 8 weeks following left anterior descending coronary artery occlusion in male Wistar rats. Depressed blood pressure, cardiac dysfunction, evidence of left ventricular remodeling and congestive heart failure were observed in the rats with myocardial infarction. Treatment with natakalim at daily oral doses of 1, 3 or 9 mg/kg/day for 8 weeks prevented these changes. Natakalim also prevented the progression to cardiac failure, which was demonstrated by the increase in right ventricular weight/body weight (RVW/BW) and relative lung weight, signs of cardiac dysfunction, as well as the overexpression of atrial and brain natriuretic peptide mRNAs. Our results also demonstrated that natakalim enhanced the downregulation of endothelium-derived nitric oxide, attenuated the upregulation of inducible nitric oxide synthase-derived nitric oxide (NO), inhibited the upregulated endothelin system and corrected the imbalance between prostacyclin and thromboxane A2. Overall, our findings suggest that natakalim prevents post-infarction hypertrophy and cardiac failure by restoring the coordinated balance between endothelial function and cardiac hypertrophy.Endothelial dysfunction can lead to congestive heart failure and the activation of endothelial ATP-sensitive potassium (K However, deteriorated LVR may eventually lead to congestive heart failure (CHF) ,2. Thereet al , it was ATP) is widely distributed in the cardiovascular system and plays important roles. KATP consists of inward rectifier potassium channel subunits (Kir6s) and regulative sulfonylurea receptors (SURs)  ; the SURs (SURs) . It has s (SURs) . Our labs (SURs) ,12. Ther subtype . Based oThe progression from occlusion of the left anterior descending coronary artery (LAD) to post-infarction CHF in rats is similar to what occurs when a patient survives a large MI but subsequently develops heart failure ,16. HoweNatakalim was synthesized at the Thadweik Academy of Medicine . All other chemicals and materials were obtained from local commercial sources.All procedures were performed in accordance with the protocol outlined in the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health  and approved by the local animal care and use committee. Experiments were performed using healthy adult male Wistar rats , and the animals were divided into 6 groups (n=9–11) as follows: the sham-operated group, which included animals that underwent a similar procedure without left coronary artery ligation and were treated with distilled water; the model group, which included rats with MI induced by LAD ligation that were treated with distilled water; rats with MI that were treated with 1, 3 or 9 mg/kg/day of natakalim; and rats with MI treated with a positive control drug (lisinopril) at 15 mg/kg/day. No significant difference was found among all the experimental groups as regards age or body weight (BW) prior to surgery.The rat model of MI was implemented as previously described , with slp/dtmax), physiological velocity of contractile element shorting (Vpm) and maximal velocity of contractile element shorting (Vmax) were recorded.On day 56, following anesthesia with a mixture of xylazine (5 mg/kg) and pentobarbital , the right carotid was cannulated with a polyethylene catheter (outer diameter of 0.96 mm) to measure the carotid arterial pressure. Subsequently, a catheter was inserted along the right carotid artery into the left ventricle, and the signals were recorded on an 8-channel direct-writing oscillograph  and digitally sampled (1 kHz) on a personal computer equipped with an analog-to-digital interface . The heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal rate of left ventricular systolic and diastolic pressure /BW ratio (HW/BW) was calculated by dividing the HW by the BW; the left ventricles (including interventricular septum) and right ventricular free walls were then collected separately and weighed. The left ventricular weight (LVW)/BW (LVW/BW) ratio, the right ventricular weight (RVW)/BW ratio (RVW/BW) and the lung weight (LW)/BW ratio (LW/BW) were calculated.The hearts were immersion-fixed in neutral 10% buffered formalin and paraffin sections (5 μm) were cut. The myocyte cross-sectional area and myocardial fibrosis were quantitatively analyzed using NIH Image 1.61 software  in digitized microscopic images. For measurement of the cross-sectional area, 100 cells  from the left ventricular mid-lateral free wall  were randomly selected and analyzed. Interstitial myocardial fibrosis in the tissue sections was quantitatively analyzed by morphometry . The collagen in the myocardial interstitial spaces was visualized and the whole areas of the sections were scanned. The total interstitial fibrosis index was defined as the sum of the total area of collagen in the entire visual field divided by the sum of total connective tissue area plus the myocardial area in the entire visual field. All the images were digitized and transformed into binary images, and the areas occupied by collagen were calculated by an automatic area-quantification program using NIH Image software.Myocardial samples were routinely fixed in 2.5% glutaraldehyde in 0.1 M phosphate buffer (pH 7.3) and then fixed in buffered 1% osmium tetroxide for 1 h. The samples were then dehydrated in a series of ethanol  and embedded in Epon 812. Thin sections were stained with uranyl acetate and lead citrate and examined under a Philips CM-120 electron microscope . Muscle fiber and mitochondrial abnormalities were evaluated.2 and TXA2 levels were measured using commercial radioimmunoassay kits  according to the manufacturer’s instructions. The hydroxyproline content in the hearts was measured using a commercial kit (Nanjing Jiancheng Bioengineering Institute) according to the manufacturer’s instructions.Blood was obtained from the right carotid artery with a polyethylene catheter at the time of sacrifice. The level of NO in serum was measured using the NO Detection kit  according to the manufacturer’s instructions. ET-1, PGIImmunohistochemical staining was performed using the UltraSensitive™ S-P kit  according to the manufacturer’s instructions. Anti-endothelin receptor A and B (Sigma-Aldrich) were used as primary antibodies at a 1:100 dilution. Images from the entire sections were acquired using a digital camera system . Confocal images were then transferred to a personal computer using the NIH Image software package for image analysis, as previously reported  and withProtein was isolated from frozen non-infarcted left ventricular tissue using cell lysis buffer for western blotting  in accordance with the manufacturer’s instructions. Equal amounts of protein extracts were separated by 8% SDS-PAGE gel and then transferred onto PVDF membranes using a Bio-Rad transfer blotting system . The membranes were incubated with antibodies against endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) . Proteins were visualized using an enhanced chemiluminescence detection system . Anti-GAPDH antibody (BioEasy) was used to control for equal protein loading.Total RNA was extracted from the cardiac tissue of rats using TRIzol reagent according to the manufacturer’s instructions  and converted to cDNA using the Quantscript RT kit . Quantitative PCR was performed using the Real-Time PCR iCycler iQ5 System (Bio-Rad Laboratories) and SYBR-Green PCR Master Mix  in accordance to the manufacturer’s instructions. The expression levels of GAPDH were used for sample normalization. Primers for rat atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and GAPDH were as follows: ANP sense, 5′-ATT TCA AGA ACC TGC TAG ACC-3′ and antisense, 5′-CAA TCC TGT CAA TCC TAC CC-3′, 300 bp; BNP sense, 5′-GGA CCA AGG CCC TAC AAA AGA ACT-3′ and antisense, 5′-ACA ACC TCA GCC CGTCAC AGC-3′, 176 bp; GAPDH sense, 5′-AAA CCT CCA AGT ATG ATG AC-3′ and antisense, 5′-TTG TCA TAC CAG GAA ATG AGC-3′, 197 bp. The reactions were incubated at 95°C for 1 min, followed by 40 cycles at 95°C for 15 sec, 66.5°C for 15 sec and 72°C for 45 sec.In this stuyd, the results are expressed as the means ± SD. Statistical analysis of the data was performed using one-way ANOVA with the SPSS 13 software program. Probability values  ≤0.05 were considered to indicate statistically significant differences.in vivo left ventricular function measurements for all the groups are shown in p/dtmax, Vpm, Vmax and the diastolic cardiac parameter −dp/dtmax, were all significantly decreased in the rats with MI. By contrast, the diastolic cardiac parameter, LVEDP, was significantly increased. These changes were prevented by treatment with natakalim in a dose-dependent manner. Long-term treatment with natakalim did not affect the HR of the rats in the MI group.Carotid arterial pressure and cardiac function were measured 8 weeks following LAD occlusion. As shown in The results at 8 weeks for all groups are shown in The transition from LVR to failure in experimental models is characterized by pulmonary, chronic, right ventricular hypertrophy and the overexpression of ANP and BNP mRNAs, 2 molecular markers of heart failure ,12. As seNOS protein expression was significantly reduced in the MI group; however, the serum NO concentration and iNOS protein expression were significantly increased P<0.01; . TreatmeA and ETB were significantly increased in the rats following MI  and thromboxane B2 (TXB2), metabolites of PGI2 and TXA2, respectively, were used to estimate the plasma levels of PGI2 and TXA2, respectively, due to their short half-lives. In the rats with CHF induced by MI, the concentration of plasma 6-keto-PGF1a was significantly decreased  natakalim reverses pathological LVR in a rat model of LAD ligation; ii) natakalim prevents the progression from hypertrophy to CHF; iii) the underlying mechanisms of action of natakalim may be attributed to the restoration of a coordinated balance between endothelial function and cardiac hypertrophy by the correction of endothelial dysfunction, the decrease in NO and the increase in PGICHF is caused by multiple factros that result from the heart being unable to pump sufficient blood to meet the metabolic requirements of the body. The heart undergoes a compensatory remodeling process in response to initial myocardial insults. The remodeling initially helps the heart to preserve pump function; however, the heart ultimately becomes maladaptive and fails to function. Ischemic heart disease, the most important etiology of CHF, accounts for up to two-thirds of all CHF cases. Hypertension is another important factor; thus, the rat model of pressure overload that leads to the development of concentric hypertrophy and systolic dysfunction is widely used to simulate the progression of hypertensive heart disease . We haveThe LAD ligation model involves the MI-induced progression from hypertrophy to cardiac failure and has been characterized extensively –18. In tHowever, the mechanisms responsible for the progression of LVR to heart failure remain poorly understood. An increasing body of evidence has drawn attention to the role of the coronary endothelium ,19,20. C2 and TXA2 , PGIand TXA2 ,4,19,20.owing MI .Previous studies have suggested that LVR and the development of failure are regulated by eNOS, iNOS and NO. At a low concentration, NO synthesized by eNOS in the endotheliocyte contributes to the maintenance of vascular tone and function, protects against myocyte hypertrophy and apoptosis and preserves cardiomyocyte contractility . CompareA and ETB receptors, has been implicated in pathological states, such as ventricular remodeling and CHF following MI (A and ETB receptors, which are found in a variety of cells of the cardiovascular system (A and ETB receptor antagonists prevent progressive LVR and improve cardiac function in rats with a large MI (The endothelin system, particularly ET-1 and the ETowing MI . ET-1 isr system . Elevater system . Moreovelarge MI ,32,33. T2 and TXA2 are active metabolites of arachidonic acid and PGI2 is thought to be a physiological antagonist of TXA2. PGI2 is generated by vascular endothelial cells, which possess strong vasodilator, anti-aggregatory and antihypertrophic effects. TXA2 is generated by activated platelets and neutrophilic granulocytes when vascular endothelial cells are injured, and TXA2 exhibits pro-aggregatory, vasoconstrictor properties and stimulates vascular remodeling (2 receptor IP knockout mice develop significant LVR and severe myocardial fibrosis following MI, aortic banding or salt-sensitive hypertension (2 and TXA2 is deleterious for the circulatory system and can lead to vascular diseases, such as atherosclerosis, MI, post-MI LVR and hypertension.PGImodeling . PGI2 rertension –37. ThusATP channels are membrane sensors of energy metabolism, and play an important role in a number of diseases, such as MI and CHF. It has been reported that the SUR2B/Kir6.1 subtype is mainly found in the endothelium, and it affects the production and release of endothelial autacoids, such as NO, PGI2 and ET-1 (ATP channels in endotheliocytes and promotes the secretion of NO and PGI2 and inhibits the production of ET-1 in endotheliocytes (A and ETB receptors, suppressing the endothelin system. Additionally, natakalim increased the plasma PGI2 concentration and decreased the plasma TXA2 concentration, which corrected the imbalance between PGI2 and TXA2. Therefore, as previously noted, natakalim can correct coronary endothelial dysfunction in the non-infarcted myocardium following post-MI heart failure.Kand ET-1 . A serieliocytes –14,39. I2 and TXA2. Thus, natakalim may provide a novel therapeutic strategy for correcting endothelial dysfunction. Although natakalim appears to be suitable for the clinical treatment of coronary heart disease and post-infarction heart failure, a series of well-designed trials is required in order to confirm our results.In conclusion, to the best of our knowledge, the present study demonstrates for the first time that natakalim counteracts cardiac hypertrophy and prevents the progression to heart failure induced by MI. The underlying molecular mechanisms involved the restoration of the coordinated balance between endothelial function and cardiac hypertrophy by correcting endothelial dysfunction, including the amelioration of the endothelium-derived NO system, the inhibition of the endothelin system and the rectification of the imbalance between PGI


