Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3-Year Results of the SUCCOUR Trial.

BACKGROUND: Global longitudinal strain (GLS) can predict cancer therapeutics-related cardiac dysfunction and guide initiation of cardioprotection (CPT). OBJECTIVES: In this study, the authors sought to determine whether echocardiography GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care at 3 years. METHODS: In this international multicenter prospective randomized controlled trial, patients were enrolled from 28 international sites. All patients treated with anthracyclines with another risk factor for heart failure were randomly allocated to GLS-guided (>12% relative reduction in GLS) or ejection fraction (EF)-guided (>10% absolute reduction of EF to <55%) CPT. The primary end point was the change in 3-dimensional (3D) EF (ΔEF) from baseline to 3 years. RESULTS: Among 331 patients enrolled, 255 (77%, age 54 ± 12 years, 95% women) completed 3-year follow-up (123 in the EF-guided group and 132 in the GLS-guided group). Most had breast cancer (n = 236; 93%), and anthracycline followed by trastuzumab was the most common chemotherapy regimen (84%). Although 67 (26%) had hypertension and 32 (13%) had diabetes mellitus, left ventricular function was normal at baseline (EF: 59% ± 6%, GLS: 20.7% ± 2.3%). CPT was administered in 18 patients (14.6%) in the EF-guided group and 41 (31%) in the GLS-guided group (P = 0.03). Most patients showed recovery in EF and GLS after chemotherapy; 3-year ΔEF was -0.03% ± 7.9% in the EF-guided group and -0.02% ± 6.5% in the GLS-guided (P = 0.99) group; respective 3-year EFs were 58% ± 6% and 59% ± 5% (P = 0.06). At 3 years, 17 patients (5%) had cancer therapeutics-related cardiac dysfunction (11 in the EF-guided group and 6 in the GLS guided group; P = 0.16); 1 patient in each group was admitted for heart failure. CONCLUSIONS: Among patients taking potentially cardiotoxic chemotherapy for cancer, the 3-year data showed improvement of LV dysfunction compared with 1 year, with no difference in ΔEF between GLS- and EF-guided CPT. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628).

Assessment of Left Ventricular Reverse Remodeling by Cardiac MRI in Patients Undergoing Repair Surgery for Severe Aortic or Mitral Regurgitation.

OBJECTIVE: To evaluate left ventricular (LV) reverse remodeling after repair surgery for mitral regurgitation (MR) or aortic regurgitation (AR), aiming at determining optimal preoperative thresholds for normalization of LV volumes and function after surgery. DESIGN: Observational prospective cohort study. SETTING: Single-center, academic, tertiary care cardiovascular center. PARTICIPANTS: Patients and volunteers. INTERVENTIONS: Cardiac magnetic resonance with measurement of indexed LV end-diastolic volume (LVEDVi) and end-systolic volume (LVESVi), mass (LVmassi), and ejection fraction (LVEF) was performed preoperatively and postoperatively. MEASUREMENTS AND MAIN RESULTS: The authors included 29 patients with AR and 59 patients with MR (46 ± 12 and 56 ± 12 years, follow-up 222 ± 57 days). Both AR and MR repair resulted in a significant reduction of LV volumes and mass (respectively, delta change in LVEDVi -55 mL/m² and -43 mL/m²; in LVESVi -26 mL/m² and -10 mL/m²; and in LVmassi -24 g/m² and -12 g/m²; p < 0.001 for all). Yet despite the absence of perioperative necrosis, 7 (24%) patients with AR had persistent LV dilatation (LVEDVi >106 mL/m²) relative to controls and 16 (27%) patients with MR developed systolic LV dysfunction (LVEF <50%) postoperatively. Binary logistic regression analysis indicated preoperative LV volumes as the most accurate parameter for predicting both incomplete LV reverse remodeling in AR and LV dysfunction in MR. Receiver operating characteristic-determined thresholds were LVEDVi >155 mL/m² for AR and >129 mL/m² for MR. CONCLUSION: Although both AR and MR repair allow significant reverse postoperative LV remodeling, persistent LV dilatation after AR correction and systolic LV dysfunction after MR repair are common and best predicted by increased preoperative LV volumes. This highlights the importance of considering LV volumes in the decision-making process.

