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1.
Eur J Heart Fail ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068051

RESUMO

The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) has recently issued a position paper on the role of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF). The present document provides an update of the position paper, based of new clinical trial evidence. Accordingly, the following recommendations are given: Canagliflozin, dapagliflozin empagliflozin, or ertugliflozin have consistently demonstrated to be effective for the prevention of HF hospitalisation in patients with T2DM and established CV disease or at high CV risk. The specifically listed agents are recommended. Dapagliflozin or empagliflozin are recommended to reduce the combined risk of HF hospitalisation and CV death in symptomatic patients with HF and reduced ejection fraction, already receiving guideline directed medical therapy, regardless of the presence of T2DM.

2.
Am J Med ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33010226

RESUMO

PURPOSE: We evaluated whether the severe acute respiratory syndrome coronavirus 2 pandemic was associated with changes in the pattern of acute cardiovascular admissions across European centres. METHODS: We set-up a multi-centre, multi-national, pan-European observational registry in 15 centres from 12 countries. All consecutive acute admissions to emergency departments and cardiology departments throughout a 1-month period during the COVID-19 outbreak were compared with an equivalent 1-month period in 2019. The acute admissions to cardiology departments were classified into 5 major categories: acute coronary syndrome, acute heart failure, arrhythmia, pulmonary embolism and other. RESULTS: Data from 54331 patients were collected and analysed. Nine centres provided data on acute admissions to emergency departments comprising 50384 patients: 20226 in 2020 vs 30158 in 2019 - incidence rate ratio (IRR) with 95% confidence interval (95%CI): 0.66(0.58-0.76). The risk of death at the emergency departments was higher in 2020 vs 2019: odds ratio (OR) with 95%CI: 4.1(3.0-5.8), P<0.0001. All 15 centers provided data on acute cardiology departments admissions: 3007 patients in 2020 vs 4452 in 2019, respectively, IRR(95%CI): 0.68(0.64-0.71). In 2020, there were less admissions with IRR(95%CI): acute coronary syndrome: 0.68(0.63-0.73), acute heart failure: 0.65(0.58-0.74), arrhythmia: 0.66(0.60-0.72), other: 0.68(0.62-0.76); we found a relatively higher percentage of pulmonary embolism admissions in 2020: OR(95%CI): 1.5(1.1-2.1), P=0.02. Among patients with acute coronary syndrome there were fewer admissions with unstable angina: 0.79(0.66-0.94), non-ST segment elevation myocardial infarction: 0.56(0.50-0.64) and ST-segment elevation myocardial infarction: 0.78(0.68-0.89). CONCLUSION: In the European centres during the COVID-19 outbreak, there were fewer acute cardiovascular admissions. Also, fewer patients were admitted to the emergency departments with 4-times higher death risk at the emergency departments.

3.
Circulation ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034202

RESUMO

Background: A systemic pro-inflammatory state has been hypothesized to mediate the association between comorbidities and abnormal cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). We conducted a proteomic analysis to investigate this paradigm. Methods: In 228 HFpEF patients from the multicenter PROMIS-HFpEF study, 248 unique circulating proteins were quantified by a multiplex immunoassay (Olink) and used to recapitulate systemic inflammation. In a deductive approach, we performed principal component (PC) analysis to summarize 47 proteins known a priori to be involved in inflammation. In an inductive approach, we performed unbiased weighted co-expression network analyses of all 248 proteins to identify clusters of proteins that overrepresented inflammatory pathways. We defined comorbidity burden as the sum of 8 common HFpEF comorbidities. We used multivariable linear regression and statistical mediation analyses to determine whether and to what extent inflammation mediates the association of comorbidity burden with abnormal cardiac structure/function in HFpEF. We also externally validated our findings in an independent cohort of 117 HFpEF cases and 30 comorbidity controls without HF. Results: Comorbidity burden was associated with abnormal cardiac structure/function and with PCs/clusters of inflammation proteins. Systemic inflammation was also associated with increased mitral E velocity, E/e' ratio, and tricuspid regurgitation (TR) velocity; and worse right ventricular function (tricuspid annular plane systolic excursion [TAPSE] and right ventricular. [RV] free wall strain). Inflammation mediated the association between comorbidity burden and mitral E velocity (proportion mediated 19-35%), E/e' ratio (18-29%), TR velocity (27-41%), and tricuspid annular plane systolic excursion (13%) (P<0.05 for all) but not RV free wall strain. TNF-R1, UPAR, IGFBP-7 and GDF-15 were the top individual proteins that mediated the relationship between comorbidity burden and echocardiographic parameters. In the validation cohort, inflammation was upregulated in HFpEF cases versus controls, and the most prominent inflammation protein cluster identified in PROMIS-HFpEF was also present in HFpEF cases (but not controls) in the validation cohort. Conclusions: Proteins involved in inflammation form a conserved network in HFpEF across 2 independent cohorts and may mediate the association between comorbidity burden and echocardiographic indicators of worse hemodynamics and RV dysfunction. These findings support the comorbidity-inflammation paradigm in HFpEF.

