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1.	Bjurman, Christian, 1983, et al. (författare) Small changes in Troponin T levels are common in patients with non-ST-elevation myocardial infarction and are linked to higher mortality 2013 Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 62:14, s. 1231-1238 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE:To examine the extent of change in Troponin T levels in patients with non-ST-elevation myocardial infarction (NSTEMI).BACKGROUND:Changes in cardiac troponin levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20-230 % and an absolute change of 7- 9 ng/L have been suggested as cut-off points.METHOD:In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitive cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1178 patients with a final diagnosis of NSTEMI presenting <24h after symptom onset.RESULTS:After six hours of observation, the relative change in the hs-cTnT level remained <20 % in 26 % and the absolute change <9 ng/L in 12 % of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p=0.002) and in multivariate analyses (HR 1.61 (1.17-2.21) p=0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT changeCONCLUSION:Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT.
2.	Fu, Michael, 1963, et al. (författare) Agonist-like activity of antibodies to angiotensin II receptor subtype 1 (AT1) from rats immunized with AT1 receptor peptide. 1999 Ingår i: Blood pressure. - 0803-7051. ; 8:5-6, s. 317-24 Tidskriftsartikel (refereegranskat)abstract In the present study, rats were immunized with angiotensin II receptor subtype 1 (AT1) receptor peptides for 3 months to see if the immunization produced specific anti-AT1 receptor antibodies and if continuous stimulation for 3 months affected blood pressure or induced morphological changes in the organs containing AT1 receptors. Our results showed that there were constant high levels of circulating antibodies throughout the study period in all rats of the immunized group, but not in the control rats, and that there were almost no significant cross-reactions of antisera with AT2 receptor peptide and alpha1 adrenoceptor peptide, except in four rats, which showed low cross-reactions with alpha1 adrenoceptor and AT2 receptor peptides. When an affinity-purified anti-AT1 receptor antibody was used, it specifically displayed the AT1-stimulatory positive chronotropic effect and also localized AT1 receptors. However, in the immunized group, saturation binding of AT1 in homogenates from kidneys showed no difference either in maximal binding sites (Bmax) or in antagonist affinity (Kd). No difference in mRNA of AT1a was found in either kidney or heart, and no morphological changes in the organs were observed, as compared with the control group. Furthermore, immunization did not cause hypertension. In conclusion, the synthetic peptide corresponding to the second extra-cellular loop of the human AT1 receptor was able to produce highly specific and functionally active anti-AT1 receptor antibodies, but unable to induce pathological structural changes or hypertension.
3.	Hammarsten, Ola, et al. (författare) Troponin T percentiles from a random population sample, emergency room patients and patients with myocardial infarction 2012 Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 58:3, s. 628-637 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: High-sensitivity cardiac troponin T (cTnT) assays detect small clinically important myocardial infarctions (MI) but also yield higher rates of false-positive results owing to increased concentrations sometimes present in patients without MI. Better understanding is needed of factors influencing the 99th percentile of cTnT concentrations across populations and the frequency of changes in cTnT concentrations >20% often used in combination with increased cTnT concentrations for diagnosis of MI. METHODS: cTnT percentiles were determined by use of the Elecsys® hscTnT immunoassay (Modular® Analytics E170) in a random population sample, in emergency room (ER) patients, and in patients with non–ST-elevation MI (NSTEMI). Changes in cTnT concentrations were determined in hospitalized patients without MI. RESULTS: The 99th cTnT percentile in a random population sample (median age, 65 years) was 24 ng/L. In ER patients <65 years old without obvious conditions that increase cTnT, the 99th cTnT percentile was 12 ng/L with little age dependence, whereas in those >65 years old it was 82 ng/L and highly age dependent. In hospitalized patients without MI the 97.5th percentile for change in the cTnT concentration was 51%–67%. cTnT remained below the 99th percentile (12 ng/L) in 1% of patients with NSTEMI until 8.5 h after symptom onset and 6 h after ER arrival. CONCLUSIONS: Age >65 years was the dominant factor associated with increased cTnT in ER patients. This age association was more prominent in ER patients than in a random population sample. Changes in serial cTnT concentrations >20% were common in hospitalized patients without MI.
4.	Josefsson, Axel, 1984, et al. (författare) Impact of peri-transplant heart failure & left-ventricular diastolic dysfunction on outcomes following liver transplantation 2012 Ingår i: Liver International. - : Wiley. - 1478-3231 .- 1478-3223. ; 32:8, s. 1262-1269 Tidskriftsartikel (refereegranskat)abstract Background & Aims: Assess the prevalence of peri-transplant heart failure and its potential relation to post-transplant morbidity and mortality. Methods: A retrospective study was performed on 234 consecutive cirrhotic patients undergoing liver transplantation in a single European center from 1999 to 2007 (mean age 52, 30% women, 36% with alcoholic liver disease, 24% with viral hepatitis, 18% cholestatic liver disease). Left ventricular diastolic dysfunction was defined as E/A ratio <= 1. We used the Boston classification for heart failure to assess the prevalence of peri-transplant heart failure. Patients were followed up for a mean of 4 years post-transplant (0.5-9 years). Results: Eighteen per cent of patients demonstrated diastolic dysfunction pretransplant. During the peri-transplantation period highly possible heart failure occurred in 27%. In logistic regression analysis, heart failure was independently related to lower mean arterial blood pressure (OR 0.94, 95% CR 0.91-0.98) and prolonged corrected QT time on ECG (OR 9.10, 95% CI 3.77-21.93) pretransplant. Peri-transplant mortality amounted to 5%, and was independently related to heart failure (OR 15.11, 95% CI 1.76-129.62) and the peri-transplant need of dialysis (OR 14.18, 95% CI 1.65-121.89). Heart failure was also associated with longer stay in the intensive care unit and peri-transplant cardiac events (P < 0.05). Long-term transplant-free mortality was independently related to diastolic dysfunction at baseline (Hazard ratio 4.82, 95% CI 1.78-13.06). Conclusion: Heart failure occurs in approximately a quarter of patients with cirrhosis following liver transplantation and it is an independent predictor of mortality and morbidity.
5.	Massie, Barry M, et al. (författare) Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure. 2010 Ingår i: The New England journal of medicine. - 1533-4406. ; 363:15, s. 1419-28 Tidskriftsartikel (refereegranskat)abstract Worsening renal function, which is associated with adverse outcomes, often develops in patients with acute heart failure. Experimental and clinical studies suggest that counterregulatory responses mediated by adenosine may be involved. We tested the hypothesis that the use of rolofylline, an adenosine A1-receptor antagonist, would improve dyspnea, reduce the risk of worsening renal function, and lead to a more favorable clinical course in patients with acute heart failure.
6.	Matsui, S, et al. (författare) Protective effect of bisoprolol on beta-1 adrenoceptor peptide-induced autoimmune myocardial damage in rabbits. 2000 Ingår i: Herz. - 0340-9937. ; 25:3, s. 267-70 Tidskriftsartikel (refereegranskat)abstract Idiopathic dilated cardiomyopathy is a severe disease of unknown etiology. Accumulating evidence suggests that agonist-like autoantibodies against the beta 1 adrenoceptor in the circulation of dilated cardiomyopathy may play an important role. The aim of this study was to evaluate the effects of the selective beta 1-adrenoceptor blocker, bisoprolol, on beta 1-adrenoceptor peptide induced autoimmune myocardial damage. In the animal model of autoimmune cardiomyopathy induced by active immunization of rabbits with beta 1-adrenoceptor peptide, bisoprolol was given at a dose of 3 mg/day throughout the study period. Our results showed high titer of anti-beta 1-adrenoceptor antibody in the immunized group throughout the study but not in the group receiving only bisoprolol. Cross-reactivity to beta 2 adrenoceptors was observed in some of the immunized rabbits, but disappeared almost entirely after 6 months. As compared to the beta 1-adrenoceptor peptide immunized group without bisoprolol treatment, bisoprolol treated beta 1-receptor peptide immunized group showed increase in the wall thickness and decreases in cavity dimension in anatomical measurements and only mild alterations in macro- and microscopic examinations. Thus, our study clearly demonstrated a beneficial effect of bisoprolol in rabbits who have developed autoimmune myocardial damage.
7.	Sylvén, C, et al. (författare) Beta 1 and beta 2 adrenoceptor ligand and mRNA expression in dilated cardiomyopathy. 1995 Ingår i: Biological & pharmaceutical bulletin. - : Pharmaceutical Society of Japan. - 0918-6158 .- 1347-5215. ; 18:10, s. 1430-4 Tidskriftsartikel (refereegranskat)abstract beta 1 and beta 2 adrenoceptor ligand activity has been shown to be down-regulated in failing myocardium. It is the aim of this study to test the hypothesis that also mRNA levels are down-regulated in dilated cardiomyopathy. beta 1 and beta 2 adrenoceptor ligand activities and mRNA expressions were analyzed in left ventricular biopsies from six organ donor hearts, in papillary muscles from seven patients operated on for mitral regurgitation, and in six explanted hearts as the result of dilated cardiomyophathy. mRNA levels were determined by solution hybridization. beta 1 ligand activity was decreased in the cases of mitral regurgitation (p < 0.01) and dilated cardiomyopathy (p < 0.001). beta 2 ligand activity did not differ between the three groups. mRNA expression was depressed in mitral regurgitation regarding both beta 1 (p < 0.001) and beta 2 (p < 0.01), while no differences were observed in dilated cardiomyopathy as compared to the donor hearts. The regulation of beta 1 and beta 2 adrenoceptor ligand activity and mRNA expression appears to follow a specific pattern in dilated cardiomyopathy. The specific down-regulation of beta 1 ligand activity seems to occur at a posttranslational level.
8.	Wallukat, G, et al. (författare) Autoantibodies against M2 muscarinic receptors in patients with cardiomyopathy display non-desensitized agonist-like effects. 1999 Ingår i: Life sciences. - 0024-3205. ; 64:6-7, s. 465-9 Tidskriftsartikel (refereegranskat)abstract Circulating autoantibodies against the human M2 muscarinic receptors have been previously shown in 38% of patients with idiopathic dilated cardiomyopathy. The functional properties of these autoantibodies are reported herein. They were able to decrease the cell beating frequency of myocytes in cultured neonatal rat heart cells in a dose-dependent manner without desensitization over a period of more than 5 hours whereas the non-specific muscarinic receptor agonist carbachol also inhibited the heart cell beating frequency but was desensitized within 1 hour. In the same cell culture, anti-M2 muscarinic receptor autoantibodies were not able to induce internalization of muscarinic receptor whereas carbachol did. These results demonstrate for the first time that anti-M2 muscarinic receptor autoantibodies from patients with idiopathic dilated cardiomyopathy have stimulatory muscarinic activity in vitro, which differ from normal muscarinic agonists by non-desensitization.
