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Butler J.,Emory University | Fonarow G.C.,University of California at Los Angeles | Zile M.R.,Medical University of South Carolina | Lam C.S.,National University of Singapore | And 28 more authors.
JACC: Heart Failure | Year: 2014

The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the Food and Drug Administration and included representatives from academia, industry, and regulatory agencies. This document summarizes the proceedings from this meeting. © 2014 American College of Cardiology Foundation.


Jasaityte R.,Catholic University of Leuven | Claus P.,Catholic University of Leuven | Teske A.J.,Catholic University of Leuven | Teske A.J.,University Utrecht | And 7 more authors.
JACC: Cardiovascular Imaging | Year: 2013

Objectives: The aim of this study was to test the hypothesis that the noninvasively constructed slope of the relationship between left ventricular (LV) regional systolic strain and stretch during atrial contraction represents LV inotropic state. Background: LV systolic response to a changing preload depends on its inotropic state. Changing the preload has allowed constructing the slope of the end-systolic pressure-volume relationship that is used as an invasive measurement of LV inotropy. We assumed that the slope of the relationship between regional systolic LV strain (total-S) and stretch during atrial contraction (preS) depends on the LV inotropic state as well and can thus be used as a LV inotropy index. Methods: Strain curves (tissue Doppler) were extracted from 27 healthy individuals to determine the normal stretch-strain relationship at rest, during a low-dose dobutamine (LD) challenge and during passive leg-lift (LL). The method was also applied in 7 patients with breast cancer before and after chemotherapy with anthracyclines. Results: PreS and total-S correlated closely in all subjects (r = 0.82). Total-S values increased (p < 0.05) with LD (-20.44 ± 3.89% vs. -24.24 ± 5.55%) and LL (-19.65 ± 3.77% vs. -24.05 ± 3.67%), whereas preS increased only with LL (5.96 ±1.72% vs. 8.61 ± 2.18%), but not with LD (6.83 ± 2.34% vs. 7.29 ± 2.24%). No changes of total-S or preS were observed after the exposure to chemotherapy (-21.23 ± 2.93% vs. -21.49 ± 2.89% and 8.11 ± 1.03% vs. 8.59 ± 1.73%, respectively). The slope of stretch-strain relationship got steeper with LD (-1.47 ± 0.36 vs. -2.34 ± 0.36, p < 0.05), declined after the chemotherapy (-1.68 ± 0.15 to -0.86 ± 0.23, p < 0.05) and did not change with LL (-1.39 ± 0.57 vs. -1.51 ± 0.38, p = NS). Conclusions: The slope of the regional stretch-strain relationship can be regarded as a noninvasive index of myocardial inotropic state. It gets steeper with increasing inotropy, does not change with preload induced changes of LV systolic function, and flattens after the exposure to a cardiotoxic drug. © 2013 American College of Cardiology Foundation.


Chioncel O.,Institute of Emergency for Cardiovascular Diseases | Ambrosy A.P.,Stanford University | Filipescu D.,Institute of Emergency for Cardiovascular Diseases | Bubenek S.,Institute of Emergency for Cardiovascular Diseases | And 5 more authors.
Journal of Cardiovascular Medicine | Year: 2015

Aim The present study aims to describe the epidemiology, baseline clinical characteristics, in-hospital management, and outcome of patients hospitalized for heart failure admitted directly or transferred to the ICU. Methods and results The Romanian Acute Heart Failure Syndromes (RO-AHFS) registry prospectively enrolled 3224 consecutive patients between January 2008 and May 2009 admitted with a primary diagnosis of heart failure. Participants were classified by ICU admission status (i.e. ICU+/ICU-). Independent clinical predictors of ICU admission and in-hospital mortality were identified using multivariable logistic regression analysis. Overall, 10.7% of patients required ICU level care, 32% as a direct ICU admission, with 68% as an ICU transfer during hospitalization. Patients admitted to the ICU had a mean age of 68.1±11.3 years, 61% were men, 67% had an ischemic cause, and 44% presented with de-novo heart failure. ICU+ patients more frequently presented with low SBP and pulse pressure and abnormal renal function. Mechanical ventilation was required in 32.7% and intravenous inotropes were administered to 56.7% of ICU+ patients. ICU+ patients had higher in-hospital mortality compared to ICU-patients (17.3 vs. 6.5%). Patients admitted directly to the ICU had a 15.3% mortality rate compared to 18.4% in those transferred after admission. Age, serum sodium, SBP below 110 mmHg, and left-ventricular ejection fraction less than 45% were predictive of ICU admission, whereas for ICU+ patients, age, vasopressor, and mechanical ventilation utilization were predictive of mortality. Conclusions Patients admitted directly or transferred to the ICU are at a high risk of in-hospital mortality. Clinical variables commonly measured at the time of admission may facilitate disposition decision-making including early triage to the ICU. © Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Erven K.,University Hospital Gasthuisberg | Jurcut R.,Institute of Emergency for Cardiovascular Diseases | Weltens C.,University Hospital Gasthuisberg | Giusca S.,Institute of Emergency for Cardiovascular Diseases | And 4 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2011