Imaging techniques may contribute to the proper risk assessment of patients with coronary artery disease (CAD). Especially, cardiac magnetic resonance imaging (CMR) is able to provide important prognostic information by detection of myocardial scarring  and reversible ischemia. Therefore, objective of the present study was to quantify the extent of total ischemic myocardium (TIM) by the combination of LGE and reversible ischemia by CMR and to correlate the results with long-term outcome and prognosis in patients with known or suspected CAD.Consecutive patients referred for CMR imaging were prospectively screened and enrolled from 2003 to 2007. Besides functional and volumetric assessment, adenosine perfusion and LGE imaging were performed on a 1.5 T whole-body scanner. TIM was assessed and quantified by combination of reversible ischemia and LGE as follows: perfusion deficits and LGE were identified and quantified by a semi-automatic approach on short-axis images. TIM was defined as area of reversible perfusion deficit plus area of LGE and expressed as percentage of global myocardium. Primary endpoint was defined as cardiac death, nonfatal myocardial infarction or stroke.Our study population consisted of 845 consecutive patients. Mean follow-up was 4.1 ± 1.8 years. During this time, 61 primary endpoints occurred with total yearly event rates of 2.1% in the first, 1.2% in the second and .7% in the third year, respectively. A 36% cutoff for TIM was defined by ROC analysis. Primary endpoints occurred in 15 patients with TIM higher than the cutoff (event rate 33%). In contrast, primary endpoints were observed in only 5.8% (46) of patients with low or absent TIM . On multivariate analysis, TIM was the strongest independent predictor for the occurrence of a primary endpoint with a hazard ratio of 3.4.TIM can easily be assessed and quantified by the provided CMR algorithm in daily clinical routine. TIM >36% of myocardial mass is strongly associated with the occurrence of major clinical adverse events and thus owns important prognostic value.None.


Ventricular tachycardia (VT) may cause sudden death late after repair of congenital heart disease. Radiofrequency catheter ablation (CA) of VT can be effective but may be hampered by hypertrophied myocardium or prosthetic material. A 33-year-old man with congenitally corrected transposition of the great arteries (ccTGA) had undergone a double switch operation (DSO) with the combined Mustard and Rastelli procedures when he was 10 years old. He developed sustained VT 16 years after the surgery. An electrophysiological study was performed using a 3D mapping system. During the VT, abnormal fragmented potentials were identified in the right ventricular side near the patch of ventricular septal defect. Radiofrequency energy was delivered at the site with changes in the QRS morphology. Electroanatomical mapping of the left ventricle was performed via a retrograde transaortic approach. Successful ablation of the fractionated potentials was likewise achieved on the left side. We report, to our knowledge, the first case of a successful radiofrequency CA of VT in a patient with ccTGA after a DSO. A slow conduction zone, which was proved to be part of the tachycardia substrate, existed around the patch of ventricular septal defect. Fragmented activities during VT were recorded from both ventricles. The tachycardia circuit was eliminated after ablating the right and left sides of the ventricular septal defect patch. Surgical treatment has improved the long-term prognosis of patients with congenital heart disease (CHD), but late ventricular tachycardia (VT) remains a risk for patients who have undergone ventriculotomies  had situs inversus of the viscera and atria, D-loop of the ventricles, and d-transposition of the great arteries: {I, D, D}, VSD and pulmonary stenosis. He had undergone a double switch operation (DSO) with the combined Mustard and Rastelli procedures Fig. a when he®, St. Jude Medical, St. Paul, MN, USA)  was performed under local anesthesia. At baseline, the heart showed sinus rhythm Fig. a. A 5-FrSA) Fig. a, b, by SA) Fig. c. At thiSA) Fig. c. RadiofSA) Fig. d. Thus, SA) Fig. a, b. SucSA) Fig. c. The siAlthough surgical treatment has improved the prognosis of complex CHD, the problem of remote ventricular arrhythmias remains unresolved. For instance, the incidence of VT is 11.9 %, with an 8.3 % risk of sudden death by 35 years of follow-up after repair of tetralogy of fallot (TOF). Thus, VT is a possible cause of late sudden death  and ventriculo-arterial connections (Van Praagh In this case, the substrate of VT and the slow conduction zone existed around the suture of the VSD on the RV and the LV sides. Similar observations have been reported in VT associated with TOF, for which both the RV and LV ablations are required (Kapel et al. After CA of the RV side, the QRS morphology of VT changed, probably due to modification of the exit from the slow conduction zone. Although we could not complete the whole activation map of the VT due to the difficulty of catheter manipulation, we were successfully able to ablate the sites of diastolic fractionated potentials.To the best of our knowledge, there has never been a case report describing CA of VT after DSO.This report highlights ccTGA, which is of special interest because this is the first case of a successful CA of VT in a patient after a DSO and the tachycardia circuit was eliminated after ablating the right and left sides of the VSD patch.


Diastolic function has been little explored in d-transposition of the great arteries palliated by atrial switch (d-TGA). However, early detection of diastolic dysfunction could be of major clinical interest and could explain clinical status in this population. We aimed: 1/ to characterize diastolic function in d-TGA after atrial switch from velocity encoded cardiac magnetic resonance (CMR) data and 2/ to study associations between diastolic function indices and objective measurements of clinical status evaluated by exercise test.Forty five patients  with atrially switched d-TGA and 45 healthy subjects matched for age and sex were prospectively included. CMR examination was performed in both groups, and cardio-pulmonary exercise test was performed within 24 hours in patients. CMR tricuspid, mitral inflow and systemic ventricular outflow tract velocities and flow-rates were analyzed using custom software to estimate diastolic parameters (figure). Pulmonary vein baffle, atrial areas and right atrial strain as [ / maximal atrial area] were also measured.CMR diastolic parameters were significantly different in d-TGA patients as compared to controls. In d-TGA patients, parameters of systemic right ventricular (RV) relaxation were markedly impaired compared to left ventricle of controls, as reflected by a significant increase in deceleration and isovolumic relaxation times (p<0.01). Early trans-tricuspid peak filling-rate (Ef) and RV filling duration were negatively correlated with systemic RV remodeling index (Mass/volume) . Systemic RV stroke volume and Ef were significantly associated with baffle size . While peak VO2 was not related to systemic RV volumes, RVEF and to RV Mass, it was significantly associated with systemic ventricle filling indices, such as Ef/filling volume, A wave, filling volume. In multivariate analysis, a significant association was found between RA strain and exercise peak oxygen uptake  in d-TGA patients, while systemic RV ejection fraction was not correlated with exercise performances. Such associations were independent of age, gender and body mass index.In d-TGA after atrial switch, systemic RV exposed to systolic dysfunction can be also characterized by an early impairment of diastolic function. Systemic RV diastolic dysfunction is characterized by abnormal RV relaxation that limits cardiac output augmentation.This work was supported by Assistance Publique Hôpitaux de Paris. The authors were totally independent of the funder for all scientific aspects of the research.