Late diagnosis of a congenitally corrected transposition of the great arteries discovered at pacemaker implantation in a patient previously diagnosed with dextrocardia and situs solitus.

Congenitally corrected transposition of the great arteries (CCTGA) should not be missed in patients with dextrocardia and situs solitus. We report a case of a 56-year-old man with late diagnosis of CCTGA after ventricular lead replacement. Free LV wall pacing may be favorable in these patients so to prevent deterioration of the systemic RV function.

Prognostic significance of LGE by CMR in aortic stenosis patients undergoing valve replacement.

BACKGROUND: Prior studies have shown that late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) can detect focal fibrosis in aortic stenosis (AS), suggesting that it might predict higher mortality risk. OBJECTIVES: This study was conducted to evaluate whether LGE-CMR can predict post-operative survival in patients with severe AS undergoing aortic valve replacement (AVR). METHODS: We prospectively evaluated survival (all-cause and cardiovascular disease related) according to LGE-CMR status in 154 consecutive AS patients (96 men; mean age: 74 ± 6 years) without a history of myocardial infarction undergoing surgical AVR and in 40 AS patients undergoing transcatheter aortic valve replacement (TAVR). RESULTS: LGE was present in 29% of patients undergoing surgical AVR and in 50% undergoing TAVR. During a median follow-up of 2.9 years, 21 patients undergoing surgical AVR and 20 undergoing TAVR died. In surgical AVR, the presence of LGE predicted higher post-operative mortality (odds ratio: 10.9; 95% confidence interval [CI]: 1.2 to 100.0; p = 0.02) and worse all-cause survival (73% vs. 88%; p = 0.02 by log-rank test) and cardiovascular disease related survival (85% vs. 95%; p = 0.03 by log-rank test) on 5-year Kaplan-Meier estimates of survival after surgical AVR. Multivariate Cox analysis identified the presence of LGE (hazard ratio: 2.8; 95% CI: 1.3 to 6.9; p = 0.025) and New York Heart Association functional class III/IV (hazard ratio: 3.2; 95% CI: 1.1 to 8.1; p < 0.01) as the sole independent predictors of all-cause mortality after surgical AVR. The presence of LGE also predicted higher all-cause mortality (p = 0.05) and cardiovascular disease related mortality (p = 0.03) in the subgroup of patients without angiographic coronary artery disease (n = 110) and higher cardiovascular disease related mortality in 25 patients undergoing transfemoral TAVR. CONCLUSIONS: The presence of LGE indicating focal fibrosis or unrecognized infarct by CMR is an independent predictor of mortality in patients with AS undergoing AVR and could provide additional information in the pre-operative evaluation of risk in these patients.

Impact of preoperative symptoms on postoperative survival in severe aortic stenosis: implications for the timing of surgery.

BACKGROUND: The impact of symptoms on the natural history of patients with severe aortic stenosis (SAS) has been well documented. By contrast, the implications of preoperative symptoms on postoperative outcomes remain poorly defined. METHODS: The long-term survival of 812 patients greater than 65 years old with SAS undergoing bioprosthetic aortic valve replacement (AVR) was analyzed according to their preoperative symptoms. RESULTS: Operative mortality was larger in New York Heart Association (NYHA) III-IV than in NYHA I-II patients (10% vs 6%, p = 0.036). Abrupt symptomatic deterioration from NYHA I to NYHA III-IV within the month preceding surgery was observed in 18% of NYHA III-IV patients and resulted in an increased operative mortality (17% vs 5% in NYHA I, p = 0.035). Long-term survival was also significantly worse in NYHA III-IV than in NYHA I-II patients (56% vs 72%, p = 0.002). Reduced long-term survival of NYHA III/IV patients was observed in subgroups with a left ventricular ejection fraction (LVEF) 0.50 or greater (58 vs. 74%, p = 0.008) and in those with a systolic pulmonary artery pressure (SPAP) less than 40 mm Hg (60% vs 74%, p = 0.014). By contrast, the presence of class III-IV symptoms did not influence outcome in patients with a LVEF less than 0.50 (51 vs. 55%, p = 0.34) or with a SPAP 40 mm Hg or greater (43% vs 48%, p = 0.78). CONCLUSIONS: In patients with SAS, preoperative NYHA III-IV symptoms, particularly of recent onset, are independently associated with excess short- and long-term postoperative mortality. This was particularly evident in patients with normal LV function or pulmonary artery pressures. These findings plead in favor of an earlier surgical correction of SAS, before the onset of severe symptoms, especially in low-risk patients.