5.
ESC Heart Fail ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021347

RESUMO

AIMS: A substantial shift in the field of pulmonary hypertension (PH) is ongoing, as the previous practice of mean pulmonary arterial wedge pressure (PAWPM ) is no longer supported. Instead, aiming for a better estimate of end-diastolic pressures (EDP), instantaneous PAWP at mid-A-wave (PAWPmid-A ) or, in the absence of an A-wave, at 130-160 ms following QRS onset has recently been recommended. Electrocardiogram-gated PAWP (PAWPQRS ) has also been proposed. The quantitative differences as well as the diagnostic and prognostic utility of these novel PAWP measurements have not been evaluated. We set out to address these issues. METHODS AND RESULTS: Pressure tracings of 141 patients with PH due to left heart disease (PH-LHD) and 43 with primary pulmonary arterial hypertension (PAH) were analysed. PAWP was measured as follows: (i) mean pressure (PAWPM ); (ii) per the latest consensus approach [PAWPmid-A , or in atrial fibrillation 130, 140, 150, and 160 ms following QRS onset (PAWP130-160 )]; (iii) at QRS onset (PAWPQRS ); and (iv) Z-point (PAWPZ ). For each PAWP, the corresponding pulmonary vascular resistance (PVR) and diastolic pressure gradient were calculated. The cohort comprised 45% female. Mean age was 66 ± 15. PAWPmid-A was in good agreement with PAWPZ (17.3 [14.5 to 21.2] vs. 17.6 [14.2 to 21.6] mmHg, P = 0.63), whereas PAWPQRS provided significantly lower values (15.3 [12.5 to 19.2] mmHg, P < 0.001). In atrial fibrillation, PAWP130 and PAWPQRS yielded the optimal temporal and quantitative analyses of EDPs. The ability to differentiate PAH from PH-LHD was similar for the various PAWP measurements [PAWPM : area under the curve (AUC) 0.98, confidence interval (CI) 0.96-0.99; PAWPmid-A/130 : AUC 0.94, CI 0.91-0.98; PAWPQRS : AUC 0.96, CI 0.94-0.99, P < 0.001 for all]. PVR based on instantaneous PAWP measurements failed to provide superior prognostic information in PH-LHD as compared with conventional PVR. CONCLUSIONS: Although instantaneous PAWP measurement might better represent EDP, they nevertheless fail to yield incremental diagnostic or prognostic information in PH-LHD as compared with conventional measurements.

6.
J Card Fail ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32956814

RESUMO

BACKGROUND: An increase in the pulmonary capillary wedge pressure (PAWP) has been shown to impact on the inherent relationship between the pulmonary arterial compliance (PAC) and pulmonary vascular resistance (PVR), thus augmenting the pulsatile relative to the resistive load of the right ventricle. However, the PAWP comprises the integration of both the steady and the pulsatile pressure components. We sought to address the differential impact of the these distinct PAWP components on the PAC-PVR relationship in a cohort of patients with heart failure. METHODS AND RESULTS: The study population consisted of 192 patients with hemodynamic findings diagnostic for heart failure. Off-line analysis was performed using the MATLAB software. The steady and pulsatile PAWP components were calculated as mid-A pressure and mean pressure during the V-wave oscillation, respectively. The PAC and PVR were hyperbolically and inversely associated and the subgroup of patients with PAWP above the median (>18 mm Hg) displayed a significant left and downward shift of the curve fit (P < .001). The shift in the PAC-PVR fit between patients with higher versus low steady PAWP was not significant (P = .43). In contrast, there was a significant downward and leftward shift of the PVR-PAC curve fit for the subgroup with a higher pulsatile PAWP (P < .001). Furthermore, only the pulsatile PAWP was significantly associated with the time-constant of the pulmonary circulation, assessed as the PAC × PVR product (P < .001). CONCLUSIONS: In patients with heart failure, the pulsatile rather than the steady PAWP component stands for the previously documented shift of the PAC-PVR relationship occurring at an elevated PAWP.