9.	Zhou, J. M., et al. (författare) Digoxin is associated with worse outcomes in patients with heart failure with reduced ejection fraction 2020 Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 7:1, s. 139-147 Tidskriftsartikel (refereegranskat)abstract Aims The aim of this study was to investigate the impact of digoxin use on the outcomes of patients with heart failure with reduced ejection fraction (HFrEF) and its possible interaction with atrial fibrillation or use of currently guideline-recommended treatments in the real world in China. Methods and results Patients hospitalized with HFrEF from 45 hospitals participating in the China National Heart Failure Registration Study (CN-HF) were enrolled to assess the all-cause mortality, HF mortality, all-cause re-hospitalization, and HF re-hospitalization associated with digoxin use. Eight hundred eighty-two eligible HFrEF patients in the CN-HF registry were included: 372 patients with digoxin and 510 patients without digoxin. Among them, 794 (90.0%) patients were followed up for the endpoint events, with a median follow-up of 28.6 months. Kaplan-Meier survival analysis showed that the all-cause mortality (P < 0.001) and all-cause re-hospitalization (P = 0.020) were significantly higher in digoxin group than non-digoxin group, while HF mortality (P = 0.232) and HF re-hospitalization (P = 0.098) were similar between the two groups. The adjusted Cox proportional-hazards regression analysis demonstrated that digoxin use remained as an independent risk factor for increased all-cause mortality [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.27-2.44; P = 0.001] and all-cause re-hospitalization (HR 1.27; 95% CI 1.03-1.57; P = 0.029) in HFrEF patients and the predictive value of digoxin for all-cause mortality irrespective of rhythm or in combination with other guideline-recommended therapies. Conclusions Digoxin use is independently associated with increased risk of all-cause mortality and all-cause re-hospitalization in HFrEF patients.
10.	Zhou, Yan-Li, et al. (författare) Increased stromal-cell-derived factor 1 enhances the homing of bone marrow derived mesenchymal stem cells in dilated cardiomyopathy in rats. 2010 Ingår i: Chinese medical journal. - 0366-6999. ; 123:22, s. 3282-7 Tidskriftsartikel (refereegranskat)abstract Stem cell transplantation has been shown to have beneficial effects on dilated cardiomyopathy. However, mechanism for stem cell homing to cardiac tissue in dilated cardiomyopathy has not yet been elucidated.
11.	Almodares, Qays, et al. (författare) Larger right atrium than left atrium is associated with all-cause mortality in elderly patients with heart failure 2017 Ingår i: Echocardiography - a Journal of Cardiovascular Ultrasound and Allied Techniques. - : Wiley. - 0742-2822. ; 34:5, s. 662-667 Tidskriftsartikel (refereegranskat)abstract BackgroundWhile left atrial (LA) enlargement is known as an early sign of left heart disease with prognostic implications in heart failure (HF), the importance of right atrial (RA) enlargement is less well studied, and the prognostic implications of interatrial size comparison are insufficiently understood. The aim of this study was to test the hypothesis that RA area larger than LA area in apical four-chamber view is associated with all-cause mortality in elderly patients with HF independent of left ventricular ejection fraction (LVEF). MethodsRetrospectively, 289 patients above 65years hospitalized for HF between April 2007 and April 2008, and who underwent an echocardiogram, were enrolled. All-cause mortality was registered during a follow-up of at least 56months. Baseline parameters measured were RA area, LA area, LA volume, LVEF, left ventricular mass (LVM), tissue Doppler systolic velocity of right ventricular free wall (SmRV), presence of severe tricuspid regurgitation (TR), tricuspid gradient, central venous pressure, systolic pulmonary artery pressure, as well as some parameters of diastolic function. ResultsIn univariate analysis RA larger than LA was associated with all-cause mortality (hazard ratio [HR] of 1.88, P<.001). The relation of RA larger than LA to all-cause mortality remained even after adjusting for age, heart rate, LVEF, atrial fibrillation, percutaneous coronary intervention, LVM index, LA volume index, SmRV, and the presence of severe TR (HR: 1.79, P=.04). ConclusionRA larger than LA, independently of LVEF, is associated with all-cause mortality in elderly patients hospitalized due to HF.
12.	Baba, Akiyasu, et al. (författare) Antigen-specific effects of autoantibodies against sarcolemmal Na-K-ATPase pump in immunized cardiomyopathic rabbits. 2006 Ingår i: International journal of cardiology. - : Elsevier BV. - 0167-5273. ; 112:1, s. 15-20 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: We examine antigen-specific actions of autoantibodies directed against sarcolemmal Na-K-ATPase. BACKGROUND: Autoantibodies against some receptors or pumps were detected in patients with dilated cardiomyopathy. Although immunoglobulin adsorption therapy improved cardiac function in such patients, direct pathogenic effects of autoantibodies remain to be proven. METHODS: Japanese white rabbits were immunized once a month with purified Na-K-ATPase (NKA rabbits, n=10) or a synthetic peptide corresponding to the second extracellular loop of beta1-adrenergic receptors (beta rabbits, n=10), respectively. Control rabbits (n=10) received vehicle in the same manner. RESULTS: At 6 months, cardiac hypertrophy along with increased left ventricular end-diastolic pressure was observed in both NKA and beta rabbits, and inhibitory G protein level increased in both NKA and beta rabbits. Histological findings showed similar myocyte hypertrophy and interstitial fibrosis in both rabbits. Enzymatic activities of Na-K-ATPase were lower in NKA rabbits than in other groups. Immunoblotting showed that alpha3-isoform of Na-K-ATPase was selectively reduced in myocardium from NKA rabbits. CONCLUSIONS: Our present findings suggested that isoform-specific alterations of myocardial Na-K-ATPase activity were induced by immunizing rabbits. This was not secondary change due to cardiac hypertrophy. Thus, autoantibodies against sarcolemmal Na-K-ATPase have antigen-specific effect on the heart in vivo.
13.	Baba, Akiyasu, et al. (författare) Autoantibodies against M2-muscarinic acetylcholine receptors: new upstream targets in atrial fibrillation in patients with dilated cardiomyopathy. 2004 Ingår i: European heart journal. - : Oxford University Press (OUP). - 0195-668X. ; 25:13, s. 1108-15 Tidskriftsartikel (refereegranskat)abstract AIM: To characterise the clinical significance of M2-muscarinic acetylcholine receptor autoantibodies (M2-AAB) in patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: Sera from 104 patients with DCM, age-matched with 104 patients with idiopathic atrial fibrillation (Af) and 104 healthy control subjects, were screened for M2-AAB by enzyme-linked immunosorbent assay (ELISA). IgG purified by Protein-A column was also used as a primary antibody in ELISA. In DCM, M2-AAB were detected in 40% of patients using whole sera and in 36% of patients using purified IgG. M2-AAB were also found in several patients with idiopathic Af (23%, 23%), and these frequencies were significantly higher than those in healthy subjects (8%, 8%). Af was more common in AAB-positive than in AAB-negative patients with DCM. Multivariable analysis confirmed that M2-AAB were independent predictors of the presence of Af in such patients. We determined electrophysiological changes by adding patient purified M2-AAB to chick embryos. Purified IgG from both Af and DCM patients exhibited negative chronotropic effects and induced supraventricular arrhythmias. CONCLUSION: M2-AAB may play a role in mediating the development of Af in patients with DCM.
14.	Baba, Akiyasu, et al. (författare) Autoantibodies in atrial fibrillation: actor, biomaker or bystander? 2008 Ingår i: Autoimmunity. - : Informa UK Limited. - 1607-842X .- 0891-6934. ; 41:6, s. 470-2 Forskningsöversikt (refereegranskat)abstract Atrial fibrillation (AF) is one of the most common arrhythmias in patients with congestive heart failure, although the underlying mechanism has still to be determined. There is increasing evidence to suggest that autoimmunity may play an important role in the pathogenesis of AF. To date, at least three types of autoantibody have been found in AF: the anti-myosin heavy chain autoantibody, the anti-M2 muscarinic receptor autoantibody and the anti-heat shock protein autoantibody. The question is: are these autoantibodies actors, biomakers or merely bystanders? How much knowledge do we have?
15.	Barywani, Salim B., 1968, et al. (författare) Acute coronary syndrome in octogenarians: association between percutaneous coronary intervention and long-term mortality 2015 Ingår i: Clinical Interventions in Aging. - : Informa UK Limited. - 1178-1998. ; 10, s. 1547-1553 Tidskriftsartikel (refereegranskat)abstract Aim: Evidence of improved survival after use of percutaneous coronary intervention (PCI) in elderly patients with acute coronary syndrome (ACS) is limited. We assessed the association between PCI and long-term mortality in octogenarians with ACS. Methods and results: We followed 353 consecutive patients aged >= 80 years hospitalized with ACS during 2006-2007. Among them, 182 were treated with PCI, whereas 171 were not. PCI-treated patients were younger and more often male, and had less stroke and dependency in activities of daily living, but there were no significant differences in occurrence of diabetes mellitus, chronic obstructive pulmonary disease, hypertension, and uncured malignancies between the two groups. The association between PCI and all-cause mortality was assessed in the overall cohort and a 1: 1 matched cohort based on propensity score (PS). In overall cohort, 5-year all-cause mortality was 46.2% and 89.5% in the PCI and non-PCI groups, respectively. Cox regression analysis in overall cohort by adjustment for ten baseline variables showed statistically significant association between PCI and reduced long-term mortality (P < 0.001, hazard ratio 0.4, 95% confidence interval [CI] 0.2-0.5). In propensity-matched cohort, 5-year all-cause mortality was 54.9% and 83.1% in the PCI and non-PCI groups, respectively. Kaplan-Meier survival curves and log rank test showed significantly improved mean survival rates (P=0.001): 48 months (95% CI 41-54) for PCI-treated patients versus 35 months (95% CI 29-42) for non-PCI-treated patients. Furthermore, by performing Cox regression analysis, PCI was still associated with reduced long-term mortality (P=0.029, hazard ratio 0.5, 95% CI 0.3-0.9) after adjustment for PS and confounders: age, male sex, cognitive deterioration, uncured malignancies, left ventricular ejection fraction <45%, estimated glomerular filtration rate < 35 mL/min, ST-segment elevation myocardial infarction, mitral regurgitation, and medication at discharge with clopidogrel and statins. Conclusion: In octogenarians with ACS, PCI was associated with improved survival from all-cause death over 5 years of follow-up.
