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1.
Cardiovasc Res ; 120(8): 855-868, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38613511

ABSTRACT

AIMS: Atrial fibrillation (AF) and concomitant cardiometabolic disease processes interact and combine to lead to adverse events, such as stroke, heart failure, myocardial infarction, and cardiovascular death. Circulating biomolecules provide quantifiable proxies for cardiometabolic disease processes. The aim of this study was to test whether biomolecule combinations can define phenotypes in patients with AF. METHODS AND RESULTS: This pre-specified analysis of the EAST-AFNET 4 biomolecule study assigned patients to clusters using polytomous variable latent-class analysis based on baseline concentrations of 13 precisely quantified biomolecules potentially reflecting ageing, cardiac fibrosis, metabolic dysfunction, oxidative stress, cardiac load, endothelial dysfunction, and inflammation. In each cluster, rates of cardiovascular death, stroke, or hospitalization for heart failure or acute coronary syndrome, the primary outcome of EAST-AFNET 4, were calculated and compared between clusters over median 5.1 years follow-up. Findings were independently validated in a prospective cohort of 748 patients with AF (BBC-AF; median follow-up 2.9 years).Unsupervised biomolecule analysis assigned 1586 patients (71 years old, 46% women) into four clusters. The highest risk cluster was dominated by elevated bone morphogenetic protein 10, insulin-like growth factor-binding protein 7, N-terminal pro-B-type natriuretic peptide, angiopoietin 2, and growth differentiation factor 15. Patients in the lowest risk cluster showed low concentrations of these biomolecules. Two intermediate-risk clusters differed by high or low concentrations of C-reactive protein, interleukin-6, and D-dimer. Patients in the highest risk cluster had a five-fold higher cardiovascular event rate than patients in the low-risk cluster. Early rhythm control was effective across clusters (Pinteraction = 0.63). Sensitivity analyses and external validation in BBC-AF replicated clusters and risk gradients. CONCLUSION: Biomolecule concentrations identify cardiometabolic subphenotypes in patients with AF at high and low cardiovascular risk.


Subject(s)
Atrial Fibrillation , Biomarkers , Cardiometabolic Risk Factors , Phenotype , Humans , Female , Male , Atrial Fibrillation/diagnosis , Atrial Fibrillation/blood , Atrial Fibrillation/physiopathology , Atrial Fibrillation/epidemiology , Aged , Biomarkers/blood , Risk Assessment , Middle Aged , Prospective Studies , Predictive Value of Tests , Prognosis , Time Factors , Aged, 80 and over , Europe/epidemiology
2.
Europace ; 26(4)2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38591838

ABSTRACT

AIMS: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). METHODS AND RESULTS: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. CONCLUSIONS: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF.


Subject(s)
Atrial Fibrillation , Stroke , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Stroke/etiology , Stroke/prevention & control , Risk , Hemorrhage , Anticoagulants/therapeutic use
3.
Eur Heart J ; 43(40): 4127-4144, 2022 10 21.
Article in English | MEDLINE | ID: mdl-36036648

ABSTRACT

AIMS: A strategy of systematic, early rhythm control (ERC) improves cardiovascular outcomes in patients with atrial fibrillation (AF). It is not known how this outcome-reducing effect is mediated. METHODS AND RESULTS: Using the Early treatment of Atrial Fibrillation for Stroke prevention Trial (EAST-AFNET 4) data set, potential mediators of the effect of ERC were identified in the total study population at 12-month follow up and further interrogated by use of a four-way decomposition of the treatment effect in an exponential model predicting future primary outcome events. Fourteen potential mediators of ERC were identified at the 12-month visit. Of these, sinus rhythm at 12 months explained 81% of the treatment effect of ERC compared with usual care during the remainder of follow up (4.1 years). In patients not in sinus rhythm at 12 months, ERC did not reduce future cardiovascular outcomes (hazard ratio 0.94, 95% confidence interval 0.65-1.67). Inclusion of AF recurrence in the model only explained 31% of the treatment effect, and inclusion of systolic blood pressure at 12 months only 10%. There was no difference in outcomes in patients who underwent AF ablation compared with those who did not undergo AF ablation. CONCLUSION: The effectiveness of early rhythm control is mediated by the presence of sinus rhythm at 12 months in the EAST-AFNET 4 trial. Clinicians implementing ERC should aim for rapid and sustained restoration of sinus rhythm in patients with recently diagnosed AF and cardiovascular comorbidities.