7.
ESC Heart Fail ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32909376

RESUMO

Type 2 diabetes mellitus (T2DM) is highly prevalent in the general population and especially in patients with heart failure (HF). It is not only a risk factor for incident HF, but is also associated with worse outcomes in prevalent HF. Therefore, antihyperglycaemic management in patients at risk of or with established HF is of importance to reduce morbidity/mortality. Following revision of the drug approval process in 2008 by the Food and Drug Administration and European Medicines Agency, several cardiovascular outcome trials on antihyperglycaemic drugs have recently investigated HF endpoints. Signals of harm in terms of increased risk of HF have been identified for thiazolidinediones and the dipeptidyl peptidase 4 inhibitor saxagliptin, and therefore, these drugs are not currently recommended in HF. Sulfonylureas also have an unfavourable safety profile and should be avoided in patients at increased risk of/with HF. Observational studies have assessed the use of metformin in patients with HF, showing potential safety and potential survival/morbidity benefits. Overall use of glucagon-like peptide 1 receptor agonists has not been linked with any clear benefit in terms of HF outcomes. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2i) have consistently shown to reduce risk of HF-related outcomes in T2DM with and without HF and are thus currently recommended to lower risk of HF hospitalization in T2DM. Recent findings from the DAPA-HF trial support the use of dapagliflozin in patients with HF with reduced ejection fraction and, should ongoing trials with empagliflozin, sotagliflozin, and canagliflozin prove efficacy, will pave the way for SGLT2i as HF treatment regardless of T2DM.

8.
ESC Heart Fail ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32881399

RESUMO

AIMS: The aim of this study is to study the introduction of sacubitril/valsartan (sac/val) in Sweden with regards to regional differences, clinical characteristics, titration patterns, and determinants of use and discontinuation. METHODS AND RESULTS: A national cohort of heart failure was defined from the Swedish Prescribed Drug Register and National Patient Register. A subcohort with additional data from the Swedish Heart Failure Registry (SwedeHF) was also studied. Cohorts were subdivided as per sac/val prescription and registration in SwedeHF. Median sac/val prescription rate was 20 per 100 000 inhabitants. Between April 2016 and December 2017, we identified 2037 patients with ≥1 sac/val prescription, of which 1144 (56%) were registered in SwedeHF. Overall, patients prescribed with sac/val were younger, more frequently male, and had less prior cardiovascular disease than non-sac/val patients. In SwedeHF subcohort, patients prescribed with sac/val had lower ejection fraction. Overall, younger age [hazard ratio 2.81 (95% confidence interval 2.45-3.22)], registration in SwedeHF [1.97 (1.83-2.12)], male gender [1.50 (1.37-1.64)], ischaemic heart disease [1.50 (1.39-1.62)], lower left ventricular ejection fraction [3.06 (2.18-4.31)], and New York Heart Association IV [1.50 (1.22-1.84)] were predictors for sac/val use. As initiation dose in the sac/val cohort, 38% received 24/26 mg, 54% 49/51 mg, and 9% 97/103 mg. Up-titration to the target dose was achieved in 57% of the overall cohort over a median follow-up of 6 months. The estimated treatment persistence for any dose at 360 days was 82%. CONCLUSIONS: Implementation of sac/val in Sweden was slow and varied five-fold across different regions; younger age, male, SwedeHF registration, and ischaemic heart disease were among the independent predictors of receiving sac/val. Overall, treatment persistence and tolerability was high.