Purpose: To investigate the occurrence of early radiation-induced changes in regional cardiac function using strain rate imaging (SRI) by tissue Doppler echocardiography. Methods and Materials: We included 20 left-sided and 10 right-sided breast cancer patients receiving radiotherapy (RT) to the breast or chest wall. Standard echocardiography and SRI were performed before RT (baseline), immediately after RT (post-RT), and at 2 months follow-up (FUP) after RT. Regional strain (S) and strain rate (SR) values were obtained from all 18 left ventricular (LV) segments. Data were compared to the regional radiation dose. Results: A reduction in S was observed post-RT and at FUP in left-sided patients (Spost-RT: -17.6 ± 1.5%, and SFUP: -17.4 ± 2.3%, vs. Sbaseline: -19.5 ± 2.1%, p < 0.001) but not in right-sided patients. Within the left-sided patient group, S and SR were significantly reduced after RT in apical LV segments (Spost-RT: -15.3 ± 2.5%, and SFUP: -14.3 ± 3.7%, vs. S baseline: -19.3 ± 3.0%, p < 0.01; and SRpost-RT: -1.06 ± 0.15 s -1, and SRFUP: -1.16 ± 0.28 s -1, vs. SRbaseline: -1.29 ± 0.27s -1, p = 0.01), but not in mid- or basal segments. Furthermore, we observed that segments exposed to more than 3 Gy showed a significant decrease in S after RT (Spost-RT: -16.1 ± 1.6%, and SFUP: -15.8 ± 3.4%, vs. Sbaseline: -18.9 ± 2.6%, p < 0.001). This could not be observed in segments receiving less than 3 Gy. Conclusions: SRI shows a dose-related regional decrease in myocardial function after RT. It might be a useful tool in the evaluation of modern RT techniques, with respect to cardiac toxicity. © 2011 Elsevier Inc.


Erven K.,University Hospital Gasthuisberg | Florian A.,University Hospital Gasthuisberg | Florian A.,Institute of Emergency for Cardiovascular Diseases | Slagmolen P.,University Hospital Gasthuisberg | And 6 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2013

Purpose: Strain rate imaging (SRI) is a new echocardiographic modality that enables accurate measurement of regional myocardial function. We investigated the role of SRI and troponin I (TnI) in the detection of subclinical radiation therapy (RT)-induced cardiotoxicity in breast cancer patients. Methods and Materials: This study prospectively included 75 women (51 left-sided and 24 right-sided) receiving adjuvant RT to the breast/chest wall and regional lymph nodes. Sequential echocardiographs with SRI were obtained before RT, immediately after RT, and 8 and 14 months after RT. TnI levels were measured on the first and last day of RT. Results: Mean heart and left ventricle (LV) doses were both 9 ± 4 Gy for the left-sided patients and 4 ± 4 Gy and 1 ± 0.4 Gy, respectively, for the right-sided patients. A decrease in strain was observed at all post-RT time points for left-sided patients (-17.5% ± 1.9% immediately after RT, -16.6% ± 1.4% at 8 months, and -17.7% ± 1.9% at 14 months vs -19.4% ± 2.4% before RT, P<.01) but not for right-sided patients. When we considered left-sided patients only, the highest mean dose was given to the anterior left ventricular (LV) wall (25 ± 14 Gy) and the lowest to the inferior LV wall (3 ± 3 Gy). Strain of the anterior wall was reduced after RT (-16.6% ± 2.3% immediately after RT, -16% ± 2.6% at 8 months, and -16.8% ± 3% at 14 months vs -19% ± 3.5% before RT, P<.05), whereas strain of the inferior wall showed no significant change. No changes were observed with conventional echocardiography. Furthermore, mean TnI levels for the left-sided patients were significantly elevated after RT compared with before RT, whereas TnI levels of the right-sided patients remained unaffected. Conclusions: In contrast to conventional echocardiography, SRI detected a regional, subclinical decline in cardiac function up to 14 months after breast RT. It remains to be determined whether these changes are related to clinical outcome. In the meantime, we encourage the use of radiation techniques that minimize the exposure of the anterior LV wall in left-sided patients. © 2013 Elsevier Inc.

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