Aortic valve area, stroke volume, left ventricular hypertrophy, remodeling, and fibrosis in aortic stenosis assessed by cardiac magnetic resonance imaging: comparison between high and low gradient and normal and low flow aortic stenosis.

BACKGROUND: Recent works using echocardiography suggested that low gradient (LG), low flow (LF) aortic stenosis (AS) has more pronounced left ventricular (LV) concentric remodeling, smaller LV cavity size, and more interstitial fibrosis compared with high gradient (HG) normal flow (NF) AS. Therefore, we evaluated the accuracy of echocardiographic measurements and compared remodeling and fibrosis in different types of AS by cardiac magnetic resonance (CMR). METHODS AND RESULTS: A total of 128 patients (73±11 years of age; 75 men) with aortic valve area (AVA) <0.6 cm(2)/m(2) and ejection fraction >50% by echocardiography underwent CMR to measure planimetric AVA, phase-contrast indexed stroke volume, LV mass, and focal fibrosis. Using <40 mm Hg and indexed stroke volume <35 mL/m(2) by echocardiography as criteria for LG and LF, 69 (54%) patients were HG/NF, 28 (22%) HG/LF, 17 (13%) LG/NF, and 14 (11%) LG/LF AS. LV outflow tract area, indexed stroke volume, and AVA correlated well between echocardiography and CMR (r=0.7, 0.61, and 0.65, respectively; P<0.001 for all). By CMR, however, planimetric AVA was larger in LF/LG (0.54±0.08 cm(2)/m(2)) and LG/NF (0.61±0.08 cm(2)/m(2)) than in HG/LF (0.46±0.07 cm(2)/m(2); P<0.05) AS, and indexed LV mass was lower in LG/LF (75±12 g/m(2)) and LG/NF (81±18 g/m(2)) than in HG/LF (100±27 g/m(2); P<0.05) AS. All groups of AS had similar LV volumes, predominantly concentric hypertrophy remodeling, and similar amounts of focal fibrosis. CONCLUSIONS: CMR confirmed overall accuracy of echocardiographic classification of AS but demonstrated that LG/LF and LG/NF AS have larger AVA, less LV hypertrophy, and similar focal fibrosis compared with HG/LF AS. This challenges the view that LG/LF AS is a more advanced state of AS.

Evaluation of aortic bioprosthesis stenosis by multidetector CT.

Because visualization the bioprosthesis leaflets is often hampered by shadowing artifacts from to the metal in the annulus or the struts, visualization and determination of the etiology of bioprosthesis valve dysfunction may be often difficult by transthoracic and even transesophageal echocardiography. We demonstrate two cases in which 256 slice-multidetector row computed tomography was able to visualize acute aortic bioprosthesis thrombosis. In the first case we could demonstrate thrombosis of the valve by comparing images to a computed tomography exam performed 4 months earlier. In the second case we demonstrate the disappearance the thrombus and normalization of restrained valve opening in a follow-up CT study, performed after 2 months of oral anticoagulation.

Iron overload in polytransfused patients without heart failure is associated with subclinical alterations of systolic left ventricular function using cardiovascular magnetic resonance tagging.