16.	Barywani, Salim B., 1968, et al. (författare) Does the target dose of neurohormonal blockade matter for outcome in Systolic heart failure in octogenarians? 2015 Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 187, s. 666-672 Tidskriftsartikel (refereegranskat)abstract Background: In elderly patients with chronic heart failure (CHF), a gap exists between widespread use of lower doses of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-receptor blockers (ARBs) and beta-blockers (BBs) and guideline recommendations. Therefore, the aim of the present study was to investigate whether patients receiving >= 50% target dose outperform those receiving <50% target dose, despite maximum up-titration, and whether the target dose outperforms all other doses. Methods and Results: Patients (n=185) aged >= 80 years with CHF and left ventricular ejection fraction >= 40% referred (between January 2000 and January 2008) to two CHF outpatient clinics at two university hospitals, were included and retrospectively studied. Of the study population, 53% received the target dose of ACEIs/ARBs, whereas 26% received <50% of the target dose. Half received <50% of the target dose of BBs and 21% received the target dose. After >= 5 years of follow-up, all-cause mortality was 76.8%. Patients who received the target dose of ACEIs/ARBs had higher survival rates from all-cause mortality than those receiving <50% of target dose (HR = 0.6, 95% CI 0.4-0.9, P = 0.033), but those receiving >= 50% of target dose did not statistically differ from those who achieved target dose. This dose-survival relationship was not the case for BBs. Conclusions: Target dose of ACEIs/ARBs is associated with reduced all-cause five-year mortality in very old patients with systolic heart failure, despite that this was achievable in only about half of the patients. However, the clinical outcome of BB therapy is independent of BB dose when the target heart rate is achieved. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
17.	Barywani, Salim B., 1968, et al. (författare) Predictors of long-term outcome of percutaneous coronary intervention in octogenarians with acute coronary syndrome 2014 Ingår i: IJC Heart and Vessels. - : Elsevier BV. - 2214-7632. ; 4:1, s. 138-144 Tidskriftsartikel (refereegranskat)abstract The majority of patients with acute coronary syndrome (ACS) are elderly. Limited evidence makes decision-making on the use of percutaneous coronary intervention (PCI) mainly empirical. Old age is one risk factor, but other factors than age may have an impact on mortality as well. Therefore, we investigated predictors of long-term all-cause mortality among octogenarians who have undergone PCI due to ACS. A total of 182 patients ≥. 80 years who underwent PCI during 2006-2007 at Sahlgrenska University Hospital were studied consecutively from recorded clinical data. All-cause five-year mortality of follow-up was 46.2%. Mean age was 83.7. ±. 2.8, 62% were male, 76% were in sinus rhythm, and 42% had left ventricular ejection fraction. < 45%. Indications for PCI were STEMI (52%), NSTEMI (36%) and unstable angina (11%). Multivariate analysis in two steps identified atrial fibrillation, moderate tricuspid valve regurgitation, moderate mitral valve regurgitation, dependency in ADL and eGFR. ≤. 30. ml/min at the first step and moderate mitral valve regurgitation, atrial fibrillation and eGFR. ≤. 30 ml/min at the last step, as independent predictors of all-cause mortality. Kaplan Meier analysis of positive parameters from both steps of multivariate analysis showed high significant difference in survival between patients having these parameters and those who were free from these parameters, with worst prognosis in patients with accumulation of these parameters. Accordingly, we have, in an octogenarian patient cohort who suffered from ACS, undergone PCI in daily clinical practice, identified five prognostic predictors for all-cause death after five years' follow-up.
18.	Barywani, Salim B., 1968, et al. (författare) Prognostic significance of mitral regurgitation in long-term all-cause mortality in patients aged >/=80 years with acute coronary syndrome. [Int J Cardiol. 2014, 176(2):340-5] 2016 Ingår i: International journal of cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 206 Annan publikation (övrigt vetenskapligt/konstnärligt)
19.	Basic, Carmen, 1975, et al. (författare) Heart failure outcomes in low-risk patients with atrial fibrillation: a case-control study of 680 523 Swedish individuals 2023 Ingår i: Esc Heart Failure. - 2055-5822. ; 10:4, s. 2281-2289 Tidskriftsartikel (refereegranskat)abstract AimsKnowledge of long-term outcomes in patients with atrial fibrillation (AF) remains limited. We sought to evaluate the risk of new-onset heart failure (HF) in patients with AF and a low cardiovascular risk profile. Methods and resultsData from the Swedish National Patient Register were used to identify all patients with a first-time diagnosis of AF without underlying cardiovascular disease at baseline between 1987 and 2018. Each patient was compared with two controls without AF from the National Total Population Register. In total, 227 811 patients and 452 712 controls were included. During a mean follow-up of 9.1 (standard deviation 7.0) years, the hazard ratio (HR) for new-onset HF was 3.55 [95% confidence interval (CI) 3.51-3.60] in patients compared with controls. Women with AF (18-34 years) had HR for HF onset 24.6 (95% CI 7.59-80.0) and men HR 9.86 (95% CI 6.81-14.27). The highest risk was within 1 year in patients 18-34 years, HR 103.9 (95% CI 46.3-233.1). The incidence rate within 1 year increased from 6.2 (95% CI 4.5-8.6) per 1000 person-years in young patients (18-34 years) to 142.8 (95% CI 139.4-146.3) per 1000 person-years among older patients (>80 years). ConclusionsPatients studied had a three-fold higher risk of developing HF compared with controls. Young patients, particularly women, carry up to 100-fold increased risk to develop HF within 1 year after AF. Further studies in patients with AF and low cardiovascular risk profile are needed to prevent serious complications such as HF.
20.	Basic, Carmen, 1975, et al. (författare) Många patienter med systolisk hjärtsvikt är underbehandlade 2021 Ingår i: Läkartidningen 21-22/2021. ; :21-22 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
21.	Basic, Carmen, 1975, et al. (författare) Sex-related differences among young adults with heart failure in Sweden 2022 Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 362, s. 97-103 Tidskriftsartikel (refereegranskat)abstract Background: Differences between the sexes among the non-elderly with heart failure (HF) have been insufficiently evaluated. This study aims to investigate sex-related differences in early-onset HF. Methods: Patients aged 18 to 54 years who were registered from 2003 to 2014 in the Swedish Heart Failure Register were included. Each patient was matched with two controls from the Swedish Total Population Register. Data on comorbidities and outcomes were obtained through the National Patient Register and Cause of Death Register. Results: We identified 3752 patients and 7425 controls. Of the patients, 971 (25.9%) were women and 2781 (74.1%) were men with a mean (standard deviation) age of 44.9 (8.4) and 46.4 (7.3) years, respectively. Men had more hypertension and ischemic heart disease, whereas women had more congenital heart disease and obesity. During the median follow-up of 4.87 years, 26.5 and 24.7 per 1000 person-years male and female patients died, compared with 3.61 and 2.01 per 1000 person-years male and female controls, respectively. The adjusted hazard ratios for all-cause mortality, compared with controls, were 4.77 (3.78-6.01) in men and 7.84 (4.85-12.7) in women (p for sex difference = 0.11). When HF was diagnosed at 30, 35, 40, and 45 years, women and men lost up to 24.6 and 24.2, 24.4 and 20.9, 20.5 and 18.3, and 20.7 and 16.5 years of life, respectively. Conclusion: Long-term mortality was similar between the sexes. Women lost more years of life than men.
22.	Basic, Carmen, 1975, et al. (författare) Young patients with heart failure: clinical characteristics and outcomes. Data from the Swedish Heart Failure, National Patient, Population and Cause of Death Registers 2020 Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 22:7, s. 1125-1132 Tidskriftsartikel (refereegranskat)abstract Aims The prevalence and hospitalizations of patients with heart failure (HF) aged <55 years have increased in Sweden during the last decades. We aimed to compare characteristics of younger and older patients with HF, and examine survival in patients All patients >= 18 years in the Swedish Heart Failure Register from 2003 to 2014 were included. Data were merged with National Patient and Cause of Death Registers. Among 60 962 patients, 3752 (6.2%) were <55 years, and were compared with 7425 controls from the Population Register. Compared with patients >= 55 years, patients <55 years more frequently had registered diagnoses of obesity, dilated cardiomyopathy, congenital heart disease, and an ejection fraction <40% (9.8% vs. 4.7%, 27.2% vs. 5.5%, 3.7% vs. 0.8%, 67.9% vs. 45.1%, respectively; allP < 0.001). One-year all-cause mortality was 21.2%, 4.2%, and 0.3% in patients >= 55 years, patients <55 years, and controls <55 years, respectively (allP < 0.001). Patients <55 years had a five times higher mortality risk compared with controls [hazard ratio (HR) 5.48, 95% confidence interval (CI) 4.45-6.74]; the highest HR was in patients 18-34 years (HR 38.3, 95% CI 8.70-169; bothP < 0.001). At the age of 20, the estimated life-years lost was up to 36 years for 50% of patients, with declining estimates with increasing age. Conclusion Patients with HF <55 years had different comorbidities than patients >= 55 years. The highest mortality risk relative to that of controls was among the youngest patients.
23.	Bjurman, Christian, 1983, et al. (författare) Assessment of a multi-marker risk score for predicting cause-specific mortality at three years in older patients with heart failure and reduced ejection fraction. 2015 Ingår i: Cardiology journal. - 1897-5593. ; 22:1, s. 31-6 Tidskriftsartikel (refereegranskat)abstract Due to increasing co-morbidity associated with aging, heart failure (HF) has become more prevalent and heterogeneous in older individuals, and non-cardiovascular (CV) mortality has increased. Previously, we defined a multi-marker modality that included cystatin C (CysC), troponin T (TnT), and age. Here, we validated this multi-marker risk score by evaluating its predictions of all-cause mortality and CV mortality in an independent population of older individuals with HF and reduced ejection fraction (HFrEF).
