Variability of Myocardial Strain During Isometric Exercise in Subjects With and Without Heart Failure.
ABSTRACT: Background: Fast strain-encoded cardiac magnetic resonance imaging (cMRI, fast-SENC) is a novel technology potentially improving characterization of heart failure (HF) patients by quantifying cardiac strain. We sought to describe the impact of isometric handgrip exercise (HG) on cardiac strain assessed by fast-SENC in HF patients and controls. Methods: Patients with stable HF and controls were examined using cMRI at rest and during HG. Left ventricular (LV) global longitudinal strain (GLS) and global circumferential (GCS) were derived from image analysis software using fast-SENC. Strain change < -0.5 and > +0.5 was classified as increase and decrease, respectively. Results: The study population comprised 72 subjects, including HF with reduced, mid-range and preserved ejection fraction and controls (HFrEF n = 18 HFmrEF n = 18, HFpEF n = 17, controls: n = 19). In controls, LV GLS remained stable in 36.8%, increased in 36.8% and decreased in 26.3% of subjects during HG. In HF subgroups, similar patterns of LV GLS response were observed (HFpEF: stable 41.2%, increase 35.3%, decrease: 23.5%; HFmrEF: stable 50.0%, increase 16.7%, decrease: 33.3%; HFrEF: stable 33.3%, increase 22.2%, decrease: 44.4%, p = 0.668). Mean change between LV GLS at rest and during HG ranged close to zero with broad standard deviation in all subgroups and was not significantly different between subgroups (+1.2 ± 5.4%, -0.6 ± 8.3%, -1.7 ± 10.7%, and -3.1 ± 19.4%, p = 0.746 in controls, HFpEF, HFmrEF and HFrEF, respectively). However, the absolute value of LV GLS change-irrespective of increase or decrease-was significantly different between subgroups with 4.4 ± 3.2% in controls, 5.9 ± 5.7% in HFpEF, 6.8 ± 8.3% in HFmrEF and 14.1 ± 13.3% in HFrEF (p = 0.005). The absolute value of LV GLS change significantly correlated with resting LVEF, NTproBNP and Minnesota Living with Heart Failure questionnaire scores. Conclusion: The response to isometric exercise in LV GLS is heterogeneous in all HF subgroups and in controls. The absolute value of LV GLS change during HG exercise is elevated in HF patients and associated with measures of HF severity. The diagnostic utility of fast-SENC strain assessment in conjunction with HG appears to be limited. Trial Registration: URL: https://www.drks.de; Unique Identifier: DRKS00015615.
Project description:The characteristics and optimal management of heart failure with a moderately reduced ejection fraction (HFmrEF, LV-EF 40-50%) are still unclear. Advanced cardiac MRI offers information about function, fibrosis and inflammation of the myocardium, and might help to characterize HFmrEF in terms of adverse cardiac remodeling. We, therefore, examined 17 patients with HFpEF, 18 with HFmrEF, 17 with HFrEF and 17 healthy, age-matched controls with cardiac MRI (Phillips 1.5 T). T1 and T2 relaxation time mapping was performed and the extracellular volume (ECV) was calculated. Global circumferential (GCS) and longitudinal strain (GLS) were derived from cine images. GLS (-15.7 ± 2.1) and GCS (-19.9 ± 4.1) were moderately reduced in HFmrEF, resembling systolic dysfunction. Native T1 relaxation times were elevated in HFmrEF (1027 ± 40 ms) and HFrEF (1033 ± 54 ms) compared to healthy controls (972 ± 31 ms) and HFpEF (985 ± 32 ms). T2 relaxation times were elevated in HFmrEF (55.4 ± 3.4 ms) and HFrEF (56.0 ± 6.0 ms) compared to healthy controls (50.6 ± 2.1 ms). Differences in ECV did not reach statistical significance. HFmrEF differs from healthy controls and shares similarities with HFrEF in cardiac MRI parameters of fibrosis and inflammation.