10.
Int J Cardiol ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32941871

RESUMO

BACKGROUND: Accurate non-invasive estimation of right atrial pressure (RAP) is essential to assess volume status and optimize therapy in heart failure (HF). This study aimed to evaluate the utility of right atrial reservoir strain (RASr) assessed by speckle-tracking echocardiography to identify elevated RAP in HF and compare diagnostic performance with estimated RAP employing inferior vena cava size and collapsibility (RAPIVC), in addition to RA area. METHOD: Association between RASr and invasive RAP (RAPInvasive) was examined in 103 HF subjects that underwent standard echocardiography with speckle-tracking strain analysis directly followed by right heart catheterization. The discriminatory ability of RASr to identify RAPInvasive > 7 mmHg was evaluated and compared with RAPIVC and RA area. RESULTS: RASr demonstrated association with RAPInvasive (ß = -0.41, p < 0.001) and was an independent predictor when adjusted for potential confounders (ß = -0.25, p < 0.001). Further, RASr showcased strong discriminatory ability to identify subjects with RAPInvasive > 7 mmHg (AUC = 0.78; 95% CI 0.68-0.87; p < 0.001). At a cut-off value of -15%, RASr displayed 78% sensitivity and 72% specificity to identify elevated RAPInvasive. In comparison, RAPIVC (AUC = 0.71; 95% CI 0.61-0.81; p < 0.001) demonstrated 89% sensitivity and 32% specificity with high false positive rate. RA area (AUC = 0.66; 95% CI 0.55-0.76, p = 0.005) displayed 64% sensitivity and 53% specificity. CONCLUSIONS: RASr demonstrates good ability to identify elevated RAP and relatively stronger diagnostic performance when compared with conventional non-invasive measures. RASr may be useful as a novel noninvasive estimate of RAP in HF management.

11.
J Card Fail ; 2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-32846205

RESUMO

BACKGROUND: Coronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF. METHODS AND RESULTS: We assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and (5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of <2.5. Time to CV death/first hospitalization was compared by log-rank test and recurrent HF and all-cause hospitalizations by Poisson test. Of 263 patients enrolled, 257 were evaluable at 1 year. Where the coronary flow reserve was interpretable (n = 201), CMD was present in 150 (75%). The median follow-up was 388 days (Q1, Q3 365, 418). The outcome of CV death/first HF hospitalization occurred in 15 patients (4 CV deaths). The incidence rate was in CMD 96 per 1000 person-years, 95% confidence interval 54-159, vs non-CMD 0 per1000 person-years, 95% confidence interval 0-68, P = .023, and remained significant after accounting for selected clinical variables. In patients with CMD, the incidence rates were significantly higher also for CV death/recurrent HF hospitalizations, all-cause death/first HF, and recurrent but not first all-cause hospitalization. CONCLUSIONS: In this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CV- and HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF.

12.
Heart ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769169

RESUMO

OBJECTIVE: It is not fully understood whether and how socioeconomic status (SES) has a prognostic impact in patients with heart failure (HF). We assessed SES and its association with patient characteristics and outcomes in a contemporary and well-characterised HF cohort. METHODS: Socioeconomic risk factors (SERF) were defined in the Swedish HF Registry based on income (low vs high according to the annual median value), education level (no degree/compulsory school vs university/secondary school) and living arrangement (living alone vs cohabitating). RESULTS: Of 44 631 patients, 21% had no, 33% one, 30% two and 16% three SERF. Patient characteristics strongly and independently associated with lower SES were female sex and no specialist referral. Additional independent associations were older age, more severe HF, heavier comorbidity burden, use of diuretics and less use of HF devices. Lower SES was associated with higher risk of HF hospitalisation/mortality, and overall cardiovascular and non-cardiovascular events. These associations persisted after extensive adjustment for patient characteristics, treatments and care. The magnitude of the association increased linearly with the increasing number of coexistent SERF: HR (95% CI) 1.09 (1.05 to 1.13) for one, 1.16 (1.12 to 1.20) for two and 1.22 (1.18 to 1.28) for three SERF (p<0.01). CONCLUSIONS: In a contemporary and well-characterised HF cohort and after comprehensive adjustment for confounders, lower SES was linked with multiple factors such as less use of HF devices and age, but most strongly with female sex and lack of specialist referral; and associated with greater risk of morbidity/mortality.