24.	Bjurman, Christian, 1983, et al. (författare) Assessment of a multimarker strategy for prediction of mortality in older heart failure patients: a cohort study 2013 Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 3:3 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Primarily to develop a multimarker score for prediction of 3-year mortality in older patients with decompensated heart failure (HF). DESIGN: Prospective cohort study. SETTING: Secondary care. Single centre. PATIENTS AND BIOMARKERS: 131 patients, aged >/=65 years, with decompensated HF were included. Assessment of biomarkers was performed at discharge. PRIMARY OUTCOME MEASURE: 3-year mortality. RESULTS: Mean age was 73+/-11 years; mean left ventricular ejection fraction , 43+/-14%; 53% were male. The 3-year mortality was 53.4%. The following N-terminal brain natriuretic peptide (NTproBNP) levels could optimally stratify mortality: <2000 ng/l (n=39), 30.8% mortality; 2000-8000 ng/l (n=58), 51.7% mortality; and >8000 ng/l (n=34), 82.4% mortality. However, in the 2000-8000 ng/l range, NTproBNP levels had low-prognostic capacity, based on the area under the receiver operating characteristic curve (AUC=0.53; 95% CI 0.40 to 0.67). In this group, multivariate analysis identified age, cystatin C (CysC), and troponin T (TnT) levels as independent risk factors. A risk score based on these three risk factors separated a high-risk and low-risk groups within the NTproBNP range of 2000-8000 ng/l. The score exhibited a significantly higher AUC (0.75; 95% CI 0.62 to 0.86) than NTproBNP alone (p=0.03) in this NTproBNP group and had similar prognostic capacity as NTproBNP in patients below or above this NTproBNP range (p=0.57). Net reclassification improvement and integrated discriminatory improvement in the group with NTproBNP levels between 2000 and 8000 ng/l was 54% and 23%, respectively, and in the whole cohort 22% and 11%, respectively. CONCLUSIONS: Our results suggested that, to assess risk in HF, older patients required significantly higher levels of NTproBNP than younger patients. Furthermore, a risk score that included TnT and CysC at discharge, and age could improve risk stratification for mortality in older patients with HF in particular when NTproBNP was moderately elevated.
25.	Bjurman, Christian, 1983, et al. (författare) Cystatin C in a composite risk score for mortality in patients with infective endocarditis: a cohort study 2012 Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 2:4 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To develop a multimarker prognostic score for infective endocarditis (IE). DESIGN: Retrospective case-control. SETTING: Secondary care. Single centre. PARTICIPANTS: 125 patients with definite IE. PRIMARY OUTCOME MEASURES: 90-day and 5-year mortality. RESULTS: Mean age was 62.7+/-17 years. The 90-day and 5-year mortality was 10.4% and 33.6%, respectively. CysC levels at admission and over 20% increases in CysC levels during 2 weeks of treatment were prognostic for 90-day and 5-year mortality independent of creatinine estimated glomerular filtration rate. In multivariate analyses, CysC (OR 5.42, 95% CI 1.90 to 15.5, p=0.002) and age (OR 1.06, 95% CI 1.02 to 1.10, p=0.002) remained prognostic for 5-year mortality. NT-proBNP, TnT, C reactive protein and interleukin 6 were also linked to prognosis. A composite risk scoring system using levels of CysC, NT-proBNP, age and presence of mitral valve insufficiency was able to separate a high-risk and a low-risk group. CONCLUSIONS: CysC levels at admission and increase in CysC after 2 weeks of treatment were independent prognostic markers for both 90-day and 5-year mortality in patients with IE. A multimarker composite risk scoring system including CysC identified a high-risk group.
26.	Bjurman, Christian, 1983, et al. (författare) Decreased admissions and hospital costs with a neutral effect on mortality following lowering of the troponin T cutoff point to the 99th percentile 2017 Ingår i: Cardiology journal. - 1897-5593 .- 1898-018X. ; 24:6, s. 612-622 Tidskriftsartikel (refereegranskat)abstract Background: The implementation of high-sensitivity cardiac troponin T (hs-cTnT) assays and a cutoff based on the 99th cTnT percentile in the evaluation of patients with suspected acute coronary syndrome has not been uniform due to uncertain effects on health benefits and utilization of limited resources.Methods:Clinical and laboratory data from patients with chest pain or dyspnea at the emergency department (ED) were evaluated before (n = 20516) and after (n = 18485) the lowering of the hs-cTnT cutoff point from 40 ng/L to the 99th hs-cTnT percentile of 14 ng/L in February 2012. Myocardial infarction (MI) was diagnosed at the discretion of the attending clinicians responsible for the patient.Results:Following lowering of the hs-cTnT cutoff point fewer ED patients with chest pain or dyspnea as the principal complaint were analyzed with an hs-cTnT sample (81% vs. 72%, p < 0.001). Overall 30-day mortality was unaffected but increased among patients not analyzed with an hs-cTnT sample (5.3% vs. 7.6%, p < 0.001). The MI frequency was unchanged (4.0% vs. 3.9%, p = 0.72) whereas admission rates decreased (51% vs. 45%, p < 0.001) as well as hospital costs. Coronary angiographies were used more frequently (2.8% vs. 3.3%, p = 0.004) but with no corresponding change in coronary interventions.Conclusions:At the participating hospital, lowering of the hs-cTnT cutoff point to the 99th percentile decreased admissions and hospital costs but did not result in any apparent prognostic or treatment benefits for the patients.
27.	Bjurman, Christian, 1983, et al. (författare) High-sensitive cardiac troponin, NT-proBNP, hFABP and copeptin levels in relation to glomerular filtration rates and a medical record of cardiovascular disease 2015 Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 48:4-5, s. 302-307 Tidskriftsartikel (refereegranskat)abstract Background: Elevation of cardiac markers in patients with renal dysfunction has not been fully assessed reducing the diagnostic usefulness of these biomarkers. Objective: To examine the effects of renal function and a medical record of cardiovascular disease on levels of cardiac biomarkers. Methods: Serum samples were collected from 489 patients referred for GFR measurement using Cr51-EDTA or iohexol plasma clearance (measured GFR). The cardiac biomaiters Troponin T (hs-cTnT), Troponin I (hsTnI), N-Terminal pro Brain Natriuretic Peptide (NTproBNP), Copeptin, Human Fatty Acid Binding Protein (hFABP), as well as the kidney function biomarkers creatinine and cystatin C, were measured. Regression was used to analyse the relationship between biomarker levels and the glomerular filtration rate (GFR) between 15 and 90 mL/min/1.73 m(2). Results: Compared with normal kidney function, the estimated increases in the studied cardiac biomarkers at a CUR of 15 mL/mM/1.73 m(2) varied from 2-fold to 15 fold but were not very different between patients with or without a medical record of cardiovascular disease and were most prominent for cardiac biomarkers with low molecular weight. hs-cTnT levels correlated more strongly to measured CUR and increased more at low CUR compared to hs-cTnI. For hFABP and NT-proBNP increases at low kidney function were more correctly predicted by a local Cystatin C-based eGFR formula compared with creatinine-based eGFR (using the MDRD or CKD-EPI equations) Conclusion: The extent of the elevation of cardiac markers at low renal function is highly variable. For hFABP and NTproBNP Cystatin C-based eGFR provides better predictions of the extent of elevation compared to the MDRD or CKD-EPI equations. (C) 2015 The Authors. The Canadian Society of Clinical Chemists. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd,40/).
28.	Bkaily, Ghassan, et al. (författare) Modulation of intracellular Ca2+ via L-type calcium channels in heart cells by the autoantibody directed against the second extracellular loop of the alpha1-adrenoceptors. 2003 Ingår i: Canadian journal of physiology and pharmacology. - : Canadian Science Publishing. - 0008-4212 .- 1205-7541. ; 81:3, s. 234-46 Tidskriftsartikel (refereegranskat)abstract The effects of methoxamine, a selective alpha1-adrenergic receptor agonist, and the autoantibody directed against the second extracellular loop of alpha1-adrenoceptors were studied on intracellular free Ca2+ levels using confocal microscopy and ionic currents using the whole-cell patch clamp technique in single cells of 10-day-old embryonic chick and 20-week-old fetal human hearts. We observed that like methoxamine, the autoantibody directed against the second extracellular loop of alpha1-adrenoreceptors significantly increased the L-type calcium current (I(Ca(L))) but had no effect on the T-type calcium current (I(Ca(T))), the delayed outward potassium current, or the fast sodium current. This effect of the autoantibody was prevented by a prestimulation of the receptors with methoxamine and vice versa. Moreover, treating the cells with prazosin, a selective alpha1-adrenergic receptor antagonist blocked the methoxamine and the autoantibody-induced increase in I(Ca(L)), respectively. In absence of prazosin, both methoxamine and the autoantibody showed a substantial enhancement in the frequency of cell contraction and that of the concomitant cytosolic and nuclear free Ca2+ variations. The subsequent addition of nifedipine, a specific L-type Ca2+ channel blocker, reversed not only the methoxamine or the autoantibody-induced effect but also completely abolished cell contraction. These results demonstrated that functional alpha1-adrenoceptors exist in both 10-day-old embryonic chick and 20-week-old human fetal hearts and that the autoantibody directed against the second extracellular loop of this type of receptors plays an important role in stimulating their activity via activation of L-type calcium channels. This loop seems to have a functional significance by being the target of alpha1-receptor agonists like methoxamine.
