Synthesis and Investigation of 2,6-Bis(picrylamino)-3,5-dinitro-pyridine (PYX) and Its Salts.

2,6-Bis(picrylamino)pyridine (1; pre-PYX) and 2,6-bis(picrylamino)-3,5-dinitropyridine (2; PYX) were synthesized using an improved literature method. Compounds 1 and 2 were reinvestigated in detail and the X-ray structures (1: ρ=1.698 g cm(-3) at 173 K; 2: ρ=1.757 g cm(-3) at 298 K) are given. The reactions of 2 with different bases, such as alkali metal hydroxides (sodium, potassium, rubidium, cesium), and N-bases (ammonia, hydrazine, hydroxylamine, guanidinium carbonate, aminoguanidine bicarbonate) are reported, as well as metathesis reactions producing energetic salts. Several energetic compounds were synthesized and characterized for the first time using vibrational (IR, Raman) and multinuclear NMR spectroscopy, mass spectrometry, elemental analysis, and DSC. The crystal structures of four energetic salts were determined using low temperature single-crystal X-ray diffraction. Heats of formation for the metal-free species were calculated using the Gaussian 09 software. Detonation parameters were estimated using the EXPLO5 program. The sensitivities towards impact, friction, and electrostatic discharge were also determined.

Synthesis and Investigation of Advanced Energetic Materials Based on Bispyrazolylmethanes.

Herein we present the preparation and characterization of three new bispyrazolyl-based energetic compounds with great potential as explosive materials. The reaction of sodium 4-amino-3,5-dinitropyrazolate (5) with dimethyl iodide yielded bis(4-amino-3,5-dinitropyrazolyl)methane (6), which is a secondary explosive with high heat resistance (Tdec =310 °C). The oxidation of this compound afforded bis(3,4,5-trinitropyrazolyl)methane (7), which is a combined nitrogen- and oxygen-rich secondary explosive with very high theoretical and estimated experimental detonation performance (Vdet (theor)=9304 m s-1 versus Vdet (exp)=9910 m s-1 ) in the range of that of CL-20. Also, the thermal stability (Tdec =205 °C) and sensitivities of 7 are auspicious. The reaction of 6 with in situ generated nitrous acid yielded the primary explosive bis(4-diazo-5-nitro-3-oxopyrazolyl)methane (8), which showed superior properties to those of currently used diazodinitrophenol (DDNP).

Synthesis, characterisation and crystal structures of two bi-oxadiazole derivatives featuring the trifluoromethyl group.

The synthesis, characterisation, and crystal structure determination of the closely related compounds 3,3'-bi-(5-trifluoromethyl-1,2,4-oxadiazole) and 5,5'-bi-(2-trifluoromethyl-1,3,4-oxadiazole) are reported. These two compounds are known for their bioactivity; however, in this study they serve as model compounds to evaluate the suitability of the heterocyclic oxadiazole ring system for energetic materials when the fluorine atoms in the exocyclic CF3 groups are substituted successively by nitro groups. Quantum chemical calculations for the bi-1,3,4-oxadiazole derivatives with difluoronitromethyl, fluorodinitromethyl, and trinitromethyl groups have been carried out and predict promising energetic performances for both explosive and propulsive applications.

Effect of cardiac resynchronization therapy in patients without left intraventricular dyssynchrony.

AIMS: To evaluate the effects of cardiac resynchronization therapy (CRT) on long-term survival of patients without baseline left ventricular (LV) mechanical dyssynchrony. METHODS AND RESULTS: A total of 290 heart failure patients (age 67 ± 10 years, 77% males) without significant baseline LV dyssynchrony (<60 ms as assessed with tissue Doppler imaging) were treated with CRT. Patients were divided according to the median LV dyssynchrony measured after 48 h of CRT into two groups. All-cause mortality was compared between the subgroups. In addition, the all-cause mortality rates of these subgroups were compared with the all-cause mortality of 290 heart failure patients treated with CRT who showed significant LV dyssynchrony (≥60 ms) at baseline. In the group of patients without significant LV dyssynchrony, median LV dyssynchrony increased from 22 ms (inter-quartile range 16-34 ms) at baseline to 40 ms (24-56 ms) 48 h after CRT. The cumulative mortality rates at 1-, 2-, and 3-year follow-up of patients with LV dyssynchrony ≥40 ms 48 h after CRT implantation were significantly higher when compared with patients with LV dyssynchrony <40 ms (10, 17, and 23 vs. 3, 8, and 10%, respectively; log-rank P< 0.001). Finally, the cumulative mortality rates at 1-, 2-, and 3-year follow-up of patients with baseline LV dyssynchrony were 3, 8, and 11%, respectively (log-rank P= 0.375 vs. patients with LV dyssynchrony <40 ms). Induction of LV dyssynchrony after CRT was an independent predictor of mortality (hazard ratio: 1.247; P= 0.009). CONCLUSION: In patients without significant LV dyssynchrony, the induction of LV dyssynchrony after CRT may be related to a less favourable long-term outcome.