13.
Circ Res ; 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32815777

RESUMO

Rationale: Hyperglycemia-induced reactive oxygen species (ROS) are key mediators of cardiac dysfunction. JunD, a member of the Activated Protein-1 (AP-1) family of transcription factors, is emerging as a major gatekeeper against oxidative stress. However, its contribution to redox state and inflammation in the diabetic heart remains to be elucidated. Objective: The present study investigates the role of JunD in hyperglycemia-induced and ROS-driven myocardial dysfunction. Methods and Results: JunD mRNA and protein expression were reduced in the myocardium of mice with streptozotocin-induced diabetes as compared to controls. JunD downregulation was associated with oxidative stress and left ventricular dysfunction assessed by electron spin resonance spectroscopy as well as conventional and 2D speckle-tracking echocardiography. Furthermore, myocardial expression of free radical scavenger superoxide dismutase 1 and aldehyde dehydrogenase 2 was reduced, whereas the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits NOX2 and NOX4 were upregulated. The redox changes were associated with increased NF-kappaB binding activity and expression of inflammatory mediators. Interestingly, mice with cardiac-specific overexpression of JunD via the α-myosin heavy chain promoter (α-MHC-JunDtg) were protected against hyperglycemia-induced cardiac dysfunction. We also showed that JunD was epigenetically regulated by promoter hypermethylation, posttranslational modification of histone marks and translational repression by miRNA-673/menin. Reduced JunD mRNA and protein expression were confirmed in left ventricular specimens obtained from patients with type 2 diabetes and heart failure as compared to non-diabetic subjects. Conclusions: Here we show that a complex epigenetic machinery involving DNA methylation, histone modifications and microRNAs mediates hyperglycemia-induced JunD downregulation and myocardial dysfunction in experimental and human diabetes. Our results pave the way for tissue-specific therapeutic modulation of JunD to prevent diabetic cardiomyopathy.

15.
Eur J Heart Fail ; 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32683762

RESUMO

AIMS: The cardiorenal syndrome refers to a bidirectional relationship between the kidney and the heart. However, epidemiological evidence of cardiovascular disease (CVD) as a risk factor for chronic kidney disease (CKD) progression is actually scarce. METHODS AND RESULTS: We examined the slopes of estimated glomerular filtration rate (eGFR) decline in the 2 years before vs. after an incident hospitalization with heart failure (HF) (n = 20 420), coronary heart disease (CHD) (n = 18 152), or stroke (n = 1808) using data from a complete laboratory data collection in Stockholm, Sweden between 2006 and 2011. eGFR slopes were estimated using mixed-effect models with unstructured residual correlation. Overall, incident hospitalization with HF and CHD, but not stroke, was significantly associated with a subsequent accelerated decline in eGFR, with a faster eGFR decline and greater slope change after HF than CHD. The pre-event vs. post-event eGFR slopes (mL/min/1.73 m2 per year) were -1.67 (-1.77 to -1.57) vs. -2.76 (-2.82 to -2.71), with a Δslope of -1.09 (-1.16 to -1.02) for HF; -1.09 (-1.20 to -0.98) vs. -1.87 (-1.92 to -1.81), with a Δslope of -0.78 (-0.85 to -0.70) for CHD; and -1.00 (-1.37 to -0.63) vs. -0.99 (-1.19 to -0.78), with a Δslope of 0.02 (-0.24 to 0.27) for stroke. The accelerated declines in eGFR after HF and CHD were consistent across the spectrum of eGFR, although pre-event eGFR slopes were steeper in lower eGFR (e.g. pre-event eGFR slope for HF -0.64 (-0.76 to -0.53) for eGFR ≥60 mL/min/1.73 m2 , -1.43 (-1.57 to -1.30) for eGFR 30-59 mL/min/1.73 m2 , and -2.42 (-2.71 to -2.12) for eGFR <30 mL/min/1.73 m2 ). CONCLUSIONS: Incident hospitalization with cardiac diseases (i.e. HF and CHD) was significantly associated with a subsequent acceleration of eGFR decline.