29.	Bollano, Entela, 1970, et al. (författare) Cardiac remodeling rather than disturbed myocardial energy metabolism is associated with cardiac dysfunction in diabetic rats. 2006 Ingår i: Int J Cardiol. - : Elsevier BV. - 0167-5273. Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Diabetes mellitus (DM) alters the energy substrate metabolism in the heart and the early sign of diabetic cardiomyopathy is the diastolic dysfunction. Although it is known that the extracellular matrix must be altered in the presence of diabetes, its local regulation has not been fully elucidated. Our aim was to evaluate in vivo left ventricular (LV) structure; function and bioenergetics in streptozotocin (STZ) induced diabetes mellitus. METHODS: Cardiac function was evaluated using echocardiography in anesthetized Sprague-Dawley rats 12 weeks after injection of STZ and in age-matched control rats before and after atrial pacing. In vivo (31)P magnetic resonance spectroscopy was done to measure the phosphocreatine (PCr) to ATP ratio. Myocardial protein expression of metalloproteinases MMP-2, -9, tissue inhibitor TIMP-1, -2 and collagen was measured using Western blot. RESULTS: Bodyweight (BW) was decreased in diabetic rats. Heart weight/BW and LV mass/BW ratios were higher in diabetic animals compared to controls (2.3+/-08 vs 2.1+/-08 mg/g p<0.05). Heart rate was lower in diabetic rats (293+/-20 vs 394+/-36 bpm p<0.05). The velocity of circumferential shortening and peak aortic velocity were lower in diabetic animals and were more pronounced during atrial pacing. The basal PCr/ATP ratio was not different in the two groups. Total collagen was higher in diabetic rats (3.8+/-0.3 vs 2.9+/-01 mg/g, p<0.05). Protein expression of MMP-2 was significantly diminished in diabetic rats by approximately 60%, while MMP-9, TIMP-1 and -2 were unchanged. CONCLUSION: Streptozotocin induced diabetes led to increased LV/bodyweight, increased collagen content, and diminished MMP-2 with no change in PCr/ATP. Therefore, remodeling rather than disturbed energetics may underlie diabetic cardiomyopathy.
30.	Bollano, Entela, 1970, et al. (författare) Impairment of cardiac function and bioenergetics in adult transgenic mice overexpressing the bovine growth hormone gene. 2000 Ingår i: Endocrinology. - 0013-7227. ; 141:6, s. 2229-35 Tidskriftsartikel (refereegranskat)abstract Cardiovascular abnormalities represent the major cause of death in patients with acromegaly. We evaluated cardiac structure, function, and energy status in adult transgenic mice overexpressing bovine GH (bGH) gene. Female transgenic mice expressing bGH gene (n = 11) 8 months old and aged matched controls (n = 11) were used. They were studied with two-dimensional guided M-mode and Doppler echocardiography. The animals (n = 6) for each group were examined with 31P magnetic resonance spectroscopy to determine the cardiac energy status. Transgenic mice had a significantly higher body weight (BW), 53.2+/-2.4 vs. 34.6+/-3.7 g (P < 0.0001) and hypertrophy of left ventricle (LV) compared with normal controls: LV mass/BW 5.6+/-1.6 vs. 2.7+/-0.2 mg/g, P < 0.01. Several indexes of systolic function were depressed in transgenic animals compared with controls mice such as shortening fraction 25+/-3.0% vs. 39.9+/-3.1%; ejection fraction, 57+/-9 vs. 77+/-5; mean velocity of circumferential shortening, 4.5+/-0.8 vs. 7.0+/-1.1 circ/sec, p < 0.01. Creatine phosphate-to-ATP ratio was significantly lower in bGH overexpressing mice (1.3+/-0.08 vs. 2.1+/-0.23 in controls, P < 0.05). Ultrastructural examination of the hearts from transgenic mice revealed substantial changes of mitochondria. This study provides new insight into possible mechanisms behind the deteriorating effects of long exposure to high level of GH on heart function.
31.	Buvall, Lisa, 1976, et al. (författare) Antibodies against the beta1-adrenergic receptor induce progressive development of cardiomyopathy 2007 Ingår i: J Mol Cell Cardiol. - : Elsevier BV. - 0022-2828. ; 42:5, s. 1001-7 Tidskriftsartikel (refereegranskat)abstract Different immune disturbances have been found among patients with dilated cardiomyopathy (DCM), including antibodies directed against different cardiac antigens, such as the second extracellular loop of the beta(1)-adrenergic receptor. The aim of our study was to investigate antibodies directed against the second extracellular loop of the beta(1)-adrenergic receptor effect on cardiac functions at an early and late stage during DCM development. This was made in a mouse model, in which DCM was induced by immunization with the second extracellular loop of the beta(1)-adrenergic receptor. Mice were immunized for 14 or 25 weeks respectively with the second extracellular loop of the beta(1)-adrenergic receptor. At 14 weeks, there was no decreased heart function reviled by echocardiography at rest, but when dobutamine stress echocardiography was used, a lower cardiac reserve was shown in the mice with antibodies against the second extracellular loop of the beta(1)-adrenergic receptor. By 25 weeks, decreased heart function, dilatation of the left ventricle and thinner left ventricular posterior wall were observed. Further biochemical analyses at 25 weeks showed increased mRNA expressions for beta(1)-adrenergic receptor kinase, monocyte chemoattractant protein-1 and the brain natriuretic peptide as well as increased concentrations of complement factor 3 in sera in the immunized animals. Our data suggest a cardiotoxic effect of antibodies directed against the second extracellular loop of the beta(1)-adrenergic receptor and a capacity to induce DCM with progressive remodeling, decreased cardiac function, altered beta(1)AR signaling and upregulation of proinflammatory components.
32.	Buvall, Lisa, 1976, et al. (författare) Phenotype of early cardiomyopathic changes induced by active immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the human beta-adrenergic receptor 2006 Ingår i: Clin Exp Immunol. - : Oxford University Press (OUP). - 0009-9104. ; 143:2, s. 209-15 Tidskriftsartikel (refereegranskat)abstract In the failing human heart, due to idiopathic dilated cardiomyopathy, it has been suggested that the beta1-adrenergic receptor (beta1AR) is a potential pathogenic autoantigen. The aim of the present study was to investigate whether immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the beta1AR (beta1AR EC(II)) was able to induce the early stage of cardiomyopathy and also to investigate immunological and receptor functional parameters at a transcriptional level to permit insights into the autoimmune mechanism in cardiomyopathy. Eleven Whistar Fur rats were immunized with a beta1AR EC(II) peptide (H26R) once a month during 12 months and seven control rats were injected with vehicle according to the same procedure used for the immunized group. Cardiac function, beta1AR autoantibodies and their functional effects on cardiomyocytes were analysed. beta1AR receptor signalling, immunological and cardiomyocyte stretch markers were determined on transcriptional level. In H26R immunized rats, beta1AR autoantibodies were shown to be present and functionally active, cardiac functions in terms of fractional shortening were decreased and beta1-adrenergic receptor kinase (GRK2) mRNA were increased compared with the control group. These data have shown that immunization of rats with a putative antigenic peptide was able to induce an early stage phenotype of cardiomyopathy in the form of cardiac dysfunction and up-regulation of GRK2 as the first step in the desensitization process of the beta1AR, implying the pathological importance of the beta1AR autoantibody.
33.	Caforio, A. L., et al. (författare) Immune-mediated and autoimmune myocarditis: clinical presentation, diagnosis and management 2013 Ingår i: Heart failure reviews. - : Springer Science and Business Media LLC. - 1573-7322 .- 1382-4147. ; 18:6, s. 715-732 Tidskriftsartikel (refereegranskat)abstract According to the current WHO classification of cardiomyopathies, myocarditis is an inflammatory disease of the myocardium and is diagnosed by endomyocardial biopsy using established histological, immunological and immunohistochemical criteria; it may be idiopathic, infectious or autoimmune and may heal or lead to dilated cardiomyopathy (DCM). DCM is characterized by dilatation and impaired contraction of the left or both ventricles; it may be idiopathic, familial/genetic, viral and/or immune. The diagnosis of DCM requires exclusion of known, specific causes of heart failure, including coronary artery disease. On endomyocardial biopsy, there is myocyte loss, compensatory hypertrophy, fibrous tissue and immunohistochemical findings consistent with chronic inflammation (myocarditis) in 30-40 % of cases. In a patient subset, myocarditis and DCM represent the acute and chronic stages of an inflammatory disease of the myocardium, which can be viral, post-infectious immune or primarily organ-specific autoimmune. Here, we review the clinical presentation, etiopathogenetic diagnostic criteria, and management of immune-mediated and autoimmune myocarditis.
34.	Caforio, A. L. P., et al. (författare) Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases 2013 Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:33 Tidskriftsartikel (refereegranskat)abstract In this position statement of the ESC Working Group on Myocardial and Pericardial Diseases an expert consensus group reviews the current knowledge on clinical presentation, diagnosis and treatment of myocarditis, and proposes new diagnostic criteria for clinically suspected myocarditis and its distinct biopsy-proven pathogenetic forms. The aims are to bridge the gap between clinical and tissue-based diagnosis, to improve management and provide a common reference point for future registries and multicentre randomised controlled trials of aetiology-driven treatment in inflammatory heart muscle disease.
35.	Caforio, Alida L. P., et al. (författare) Endomyocardial biopsy: safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry 2024 Ingår i: EUROPEAN HEART JOURNAL. - 0195-668X .- 1522-9645. Tidskriftsartikel (refereegranskat)abstract Background and Aims Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. Methods Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. Results Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. Conclusions Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.