Synthesis and Investigation of 2,3,5,6-Tetra-(1H-tetrazol-5-yl)pyrazine Based Energetic Materials.

The structures and properties of several energetic compounds based on a high-nitrogen-content anion, namely 2,3,5,6-tetra(1H-tetrazol-5-yl)pyrazine (H4 TTP) are reported here for the first time. These energetic salts were synthesized by reacting H4 TTP with various alkali metal hydroxides (sodium, potassium, rubidium, caesium) and N-based (ammonia, hydrazine, hydroxylamine, guanidine carbonate, aminoguanidine bicarbonate). The resulting materials were comprehensively characterized by multinuclear (1 H, 13 C) NMR spectroscopy, infrared spectroscopy, elemental analysis, DSC, as well as low-temperature single-crystal X-ray diffraction. Heats of formation for the metal-free species as well as detonation parameters were calculated. The presented energetic materials (EMs) show high thermal stability (207 °C≤Tdec ≤300 °C), while the metal-free ionic derivatives exhibit desirable properties such as detonation velocity (6873 m s-1 ≤VC-J ≤8364 m s-1 ), detonation pressure (14.3 GPa≤pC-J ≤24.9 GPa), and specific impulse (141.4≤Isp ≤192.5 s).

A nitrogen-rich ligand as a scaffold for slow magnetic relaxation in dysprosium-based 0D and 1D architectures.

A recently designed nitrogen-rich ligand is successfully applied as a scaffold for lanthanide ions to show that the intricate chemistry of energetic materials can be combined with other fields of research, including that of molecular magnetism. Herein, we report the synthesis of two different types of molecular architectures using a single ligand template, in which the discrete monomer exhibits single-molecule magnet-like behaviour along with two well-isolated modes of magnetic relaxation.

5,5'-Bis(2,4,6-trinitrophenyl)-2,2'-bi(1,3,4-oxadiazole) (TKX-55): Thermally Stable Explosive with Outstanding Properties.

The novel, thermally stable explosive 5,5'-bis(2,4,6-trinitro-phenyl)-2,2'-bi(1,3,4-oxadiazole) (TKX-55) is reported. This compound can be prepared by means of a facile synthetic procedure and shows outstanding properties (detonation velocity, detonation pressure, sensitivity toward mechanical stimuli, and temperature of decomposition). TKX-55 was isolated and characterized by means of mass spectrometry, multinuclear (1 H, 13 C) NMR spectroscopy, and vibrational spectroscopy (IR and Raman). The structure in the crystalline state was determined by low-temperature single-crystal X-ray diffraction. From the calculated standard molar enthalpy of formation (CBS-4M) and the densities, the Chapman-Jouguet detonation properties were predicted by using the EXPLO5 V6.01 thermochemical computer code. The sensitivity of TKX-55 towards impact, friction, and electrostatic discharge was determined. The shock reactivity (explosiveness) of TKX-55 was measured by applying the small-scale shock reactivity test.

Detection of subtle left ventricular systolic dysfunction in patients with significant aortic regurgitation and preserved left ventricular ejection fraction: speckle tracking echocardiographic analysis.