Project description:The left ventricle fills in early diastole because of a progressive intraventricular pressure difference (IVPD) that extends from the left atrium to the left ventricular (LV). The aim of this study was to test the hypothesis that in patients with symptomatic heart failure (HF) regardless of LV ejection fraction (EF), an increase in left atrial (LA) pressure maintains early diastolic filling because of a preserved IVPD from the left atrium to the mid left ventricle, while the IVPD from the mid left ventricle to the apex is diminished because of reduced LV suction.One hundred fifty-one patients with HF (50 with HF with preserved EF [HFpEF; EF ? 50%] and 101 with HF with reduced EF [HFrEF; EF < 50%]) and 28 normal controls were prospectively enrolled. The IVPDs from the left atrium to the LV apex (total IVPD), the left atrium to the mid left ventricle (basilar IVPD), and the mid left ventricle to the apex (apical IVPD) were determined using color M-mode Doppler echocardiographic data to integrate the Euler equation. The propagation of early diastolic filling was also assessed by color M-mode Doppler.The mean LV EF was 0.63 ± 0.07 in patients with HFpEF, 0.32 ± 0.09 in those with HFrEF, and 0.64 ± 0.06 in controls. Peak early diastolic transmitral flow velocities (E) were similar among the groups, and basilar IVPDs were maintained in the HFpEF and HFrEF groups (HFpEF, 1.59 ± 0.62 mm Hg; HFrEF, 1.49 ± 0.75 mm Hg; controls, 1.80 ± 0.61 mm Hg; P = NS, analysis of variance). However, apical IVPDs were decreased in both HF groups (HFpEF, 1.18 ± 0.56 mm Hg [P < .01 vs controls]; HFrEF, 0.87 ± 0.48 mm Hg [P < .01 vs controls]; controls, 1.65 ± 0.62 mm Hg), resulting in decreased total IVPDs in patients with HF (HFpEF, 2.55 ± 0.80 mm Hg [P < .01 vs controls]; HFrEF, 2.16 ± 0.80 mm Hg [P < .01 vs controls]; controls, 3.17 ± 0.91 mm Hg). E/e' ratios were increased in patients with HF, consistent with elevated LA pressure. In patients with HF, E was correlated with basilar IVPD but not with apical IVPD, whereas propagation of the filling was correlated with the apical IVPD but not with the basilar IVPD.In patients with HFpEF and those with HFrEF, apical IVPDs were reduced while basilar IVPDs were maintained by elevated LA pressure, resulting in preserved E.
Project description:AIMS:Patients with aortic stenosis (AS) may have concomitant heart failure (HF) that determines prognosis despite successful transcatheter aortic valve implantation (TAVI). We compared outcomes of TAVI patients with low stroke volume index (SVI) ?35 ml/m2 body surface area in different HF classes. METHODS AND RESULTS:Patients treated by transfemoral TAVI at our center (n = 1822) were classified as 1) 'HF with preserved ejection fraction (EF)' (HFpEF, EF ?50%), 2) 'HF with mid-range EF' (HFmrEF, EF 40-49%), or 3) 'HF with reduced EF' (HFrEF, EF <40%). Patients with SVI >35 ml/m2 served as controls. The prevalence of cardiovascular disease and symptoms increased stepwise from controls (n = 968) to patients with HFpEF (n = 591), HFmrEF (n = 97), and HFrEF (n = 166). Mortality tended to be highest in HFrEF patients 30 days post-procedure, and it became significant after one year: 10.2% (controls), 13.5% (HFpEF), 13.4% (HFmrEF), and 23.5% (HFrEF). However, symptomatic improvement in survivors of all groups was achieved in the majority of patients without differences among groups. CONCLUSIONS:Patients with AS and HF benefit from TAVI with respect to symptom alleviation. TAVI in patients with HFpEF and HFmrEF led to an identical, favorable post-procedural prognosis that was significantly better than that of patients with HFrEF, which remains a high-risk population.