36.	Cao, J., et al. (författare) Prognostic value of N-terminal B-type natriuretic peptide on all-cause mortality in heart failure patients with preserved ejection fraction 2019 Ingår i: Chinese Journal of Cardiology. Zhonghua xin xue guan bing za zhi. - 0253-3758. ; 47:11, s. 875-881 Tidskriftsartikel (refereegranskat)abstract Objective: To investigate the prognostic value of N-terminal B-type natriuretic peptide (NT-proBNP) on all-cause mortality in heart failure patients with preserved ejection fraction (HFpEF) at real world scenarios. Methods: Patients who met the diagnostic criteria of HFpEF in the China National Heart Failure Registration Study (CN-HF) were divided into death and survival groups. The demographic data, physical examination, results of the first echocardiography, laboratory results at admission, complications, drug use and clinical outcomes were obtained from CN-HF. The univariate Cox proportional hazard model was used to screen the variates that might predict prognosis, and then the covariates with statistical significance were included in the multivariate Cox regression model to analyze the predictive value of baseline NT-proBNP on all-cause death. Spearman correlation analysis was used to evaluate the relationship between NT-proBNP and estimated glomerular filtration rate (eGFR), so as to further explore the predictive value of the interaction between renal dysfunction and NT-proBNP on death. Since NT-proBNP did not obey the binary normal distribution, it was expressed by the natural logarithm of NT-proBNP (LnNT-proBNP). Results: A total of 1 846 HFpEF patients were enrolled in this study, with an average age of 71.5 years, 1 017 males(55.1%), median NT-proBNP 860 ng/L, and median eGFR 73.9 ml·min-1·1.73m-2. After a median follow-up of 34 months, 213 (11.5%) patients died. Patients in the death group were older, with higher NYHA classification Ⅲ-Ⅳ ratio, longer hospital stay, higher serum potassium and NT-proBNP level, prevalence of complications of diabetes mellitus, arrhythmia and atrial fibrillation, use of angiotensin receptor antagonist(ARB), mineralocorticoid receptor antagonists (MRA), diuretic and digoxin was significantly higher in death group than in survival group. Body mass index (BMI), diastolic blood pressure, left ventricular ejection fraction (LVEF), hemoglobin, serum cholesterol(TC), serum triglycerides (TG) and eGFR, and use of angiotensin converting enzyme inhibitors (ACEI), statins and aspirin were lower in death group than in survival group. Univariate Cox regression analysis showed that NT-proBNP was a predictor of all-cause death in HFpEF patients (HR=2.522, 95%CI 2.040-3.119, P<0.001). Multivariate Cox regression analysis showed that the elevated NT-proBNP remains as the independent predictor of all-cause death in patients with HFpEF (HR=1.230, 95%CI 1.049-1.442, P=0.011) after adjusting for age, BMI, diastolic blood pressure, LVEF, hemoglobin, serum potassium, serum sodium, TC, serum high-density lipoprotein cholesterol (HDL-C), TG, eGFR, atrial fibrillation, as well as the treatment of ACEI/ARB, MRA, diuretics and digoxin. Spearman correlation analysis showed that LnNT-proBNP was negatively correlated with eGFR (r=-0.361, P<0.001), but there was no interaction between NT-proBNP and renal dysfunction in predicting death in HFpEF patients (P>0.05). Conclusion: The elevated level of NT-proBNP at admission is an independent predictor of all-cause mortality in HFpEF patients. 目的：探讨入院基线N末端B型利钠肽原（NT-proBNP）对射血分数保留的心力衰竭（HFpEF）患者全因死亡的预测价值。方法：入选中国住院患者心力衰竭注册研究（CN-HF）中符合HFpEF诊断标准的患者，根据随访期间是否死亡分为死亡组和存活组。从CN-HF中获得研究对象的人口学信息、入院时体格检查信息、入院首次超声心动图检查结果、实验室检查结果、合并症情况、用药情况和临床结局等资料。通过单因素Cox回归模型对可能预测预后的变量进行筛选，将单因素分析中与全因死亡有统计学意义的协变量纳入多因素Cox回归模型，进而分析基线NT-proBNP对全因死亡的预测价值。采用Spearman相关分析分析NT-proBNP与估算的肾小球滤过率（eGFR）的关系，并进一步探讨肾功能不全与NT-proBNP预测全因死亡的交互作用。鉴于NT-proBNP不服从二元正态分布，本研究中NT-proBNP作连续变量分析时均取自然对数（LnNT-proBNP）。结果：共1 846例患者纳入本研究，平均年龄71.5岁，男性1 017例（55.1%），NT-proBNP中位数860 ng/L，eGFR中位数73.9 ml·min-1·1.73m-2。本研究中位随访时间34（24~42）个月，随访期间全因死亡213例（11.5%）被纳入死亡组，存活1 633例（88.5%）被纳入存活组。与存活组比较，死亡组患者年龄较大，纽约心脏协会（NYHA）心功能Ⅲ~Ⅳ级者比例较高，住院时间较长，血钾、NT-proBNP较高，合并糖尿病、心律失常、心房颤动者较多，服用血管紧张Ⅱ受体阻滞剂（ARB）、盐皮质激素受体拮抗剂（MRA）、利尿剂和地高辛者较多（P均<0.05）。与存活组比较，死亡组患者体重指数（BMI）、舒张压、左心室射血分数（LVEF）较低，血红蛋白、血清总胆固醇（TC）、血清甘油三酯（TG）、eGFR较低，服用血管紧张素转化酶抑制剂（ACEI）、他汀类药物和阿司匹林者较少（P均<0.05）。单因素Cox回归分析结果显示NT-proBNP是HFpEF患者全因死亡的预测因素（HR=2.522，95%CI 2.040~3.119，P<0.001）。多因素Cox回归分析结果显示，校正了年龄、BMI、舒张压、LVEF、血红蛋白、血钾、血钠、TC、高密度脂蛋白胆固醇、TG、eGFR、心房颤动以及ACEI/ARB、MRA、利尿剂、地高辛使用情况后，NT-proBNP仍是HFpEF患者全因死亡的独立预测因素（HR=1.230，95%CI 1.049~1.442，P=0.011）。Spearman相关分析结果显示，LnNT-proBNP与eGFR呈负相关（r=-0.361，P<0.001）。而校正了混杂因素后，多因素Cox回归分析结果显示肾功能不全与NT-proBNP预测HFpEF患者全因死亡无交互作用（P>0.05）。结论：入院基线NT-proBNP是HFpEF患者全因死亡的独立预测因素。.
37.	Chan, H C, et al. (författare) Angiotensin II receptor type I-regulated anion secretion in cystic fibrosis pancreatic duct cells. 1997 Ingår i: The Journal of membrane biology. - 0022-2631. ; 156:3, s. 241-9 Tidskriftsartikel (refereegranskat)abstract The beta-adrenergic (cAMP-dependent) regulation of Cl- conductance is defective in cystic fibrosis (CF). The present study explored alternative regulation of anion secretion in CF pancreatic ductal cells (CFPAC-1) by angiotensin II (AII) using the short-circuit current (ISC) technique. An increase in ISC could be induced in CFPAC-1 cells by basolateral or apical application of AII in a concentration-dependent manner (EC50 at 3 microm and 100 nm, respectively). Angiotensin receptor subtypes were identified using specific antagonists, losartan and PD123177, for AT1 and AT2 receptors, respectively. It was found that losartan (1 microm) could completely inhibit the AII-induced ISC, whereas, PD123177 exerted insignificant effect on the ISC, indicating predominant involvement of AT1 receptors. The presence of AT1 receptors in CFPAC-1 cells was also demonstrated by immunohistochemical studies using specific antibodies against AT1 receptors. Confocal microscopic study demonstrated a rise in intracellular Ca2+ upon stimulation by AII indicating a role of intracellular Ca2+ in mediating the AII response. Depletion of intracellular but not extracellular pool of Ca2+ diminished the AII-induced ISC. Treatment of the monolayers with a Cl- channel blocker, DIDS, markedly reduced the ISC, indicating that a large portion of the AII-activated ISC was Cl--dependent. AII-induced ISC was also observed in monolayers whose basolateral membranes had been permeabilized by nystatin, suggesting that the ISC was mediated by apical Cl- channels. Our study indicates an AT1-mediated Ca2+-dependent regulatory mechanism for anion secretion in CF pancreatic duct cells which may be important for the physiology and pathophysiology of the pancreas.
38.	Chang, W, et al. (författare) Parathyroid Ca(2+)-conducting currents are modulated by muscarinic receptor agonists and antagonists. 1997 Ingår i: The American journal of physiology. - 0002-9513. ; 273:5 Pt 1 Tidskriftsartikel (refereegranskat)abstract Parathyroid cells express Ca(2+)-conducting cation currents, which are activated by raising the extracellular Ca2+ concentration ([Ca2+]o) and blocked by dihydropyridines. We found that acetylcholine (ACh) inhibited these currents in a reversible, dose-dependent manner (50% inhibitory concentration approximately equal to 10(-8) M). The inhibitory effects could be mimicked by the agonist (+)-muscarine. The effects of ACh were blunted by the antagonist atropine and reversed by removing ATP from the pipette solution (+)-Muscarine enhanced the adenosine 3',5'-cyclic monophosphate (cAMP) production by 30% but had no effect on inositol phosphate accumulation in parathyroid cells. Oligonucleotide primers, based on sequences of known muscarinic receptors (M1-M5), were used in reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify receptor cDNA from parathyroid poly (A)+ RNA. RT-PCR products displayed > 90% nucleotide sequence identity to human M2- and M4-receptor cDNAs. Expression of M2-receptor protein was further confirmed by immunoblotting and immunocytochemistry. Thus parathyroid cells express muscarinic receptors of M2 and possibly M4 subtypes. These receptors may couple to dihydropyridine-sensitive, cation-selective currents through the activation of adenylate cyclase and ATP-dependent pathways in these cells.
39.	Chen, Jie, et al. (författare) Effects of autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy on neonatal rat cardiomyocytes 2006 Ingår i: The European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 8:5, s. 460-467 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: Immunoadsorption has been shown to improve cardiac performance and reduce mortality in patients with dilated cardiomyopathy. In this study, the underlying mechanism for these beneficial effects was investigated in cultured rat cardiomyocytes. METHODS AND RESULTS: Immunoadsorption was performed in patients with dilated cardiomyopathy (n=7). Antibody-induced complement-dependent cytotoxicity was investigated by colorimetric MTT. Autoantibodies against the beta(1)-adrenoceptor were detected by ELISA and purified. Column eluent from six patients exhibited a cytotoxic effect, three patients were positive for the beta(1)-adrenoceptor autoantibodies. The purified autoantibodies were able to visualize the beta(1)-adrenoceptors by immunocytofluorescence on rat cardiomyocytes, and also displayed partial agonist properties and induced a positive chronotropic effect, which were blocked by the beta(1)-selective antagonist bisoprolol and the peptide corresponding to the beta(1)-adrenoceptor. Column eluent from one patient induced apoptosis in nick end labelling test (8.1+/-1.7% vs. 2.9+/-1.2% in control, p<0.05). CONCLUSION: Autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy have a pathophysiological role, as shown by the complement-dependent cytotoxicity and chronotropic action on rat cardiomyocytes. This implies that removal of circulating autoantibodies might be part of the underlying mechanism for improved cardiac function.