AIMS: The aim of this study was to characterize left ventricular (LV) mechanics in symptomatic and asymptomatic patients with moderate-to-severe or severe aortic regurgitation (AR) and preserved ejection fraction (left ventricular ejection fraction) using two-dimensional speckle tracking echocardiography (2D-STE). The association between baseline LV strain and development of indications for surgery in asymptomatic patients was also evaluated. METHODS AND RESULTS: A total of 129 patients with moderate-to-severe or severe AR and LVEF >50% (age 55 ± 17 years, 64% male, 53% asymptomatic at baseline) were included. Standard echocardiography and 2D-STE were performed at baseline. Compared with asymptomatic patients, symptomatic patients had significantly impaired LV longitudinal (-14.9 ± 3.0 vs. -16.8 ± 2.5%, P < 0.001), circumferential (-17.5 ± 2.9 vs. -19.3 ± 2.8%, P = 0.001), and radial (35.7 ± 12.2 vs. 43.1 ± 14.7%, P = 0.004) strains. Among 49 asymptomatic patients who were followed up, 26 developed indications for surgery (symptoms onset or LVEF ≤50%). These patients had comparable LV volumes, LVEF, and colour Doppler assessments of AR jet at baseline, but more impaired LV longitudinal (P = 0.009) and circumferential (P = 0.017) strains compared with patients who remained asymptomatic. Impaired baseline LV longitudinal (per 1% decrease, HR = 1.21, P = 0.04) or circumferential (per 1% decrease, HR = 1.22, P = 0.04) strain was independently associated with the need for surgery. CONCLUSION: Multidirectional LV strain was more impaired in symptomatic than in asymptomatic patients with moderate-to-severe or severe AR, despite preserved LVEF. In asymptomatic AR patients, longitudinal and circumferential strains identified patients who would require surgery during follow-up.

Effect of cardiac resynchronization therapy on the sequence of mechanical activation assessed by two-dimensional radial strain imaging.

Cardiac resynchronization therapy (CRT) induces left ventricular (LV) reverse remodeling by synchronizing LV mechanical activation. We evaluated changes in segmental LV activation after CRT and related them to CRT response. A total of 292 patients with heart failure (65 ± 10 years, 77% men) treated with CRT underwent baseline echocardiographic assessment of LV volumes and ejection fraction. Time-to-peak radial strain was measured for 6 midventricular LV segments with speckle-tracking strain imaging. Moreover, the time difference between the peak radial strain of the anteroseptal and the posterior segments was calculated to obtain LV dyssynchrony. After 6 months, LV volumes, segmental LV mechanical activation timings, and LV dyssynchrony were reassessed. Response to CRT was defined as ≥15% decrease in LV end-systolic volume at 6-month follow-up. Responders (n = 177) showed LV resynchronization 6 months after CRT (LV dyssynchrony from 200 ± 127 to 85 ± 86 ms; p <0.001) by earlier activation of the posterior segment (from 438 ± 141 to 394 ± 132 ms; p = 0.001) and delayed activation of the anteroseptal segment (from 295 ± 155 to 407 ± 138 ms; p <0.001). In contrast, nonresponders (n = 115) experienced an increase in LV dyssynchrony 6 months after CRT (from 106 ± 86 to 155 ± 112 ms; p = 0.001) with an earlier activation of posterior wall (from 391 ± 139 to 355 ± 136 ms; p = 0.039) that did not match the delayed anteroseptal activation (from 360 ± 148 to 415 ± 122 ms; p = 0.001). In conclusion, responders to CRT showed LV resynchronization through balanced lateral and anteroseptal activations. In nonresponders, LV dyssynchrony remains, by posterior wall preactivation and noncompensatory delayed septal wall activation.

Left atrial function by two-dimensional speckle-tracking echocardiography in patients with severe organic mitral regurgitation: association with guidelines-based surgical indication and postoperative (long-term) survival.

BACKGROUND: Left atrial (LA) mechanics in patients with severe mitral regurgitation (MR) remain largely unexplored. The aim of the present evaluation was to assess the effect of severe MR on LA function, its potential relation with conventional surgical indications, and long-term postoperative survival. METHODS: Two-dimensional speckle-tracking strain and volumetric indices of LA reservoir, conduit, and contractile function were assessed in 121 patients with severe MR and 70 controls. Patients were divided according to the presence (n = 46) or absence (n = 75) of one or more guidelines-based criteria for mitral surgery (symptoms, left ventricular ejection fraction ≤ 60%, left ventricular end-systolic diameter ≥ 40 mm, atrial fibrillation, or systolic pulmonary arterial pressure >50 mm Hg). RESULTS: In patients with severe MR compared with controls, significant LA reservoir and contractile dysfunction was observed, which was more pronounced in patients with mitral surgery indication (P < .05 for all strain and volumetric indices). Of all indices of LA function, LA reservoir strain was an independent predictor (odds ratio, 0.88; 95% confidence interval, 0.82-0.94; P < .001) and had the highest accuracy to identify patients with indications for mitral surgery (area under the receiver operating characteristic curve, 0.8; 95% confidence interval, 0.72-0.87). A total of 117 patients underwent mitral valve surgery. Patients with LA reservoir strain ≤24% showed worse survival at a median of 6.4 years (interquartile range, 4.7-8.7 years) after mitral surgery (P = .02), regardless the symptomatic status before surgery. LA reservoir strain, on top of mitral surgery indications, provided incremental predictive value for postoperative survival. CONCLUSIONS: Impaired LA reservoir strain in patients with severe organic MR relates to long-term survival after mitral valve surgery, independently of and incremental to current guidelines-based indications for mitral surgery.