In aortic stenosis(AS) with normal left ventricular ejection fraction(LV EF), circumferential and longitudinal systolic strains are reduced but the underlying mechanisms are uncertain. Conventional indices of afterload(A) per unit of myocardium are suboptimal for strain analysis and based on inaccurate assumptions about myocardial properties, while conventional contractility(C) indices address LV chamber, not myocardial properties. We have shown that the product of end-systolic pressure(P) and volume(V), divided by LV mass(M), or (PV/M), is a more effective index of A than conventional wall stress for strain analysis, while the ratio of strain to PV/M is an effective strain-based index of C. These methods were used to evaluate the mechanism of reduced LV strain in AS with preserved EF.Age and gender matched patients with AS and normal volunteers(NL) were compared (Table). CMR was performed on a 1.5T scanner, using TrueFISP cine short and LV long axis imaging and volumetrics and feature-tracking CSt, LSt and strain rates evaluated. A was quantitated as LV end-systolic PV/M, and as circumferential and meridional wall stress. C was assessed using the ratios, CSt/(PV/M), LSt/(PV/M), CSt/CWS and LSt/MWS.Table : Mean EFReduced systolic strain in AS with normal EF is due principally to reduced contractility, presumably due to known alterations in myocardial energetics, calcium handling and contractile proteins in hypertrophied myocardium. In contrast, differences in afterload are modest, so that overt "afterload excess" at the myocardial level is not seen, due to the adequacy of compensatory hypertrophy. In addition, the dependence of myocardial performance on contractile state is more marked in AS than in NL. Afterload and contractile indices based on PV/M were more useful than those based on conventional wall stress estimates.Supported by the St. Francis Research Foundation.


Orthotopic heart transplantation after univentricular palliation presents a difficult challenge due to the complex anatomy and prior surgeries.We present our surgical techniques/results in the current era.2013-2014: 23 congenital cardiac patients underwent heart transplantation. 13 of them: previous univentricular palliation: hypoplastic left heart syndrome (n = 8), d-transposition of great arteries+criss-cross-heart (n = 1), unbalanced atrioventricular septal defect (n = 1), pulmonary atresia+intact ventricular septum (n = 1) and grown-up patients (GUCH) (n = 2: 1 double-inlet-left-ventricle and 1 tricuspid atresia).Paediatric group (n = 11): age 7.1+/-4.8 years (range 1.5 months-13 years); weight 21.3+/-9.5 kilograms (range 3.5-36). GUCH-group (n = 2): age 23.5+/-0.5 years; weight 50+/-10.2 kilograms. 46.1% had undergone Fontan completion, 15.4% Fontan take-down, 30.7% bidirectional cavopulmonary shunt and 7.7% Blalock-Taussig shunt. Berlin-Heart-EXCOR-Paediatric-Device as bridge to transplantation was used in 1 patient. Bicaval technique was performed along with: hemiarch repair , pulmonary artery (PA) branches plasty , hilum-to-hilum PA reconstruction , superior venae cavae reconstruction  and stent removal from PA , inferior venae cavae  and lateral-tunnel-Fontan . Average cardiopulmonary-bypass time 257.6+/-79.3 minutes (range 120-431); total-ischemia-time 220.7+/-48.6 (range 140-287). One patient required ECMO; 4 underwent delayed sternal closure; 2 underwent diaphragm plication; 1 subacute-humoral-rejection treated with plasmapheresis. In-hospital stay 44+/-16 days (range 18-185). At follow-up (14.4+/-7.2 months), freedom from percutaneous procedures 83.3% (n = 10). 30-day mortality/follow-up mortality: zero. All of them remain with an optimal functional class.Heart transplantation following univentricular palliation is technically demanding but short-term results are excellent. An extensive surgical reconstruction (donor/heterologous tissues) is mandatory to improve outcomes. Further follow-up is necessary to evaluate the long-term results in this scenario.