BACKGROUND: It remains incompletely understood whether patients with transfusion related cardiac iron overload without signs of heart failure exhibit already subclinical alterations of systolic left ventricular (LV) dysfunction. Therefore we performed a comprehensive evaluation of systolic and diastolic cardiac function in such patients using tagged and phase-contrast CMR. METHODS: 19 patients requiring regular blood transfusions for chronic anemia and 8 healthy volunteers were investigated using cine, tagged, and phase-contrast and T2* CMR. LV ejection fraction, peak filling rate, end-systolic global midventricular systolic Eulerian radial thickening and shortening strains as well as left ventricular rotation and twist, mitral E and A wave velocity, and tissue e' wave and E/e' wave velocity ratio, as well as isovolumic relaxation time and E wave deceleration time were computed and compared to cardiac T2*. RESULTS: Patients without significant iron overload (T2* > 20 ms, n = 9) had similar parameters of systolic and diastolic function as normal controls, whereas patients with severe iron overload (T2* < 10 ms, n = 5), had significant reduction of LV ejection fraction (54 ± 2% vs. 62 ± 6% and 65 ± 6% respectively p < 0.05), of end-systolic radial thickening (+6 ± 4% vs. +11 ± 2 and +11 ± 4% respectively p < 0.05) and of rotational twist (1.6 ± 0.2 degrees vs. 3.0 ± 1.2 and 3.5 ± 0.7 degrees respectively, p < 0.05) than patients without iron overload (T2* > 20 ms) or normal controls. Patients with moderate iron overload (T2* 10-20 ms, n = 5), had preserved ejection fraction (59 ± 6%, p = NS vs. pts. with T2* > 20 ms and controls), but showed reduced maximal LV rotational twist (1.8 ± 0.4 degrees). The magnitude of reduction of LV twist (r = 0.64, p < 0.001), of LV ejection fraction (r = 0.44, p < 0.001), of peak radial thickening (r = 0.58, p < 0.001) and of systolic (r = 0.50, p < 0.05) and diastolic twist and untwist rate (r = -0.53, p < 0.001) in patients were directly correlated to the logarithm of cardiac T2*. CONCLUSION: Multiple transfused patients with normal ejection fraction and without heart failure have subclinical alterations of systolic and diastolic LV function in direct relation to the severity of cardiac iron overload. Among all parameters, left ventricular twist is affected earliest, and has the highest correlation to log (T2*), suggesting that this parameter might be used to follow systolic left ventricular function in patients with iron overload.

Incidence, determinants, and prognostic impact of operative refusal or denial in octogenarians with severe aortic stenosis.

BACKGROUND: Aortic stenosis (AS) is a common valve disease in octogenarians. Previous studies have shown that aortic valve replacement (AVR) is frequently not performed in these patients. This study investigated the incidence, determinants, and prognostic impact of AVR refusal or denial in these patients. METHODS: Between 2000 and 2007, 163 octogenarians (mean age, 84 ± 3 years) with severe AS and an indication for operation according to guidelines were prospectively included in an echocardiographic registry. Among these, 97 underwent AVR, and 66 were treated conservatively. RESULTS: Logistic regression analysis identified older age, a lower transaortic pressure gradient, a larger aortic valve area, and the presence of diabetes as independent predictors of AVR refusal or denial. Patients who underwent AVR had a 30-day mortality of 9%. Overall 5-year survival was 66% in AVR patients vs 31% in those treated conservatively (log rank p < 0.001 vs AVR). After adjustment for the propensity score, patients undergoing AVR still had a better outcome than conservatively treated patients (hazard ratio, 0.56; 95% confidence interval, 0.29 to 0.91; p = 0.022). In addition to the therapeutic decision, Cox regression analysis also identified low body weight, New York Heart Association class III/IV, and the logistic European System for Cardiac Operative Risk Evaluation as independent predictors of outcome in the overall series. CONCLUSIONS: About 40% of octogenarians with severe AS and a definite indication for operation either refuse or are denied AVR. AVR refusal or denial has a profound impact on long-term prognosis, resulting in a twofold excess mortality, even after adjustment for the propensity score.