Project description:Background: Although central apneas (CA) and obstructive apneas (OA) are highly prevalent in heart failure (HF), a comparison of apnea prevalence, predictors and clinical correlates in the whole HF spectrum, including HF with reduced ejection fraction (HFrEF), mid-range EF (HFmrEF) and preserved EF (HFpEF) has never been carried out so far. Materials and methods: 700 HF patients were prospectively enrolled and then divided according to left ventricular EF (408 HFrEF, 117 HFmrEF, 175 HFpEF). All patients underwent a thorough evaluation including: 2D echocardiography; 24-h Holter-ECG monitoring; cardiopulmonary exercise testing; neuro-hormonal assessment and 24-h cardiorespiratory monitoring. Results: In the whole population, prevalence of normal breathing (NB), CA and OA at daytime was 40, 51, and 9%, respectively, while at nighttime 15, 55, and 30%, respectively. When stratified according to left ventricular EF, CA prevalence decreased (daytime: 57 vs. 43 vs. 42%, p = 0.001; nighttime: 66 vs. 48 vs. 34%, p < 0.0001) from HFrEF to HFmrEF and HFpEF, while OA prevalence increased (daytime: 5 vs. 8 vs. 18%, p < 0.0001; nighttime 20 vs. 29 vs. 53%, p < 0.0001). In HFrEF, male gender and body mass index (BMI) were independent predictors of both CA and OA at nighttime, while age, New York Heart Association functional class and diastolic dysfunction of daytime CA. In HFmrEF and HFpEF male gender and systolic pulmonary artery pressure were independent predictors of CA at daytime, while hypertension predicted nighttime OA in HFpEF patients; no predictor of nighttime CA was identified. When compared to patients with NB, those with CA had higher neuro-hormonal activation in all HF subgroups. Moreover, in the HFrEF subgroup, patients with CA were older, more comorbid and with greater hemodynamic impairment while, in the HFmrEF and HFpEF subgroups, they had higher left atrial volumes and more severe diastolic dysfunction, respectively. When compared to patients with NB, those with OA were older and more comorbid independently from background EF. Conclusions: Across the whole spectrum of HF, CA prevalence increases and OA decreases as left ventricular systolic dysfunction progresses. Different predictors and specific clinical characteristics might help to identify patients at risk of developing CA or OA in different HF phenotypes.
Project description:AIMS:While heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) are well described, determinants and outcomes of heart failure with mid-range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical and biochemical predictors of incident HFmrEF in the community. METHODS AND RESULTS:We pooled data from four community-based longitudinal cohorts, with ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction (EF) 41-49%], HFpEF (EF ?50%), and HFrEF (EF ?40%). Predictors of incident HF subtypes were assessed using multivariable Cox models. Among 28 820 participants free of HF followed for a median of 12?years, there were 200 new HFmrEF cases, compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial infarction (multivariable adjusted P ??0.003 for all). Biomarkers that predicted HFmrEF included natriuretic peptides, cystatin-C, and high-sensitivity troponin (P ??0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95% confidence interval (CI) 1.81-2.20] than of HFmrEF (HR 1.51, 95% CI 1.20-1.90, P =?0.01 for difference), and did not differ in their association with incident HFmrEF and HFpEF (HR 1.56, 95% CI 1.41-1.73, P =?0.68 for difference). All-cause mortality following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per 1000 person-years, P =?0.02), but comparable to that of HFrEF (46 events per 1000 person-years, P =?0.78). CONCLUSIONS:We found overlap in predictors of incident HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse than HFpEF, and similar to HFrEF.
Project description:Heart failure (HF) is associated with progressive ventricular remodeling and impaired contraction that affects distinctly various regions of the myocardium. Our study applied cardiac magnetic resonance (CMR) feature tracking (FT) to assess comparatively myocardial strain at 3 distinct levels: subendocardial (Endo-), mid (Myo-) and subepicardial (Epi-) myocardium across an extended spectrum of patients with HF. 59 patients with HF, divided into 3 subgroups as follows: preserved ejection fraction (HFpEF, N?=?18), HF with mid-range ejection fraction (HFmrEF, N?=?21), HF with reduced ejection fraction (HFrEF, N?=?20) and a group of age- gender- matched volunteers (N?=?17) were included. Using CMR FT we assessed systolic longitudinal and circumferential strain and strain-rate at Endo-, Myo- and Epi- levels. Strain values were the highest in the Endo- layer and progressively lower in the Myo- and Epi- layers respectively, this gradient was present in all the patients groups analyzed but decreased progressively in HFmrEF and further on in HFrEF groups. GLS decreased with the severity of the disease in all 3 layers: Normal?>?HFpEF?>?HFmrEF?>?HFrEF (Endo-: -23.0?±?3.5?>?-20.0?±?3.3?>?-16.4?±?2.2?>?-11.0?±?3.2, p?<?0.001, Myo-: -20.7?±?2.4?>?-17.5.0?±?2.6?>?-14.5?±?2.1?>?-9.6?±?2.7, p?<?0.001; Epi-: -15.7?±?1.9?>?-12.2?±?2.1?>?-10.6?±?2.3?>?-7.7?±?2.3, p?<?0.001). In contrast, GCS was not different between the Normal and HFpEF (Endo-: -34.5?±?6.2 vs -33.9?±?5.7, p?=?0.51; Myo-: -21.9?±?3.8 vs -21.3?±?2.2, p?=?0.39, Epi-: -11.4?±?2.0 vs -10.9?±?2.3, p?=?0.54) but was, as well, markedly lower in the systolic heart failure groups: Normal?>?HFmrEF?>?HFrEF (Endo-: -34.5?±?6.2?>?-20.0?±?4.2?>?12.3?±?4.2, p?<?0.001; Myo-: -21.9?±?3.8?>?-13.0?±?3.4?>?-8.0?±?2.7. p?<?0.001; Epi-: -11.4?±?2.0?>?-7.9?±?2.3?>?-4.5?±?1.9. p?<?0.001). CMR feature tracking multilayer strain assessment identifies large range differences between distinct myocardial regions. Our data emphasizes the importance of sub-endocardial myocardium for cardiac contraction and thus, its predilect role in imaging detection of functional impairment. CMR feature tracking offers a convenient, readily available, platform to evaluate myocardial contraction with excellent spatial resolution, rendering further details about discrete areas of the myocardium. Using this technique across distinct groups of patients with heart failure (HF), we demonstrate that subendocardial regions of the myocardium exhibit much higher strain values than mid-myocardium or subepicardial and are more sensitive to detect contractile impairment. We also show comparatively higher values of circumferential strain compared with longitudinal and a higher sensitivity to detect contractile impairment. A newly characterized group of patients, HF with mid-range ejection fraction (EF), shows similar traits of decompensation but has relatively higher strain values as patients with HF with reduced EF.