Shock is a spectrum of circulatory failure that, if not properly managed, would lead to high mortality. Special diagnostic and treatment strategies are essential to save lives. However, clinical and laboratory findings are always non-specific, resulting in clinical dilemmas.Focused cardiac ultrasound (FoCUS) has emerged as one of the power tools for clinicians to answer simple clinical questions and guide subsequent management in hypotensive patients. This article will review the development and utility of FoCUS in different types of shock. The sonographic features and ultrasound enhanced management of hypotensive patients by a de novo “SIMPLE” approach will be described. Current evidence on FoCUS will also be reviewed.Focused cardiac ultrasound provides timely and valuable information for the evaluation of shock. It helps to improve the diagnostic accuracy, narrow the possible differential diagnoses, and guide specific management. SIMPLE is an easy-to-remember mnemonic for non-cardiologists or novice clinical sonographers to apply FoCUS and interpret the specific sonographic findings when evaluating patients in shock. Shock is a clinical syndrome in which there is inadequate cellular and tissue oxygenation due to circulatory failure . The preIn order to save our patients in shock, early diagnosis, and timely targeted therapy is vital. To do so in a timely manner is a challenge as clinical presentation of different types of shock may be similar. Point-of-care ultrasound (PoCUS) performed by clinicians providing direct care to the patients is considered an invaluable clinical tool to facilitate diagnosis-making, to rule out potentially fatal conditions, and to provide guidance to life-saving procedures . Among tThe name “focused cardiac ultrasound” (FoCUS) is interchangeable with “focused echocardiography,” “emergency echocardiography,” “bedside limited echocardiography,” “point-of-care cardiac ultrasound,” and “goal-directed echocardiography” . Lately,FoCUS makes use of the same five orthodox views as in transthoracic echocardiographic study (TTE), Fig.  to assesIn the assessment of hypotensive patients, several key sonographic findings should be evaluated. They include the chamber sizes, in particular the left ventricle (LV) and the right ventricle (RV), the interventricular septum (IVS), the IVC, the presence of intramural mass (commonly blood clots and myxoma), myocardial thickness and motion during systole, the presence of pericardial effusion or pleural effusion, LV systolic function and the abdominal aorta in the epigastrium. All of these can be summarized into a “SIMPLE” approach Table . It willIn addition to the five orthodox TTE views, the subcostal region or epigastrium is included in this SIMPLE scanning protocol to assess the size of IVC and abdominal aorta which may be involved in aortic dissection and aneurysmal rupture Fig. . In this2 or a LVEDA index (LVEDA/body surface area) of less than 5.5 cm2/m2 indicates significant hypovolemia [2 suggests volume overload [The size of the heart chambers reflects the preload status  and heart function based on the volume-pressure relationship of a compliant heart chamber, in the absence of pre-existing or concurrent diseases such as cardiomyopathy or massive myocardial infarction. LV end-diastole diameter (LVEDD) and LV end-diastole area (LVEDA) Fig.  can be uovolemia . Obliterovolemia . In contoverload . HoweverThe size of the RV can give clues to the right heart function. Normally, it should be smaller than the LV and the apex should be formed by LV, not RV Fig. . It is eNormally, LV appears as a circular or donut-shaped structure Fig. , and theTraditionally, the central venous pressure (CVP) has been used for fluid status assessment and monitoring. Nonetheless, it is not only invasive but also proven to correlate poorly with the blood volume status in a systematic review . Recent IVC size can be used as a surrogate measurement of preload and volume status and therefore right atrial pressure (RAP). IVC diameter can be used to estimate RA pressure. The American Society of Echocardiography suggested the cutoff value of 2.1 cm . IVC diaAortic dissection is a potentially fatal but challenging vascular emergency. The cardinal feature of this disorder is a tear of the intimal layer of the aorta causing blood to dissect between layers of the aortic wall and propagate along the vessel. Hypotension was found to present in 16.4 % of patients with aortic dissection . HoweverIntra-cardiac masses are not commonly seen on sonographic examination. But when present, in the appropriate clinical setting, they help establish the diagnosis of obstructive shock. The presence of intramural thrombus in right-sided cardiac chambers can confirm the clinical suspicion of pulmonary embolism and guide subsequent treatment . IntracaDuring systole, different parts of the LV thicken in a coordinated fashion to act as a pump to eject blood out of the heart. According to the European society of Cardiology and American Society of Echocardiography, the LV can be divided into 17 segments and each individual segment can then be graded as normal/hyperkinetic, hypokinetic (reduced thickening), akinetic (absent thickening), or dyskinetic  according to their motions during systole , 42. ThiAbnormal thickening of the myocardium  is suggestive of chronic heart conditions resulting from pressure overload . Together with gross dilatation of ventricle and atrium, detection of myocardial thickening is considered by the latest international consensus to be an essential part of FoCUS . It can The pericardial sac is a potential space for fluid to collect due to both systemic illness  and local pathology . Although difficult to detect by physical exam or chest X-ray, pericardial effusion is easily picked up by FoCUS. Usually, pericardial effusion appears as an anechoic rim surrounding the heart, best seen in the parasternal long axis view or subxyphoid four-chamber view. However, if the effusion is caused by inflammatory condition or hemorrhage , there may be echogenicity within the pericardial sac. The pericardium appears as a densely echogenic film-like reflection posterior to the anechoic pericardial effusion Fig. . SometimEchocardiography or cardiac ultrasound can give an accurate assessment of global function of the left ventricle and guide subsequent treatment . There are several options to assess the LV systolic function sonographically, including fractional shortening (FS) and LV ejection fraction (LVEF).In M-mode, FS of the left ventricle can be assessed by placing a cursor just near the tip of the mitral valve leaflets in parasternal long axis view. The M-mode tracing will show the change in LV diameter during the cardiac cycle and FS can be calculated by the following formula:The normal value should be 25–45 % for adults . If the In B-mode, the LVEF can be measured by the modified Simpson biplane method. Most modern ultrasound machines have the calculation package pre-installed. The endocardial margins of the LV are traced in systole and diastole from two different views  to calculate the volume change between systole and diastole. The normal LVEF should be >55 %, and <30 % indicates severe left ventricular systolic dysfunction . This isK = 0.79, 95 % CI 0.773 to 0.842) [Assessment of LVEF by eyeballing appears the most feasible yet reliable method for estimating the LV systolic function. It can be done through assessing the movement and thickening of the LV myocardium, the change in size and shape of the LV chamber as well as the mitral valve anterior leaflet excursion in the cardiac cycle. It was found that the accuracy of eyeballing estimation correlated well with other quantitative methods including Simpson biplane ejection fraction, fractional shortening, wall motion score index, and aortic valve (AV) plane displacement , 46. Thio 0.842) . Thus, vThe proximal part of abdominal aorta can be easily visualized by ultrasound. It should be integrated into the scanning protocol of FoCUS in addition to the IVC measurement. It lies along the mid-line of the abdomen, on the left side of the IVC, and anterior to the bony vertebra. The normal size of the abdominal aorta should be less than 3 cm. Abdominal aortic aneurysm (AAA) is diagnosed when the diameter is >3 cm. AAA can rupture and cause profound hypotension due to hypovolemia. Clinical presentation may be subtle, and reliance on physical findings alone may miss this potentially fatal condition as the sensitivity of abdominal palpation is only 68 % , 50. PoC2). The lumen of the LV may even be obliterated and the ventricular walls are seen to be “kissing” . Tng” Fig. . HyperdyEchocardiography or cardiac ultrasound definitely has a role in managing cardiogenic shock due to LV dysfunction and valvular dysfunction. LV would be dilated, and fractional shortening would be impaired Fig. . DilatedOne of the major causes for obstructive shock is cardiac tamponade. The presence of pericardial effusion and hypotension raises the suspicion of cardiac tamponade. Large amounts of effusion would cause cardiac tamponade, but even small effusions, if accumulated rapidly, can cause cardiac tamponade due to the tough, non-distensible nature of the pericardial sac. Although cardiac tamponade is essentially a clinical diagnosis, FoCUS can help to confirm the presence of pericardial effusion, provide useful real-time hemodynamic information and tamponade physiology, and guide therapeutic pericardiocentesis. Sonographic features of cardiac tamponade include RA collapse, RV diastolic collapse, distended IVC, and respiratory variation of the mitral inflow velocity. The latter is essentially the sonographic version of pulsus paradoxicus. Pulsed wave Doppler is required to detect the variation so it is out of the scope of this SIMPLE approach Table . RA collMassive pulmonary embolism causes acute RV dysfunction. RV is usually dilated with basal diameter >4 cm and RV/LV ratio >0.6. The normal triangular-shaped RV is distorted, and the apex is no longer dominated by the LV on the apical four-chamber view. The IVS shows paradoxical movement, and D-shaped LV chamber would be appreciated in the parasternal short axis view Fig. . Free flAortic dissection can be picked up by FoCUS when the intimal flap is in the aorta Fig. . The comSeptic shock represents a distinctive spectrum of hemodynamic instability. In the early stage, the afterload is reduced and left ventricular dysfunction, although present, is masked by the severely reduced afterload due to sepsis , 62. ThuSince 2001, different protocols for shock assessment have been described in the literature. Table In contrast to existing protocols like rapid ultrasound for shock and hypotension (RUSH) , abdominTo my knowledge, this is the first protocol to include two specific findings explicitly: intramural mass and intimate flap so as to improve the diagnostic power of two challenging and lethal conditions, namely massive pulmonary embolism and aortic dissection. Although abdominal assessment is not routinely included in the SIMPLE approach, combination with FAST to look for the source of intra-abdominal bleeding is indicated when FoCUS reveals features of hypovolemia. As most emergency physicians and intensivists have been using FAST scan routinely in trauma assessment, a combination of SIMPLE with FAST (SIMPLE + FAST) would easily be incorporated into their daily practices. SIMPLE + FAST suggests cardiac assessment first before abdominal assessment in order to detect obstructive and cardiogenic shock, in contrast to the FAST + RELIABLE protocol suggested by Liteplo et al. . This alAmong the literature, there is growing evidence demonstrating that FoCUS could improve the diagnostic accuracy and change the clinical management. Although the results of this evidence may not necessarily prove that FoCUS can lead to better patient survival and shorten the hospital stay, it can logically be assumed that with more accurate diagnostic capability for various types of shock, implementation of FoCUS could lead to a better clinical outcome in patients with circulatory failure.FoCUS is helpful in confirming the correct diagnoses and detecting the etiology of shock. In a randomized trial in 184 patients by Jones et al. in the emergency department, early goal-directed ultrasound at 0 min was found to correctly diagnose the etiology of shock in 80 % of patients compared 50 % of patients in the group only received standard care at the initial 15 min of presentation in the emergency department . This trk = 0.710). Ghane et al. also found similar finding in a study in 52 ED patients by using RUSH protocol (k = 0.7) [Subsequent trials on protocol-driven ultrasound for diagnosis of shock further confirmed the role of FoCUS to diagnose and differentiate different types of shock in the emergency department. Volpicelli et al. did a prospective study on 108 ED patients in undifferentiated shock by comparing the sonographic diagnosis with the final clinical diagnosis . The ultk = 0.7) . It was k = 0.7) . The comp = 0.01) and more dobutamine use  than the historical control group which was managed in a standard fashion [p = 0.04) and a reduction in acute kidney injury (20 vs 39 %). These findings are supportive of using FoCUS to guide the resuscitation of hypotensive patients. The limitations of this study include no randomization, use of historical control, and a significant number of patients (14 %) with significant valvular pathologies. Another recent study performed in ED also confirmed the impact of FoCUS findings on management plan (in 24.6 % of patients), including the use of intravenous fluid, vasoactive agents, or blood products. This study also found an excellent concordance of protocol-driven ultrasound diagnostic protocol in undifferentiated hypotension with the final diagnosis (k = 0.80). Moreover, ultrasound was also found to influence the diagnostic imaging, consultation, and patient disposition in this study. Again, the limitations are the lack of randomization and use of single ultrasound operator.Apart from correct diagnosis and differentiation of shock, the other major role of FocUS for shock is to tailor the treatment according to the underlying etiology and improve the clinical outcome of patients. In an observational study conducted on 220 patients in intensive care unit, use of FoCUS by hand-held ultrasound device was found to be associated with significantly lower fluid prescription (49 vs 66 mL/kg,  fashion . More imManaging patients in profound shock poses a very great challenge to clinicians. Correct diagnosis and timely specific treatment to restore the otherwise jeopardized circulation are vital to the survival of hypotensive patients. Throughout the past 10 years, FoCUS has emerged as one of the important allies of emergency physicians and intensivists to provide crucial answers to challenging clinical conditions. In properly trained hands, FoCUS can provide real-time valuable information on the pathology and physiology of circulation to differentiate between different types of shocks. Through the suggested SIMPLE approach, different types of shocks can be characterized according to 2D ultrasound findings and simple measurements (Table AAA, abdominal aortic aneurysm; ACES, abdominal and cardiac evaluation with sonography in shock ; ACLS, a


Cardiac MR (CMR) is the reference standard for assessing macroscopic myocardial scar. Determination of the extracellular volume fraction (ECV) by T1 estimation using the modified Look-Locker inversion recovery (MOLLI) correction enables quantitation of diffuse fibrosis. The purpose of this study is to evaluate the feasibility and reproducibility of an optimized high-resolution MOLLI (HR-MOLLI) technique at 3T and 1.5T for RV ECV calculation in healthy volunteers.25 healthy volunteers  were scanned at 3T  and 15  were scanned at 1.5T (MAGNETOM Aera). T1 mapping was performed in the axial orientation using an investigational HR-MOLLI technique with a 1 × 1 mm 2 in-plane resolution that applies motion correction with synthetic image estimation. Motion corrected images were used to generate parametric maps with (T1) and without (T1*) the MOLLI correction. The MOLLI sequence uses a 5 heart-beat (HB) acquisition, 3 HB recovery, 3 HB acquisition scheme with a single shot bSSFP diastolic readout. Images were acquired pre- and 10-25 minutes post- administration of 0.2 mmol/kg gadobenate dimeglumine . T1 and T1* parametric maps were used to quantify the T1 of tissue and blood, respectively. Two reviewers quantified basal and mid RV free wall, interventricular septal, and lateral LV wall T1 values on T1 parametric maps. RV and LV ECV ranges were calculated assuming normal hematocrit values . Global ventricular ECV values were compared using the student's t-test. Intra and inter-observer variance was measured by the intraclass correlation coefficient (ICC).Representative T1 and T1* parametric maps are shown in Figure This feasibility study demonstrates that HR-MOLLI can quantitate the global RV ECV fraction at both 1.5 and 3T with good intra- and interobserver variance. Our results demonstrated a field-strength influence on RV and LV ECV values, and showed that ECV calculations using blood pool extimates without a look-locker correction are necessary at 3T.Funding pending.