40.	Chen, Xiaojing, et al. (författare) Age-dependent differences in clinical phenotype and prognosis in heart failure with mid-range ejection compared with heart failure with reduced or preserved ejection fraction 2019 Ingår i: Clinical Research in Cardiology. - : Springer Science and Business Media LLC. - 1861-0684 .- 1861-0692. ; 108:12, s. 1394-1405 Tidskriftsartikel (refereegranskat)abstract Background: HFmrEF has been recently proposed as a distinct HF phenotype. How HFmrEF differs from HFrEF and HFpEF according to age remains poorly defined. We aimed to investigate age-dependent differences in heart failure with mid-range (HFmrEF) vs. preserved (HFpEF) and reduced (HFrEF) ejection fraction. Methods and results: 42,987 patients, 23% with HFpEF, 22% with HFmrEF and 55% with HFrEF, enrolled in the Swedish heart failure registry were studied. HFpEF prevalence strongly increased, whereas that of HFrEF strongly decreased with higher age. All cardiac comorbidities and most non-cardiac comorbidities increased with aging, regardless of the HF phenotype. Notably, HFmrEF resembled HFrEF for ischemic heart disease prevalence in all age groups, whereas regarding hypertension it was more similar to HFpEF in age ≥ 80years, to HFrEF in age < 65years and intermediate in age 65–80years. All-cause mortality risk was higher in HFrEF vs. HFmrEF for all age categories, whereas HFmrEF vs. HFpEF reported similar risk in ≥ 80years old patients and lower risk in < 65 and 65–80years old patients. Predictors of mortality were more likely cardiac comorbidities in HFrEF but more likely non-cardiac comorbidities in HFpEF and HFmrEF with < 65years. Differences among HF phenotypes for comorbidities were less pronounced in the other age categories. Conclusion: HFmrEF appeared as an intermediate phenotype between HFpEF and HFrEF, but for some characteristics such as ischemic heart disease more similar to HFrEF. With aging, HFmrEF resembled more HFpEF. Prognosis was similar in HFmrEF vs. HFpEF and better than in HFrEF. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
41.	Chen, Xiaojing, et al. (författare) Guideline-directed medical therapy in real-world heart failure patients with low blood pressure and renal dysfunction 2021 Ingår i: Clinical Research in Cardiology. - : SPRINGER HEIDELBERG. - 1861-0684 .- 1861-0692. ; 110, s. 1051-1062 Tidskriftsartikel (refereegranskat)abstract Background Among patients with heart failure and reduced ejection fraction (HFrEF), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB), beta-blockers (BB) and mineralocorticoid receptor antagonist (MRA) are known as guideline-directed medical therapy to improve prognosis. However, low blood pressure (BP) and renal dysfunction are often challenges prevent clinical implementation, so we investigated the association of different combinations of GDMT treatments with all-cause mortality in HFrEF population with low BP and renal dysfunction. Methods This study initially included 51, 060 HF patients from the Swedish Heart Failure Registry, and finally 1464 HFrEF patients with low BP (systolic BP <= 100 mmHg) and renal dysfunction (estimated glomerular filtration rate (eGFR) <= 60 ml/min/1.73m(2)) were ultimately enrolled. Patients were receiving oral medication for HF at study enrollment, and divided into four groups (group 1-4: ACEI/ARB + BB + MRA, ACEI/ARB + BB, ACEI/ARB + MRA or ACEI/ARB only, and other). The outcome is time to all-cause mortality. Results Among the study patients, 485 (33.1%), 672 (45.9%), 109 (7.4%) and 198 (13.5%) patients were in group 1-4. Patients in group 1 were younger, had highest hemoglobin, and most with EF < 30%. During a median of 1.33 years follow-up, 937 (64%) patients died. After adjustment for age, gender, LVEF, eGFR, hemoglobin when compared with the group 1, the hazard ratio for all-cause mortality in group 2 was 1.04 (0.89-1.21) (p = 0.62), group 3 1.40 (1.09-1.79) (p = 0.009), and group 4 1.71 (1.39-2.09) (p < 0.001). Conclusions In real-world HFrEF patients with low BP and renal dysfunction, full medication of guideline-directed medical therapy is associated with improved survival. The benefit was larger close to the index date and decreased with follow-up time.
42.	Chen, Xiaojing, et al. (författare) High-normal blood pressure conferred higher risk of cardiovascular disease in a random population sample of 50-year-old men: A 21-year follow-up. 2020 Ingår i: Medicine. - 1536-5964. ; 99:17 Tidskriftsartikel (refereegranskat)abstract The relationship between various categories of blood pressure (BP), subtypes of hypertension, and development of cardiovascular disease (CVD) have not been extensively studied. Therefore, our study aimed to explore this relationship in a random population sample of men born in 1943, living in Sweden and followed over a 21-year period.Participants were examined for the first time in 1993 (age 50 years), where data on medical history, concomitant diseases, and general health were collected. The examination was repeated in 2003 and with additional echocardiography also in 2014. Classification of participants according to their BP at the age of 50 years was as follows: optimal-normal BP (systolic blood pressure [SBP] <130 and diastolic BP [DBP] <85mmHg), high-normal BP (130≤SBP<140, 85≤DBP<90mmHg), isolated systolic-diastolic hypertension (ISH-IDH) (SBP ≥140 and DBP <90 or SBP <140 and DBP ≥90mmHg), and systolic-diastolic hypertension (SDH) (SBP ≥140 and DBP ≥90mmHg).During the follow-up, the incidence of heart failure (HF), CVD, and coronary heart disease were all lowest for those with optimal-normal BP. Participants with high-normal BP showed greater wall thickness and left ventricular mass index, larger LV size and larger left atrial size when compared with the optimal-normal BP group. Furthermore, those with high-normal BP, ISH-IDH, and SDH had a higher risk of CVD than those with optimal-normal BP. The adjusted relative risk of CVD was highest for SDH (hazard ratio [HR] 1.95; 95% confidence interval [95% CI] 1.37-2.79), followed by ISH-IDH (HR 1.34; 95% CI 0.93-1.95) and high-normal BP (HR 1.31; 95% CI 0.91-1.89).Over a 21-year follow-up, the participants with high-normal BP or ISH-IDH had a higher relative risk of CVD than those with optimal-normal BP.
43.	Chen, Xiaojing, et al. (författare) High prevalence of cardiac dysfunction or overt heart failure in 71-year-old men: A 21-year follow-up of "The Study of men born in 1943" 2020 Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 27:7, s. 717-725 Tidskriftsartikel (refereegranskat)abstract Background: Knowledge about long-term risk factors and the prevalence of heart failure stages in general population is limited. We aimed to study the prevalence of cardiac dysfunction and heart failure in 71-year-old men and potential risk factors in the past two decades. Design: This research was based on a randomized selected population study with longitudinal follow-up. Methods: A random sample of men born in 1943 in Gothenburg, Sweden were examined in 1993 (at 50 years of age) and re-examined 21 years later in 2014 (at 71 years of age). Cardiac dysfunction or heart failure was classified into four stages (A-D) according to American Heart Association/American College of Cardiology guidelines on heart failure. Results:Of the 798 men examined in 1993 (overall cohort), 535 (67%) were re-examined in 2014 (echo cohort). In the echo cohort 122 (23%) men had normal cardiac function, 135 (25%) were at stage A, 207 (39%) men were at stage B, 66 (12%) men were at stage C, and five (1%) men were at stage D. Multivariable logistic regression demonstrated that elevated body mass index at 50 years old was the only independent risk factor for developing heart failure/cardiac dysfunction during the subsequent 21 years. For each unit (1 kg/m(2)) of increased body mass index, the odds ratio for stages C/D heart failure vs no heart failure/stage A increased by 1.20 (95% confidence interval, 1.11-1.31, p < 0.001), after adjustment for smoking, sedentary life style, systolic blood pressure, diabetes, and hyperlipidemia. Conclusion: In a random sample of men at 71 years of age, half presented with either cardiac dysfunction or clinical heart failure. High body mass index was associated with an increased risk for developing cardiac dysfunction or heart failure over a 21-year period.
44.	Chen, Xiaojing, et al. (författare) Impact of adherence to guideline-directed therapy on risk of death in HF patients across an ejection fraction spectrum 2023 Ingår i: Esc Heart Failure. - : WILEY PERIODICALS, INC. - 2055-5822. ; 10:6, s. 3656-3666 Tidskriftsartikel (refereegranskat)abstract Aims How different degrees of adherence to guideline-directed medical therapy (GDMT) affect mortality risk in patients with heart failure (HF) in a real-world clinical setting is poorly understood. This study sought to investigate how different levels of adherence to GDMT were associated with the risk of all-cause mortality in patients with HF across a spectrum of left ventricular ejection fractions (LVEFs) in a real-world clinical setting.Methods and results A total of 64 610 HF patients with no missing value of LVEF from the Swedish Heart Failure Registry were included in the study. Patients were divided according to different LVEFs (<30%, 30-39%, 40-49%, and >= 50%) and stratified by an adherence score (good, moderate, or poor) according to the triple, double, and single one usage of GDMT: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists. The outcome is time to all-cause mortality. The mean age of the whole cohort was 73.9 +/- 12.1 years, and the proportion of patients in LVEF < 30%, 30-39%, 40-49%, and >= 50% groups was 27.6%, 26.9%, 22.1%, and 23.3%, respectively. Patients with LVEF < 30% had the highest mortality rate, almost 20% higher than those with LVEF >= 50% {hazard ratio [HR] [95% confidence interval (CI)]: 0.80 [0.71-0.90], P < 0.001}. After treatment of GDMT with good adherence, patients with LVEF < 30% had similar mortality to those with LVEF >= 50% [HR (95% CI): 0.97 (0.86-1.10), P = 0.664]. However, the percentage of moderate or poor GDMT was alarmingly high, with good adherence only in 20% of the patients.Conclusions Good adherence to GDMT works best in patients with LVEF < 50%, whereas moderate adherence to GDMT varies in efficacy depending on the components of the drug combinations.