Global longitudinal strain predicts left ventricular dysfunction after mitral valve repair.

AIMS: Despite a successful surgical procedure and adherence to current recommendations, postoperative left ventricular (LV) dysfunction after mitral valve repair (MVr) for organic mitral regurgitation (MR) may still occur. New approaches are therefore needed to detect subclinical preoperative LV dysfunction. LV global longitudinal strain (GLS), assessed with speckle-tracking echocardiographic analysis, has been proposed as a novel measure to better depict latent LV dysfunction. The aim of this study was to investigate the value of GLS to predict long-term LV dysfunction after MVr. METHODS AND RESULTS: A total of 233 patients (61% men, 61 ± 12 years) with moderate-severe organic MR who underwent successful MVr between 2000 and 2009 were included. Echocardiography was performed at baseline and long-term follow-up (34 ± 20 months) after MVr. LV dysfunction at follow-up was defined as LV ejection fraction (EF) <50% and was present in 29 (12%) patients. A cut-off value of -19.9% of GLS showed a sensitivity and specificity of 90 and 79% to predict long-term LV dysfunction. By univariate logistic regression analysis, baseline LVEF ≤60%, LV end-systolic diameter (ESD) ≥40 mm, atrial fibrillation, presence of symptoms, and GLS >-19.9% were predictors of long-term LV dysfunction. By multivariate analysis, GLS remained an independent predictor of LV dysfunction (odds ratio 23.16, 95% confidence interval: 6.53-82.10, P < 0.001), together with LVESD. CONCLUSION: In a large series of patients operated within the last decade, MVr resulted in a low incidence of long-term LV dysfunction. A GLS of >-19.9% demonstrated to be a major independent predictor of long-term LV dysfunction after adjustment for parameters currently implemented into guidelines.

Accuracy of three-dimensional versus two-dimensional echocardiography for quantification of aortic regurgitation and validation by three-dimensional three-directional velocity-encoded magnetic resonance imaging.

Quantitative assessment of aortic regurgitation (AR) remains challenging. The present study evaluated the accuracy of 2-dimensional (2D) and 3-dimensional (3D) transthoracic echocardiography (TTE) for AR quantification, using 3D 3-directional velocity-encoded magnetic resonance imaging (VE-MRI) as the reference method. Thirty-two AR patients were included. With color Doppler TTE, 2D effective regurgitant orifice area (EROA) was calculated using the proximal isovelocity surface area method. From the 3D TTE multiplanar reformation data, 3D-EROA was calculated by planimetry of the vena contracta. Regurgitant volumes (RVol) were obtained by multiplying the 2D-EROA and 3D-EROA by the velocity-time integral of AR jet and compared with that obtained using VE-MRI. For the entire population, 3D TTE RVol demonstrated a strong correlation and good agreement with VE-MRI RVol (r = 0.94 and -13.6 to 15.6 ml/beat, respectively), whereas 2D TTE RVol showed a modest correlation and large limits of agreement with VE-MRI (r = 0.70 and -22.2 to 32.8 ml/beat, respectively). Eccentric jets were noted in 16 patients (50%). In these patients, 3D TTE demonstrated an excellent correlation (r = 0.95) with VE-MRI, a small bias (0.1 ml/beat) and narrow limits of agreement (-18.7 to 18.8 ml/beat). Finally, the kappa agreement between 3D TTE and VE-MRI for grading of AR severity was good (k = 0.96), whereas the kappa agreement between 2D TTE and VE-MRI was suboptimal (k = 0.53). In conclusion, AR RVol quantification using 3D TTE is accurate, and its advantage over 2D TTE is particularly evident in patients with eccentric jets.

Changes in left ventricular function after mitral valve repair for severe organic mitral regurgitation.