Type 2 diabetes mellitus (T2DM) complicated by retinopathy is associated with altered left ventricular (LV) structure and resting myocardial dysfunction unlike T2DM without retinopathy. The myocardial response to stress has not been compared in patients with and without diabetic retinopathy. The aim of this retrospective study was to determine the relationship between retinopathy and myocardial function in patients with T2DM at rest and during exercise echocardiography.134 patients with T2DM and no evidence of underlying coronary artery disease were recruited. All patients underwent retinal photography to screen for diabetic retinopathy, and resting and exercise echocardiography. Resting echocardiography was analyzed by conventional echocardiographic parameters and speckle tracking derived global longitudinal strain (GLS). Exercise echocardiography parameters included diastolic function reserve index (DFRI) and stress GLS.The mean age of participants was 60 years and 49 % were male. Diabetic retinopathy was identified in 43 patients (32 %). Resting echocardiography revealed that those with diabetic retinopathy had a higher prevalence of impaired diastolic function, higher E/E′ ratio (LV filling pressures) and impaired resting GLS compared with those without. Exercise echocardiography revealed that those with diabetic retinopathy also had more impaired DFRI and stress GLS. Multivariable analysis showed that the presence of diabetic retinopathy was independently associated with high resting E/E′, diastolic dysfunction grade, impaired resting GLS, low DFRI and impaired stress GLS.In conclusion, the presence of diabetic retinopathy was independently associated with impaired resting myocardial function (diastolic and systolic function) and myocardial function during stress .The online version of this article (doi:10.1186/s12933-015-0281-5) contains supplementary material, which is available to authorized users. Patients with type 2 diabetes mellitus (T2DM) have altered left ventricular (LV) structure and function, independent of traditional risk factors and underlying coronary artery disease, that leads to an adverse cardiovascular outcome , 2. One A total of 323 patients with T2DM, as defined by World Health Organization criteria, were consecutively recruited at Queen Mary Hospital, Hong Kong . Patient2 and an electrocardiogram (ECG) recorded. Hypertension was defined as resting systolic or diastolic blood pressure ≥140/90 mmHg at two different clinic visits or prescription of antihypertensive medication. Data on medications were retrieved from patients’ electronic medical record. A fasting blood sample was obtained to measure HbA1c, fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL) and serum creatinine level. The estimated glomerular filtration rate (eGFR) was calculated using the Modified Diet in Renal Disease Equation [All patients underwent a complete physical examination and an interview to establish baseline characteristics. Smoking status was recorded as positive if patients currently or had ever smoked. Body-mass index (BMI) was calculated in kg/mEquation .For diabetic retinopathy screening, digital photographs of the retina covering two standard fields, focused on the optic disc and macula respectively, were taken by an optometrist using a non-mydriatic fundus camera (Topcon TRC-50DX: Type IA). The photographs were then graded by both the optometrist and an ophthalmologist at the Department of Ophthalmology, University of Hong Kong, using the UK National Screening Program for Diabetic Retinopathy Grading Scheme: no DR (R0), background (non-proliferative) DR (R1), pre-proliferative DR (R2), proliferative DR (R3), maculopathy (M1) and photocoagulation (P) . Any disTransthoracic echocardiographic examination was performed in all patients using a commercially available echocardiography system  with the patient lying in the lateral decubitus position. A 3.5-MHz transducer was used to obtain images that were digitally stored in cine-loop format. The frame rate was set at > 90 frames per second. Off-line analysis was performed using the EchoPAC version 108.1.5 . All patients were in normal sinus rhythm during the examination.The inter-ventricular septum thickness, posterior wall thickness, and LV dimension were measured in M-mode according to the current recommendations. LV volume and ejection fraction were determined from apical four and two-chamber views using the modified Simpson’s biplane method of discs. Evaluation of LV diastolic function was based on the pulsed-wave Doppler of mitral valve inflow. Peak velocity in early diastole (E-wave) and late diastole (A-wave) was measured and the E/A ratio calculated. Pulsed wave tissue Doppler imaging was used to measure the early diastolic velocity (E′) with the sample volume placed at the septum annulus. In addition, the E/E′ ratio was calculated as an estimation of LV filling pressure . LV massThe measurement of LV global longitudinal stain (GLS) provides detailed assessment of LV myocardial deformation by tracking natural acoustic markers in a frame-to-frame basis within the cardiac cycle . In brieOf the recruited patients, 55 of the 245 were physically unable to perform exercise echocardiography. Exercise echocardiography was performed in the remaining 190 patients. Regional wall motion abnormality was detected in 22 patients during stress testing, suggesting the presence of significant ischemic heart disease and 34 patients had suboptimal stress images for analysis. The number of patients with exercise echocardiography images suitable for analysis was thus 134. The mean age of the remaining participants was 60 years and 49 % were male. Diabetic retinopathy was indicated in 43 patients (32 %). Maximum exercise treadmill testing was performed using the standard Bruce protocol . All part test. Categorical variables were compared using Chi square test or Fisher’s exact test if >10 % of the cells had an expected count <5. Pearson’s correlation test was used to assess the correlation of retinopathy with myocardial function in diabetic patients. Correlation coefficients were performed in order to assess the association of METS and resting and exercise echocardiography parameters in T2DM patients. Multivariate analyses were performed to detect the independent predictors of abnormal myocardial function in patients with T2DM. In these analyses, factors independently associated with E/E′, LV diastolic dysfunction grade, resting GLS, DFRI or stress GLS were identified using an enter regression model in which each statistically significant univariate predictor of outcomes with p < 0.10 was chosen. All data analysis was performed using the commercially available statistics software SPSS for Windows (Version 17.0). All p values reported are 2-sided for consistency. A p value < 0.05 was considered statistically significant.All continuous variables and categorical variables are expressed as mean ± standard deviation and frequencies or percentages, respectively. Continuous variables were compared between patients with and without diabetic retinopathy, using independent Student’s The baseline characteristics of patients with and without diabetic retinopathy are shown in Table Conventional echocardiographic LV findings are described in Table Exercise echocardiography parameters are shown in Table Functional parameters derived from treadmill testing are shown in Table The correlation of functional capacity assessed by METS with both resting and stress echocardiography parameters is shown in Figs. Multivariable analysis adjusting for potential confounding factors of 1) resting parameters  and (2) stress parameters (DFRI and stress GLS) is shown in Additional file  resting The present study demonstrates that patients with T2DM complicated by retinopathy had impaired resting diastolic function and systolic function evaluated by 2D speckle tracking derived GLS. Exercise echocardiography revealed that they also had an altered myocardial stress response as demonstrated by an impaired DFRI, stress GLS and a lesser ∆ of GLS. Importantly, multivariate analysis further demonstrated that the presence of diabetic retinopathy was independently associated with both resting (resting diastolic dysfunction grading and GLS) and exercise (stress DFRI and GLS) echocardiography parameters.Patients with T2DM complicated by retinopathy is common and is closely associated with glycemic control –25. In aMyocardial performance during stress is clinically important and has been shown to be associated with hospitalization for heart failure . In partPatients with T2DM have impaired exercise capacity due to a variety of reasons, including a blunted response in heart rate and blood pressure and autonomic dysfunction . A studyThe present study was a cross-sectional analysis and adverse clinical outcome data were not available. The stress echocardiography parameters have nonetheless been shown to be associated with adverse outcome in patients with T2DM . Future The present study demonstrates that in patients with T2DM, the presence of retinopathy was independently associated with impaired resting and stress diastolic and systolic function. This finding suggests that patients with diabetic retinopathy have an impaired myocardial response during stress that may subsequently affect their exercise capacity and functional outcome compared with those without retinopathy.