16.
ESC Heart Fail ; 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32618139

RESUMO

AIMS: In hospitalized patients with a clinical diagnosis of acute heart failure (HF) with preserved ejection fraction (HFpEF), the aims of this study were (i) to assess the proportion meeting the 2016 European Society of Cardiology (ESC) HFpEF criteria and (ii) to compare patients with restrictive/pseudonormal mitral inflow pattern (MIP) vs. patients with MIP other than restrictive/pseudonormal. METHODS AND RESULTS: We included hospitalized participants of the ESC-Heart Failure Association (HFA) EURObservational Research Programme (EORP) HF Long-Term Registry who had echocardiogram with ejection fraction (EF) ≥ 50% during index hospitalization. As no data on e', E/e' and left ventricular (LV) mass index were gathered in the registry, the 2016 ESC HFpEF definition was modified as follows: elevated B-type natriuretic peptide (BNP) (≥100 pg/mL for acute HF) and/or N-terminal pro-BNP (≥300 pg/mL) and at least one of the echocardiographic criteria: (i) presence of LV hypertrophy (yes/no), (ii) left atrial volume index (LAVI) of >34 mL/m2 ), or (iii) restrictive/pseudonormal MIP. Next, all patients were divided into four groups: (i) patients with restrictive/pseudonormal MIP on echocardiography [i.e. with presumably elevated left atrial (LA) pressure], (ii) patients with MIP other than restrictive/pseudonormal (i.e. with presumably normal LA pressure), (iii) atrial fibrillation (AF) group, and (iv) 'grey area' (no consistent description of MIP despite no report of AF). Of 6365 hospitalized patients, 1848 (29%) had EF ≥ 50%. Natriuretic peptides were assessed in 28%, LV hypertrophy in 92%, LAVI in 13%, and MIP in 67%. The 2016 ESC HFpEF criteria could be assessed in 27% of the 1848 patients and, if assessed, were met in 52%. Of the 1848 patients, 19% had restrictive/pseudonormal MIP, 43% had MIP other than restrictive/pseudonormal, 18% had AF and 20% were grey area. There were no differences in long-term all-cause or cardiovascular mortality, or all-cause hospitalizations or HF rehospitalizations between the four groups. Despite fewer non-cardiac comorbidities reported at baseline, patients with MIP other than restrictive/pseudonormal (i.e. with presumably normal LA pressure) had more non-cardiovascular (14.0 vs. 6.7 per 100 patient-years, P < 0.001) and cardiovascular non-HF (13.2 vs. 8.0 per 100 patient-years, P = 0.016) hospitalizations in long-term follow-up than patients with restrictive/pseudonormal MIP. CONCLUSIONS: Acute HFpEF diagnosis could be assessed (based on the 2016 ESC criteria) in only a quarter of patients and confirmed in half of these. When assessed, only one in three patients had restrictive/pseudonormal MIP suggestive of elevated LA pressure. Patients with MIP other than restrictive/pseudonormal (suggestive of normal LA pressure) could have been misdiagnosed with acute HFpEF or had echocardiography performed after normalization of LA pressure. They were more often hospitalized for non-HF reasons during follow-up. Symptoms suggestive of acute HFpEF may in some patients represent non-HF comorbidities.

18.
J Card Fail ; 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32652244

RESUMO

BACKGROUND: Noncardiac surgery is increasingly offered to an older, more comorbid population. The aim was to characterize patients with the diagnosis of heart failure (HF) undergoing elective and emergency noncardiac surgery in a broad, contemporary Swedish cohort, and to assess the short- and long-term mortality in patients with HF as compared with patients without HF. METHODS AND RESULTS: Data from 200,638 and 97,129 patients undergoing elective and emergency surgical procedures at 23 Swedish university, county, and district hospitals during 2007 to 2013 were analyzed through linkage of the surgical Orbit Database to the National Patient and the Cause of Death registries. In total 7212 patients (3.6%) with a diagnosis of HF before surgery underwent elective and 6455 patients (6.6%) underwent emergency surgery. Patients with HF were older had more comorbidities, and higher mortality than patients without HF. Crude and adjusted risk ratios for 30-day mortality after elective surgery were 5.36 (95% confidence interval [CI] 4.67-6.16) and 1.79 (95% CI 1.50-2.14) (adjusted for comorbidities, surgical risk level, age, and sex). Corresponding data for emergency surgery was 3.84 (95% CI 3.58-4.12) and 1.48 (95% CI 1.31-1.62). Mortality in patients with HF after elective surgery at 30 days, 90 days, and 1 year was 3.2%, 6.5%, and 16.2% and after emergency surgery it was 13.7%, 22.4%, and 39.3%. CONCLUSIONS: Patients with HF undergoing elective or emergency noncardiac surgery in a modern surgical setting have a substantial mortality risk and HF is both a risk factor and a strong marker for increasd risk. The reasons for the high mortality are not well-understood and warrant further attention.