45.	Chen, Xiaojing, et al. (författare) Impact of changes in heart rate with age on all-cause death and cardiovascular events in 50-year-old men from the general population 2019 Ingår i: Open Heart. - : BMJ. - 2053-3624. ; 6:1 Tidskriftsartikel (refereegranskat)abstract Background Resting heart rate (RHR), a known cardiovascular risk factor, changes with age. However, little is known about the association between changes in RHR and the risk of cardiovascular events. The purpose of this study was therefore to assess the impact of RHR at baseline, and the change in RHR over time, on the risk of all-cause death and cardiovascular events. Design A random population sample of men born in 1943 who were living in Gothenburg, Sweden was prospectively followed for a 21-year period. Methods Participants were examined three times: first in 1993 and then re-examined in 2003 and 2014. At each visit, a clinical examination, an ECG and laboratory analyses were performed. Change in RHR between 1993 and 2003 was defined as a decrease if RHR decreased by 5 beats per minute (bpm), an increase if RHR increased by 5 bpm or stable if the RHR change was <4bpm). Results Participants with a baseline RHR of >75 bpm in 1993 had about a twofold higher risk of all-cause death (HR 2.3, CI 1.2 to 4.7, p=0.018), cardiovascular disease (CVD) (HR 1.8, CI 1.1 to 3.0, p=0.014) and coronary heart disease (CHD) (HR 2.2, CI 1.1 to 4.5, p=0.025) compared with those with <55 bpm in 1993. Participants with a stable RHR between 1993 and 2003 had a 44% decreased risk of CVD (HR 0.56, CI 0.35 to 0.87, p=0.011) compared with participants with an increasing RHR. Furthermore, every beat increase in heart rate from 1993 was associated with a 3% higher risk for all-cause death, 1% higher risk for CVD and 2% higher risk for CHD. Conclusion High RHR was associated with an increased risk of death and cardiovascular events in men from the general population. Moreover, individuals with an increase in RHR between 50 and 60 years of age had worse outcome. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
46.	Chen, Xiaojing, et al. (författare) Improved short and long term survival associated with percutaneous coronary intervention in the elderly patients with acute coronary syndrome 2018 Ingår i: BMC Geriatr. - : Springer Science and Business Media LLC. - 1471-2318. ; 18:1 Tidskriftsartikel (refereegranskat)abstract Background: Percutaneous coronary intervention (PCI) are increasingly used in daily clinical practice in elderly patients with acute coronary syndrome (ACS) despite limited evidence. The purpose of this study was to assess the impact of PCI on short and long term survivals in a large cohort of elderly patients with ACS from a "real world". Methods: We enrolled 491 patients aged >= 70 years admitted to our institution with ACS from 2006 to 2012. Effect of PCI on short and long term survival was evaluated in both overall and a propensity score-matched cohort. Results: The mean age of the overall cohort is 83 +/- 6 years. Among them, 285 were treated with PCI, whereas 206 were not. Patients treated with PCI were younger (82 +/- 5 vs. 85 +/- 6), more males (67% vs. 46%), with lower heart rate (77 +/- 22 vs. 84 +/- 21), higher eGFR (58 +/- 20 vs. 47 +/- 23), and less with heart failure (29% vs. 15%) (all p < 0.001). In both overall and propensity-matched population, improved survival was associated with PCI-treatment at 1 and 3 years (p < 0.001 for all comparisons). Furthermore, by using multivariate Cox proportional-hazards regression model following factors were identified as independent predictors of 3-year all-cause mortality: age (HR 1.08, 95% CI 1.00-1.16), heart rate (HR 1.02, 95% CI 1.01-1.03), eGFR (HR 3.07, 95% CI 1.63-5.77), malignancy (HR 2.03, 95% CI 1.27-4.57), prior CABG (HR 2.033, 95% CI 1.27-4.57), medication with statin (HR 0.40, 95% CI 0.19-0.86) in PCI group, whereas age (HR 1.08, 95% CI 1.03-1.13), heart rate (HR 1.01, 95% CI 1.01-1.02), hypertension (HR 1.87, 95% CI 1.01-3.49) and using of ACEI/ARB (HR 0.46, 95% CI 0.28-0.76) in non-PCI group. Conclusions: In elderly ACS patients, PCI-treatment was associated with improved 1 and 3-year survival and PCI-treated patients had different prognostic profile compared to those without PCI treatment.
47.	Chen, Xiaojing, et al. (författare) Incremental changes in QRS duration as predictor for cardiovascular disease: a 21-year follow-up of a randomly selected general population 2021 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1 Tidskriftsartikel (refereegranskat)abstract The QRS complex has been shown to be a prognostic marker in coronary artery disease. However, the changes in QRS duration over time, and its predictive value for cardiovascular disease in the general population is poorly studied. So we aimed to explore if increased QRS duration from the age of 50-60 is associated with increased risk of major cardiovascular events during a further follow-up to age 71. A random population sample of 798 men born in 1943 were examined in 1993 at 50 years of age, and re-examined in 2003 at age 60 and 2014 at age 71. Participants who developed cardiovascular disease before the re-examination in 2003 (n = 86) or missing value of QRS duration in 2003 (n = 127) were excluded. Delta QRS was defined as increase in QRS duration from age 50 to 60. Participants were divided into three groups: group 1: Delta QRS < 4 ms, group 2: 4 ms <= Delta QRS < 8 ms, group 3: Delta QRS >= 8 ms. Endpoints were major cardiovascular events. And we found compared with men in group 1 (Delta QRS < 4 ms), men with Delta QRS >= 8 ms had a 56% increased risk of MACE during follow-up to 71 years of age after adjusted for BMI, systolic blood pressure, smoking, hyperlipidemia, diabetes and heart rate in a multivariable Cox regression analysis (HR 1.56, 95% CI:1.07-2.27, P = 0.022). In conclusion, in this longitudinal follow-up over a decade QRS duration increased in almost two out of three men between age 50 and 60 and the increased QRS duration in middle age is an independent predictor of major cardiovascular events.
48.	Chen, Xiaojing, et al. (författare) The eligible population of the PARADIGM-HF trial in a real-world outpatient clinic and its cardiovascular risk between 2005 and 2016. 2020 Ingår i: Journal of cardiovascular medicine. - 1558-2035. ; 21:1, s. 6-12 Tidskriftsartikel (refereegranskat)abstract The PARADIGM-HF trial showed that sacubitril-valsartan - an angiotensin receptor-neprilysin inhibitor (ARNI) - is more effective than enalapril for some patients with heart failure. However, the eligibility of the PARADIGM-HF study to a real-world heart failure population was not well established.We made secondary analysis of patients (n=4872) with heart failure prospectively enrolled in the Swedish Heart Failure Registry from Sahlgrenska University Hospital/Östra Hospital, Sweden during 2005-2016. The eligibility of the PARADIGM-HF trial in the real world was studied based on patients whether they were either fully or partially compatible with the PARADIGM-HF population. Patients were judged to be fully eligible for the PARADIGM-HF trial if they completely met the inclusion and exclusion criteria, and partially eligible if they did not stay on target dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), despite their having been treated with ACEI/ARB for at least 6 months.Among patients who had heart failure with reduced left ventricular ejection fraction (≤40%) (HFrEF) (n=2165), 653 (30%) and 958 (44%) patients were fully and partially compatible with PARADIGM-HF criteria, respectively. In both fully and partially eligible groups, patients were more male. Despite those fully eligible patients being younger (77.6±12.7 vs. 84.0±13.7 years) than noneligible patients, they were much older than in the PARADIGM-HF trial. Moreover, those fully eligible patients had lower all-cause mortality compared with both partially and noneligible patients. However, both fully and partially eligible patients had higher all-cause mortality than that in the PARADIGM-HF trial.In a real-world outpatient clinical setting, around 1/3-1/2 of HFrEF were eligible for treatment of Sac/Val except that they are older, sicker, and carry higher risk for all-cause mortality than the PARADIGM-HF trial population.
49.	Choy, Manting, et al. (författare) Phenotypes of heart failure with preserved ejection fraction and effect of spironolactone treatment. 2022 Ingår i: ESC heart failure. - : Wiley. - 2055-5822. ; 9:4, s. 2567-2575 Tidskriftsartikel (refereegranskat)abstract The aims of this study were to explore phenotypes of heart failure with preserved ejection fraction (HFpEF) and evaluate differential effects of spironolactone treatment.A swap-stepwise algorithm was used for variable selection. Latent class analysis based on 10 selected variables was employed in a derivative set of 1540 patients from the TOPCAT trial. Cox proportional hazard models were used to evaluate the prognoses and effects of spironolactone treatment. Three phenotypes of HFpEF were identified. Phenotype 1 was the youngest with low burden of co-morbidities. Phenotype 2 was the oldest with high prevalence of atrial fibrillation, pacemaker implantation, and hypothyroidism. Phenotype 3 was mostly obese and diabetic with high burden of other co-morbidities. Compared with phenotype 1, phenotypes 2 (hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.14-1.89; P = 0.003) and 3 (HR: 2.35; 95% CI: 1.80-3.07; P < 0.001) were associated with higher risks of the primary composite outcome. Spironolactone treatment was associated with a reduced risk of the primary outcome only in phenotype 1 (HR: 0.63; 95% CI: 0.40-0.98; P = 0.042).Three distinct HFpEF phenotypes were identified. Spironolactone treatment could improve clinical outcome in a phenotype of relatively young patients with low burden of co-morbidities.
50.	Chu, S. Y., et al. (författare) Intra-aortic balloon pump on in-hospital outcomes of cardiogenic shock: findings from a nationwide registry, China 2021 Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 8:4, s. 3286-3294 Tidskriftsartikel (refereegranskat)abstract Aims The real-world usage of intra-aortic balloon pump (IABP) in various cardiogenic shocks (CS) and the association with outcomes are lacking. We aimed to investigate IABP adoption in CS in a nationwide registry in China. Methods and results We retrospectively retrieved data of 30 106 CS patients (age 67.1 +/- 14.6 years, 37.6% female patients) in the Hospital Quality Monitoring System registry from 2013 to 2016. Ischaemic heart disease was the leading cause of CS (73.9%). Hypertension, cardiomyopathy, myocarditis, valvular, and congenital heart disease were seen in 36.0%, 7.5%, 2.6%, 7.3%, and 2.4% of the population. IABP was employed in 2320 (7.7%) subjects. The association between IABP usage and primary outcome of in-hospital mortality and secondary outcomes of expenses and lengths of stay were investigated. The patients with IABP support had similar in-hospital mortality to those without IABP (39.6% vs. 38.3%, P = 0.226), but longer hospital-stay [8.0 (2.0-16.0) vs. 6.0 (2.0-13.0) days, P < 0.001] and higher expenses [7.1(4.4-11.1) vs. 2.3 (0.8-5.5) 10 000RMB, P < 0.001]. IABP support was not associated with reduced mortality in the overall CS population in multivariate regression analysis [odds ratio (OR) 1.05, 95% confidence interval (CI) 0.95-1.17], except for subgroups with myocarditis (OR 0.61, 95% Cl 0.39-0.95, P for interaction = 0.010) and those who did not receive the early percutaneous coronary intervention (PCI) (OR 0.86, 95% CI 0.75-0.97, P for interaction < 0.001). Similar results were further confirmed in the propensityscore-matched population. Conclusions In this nationwide registry of CS patients, IABP was not noted with improved survival but increased healthcare consumption. However, IABP appears protective in those with myocarditis or who failed to receive early PCI.

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