Ventricular arrhythmias are an important cause of late morbidity and sudden cardiac death in the growing population of adults with repaired congenital heart disease. Risk stratification remains challenging because of the heterogeneity of the malformations and the surgical approaches. Therapeutic interventions depend on the type of ventricular arrhythmia, which can be polymorphic ventricular tachycardia (VT) or ventricular fibrillation in patients without ventricular scars, but also potentially fatal monomorphic reentrant VTs, typical for patients with ventricular scars or obstacles. Advances in surgical techniques have improved survival and have important implications for the arrhythmia substrates and prognosis. Over the past few decades, progress has been made to determine the anatomical basis for monomorphic VT in patients with ventricular surgical scars and patch material. These substrates can be currently identified and targeted during sinus rhythm by radiofrequency catheter or surgical ablation without the need for VT induction. The review provides an update on the evolving surgical approaches, the changing VA substrates, and the potential consequences for individualized risk assessment and tailored treatment. The population of adults with repaired congenital heart disease (rCHD) is growing . SurgicaAlthough sudden death may occasionally be due to cerebral, vascular, or thrombo-embolic events, the majority is assumed to be arrhythmic SCD . Life-thAlthough systemic ventricular dysfunction is a dominant predictor for SCD in unselected populations of adults with CHD, two thirds of those who die suddenly or experience life-threatening VTs have a preserved cardiac function prior to the event , 19, 24.VAs include monomorphic ventricular tachycardia (MVT), polymorphic VT, and ventricular fibrillation. It is crucial for risk stratification and treatment to understand and identify the underlying substrate for these different VAs. VAs can occur in the absence of any surgical scar or patch material, typical for patients with left heart obstruction or atrial switch operation for simple dextro-transposition of the great arteries (d-TGA).However, MVT in these patients is uncommon. The estimated incidence rate for MVT in an unselected group of patients after atrial switch for d‑TGA was 0.5 % per year . The majThe underlying arrhythmia mechanisms are likely to be similar to those observed in other cardiac diseases with pathologic hypertrophy, fibrosis, progressive right or left ventricular dilatation, and eventually heart failure. Hypertrophy can be due to chronic pressure overload in left heart obstructions. Progressive ventricular dysfunction usually occurs if the right ventricle (RV) serves as the systemic ventricle after atrial switch operation for d‑TGA or in congenitally corrected transposition of the great arteries (ccTGA). The therapeutic options comprise treatment of residual lesions, optimal heart failure management to reduce further adverse remodeling, and ICD implantation. Specific anti-arrhythmic drugs or catheter or surgical interventions are not available.By contrast, in the presence of surgical scar and patch material, MVTs are the most common type of observed VAs. MVT after repair of TOF can serve as a paradigm of these postoperative arrhythmias , 20, 26.Indeed, more than 80 % of all treated VAs in rTOF patients who have received ICDs for primary and secondary prevention were monomorphic and fast VTs with a median heart rate of 212 bpm . These fAfter initial repair of TOF, RV hypertrophy may develop as a result of residual RVOT obstructions. Progressive RV dilatation and dysfunction can be the consequence of chronic pulmonary regurgitation, which is more likely if initial repair is performed through a right ventriculotomy combined with the use of large transannular patches Fig. . These pAreas of dense fibrosis after surgical incisions, patch material, and the valve annuli form regions of conduction block that can define reentry circuit borders and create intervening anatomical isthmuses (AIs) consisting of conducting myocardium , 26. AftThe coincidence of unexcitable anatomical boundaries and pathological remodeling over time may explain the high incidence of late macro-reentrant VT in particular in patients with rTOF.Most data on risk stratification are derived from patients with rTOF. Retrospective, observational studies have identified several factors associated with VA and SCD Tab. . CurrentRisk stratification in patients after the atrial switch operation for d‑TGA is even more challenging. Symptoms of arrhythmias and heart failure and documented atrial flutter or fibrillation have been identified as predictors of SCD. In addition, sustained VT and SCD are more likely in patients with additional anatomical lesions, impaired RV function, NYHA class III or greater, and a QRS duration of ≥140 ms . PrimaryThe currently applied arterial switch operation for d‑TGA disconnects the aorta and pulmonary trunk from their arterial roots and connects them to the correct ventricle. The LV serves as systemic ventricle that may prevent the occurrence of late VA.Repair of TOF has changed from a late transventricular repair after palliative shunt operation to a combined transatrial–transpulmonary approach, now usually performed early in life. The latter approach may prevent severe RV hypertrophy, RV and LV dysfunction, and increased intraventricular pressure and fibrosis, all factors associated with late VA and SCD. In addition, AIs 1 and 2 may also be prevented by the modern approach, whereas isthmus 3 and occasionally isthmus 4 cannot be avoided. In those patients, a positive programmed electrical stimulation (PES), defined as inducibility of a sustained MVT, may remain an important tool to prove the presence of a substrate for reentrant VT. Inducibility strongly depends on the applied induction protocol often requiring three extra stimuli and occasionally isoproterenol . Of inteA wide QRS (≥180 ms) and an increase in QRS duration have consistently been reported as important risk factors for both MVT and SCD . QRS proIn addition, replacing the valve did not eliminate the risk for MVTs, despite postoperative improvement in RV volumes and function . An empiPatients with rCHD and VA may be SCD survivors or present with often highly symptomatic, fast VTs Fig. . AccordiThere are no specific data available on the efficacy of antiarrhythmic drugs in rCHD. In general, the available drugs to prevent recurrence of reentrant VT in structural heart disease have limited efficacy. Sotalol or Amiodarone may be effective in reducing appropriate ICD therapy but their use is often hampered by serious side effects leading to drug discontinuation. The feasibility of radiofrequency catheter ablation (RFCA) in patients with rCHD was reported 20 years ago, the majority performed in TOF patients, followed by patients with VSD closure and atrial switch for complex d‑TGA . InitialOver the last decade, progress has been made in identifying the anatomical substrate for fast VTs, which is currently approachable by substrate-based ablation techniques , 20, 26.Up to 97 % of all spontaneous and induced monomorphic VTs in the contemporary population of patients with rCHD referred for RFCA or studied for risk stratification are macro-reentrant VTs with a critical reentry circuit isthmus located within anatomically defined isthmuses .These AIs can be reconstructed with point-by-point electroanatomical voltage mapping during stable sinus rhythm using three-dimensional electroanatomic mapping systems Fig. . Peak-toThe critical reentry circuit isthmus of each induced VT can be occasionally determined by activation and entrainment mapping for tolerated VT. However, considering the often hemodynamically unstable VTs, pace-mapping within AIs is often applied to determine whether the critical isthmus is likely located within an anatomically defined isthmus. The VT-related AI can be transected by connecting the adjoining anatomic boundaries by a linear RF lesion .An alternative approach for mapping of poorly tolerated VTs has applied noncontact mapping . The sysand transection of the critical AI was defined as complete procedural success and achieved in 25 of 34 adults with VT after CHD repair. None of these patients had recurrence of a monomorphic VT during 46 ± 29 months of follow-up [Demonstration of conduction block after transection of an AI is an accepted and clearly defined procedural endpoint. Accordingly, noninducibility of any VT ollow-up . These dThe 12-lead morphology of the clinically documented or induced VT may already provide an indication of the AI being involved Fig. . HoweverRisk stratification and treatment of complex VAs in patients with rCHD remain challenging and require a multidisciplinary approach. Progress has been made in understanding and delineating the substrate for MVT. The strong link between slow-conducting AIs and the often poorly tolerated VTs allows for RFCA without VT inducibility and (preventive) surgical ablation in those who need surgical re-interventions. Substrate identification may overcome the problem of lacking clinical arrhythmia predictors and could facilitate personalized risk stratification and tailored treatment in the contemporary population of patients with rCHD.


A growing body of data has demonstrated a direct relationship between epicardial fat volume(EFV) and cardiovascular diseases. In fact, EFV has been shown to be an independent predictor of coronary atherosclerosis and atrial fibrillation. Currently, there is no standard protocol for assessing EFV using cardiac magnetic resonance imaging (CMR). Quantification of peri-ventricular EFV utilizing end diastolic short-axis cine sequences has been described; however, this technique is often challenging due to inadequate visualization of the pericardium. Oftentimes, the pericardium is better visualized during the systolic phase. Thus, we sought to determine the correlation and reproducibility of conventional EFV quantification using end diastolic with end systolic short-axis slices.We prospectively studied 20 patients with atrial fibrillation (AF) from November 1, 2010 to July 31, 2012 prior to AF ablation who underwent CMR. CMR images were acquired on a 3T scanner (Siemens Trio) by SSFP using a standard short axis stack through the ventricles. Epicardial fat was assessed volumetrically in consecutive short-axis views using the multi-slice method (MSM) during both end-systole and end-diastole . End-diastolic epicardial fat volume (EDFV) slightly underestimates end-systolic epicardial fat volume (ESFV) by 2% (Table ESFV demonstrates strong correlation, level of agreement and reproducibility with EDFV. When the pericardium is inadequately visualized during the end-diastolic phase, ESFV derived from standard cine sequences offers an alternate method for evaluating epicardial fat with CMR.None.