BACKGROUND: Limited data are available on the changes in left ventricular (LV) contractile function at long-term follow-up after mitral valve repair (MVr). Moreover, assessment of LV systolic function in patients undergoing MVr is troublesome with current methods, given that mitral regurgitation is characterized by increased preload and decreased afterload, potentially masking LV dysfunction. The aim of this study was to assess the value of LV global strain (longitudinal and circumferential) measured by speckle tracking analysis for detecting changes in contractile function after MVr. METHODS: A total of 122 patients with organic mitral regurgitation who underwent successful MVr at an early stage (LV ejection fraction>60%, LV end-systolic diameter<40 mm) were included. Echocardiography was performed at baseline and at short-term (∼7 days) and long-term (1 to 3 years) follow-up after MVr. RESULTS: At baseline, LV ejection fraction and LV global strain were higher in patients than in 40 normal control individuals. By contrast, LV forward stroke volume was higher in control individuals than in patients. At short-term follow-up, a significant decrease in LV ejection fraction and LV global strain was noted as a consequence of changes in loading conditions. At long-term follow-up, LV ejection fraction and LV global strain improved significantly. Correction of LV strain for LV size showed a subtle impairment of myocardial contractility at baseline, which significantly improved over time after MVr, together with the improvement in LV forward stroke volume. CONCLUSIONS: Mitral valve repair for organic mitral regurgitation results in a significant increase in LV myocardial contractility as measured by LV global strain corrected by LV size.

Myocardial structural alteration and systolic dysfunction in preclinical hypertrophic cardiomyopathy mutation carriers.

BACKGROUND: To evaluate the presence of myocardial structural alterations and subtle myocardial dysfunction during familial screening in asymptomatic mutation carriers without hypertrophic cardiomyopathy (HCM) phenotype. METHODS AND FINDINGS: Sixteen HCM families with pathogenic mutation were studied and 46 patients with phenotype expression (Mut+/Phen+) and 47 patients without phenotype expression (Mut+/Phen-) were observed. Twenty-five control subjects, matched with the Mut+/Phen- group, were recruited for comparison. Echocardiography was performed to evaluate conventional parameters, myocardial structural alteration by calibrated integrated backscatter (cIBS) and global and segmental longitudinal strain by speckle tracking analysis. All 3 groups had similar left ventricular dimensions and ejection fraction. Basal anteroseptal cIBS was the highest in Mut+/Phen+ patients (-14.0±4.6 dB, p<0.01) and was higher in Mut+/Phen- patients as compared to controls (-17.0±2.3 vs. -22.6±2.9 dB, p<0.01) suggesting significant myocardial structural alterations. Global and basal anteroseptal longitudinal strains (-8.4±4.0%, p<0.01) were the most impaired in Mut+/Phen+ patients as compared to the other 2 groups. Although global longitudinal strain was similar between Mut+/Phen- group and controls, basal anteroseptal strain was lower in Mut+/Phen- patients (-14.1±3.8%, p<0.01) as compared to controls (-19.9±2.9%, p<0.01), suggesting a subclinical segmental systolic dysfunction. A combination of >-19.0 dB basal anteroseptal cIBS or >-18.0% basal anteroseptal longitudinal strain had a sensitivity of 98% and a specificity of 72% in differentiating Mut+/Phen- group from controls. CONCLUSION: The use of cIBS and segmental longitudinal strain can differentiate HCM Mut+/Phen- patients from controls with important clinical implications for the family screening and follow-up of these patients.

Myocardial collagen turnover after surgical ventricular restoration in heart failure patients.

AIMS: Surgical ventricular restoration (SVR) aims to normalize left ventricular (LV) volume and shape in patients with ischaemic cardiomyopathy and anterior wall scar. The chronic effects on LV function may depend on alterations in myocardial collagen metabolism. The present study evaluated myocardial collagen synthesis and degradation rates at baseline and at 6 months follow-up after SVR. We hypothesize that the chronic effects of SVR on LV function and clinical outcome depend on alterations in myocardial collagen metabolism. METHODS AND RESULTS: Serum levels of aminoterminal propeptides of type I and III collagen (PINP, PIIINP), carboxyterminal telopeptide of type I collagen (ICTP), and tenascin-C (TNC) were measured at baseline and 6 months after SVR in 24 patients. In addition, New York Heart Association (NYHA) functional class, LV volumes and function were evaluated. At follow-up, a significant improvement in NYHA class (from 3.2 ± 0.8 to 1.4 ± 0.6, P< 0.001) and LV ejection fraction (from 28 ± 9 to 35 ± 7%, P< 0.001) was found, whereas E/A ratio tended to increase (from 1.4 ± 1.1 to 1.9 ± 1.1, P= 0.064). Serum levels of PINP, PIIINP, ICTP, and TNC increased significantly (PINP: from 37 ± 15 to 67 ± 26 µg/L, P< 0.001; PIIINP: from 4.9 ± 1.7 to 7.9 ± 4.0 µg/L, P< 0.001; ICTP: from 5.9 ± 3.7 to 10.0 ± 5.3 µg/L, P< 0.001; TNC: from 30 ± 20 to 44 ± 23 µg/L, P= 0.020). At follow-up, an LV ejection fraction <34% and E/A ratio ≥ 2.0 were significantly associated with increased serum levels of PIIINP and ICTP. CONCLUSION: In patients who underwent SVR, myocardial collagen metabolism was significantly enhanced 6 months after surgery. Serum levels of myocardial collagen turnover biomarkers were related to post-surgical LV systolic and diastolic function.