Project description:Background A thorough analysis of noncardiac determinants of mortality in heart failure (HF) is missing. Furthermore, evidence conflicts on the outcome of patients with HF and no or mild systolic dysfunction. We aimed to investigate the prevalence of noncardiac and cardiac causes of death in a cohort of chronic HF patients, covering the whole spectrum of systolic function. Methods and Results We enrolled 2791 stable HF patients, classified into HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction [EF] <40%), HR with midrange EF (HFmrEF; left ventricular EF 41-49%), or HF with preserved EF (HFpEF; left ventricular EF ?50%), and followed up for all-cause, cardiac, and noncardiac mortality (adjudicated as due to cancer, sepsis, respiratory disease, renal disease, or other causes). Over follow-up of 39 months, adjusted mortality was lower in HFpEF and HFmrEF versus HFrEF (hazard ratio: 0.75 [95% CI, 0.67-0.84], <i>P</i><0.001 for HFpEF; hazard ratio: 0.78 [95% CI, 0.63-0.96], <i>P</i>=0.017 for HFmrEF). HFrEF had the highest rates of cardiac death, whereas noncardiac mortality was similar across left ventricular EF categories. Noncardiac causes accounted for 62% of deaths in HFpEF, 54% in HFmrEF and 35% in HFrEF; cancer was twice as frequent as a cause of death in HFpEF and HFmrEF versus HFrEF. Yearly rates of noncardiac death exceeded those of cardiac death since the beginning of follow-up in HFpEF and HFmrEF. Conclusions Noncardiac death is a major determinant of outcome in stable HF, exceeding cardiac-related mortality in HFpEF and HFmrHF. Comorbidities should be regarded as main therapeutic targets and objects of dedicated quality improvement initiatives, especially in patients with no or mild systolic dysfunction.
Project description:BACKGROUND:Heart failure (HF) with mid-range ejection fraction (EF) (HFmrEF) has attracted increasing attention in recent years. However, the understanding of HFmrEF remains limited, especially among Asian patients. Therefore, analysis of a Chinese HF registry was undertaken to explore the clinical characteristics and prognosis of HFmrEF. METHODS:A total of 755 HF patients from a multi-centre registry were classified into three groups based on EF measured by echocardiogram at recruitment: HF with reduced EF (HFrEF) (n = 211), HFmrEF (n = 201), and HF with preserved EF (HFpEF) (n = 343). Clinical data were carefully collected and analyzed at baseline. The primary endpoint was all-cause mortality and cardiovascular mortality while the secondary endpoints included hospitalization due to HF and major adverse cardiac events (MACE) during 1-year follow-up. Cox regression and Logistic regression were performed to identify the association between the three EF strata and 1-year outcomes. RESULTS:The prevalence of HFmrEF was 26.6% in the observed HF patients. Most of the clinical characteristics of HFmrEF were intermediate between HFrEF and HFpEF. But a significantly higher ratio of prior myocardial infarction (p = 0.002), ischemic heart disease etiology (p = 0.004), antiplatelet drug use (p = 0.009), angioplasty or stent implantation (p = 0.003) were observed in patients with HFmrEF patients than those with HFpEF and HFrEF. Multivariate analysis showed that the HFmrEF group presented a better prognosis than HFrEF in all-cause mortality [p = 0.022, HR (95%CI): 0.473(0.215-0.887)], cardiovascular mortality [p = 0.005, HR (95%CI): 0.270(0.108-0.672)] and MACE [p = 0.034, OR (95%CI): 0.450(0.215-0.941)] at 1 year. However, no significant differences in 1-year outcomes were observed between HFmrEF and HFpEF. CONCLUSION:HFmrEF is a distinctive subgroup of HF. The strikingly prevalence of ischemic history among patients with HFmrEF might indicate a key to profound understanding of HFmrEF. Patients in HFmrEF group presented better 1-year outcomes than HFrEF group. The long-term prognosis and optimal medications for HFmrEF require further investigations.