19.
Eur J Heart Fail ; 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32558989

RESUMO

AIMS: Both left ventricular (LV) and left atrial (LA) dysfunction and remodelling contribute to adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Danicamtiv is a novel, cardiac myosin activator that enhances cardiomyocyte contraction. METHODS AND RESULTS: We studied the effects of danicamtiv on LV and LA function in non-clinical studies (ex vivo: skinned muscle fibres and myofibrils; in vivo: dogs with heart failure) and in a randomized, double-blind, single- and multiple-dose phase 2a trial in patients with stable HFrEF (placebo, n = 10; danicamtiv, n = 30; 50-100 mg twice daily for 7 days). Danicamtiv increased ATPase activity and calcium sensitivity in LV and LA myofibrils/muscle fibres. In dogs with heart failure, danicamtiv improved LV stroke volume (+10.6 mL, P < 0.05) and LA emptying fraction (+10.7%, P < 0.05). In patients with HFrEF (mean age 60 years, 25% women, ischaemic heart disease 48%, mean LV ejection fraction 32%), treatment-emergent adverse events, mostly mild, were reported in 17 patients (57%) receiving danicamtiv and 4 patients (40%) receiving placebo. Danicamtiv (at plasma concentrations ≥2000 ng/mL) increased stroke volume (up to +7.8 mL, P < 0.01), improved global longitudinal (up to -1.0%, P < 0.05) and circumferential strain (up to -3.3%, P < 0.01), decreased LA minimal volume index (up to -2.4 mL/m2 , P < 0.01) and increased LA function index (up to 6.1, P < 0.01), when compared with placebo. CONCLUSIONS: Danicamtiv was well tolerated and improved LV systolic function in patients with HFrEF. A marked improvement in LA volume and function was also observed in patients with HFrEF, consistent with pre-clinical findings of direct activation of LA contractility.

20.
ESC Heart Fail ; 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32548911

RESUMO

AIMS: Left ventricular ejection fraction (EF) is required to categorize heart failure (HF) [i.e. HF with preserved (HFpEF), mid-range (HFmrEF), and reduced (HFrEF) EF] but is often not captured in population-based cohorts or non-HF registries. The aim was to create an algorithm that identifies EF subphenotypes for research purposes. METHODS AND RESULTS: We included 42 061 HF patients from the Swedish Heart Failure Registry. As primary analysis, we performed two logistic regression models including 22 variables to predict (i) EF≥ vs. <50% and (ii) EF≥ vs. <40%. In the secondary analysis, we performed a multivariable multinomial analysis with 22 variables to create a model for all three separate EF subphenotypes: HFrEF vs. HFmrEF vs. HFpEF. The models were validated in the database from the CHECK-HF study, a cross-sectional survey of 10 627 patients from the Netherlands. The C-statistic (discrimination) was 0.78 [95% confidence interval (CI) 0.77-0.78] for EF ≥50% and 0.76 (95% CI 0.75-0.76) for EF ≥40%. Similar results were achieved for HFrEF and HFpEF in the multinomial model, but the C-statistic for HFmrEF was lower: 0.63 (95% CI 0.63-0.64). The external validation showed similar discriminative ability to the development cohort. CONCLUSIONS: Routine clinical characteristics could potentially be used to identify different EF subphenotypes in databases where EF is not readily available. Accuracy was good for the prediction of HFpEF and HFrEF but lower for HFmrEF. The proposed algorithm enables more effective research on HF in the big data setting.

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