Prediction of response to cardiac resynchronization therapy combining two different three-dimensional analyses of left ventricular dyssynchrony.

Triplane tissue synchronization imaging (TSI) and real-time 3-dimensional echocardiography (RT3DE) provide different characterizations of left ventricular (LV) mechanics and dyssynchrony. Triplane TSI assesses differences in time to peak systolic segmental myocardial tissue velocities, whereas RT3DE evaluates differences in time to minimum end-systolic regional volumes. Whether an approach using the 2 3D techniques predicts better significant reverse remodeling after cardiac resynchronization therapy (CRT) remains unknown. In 166 patients (mean age 66 ± 9 years, 78% men) treated with CRT, baseline LV dyssynchrony was assessed using RT3DE and triplane TSI. LV dyssynchrony was defined by a systolic dyssynchrony index ≥6.4% when assessed with RT3DE and SD of time to peak velocity of 12 segments (Ts-SD-12) ≥33 ms with triplane TSI. CRT response was defined by ≥15% decrease in LV end-systolic volume at 6-month follow-up. Mean LV dyssynchrony using Ts-SD-12 was 48 ± 26 ms and mean systolic dyssynchrony index was 8.51 ± 3.81%. Response to CRT was observed in 86.3% of patients showing LV dyssynchrony with the 2 methods. In contrast, 97% of patients who did not show significant LV dyssynchrony with any of the techniques were nonresponders (p <0.001). Importantly, systolic dyssynchrony index and LV dyssynchrony using Ts-SD-12 were independent predictors of response to CRT (p <0.001 for each technique). Assessment of LV dyssynchrony with the 2 techniques showed incremental value for prediction of significant LV reverse remodeling over its assessment with only 1 technique (chi-square 90.18, p <0.001). In conclusion, the combined use of 2 different 3D techniques to assess LV dyssynchrony permits accurate prediction of response to CRT.

Surgical ventricular restoration for patients with ischemic heart failure: determinants of two-year survival.

BACKGROUND: Surgical ventricular restoration (SVR) improves left ventricular (LV) systolic function by partially restoring the normal geometry of the left ventricle. However, the beneficial effects of this surgical procedure on long-term clinical outcome remain controversial. The present study aimed to evaluate the independent determinants of 2-year morbidity and mortality rates after SVR. METHODS: Seventy-nine patients with ischemic heart disease and LV ejection fraction of 0.35 or less were included. All patients underwent SVR and additionally coronary artery bypass grafting or mitral valve surgery if clinically indicated. Clinical and echocardiographic examination was performed before SVR and at 6 months' follow-up. The primary end point was a composite of all-cause mortality and hospitalizations for heart failure. RESULTS: At 6 months' follow-up a significant improvement in heart failure symptoms was noted. In addition, LV ejection fraction increased from 0.27 ± 0.07 to 0.36 ± 0.10 (p < 0.001). During a median follow-up of 2.7 years, the primary end point was recorded in 22% of the patients. Baseline New York Heart Association functional class IV and a 6-month follow-up LV end-systolic volume index of at least 60 mL/m(2) were independently associated with worse outcome (hazard ratio, 5.4; 95% confidence interval, 1.9 to 15.2; p < 0.001; hazard ratio, 2.7; 95% confidence interval, 1.3 to 5.6; p < 0.001, respectively). CONCLUSIONS: Advanced heart failure status at baseline and large residual postsurgery LV end-systolic volume index were independently associated with increased mortality and heart failure hospitalization rates at 2 years' follow-up after SVR.