Project description:<h4>Background</h4>Clinical features and outcomes of heart failure (HF) with mid-range ejection fraction (HFmrEF) remain controversial. Thus, we systematically reviewed literatures of clinical research to assess and analyze characteristics and prognosis of patients with HFmrEF.<h4>Methods</h4>PubMed, Embase, and Web of Science were searched for cohort studies up to April 23, 2019. Clinical features and multivariate adjusted hazard ratios (HRs) of endpoints of short-term all-cause mortality (SAM), long-term all-cause mortality (LAM), long-term cardiovascular death (LCD) and long-term HF rehospitalization (LHR) among patients with HFmrEF and HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction (HFrEF) were well addressed. The primary outcome was LAM.<h4>Results</h4>Totally 19 studies were included in this study with 164,678 patients enrolled. The follow-up time of LAM was 3.6?±?2.5 years. HRs of LAM, SAM, LCD, LHR indicated that the risks of patients with HFmrEF were higher than HFpEF patients but lower than HFrEF patients, as for LAM, HFmrEF:HFpEF (reference) HR: 1.07, 95% confidence interval (CI): 1.00-1.15 (I?=?63%, P?=?0.0005); HFmrEF:HFrEF (reference) HR: 0.80, 95% CI: 0.73-0.88 (I?=?70%, P?<?0.0001). However, HFmrEF patients had the lowest rate in LAM (30.94%), SAM (2.73%), LCD (17.45%), LHR (26.36%) compared with the other two groups.<h4>Conclusions</h4>This systematic review and meta-analysis compared features and prognosis between patients with HFmrEF and HFpEF, HFrEF by HRs. There appeared a special "separation phenomenon" showing rates of endpoints were inconsistent with their hazards in patients with HFmrEF compared with HFpEF patients.
Project description:AIMS:Heart failure with mid-range ejection fraction (HFmrEF) has been proposed as a distinct HF phenotype, but whether patients on this category fare worse, similarly, or better than those with HF with reduced EF (HFrEF) or preserved EF (HFpEF) in terms of rehospitalization risks over time remains unclear. METHODS AND RESULTS:We prospectively included 2961 consecutive patients admitted for acute HF (AHF) in our institution. Of them, 158 patients died during the index admission, leaving the sample size to be 2803 patients. Patients were categorized according to their EF: HFrEF if EF ? 40% (n = 908, 32.4%); HFmrEF if EF = 41-49% (n = 449, 16.0%); and HFpEF if EF ? 50% (n = 1446, 51.6%). Covariate-adjusted incidence rate ratios (IRRs) were used to evaluate the association between EF status and recurrent all-cause and HF-related admissions. At a median follow-up of 2.6 years (inter-quartile range: 1.0-5.3), 1663 (59.3%) patients died, and 6035 all-cause readmissions were registered in 2026 patients (72.3%), 2163 of them HF related. Rates of all-cause readmission per 100 patients-years of follow-up were 150.1, 176.9, and 163.6 in HFrEF, HFmrEF, and HFpEF, respectively (P = 0.097). After multivariable adjustment, when compared with that of patients with HFrEF and HFpEF, HFmrEF status was not significantly associated with a different risk of all-cause readmissions (IRR = 0.99; 95% confidence interval [CI], 0.77-1.27; P = 0.926; and IRR = 0.93; 95% CI, 0.74-1.18; P = 0.621, respectively) or HF-related readmissions (IRR = 1.06; 95% CI, 0.77-1.46; P = 0.725; and IRR = 1.11; 95% CI, 0.82-1.50; P = 0.511, respectively). CONCLUSIONS:Following an admission for AHF, patients with HFmrEF had a similar rehospitalization burden and a similar risk of recurrent all-cause and HF-related admissions than had patients with HFrEF or HFpEF. Regarding morbidity risk, HFmrEF seems not to be a distinct HF phenotype.