There is a growing appreciation for the adverse long-term impact of right-sided valvular dysfunction in patients with congenital heart disease. Although right-sided valvular stenosis and/or regurgitation is often better tolerated than left-sided valvular dysfunction in the short and intermediate term, the long-term consequences are numerous and include, but are not limited to, arrhythmias, heart failure, and multi-organ dysfunction. Surgical right-sided valve interventions have been performed for many decades, but the comorbidities associated with multiple surgeries are a concern. Transcatheter right-sided valve replacement is safe and effective and is being performed at an increasing number of centers around the world. It offers an alternative to traditional surgical techniques and may potentially alter the decision making process whereby valvular replacement is performed prior to the development of long-term sequelae of right-sided valvular dysfunction. The progress of congenital heart disease (CHD) surgical interventions over the past few decades has allowed more children to survive well into adulthood. Most of these patients will require multiple surgical procedures over their lifetime. This can be associated with increased morbidity and mortality , 2 due tPulmonary valve disease in the congenital population can be native or post-operative. Native pulmonary valve dysfunction may be isolated, as in congenital pulmonary stenosis, or may be a part of a recognized condition such as tetralogy of Fallot. Surgical valve or conduit placement is often not performed in infancy or early childhood in preference to procedures that alleviate pulmonic stenosis such as pulmonary valvotomy and subannular or transannular patch placement. These techniques invariably leave the patient with chronic severe pulmonary regurgitation. Surgical pulmonary valve interventions usually consist of valve replacement with either bioprosthetic valves or valved conduits. Rarely, patients may undergo mechanical pulmonic valve replacement. Bioprosthetic valves and conduits  invariably develop progressive dysfunction within 10–20 years of implantation with resultant stenosis and/or regurgitation .Although pulmonary valve dysfunction is generally well tolerated, patients often develop progressive exertional limitations and may develop ventricular and supraventricular arrhythmias. Decompensated congestive heart failure is a late manifestation that usually occurs well after the development of exertional symptoms. In patients with progressive stenosis, right ventricular hypertrophy develops as a compensatory mechanism for the increased pressure with resultant right ventricular diastolic dysfunction and eventually systolic dysfunction ensues . Severe 2 or right ventricular end-systolic volume (RVESV) >80 ml/m2) [The timing of pulmonary valve replacement in these patients is controversial , 17. Sev0 ml/m2) –23. Ther0 ml/m2) . It does0 ml/m2) .Native tricuspid valve dysfunction in patients with congenital heart disease is often associated with Ebstein anomaly, which may result in chronic severe tricuspid regurgitation. Severe tricuspid regurgitation is often well tolerated for decades. However, much like pulmonic regurgitation, eventual clinical sequelae will emerge. These include the development of ventricular and supraventricular arrhythmias, elevated central venous pressure with resultant multi-organ congestion , and progressive right ventricular dysfunction. Native tricuspid valve regurgitation may occur as a result of progressive right ventricular and tricuspid annular dilation or in patients with severely elevated right ventricular systolic pressure due to severe pulmonary hypertension or right ventricular outflow obstruction. Therefore, it is common for patients with RVOT dysfunction, as in repaired tetralogy of Fallot or pulmonic stenosis, to develop secondary tricuspid regurgitation. Surgical techniques for tricuspid valve repair include the placement of annular bands or rings as well as more complex operations to relocate or augment the tricuspid valve leaflets (as in Ebstein’s). Progressive tricuspid regurgitation is common during long-term follow-up of these patients and manifests in a similar clinical manner to native tricuspid regurgitation. If surgical valve replacement is warranted, bioprosthetic valves are preferred, although there is limited data on the safety and efficacy of mechanical prostheses. Bioprosthetic tricuspid valves can become dysfunctional over time and generally require replacement within a decade. Progressive regurgitation and/or stenosis may occur with the clinical sequelae of elevated central venous pressure and reduced cardiac output , 27.Echocardiography is a widely available and cost-effective tool for the assessment of congenital cardiac structure and function. It is universally utilized for the diagnosis of stenotic or regurgitant valvular lesions using qualitative measures such as color Doppler Fig. , and denCardiac tomography angiography (CTA) has become an integral part of the evaluation of patients with aortic valve disease prior to transcatheter aortic valve replacement (TAVR). CTA is not as widely utilized for the evaluation of patients with congenital heart disease, as many centers prefer to use cardiac MRI due to concerns over radiation and its limitations in functional assessment due to the lack of blood velocity measurements. Also, CTA requires the injection of iodinated contrast, which is nephrotoxic, and therefore the use of this modality is limited in patients with advanced renal dysfunction. However, ECG-gated chest CTA can provide excellent spatial and temporal resolution and is extremely useful in the assessment of right ventricular outflow tract abnormalities, both native and post-operative . MoreoveCardiac Magnetic Resonance Imaging (CMR) is widely used for the assessment of congenital heart disease, as it provides anatomic data as well as qualitative and quantitative measurements of valvular regurgitation and/or stenosis. In addition, it provides accurate ventricular dimensions and function. CMR is especially useful for measuring pulmonary regurgitant volume and right ventricular volumes, which are critical parameters for determining the optimal timing for intervening on pulmonary valve regurgitation –39. CMR Diagnostic cardiac catheterization was once utilized universally in patients with congenital heart disease but has been supplanted over the past 30 years by the aforementioned non-invasive imaging tools. In cases where the non-invasive data is inconclusive or contradictory, diagnostic catheterization may be necessary. In patients with right-sided congenital valvular disease, catheterization provides direct pressure measurements, facilitates angiography, and allows for accurate measurement of shunts. Moreover, in patients with pulmonary hypertension, catheterization allows for the calculation of pulmonary arterial resistance and determination of pulmonary vasoreactivity. Additionally, invasive hemodynamic assessment during steady state alterations, such as volume loading, stress testing, or infusion of inotropic medications can provide valuable information. That being said, the majority of patients today undergo invasive catheterization mainly for interventional purposes; however, the hemodynamic data gathered pre- and post-intervention is integral to their management.Indications for intervention are often based on symptomatology, severity of the stenosis or regurgitation, right ventricular volume and function, and the burden of arrhythmias , 38, 40.Transcatheter pulmonary valve (TCPV) replacement can alleviate RVOT conduit dysfunction whether due to stenosis, regurgitation, or both, thereby delaying the need for open heart surgery and essentially decreasing the number of operations with their associated morbidities , 42. TheShort-term outcomes of the Melody valve have proven the durability of the valve –50. FurtStent fracture and endocarditis have been the primary causes for re-intervention , 58, 59•Transcatheter pulmonary valve replacement has also been successfully performed within failed bioprosthetic valves, not as part of RV-PA conduits, with excellent outcomes including freedom from repeat intervention of 92 % at 1 year and 92 % at 2 years . The MelIn the subset of congenital heart disease patients with native RVOT or RVOT patch repairs, there is a growing body of literature on the utility of commercially available valves used off-label. In a retrospective trial of 31 patients, Melody pulmonary valve implantation in native RVOT due to either stenosis or regurgitation was safe and feasible; however, there was a high stent fracture rate of 32 % despite pre-stenting . BoudjemThe timing of pulmonary valve replacement in asymptomatic patients remains somewhat controversial , 52, 53.In congenital heart disease patients, prior surgical repair often involves annuloplasty rings with tricuspid valve repair, and less often tricuspid valve replacement. The risk of recurrent regurgitation in tricuspid valve repair is high and many will eventually require valve replacement . BioprosIn native valves, the MitraClip  has been used from a transjugular approach; however, the tricuspid valve morphology  makes it more difficult to successfully position the Mitraclip . Other dCaval transcatheter valve implantation is another potential treatment option for severe tricuspid valve regurgitation, where valves are implanted in the superior and inferior vena cavae, with several case reports demonstrating hemodynamic success , 87, 88.Right-sided transcatheter valvular implantation in patients with congenital heart disease and conduit or bioprosthetic valve dysfunction is not only gaining momentum with enormous potential for growth and innovation but is also quickly becoming the new standard of care. The minimally invasive and effective techniques of transcatheter valvular implantation have allowed for a reduction in the number of open cardiac surgeries that a patient with CHD can anticipate undergoing over a lifetime, therefore affecting the morbidity of this growing patient population. The use of TCPV in native RVOT is increasing, especially with the advent of large-diameter TCPV. There is a growing body of data on the efficacy and safety of transcatheter valve interventions in patients with tricuspid valve dysfunction. Pre-procedural planning with the use of multiple imaging modalities is integral to procedural success, and it is critical to combine both structural and functional data for determining the correct timing of any intervention. An interdisciplinary team approach is most ideal, with incorporation of hybrid procedures using both surgical and catheter-based techniques. A larger body of evidence with intermediate and long-term outcomes is needed to assess the longevity of these new techniques in comparison to the current surgical gold standard.


T2 is sensitive to hemoglobin oxygen saturation (%HbO2). Non-invasive, rapid in-vivo quantification of %HbO2 based on the T2 of blood may be useful in patients with congenital heart disease. Although single-shot, T2-prepared SSFP enables rapid myocardial T2 quantification , flow se0, 2.5x2x8 mm3, 1NEX, free breathing), were acquired on a 1.5T MRI system  using both schemes with preparation times: TET2p = 0,30/33,40,60,80,100,120,140,160,180 and 200 ms. Multi-Echo Spin Echo (MESE)  was used to measure T2 in a phantom with blood-mimicking fluid as a reference standard. Quantitative T2 values were measured in the same phantom and in the right (RV) and left (LV) ventricles in a four-chamber view in five volunteers (mean age: 28 ± 14 years). Paired t-tests were performed (p < 0.05 significant) to assess significant differences between RV and LV T2, and between the different preparation pulses.Malcolm-Levitt (MLEV) T2 preparation pulses were implemented with two different schemes: 4 (MLEV4) and 8 refocusing pulses (MLEV8). Quantitative T2 maps (TR = 3099-3712 ms, FA = 40Phantom T2 values were: MESE T2 = 130 ms, MLEV4 = 101 ms and MLEV8 = 135 ms. Images from a volunteer are shown in Figure The standard T2 preparation pulse uses 4 refocusing pulses; wide pulse spacing increases flow sensitivity and leads to heterogeneity and signal loss in the blood pool at longer preparation times. We doubled the number of refocusing pulses to keep the pulse spacing short and minimize signal loss due to flow. Our preliminary results show increased T2 homogeneity within the LV blood pool, greater difference between venous and arterial T2, and blood T2 values that more closely match those previously reported. In future studies, the MLEV8 pulse will be further explored in vitro and in vivo for accurate calibration and estimation of %HbO2 from quantitative T2 maps.AHA 13PRE16950001.


Duchenne/Becker muscular dystrophy (D/BMD) is associated with early onset cardiomyopathy, with cardiac fibrosis amongst the earliest manifestations. Changes in conventional estimates of cardiac function  may occur late in Duchenne and Becker muscular dystrophy (DMD/BMD). Cardiac MRI tagging is a noninvasive imaging biomarker for quantifying ventricular dysfunction in DMD/BMD cardiomyopathy. In particular, estimates of ventricular rotational mechanics  may provide insight to early ventricular dysfunction. Furthermore, myocardial fibrosis in DMD/BMD patients is frequently reported and could significantly impact LV rotational mechanics. However, the functional consequences of myocardial fibrosis in these patients are incompletely understood. The objective of this study was to quantify LV rotational mechanics in pediatric DMD/BMD patients with normal EF (N-EF) or low EF (L-EF) and with (f+) or without (f-) fibrosis.Seventeen (N=17) male pediatric subjects (13.7±4.5 years old) genetically diagnosed with DMD/BMD consented to participate in an IRB approved study. Each patient underwent a cardiac 3T MRI exam that included evaluation of functional status with cine MRI, cardiac tagging MRI, and ventricular scar evaluation. Ten (M=10) non-aged-matched (29±4.3 years old) healthy volunteers were also evaluated to provide context for interpreting the pediatric data. LV mass, LVESV, LVEDV, and LVEF were calculated. The normal EF cut-off was >55.9% for 8-15 year-olds  and >53.2% for 16-20 year-olds :65-76). The presence or absence of myocardial fibrosis was determined by consensus agreement. Comparisons were made using t-tests with Holm-Sidak correction.-1. The table shows lower LV-PT and LV-NUR in the EF-n/f- group compared to controls. LV-PT and LV-NUR significantly decreased in the N-EF/f+ group. LV-PT and LV-NUR were further decreased in the L-EF/f+ and were lowest in the L-EF/f+ group. T-tests with Holm-Sidak correction showed significant difference between L-EF/f- and L-EF/f+ in LV-PT. No significant difference was detected for LV-NUR.The volunteers had LV peak twist (LV-PT) of 12.2 ± 2.6° and lower LV normalized untwist rate (LV-NUR) -12.5 ± 2.1° sLV-PT and LV-NUR are lower in patients with DMD/BMD despite normal EF, compared to the healthy volunteers. Both low EF and the presence of fibrosis are associated further decreased LV-PT and LV-NUR. Fibrosis alone has a significant effect on LV rotational mechanics and should be further evaluated.AHA 13BGIA14530010 to Daniel B. Ennis, AHA 11PRE6080005 to Meral L. Reyhan


Left ventricular ejection fraction (LVEF) is the primary risk stratification tool used for therapeutic decision making related to device therapy. However, an influence of right ventricular dysfunction on cardiovascular events is becoming apparent. The incremental prognostic value of right ventricular ejection fraction (RVEF) on future arrhythmic events among those being considered for device therapy has not been well examined. In this study we evaluate the significance of MRI-based measurement of RVEF versus other clinical and MRI-based variables for their ability to predict Sudden Cardiac Death (SCD) or Appropriate ICD therapy.Consecutive patients with cardiomyopathy were evaluated for device candidacy. All patients underwent a standard Late Gadolinium Enhancement (LGE) MRI protocol followed by a blinded core-laboratory based quantification of left ventricle (LV) and right ventricle (RV) volumes, ejection fraction (EF) and total hyperenhancement (HE). Patients were stratified according to the presence or absence of significant RV systolic dysfunction, defined as an RVEF ≤45%. All patients were followed for the occurrence of SCD or appropriate ICD therapy. The secondary outcome was heart failure admission or non-sudden cardiac death. All clinical and MRI-based variables were evaluated for associations with the primary and secondary outcomes with Cox proportional multivariable regression analysis also performed.A total of 318 patients  were followed over a median of 467 days. At the end of follow-up 49 patients (15.4%) suffered a primary outcome (10 SCD and 39 appropriate therapies). Baseline clinical characteristics were similar among those with and without the primary outcome with the exception of prior history of ventricular arrhythmia and ischemic etiology (p < 0.05). Following adjustment for etiology, LVEF, LVEDV, and Total HE, those with an RVEF≤45% were more likely to experience the primary outcome  and the secondary outcome  of interest.Patients with right ventricular dysfunction, defined as RVEF≤45% by cardiac MRI, are at an increased risk of future arrhythmic events. Similarly, these individuals are at an elevated risk of heart failure admission and non-sudden cardiac death.This research was supported by the Imaging in Cardiovascular Therapeutic grant from the Ontario Research Fund and the Canada Foundation of Innovation.


Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease  and myocardial infarction  with a mean LVEF of 59.9% ± 9.3%. The mean left ventricular mass index (LVMI) was 52.1 ± 21.2 g/m2.7 and 485 (48.2%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP  with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7% increase in LVMI  compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition.Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients ( Cytochrome P450 17A1 (CYP17A1) is a key enzyme in the synthesis and metabolism of steroid hormones. As a unique protein of the cytochrome P450 family it catalyzes two distinct types of substrate oxidation . This inIn the clinical context, CYP17A1 has primarily emerged as relevant for androgen dependent oncological diseases ,9,10. InThe evidence supporting a role of CYP17A1 in the cardiovascular field is still scarce. Notably, the first case report of 17alpha hydroxylase deficiency, published in the year 1966, already pointed to hypertension as a phenotypic characteristic . ConcordThe present study focused on 1007 patients with arterial hypertension and associated cardiovascular organ damage that were treated according to European guidelines . We testn = 883; 87.7%) and angiotensin-converting enzyme inhibitors .The characteristics of the study cohort are summarized in 2.7. Left ventricular hypertrophy defined as LVMI ≥ 50 g/m2.7 in men and ≥47 g/m2.7 in women was observed in 485 (48.2%) patients according to de Simone et al. [Echocardiographic parameters of the study cohort are demonstrated in e et al. . The meaThe polymorphisms rs619824, rs743572, rs1004467, rs11191548, and rs17115100 were analysed for their relations to mean systolic and diastolic 24 h BP and LVMI. Allele and genotype frequencies are indicated in Multivariate adjusted analyses resulted in no significant associations of any investigated SNP with mean 24 h systolic or diastolic BP. Further separate analysis for mean day-time or night-time blood pressure phenotypes also demonstrated no significant associations, respectively (not shown).p = 0.017). In analogue comparison the T allele of rs17115100 exhibited a trend to increased LVMI (p = 0.059). Correlation analyses of the SNP alleles with the use of betablockers or angiotensin-converting enzyme inhibitors in patients with LVH led to no significant results.Results of multivariate adjusted analyses are presented in 2.7 in men or ≥47 g/m2.7 in women [The present study aimed to investigate genetic associations of variants in or nearby the CYP17A1 gene with 24 h BP and left ventricular mass in treated high risk patients with arterial hypertension and associated cardiovascular organ damage. Thus, about four out of five patients had coronary heart disease and about a half had myocardial infarction at least one month before enrolment in the study. However, in agreement with the inclusion criteria in the study, left ventricular function was well preserved with a minimum LVEF of 40% in each patient and an overall mean LVEF of about 60% observed in the study. About half of all patients demonstrated left ventricular hypertrophy (LVH) defined as LVMI ≥ 50 g/min women .In the present study, there was no significant association of any investigated SNP with mean 24 h systolic or diastolic BP. For two of the five investigated SNPs , significant relations to BP have previously been described. Thus, two genome wide association studies (GWAS) with cohorts each consisting of more than 29 thousand subjects of European ancestry and which were heterogeneous for the presence of hypertension and antihypertensive treatment revealed significant associations with increased systolic BP for the A allele of rs1004467 . StudiesIn parallel to the GWAS results, a Chinese study including 3210 unrelated individuals from Beijing and Shanghai described the A allele of rs1004467 and the T allele of rs11191548 as significantly related to increased risk of hypertension. In two case-control studies with Chinese children, analogous associations of both alleles with increased systolic BP were only found in girls  or in thNevertheless, the relation of the rs1004467 A allele with increased systolic BP could not be replicated in a cohort of 3077 Chinese children . In contTherefore, results of different studies about the associations of the SNPs in CYP17A1 gene with BP are so far heterogeneous and seem to depend on the context of the study.Notably, in the present study, the C allele of rs11191548 was significantly related to a 7% increase in LVMI compared to non-carriers. Furthermore, rs17115100 indicated a trend of the T allele towards elevated LVMI. These findings are novel and emerged in a typical clinical setting because patients with arterial hypertension were under pharmacotherapy according to guidelines.2.7 for men, 47 g/m2.7 for women [Left ventricular mass may be considered as a parameter that integrates BP levels for the long-term and which is more resistant against transient influences than BP values. Moreover, increased LVMI above the cut-off values (50 g/mor women ) constitor women ,39. Notain vitro including the expression of hypertrophic markers such as A- or B-type natriuretic peptides  or cardiotrophin-1 [At the molecular level, CYP17A1 catalyses the metabolic pathway from pregnenolone to 17alpha hydroxy-pregnenolone which is an intermediate substance in the synthesis of cortisol and sex steroids. Competitive to this synthetic pathway pregnenolone can be metabolized to aldosterone . The molrophin-1 ,46. Therrophin-1 .Clinical studies consistently indicated positive correlations between plasma aldosterone levels and left ventricular mass in hypertensive patients ,50,51,52Overall, these experimental and clinical studies point to CYP17A1 as a key enzyme in the generation and metabolism of humoral factors which are involved in the pathogenesis of LVH. Accordingly, CYP17A1 has been discussed as drug target for treatment of hypertensive target organ damage .The present study describes the SNP rs11191548 as significantly associated with left ventricular mass in patients with hypertension under pharmacotherapy. Therefore, this SNP may be a relevant marker for the risk to develop LVH in an individual patient. Consequently, screening of patients may offer the possibility for a more personalized medicine in the future including the early onset of preventive strategies. Nevertheless, further studies are necessary to implement this concept.This study has important limitations. Left ventricular mass was calculated according to the American Society of Echocardiography-recommended formula for estimation of left ventricular mass from left ventricular linear dimensions . The forThe presented results raise the hypothesis that rs11191548 may influence the activity of CYP17A1. Nevertheless the underlying molecular mechanisms are so far unclear and should be clarified by experimental studies.et al. [2) = 186 × (serum creatinine in mg/dL)−1.154 × (age in years)−0.203 ×  × (1.210 if African-American). This study complies with the Declaration of Helsinki, written informed consent was obtained from all subjects, and the local Ethics Committee of the Campus Benjamin Franklin  approved the study protocol.In this study 1007 Caucasian subjects  who participated in a cardiological inpatient rehabilitation program were analysed. All patients had a diagnosis of arterial hypertension according to guidelines criteria defined as average BP of at least 140 mmHg systolic or at least 90 mmHg diastolic . All patet al. : eGFR  with the pre-designed tested assays from the manufacturer. More details are described in the supplemental digital content. Our overall combined genetic analyses included the independent analysis of recessive (YY vs. YX plus XX) and dominant (YX plus YY vs. XX) models.Genotyping for CYP17A1 polymorphisms was performed by PCR with the fluorescence based TaqManp less than 0.05 were considered statistically significant. Correlation analyses were performed using chi-squared tests or Fisher’s exact test, as appropriate. p-values below 0.05 were considered significant.All statistical analyses were carried out using SAS 9.2  or SPSS 20 .Parameters, indicated in As conclusion, the CYP17A1 polymorphism rs11191548 has been identified as associated with LVMI in high risk patients with arterial hypertension and associated organ damage. The result supports a role of CYP17A1 in the modulation of LVMI and thus cardiac hypertrophy in this clinical condition.