Subject(s)
Atrial Fibrillation , Humans , Atrial Fibrillation/therapy , Catheter Ablation , Secondary Prevention , Stroke/prevention & control , Treatment Outcome
4.
Europace ; 24(6): 899-909, 2022 07 15.
Article in English | MEDLINE | ID: mdl-34792111

ABSTRACT

AIMS: To evaluate the effectiveness and safety of dronedarone compared with other commonly used antiarrhythmic drugs (AADs) for preventing atrial fibrillation (AF) recurrences. METHODS AND RESULTS: An international observational cohort study in Germany, Spain, Italy, and the USA enrolling patients with AF receiving AAD therapy. Patients with New York Heart Association (NYHA) Class IV heart failure were excluded. Participants were followed for up to 18 months, regardless of discontinuation or subsequent AAD switches. Atrial fibrillation recurrence was captured by hospitalization, emergency room visit, or electrocardiogram-based documentation of AF. Confounding bias was controlled for in the analysis of AF recurrence using multivariate models of 19 variables for adjustment. A total of 1009 participants [mean age 67.2 (10.8) years, male to female ratio 1.3] were recruited from 170 centres, 693 (69%) of which were from across Europe and the remaining 316 (31%) from the USA. At the time of enrolment, participants were taking dronedarone (51%) or other AADs (49%) [flecainide or propafenone (42%), sotalol (11%), and amiodarone (47%)]. No significant differences in the risk of first confirmed AF recurrence with dronedarone vs. other AADs [crude hazard ratio (HR) 1.10 (95% confidence interval 0.85-1.42); adjusted HR 1.16 (0.87-1.55)] were found, irrespective of whether univariate or multivariate models were used. Reported safety events were in accordance with the known safety profile of dronedarone. CONCLUSION: In this population of patients from either Europe or the USA receiving dronedarone or another AAD, the effectiveness of dronedarone was comparable to that observed for other AADs in preventing first AF recurrence.


Subject(s)
Amiodarone , Atrial Fibrillation , Aged , Amiodarone/adverse effects , Anti-Arrhythmia Agents/adverse effects , Atrial Fibrillation/chemically induced , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Cohort Studies , Dronedarone/adverse effects , Female , Humans , Male
5.
Europace ; 23(3): 329-344, 2021 03 08.
Article in English | MEDLINE | ID: mdl-33555020

ABSTRACT

AIMS: The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes. METHODS AND RESULTS: This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence. CONCLUSION: The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.


Subject(s)
Atrial Fibrillation , Stroke , Anticoagulants/adverse effects , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Atrial Fibrillation/therapy , Consensus , Humans , Risk Assessment , Risk Factors , Stroke/diagnosis , Stroke/epidemiology , Stroke/prevention & control , Treatment Outcome
6.
Cardiol Ther ; 8(2): 283-295, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31376090

ABSTRACT

INTRODUCTION: Patient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation. METHODS: ROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up). RESULTS: A total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation. CONCLUSIONS: Study drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. CLINICALTRIALS.GOV: NCT00403767. FUNDING: The ROCKET AF trial was funded by Johnson & Johnson and Bayer.

7.
Europace ; 18(8): 1135-42, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27174904

ABSTRACT

AIMS: The high costs associated with treatment for atrial fibrillation (AF) are primarily due to hospital care, but there are limited data to understand the reasons for and predictors of hospitalization in patients with AF. METHODS AND RESULTS: The ROCKET AF trial compared rivaroxaban with warfarin for stroke prophylaxis in AF. We described the frequency of and reasons for hospitalization during study follow-up and utilized Cox proportional hazards models to assess for baseline characteristics associated with all-cause hospitalization. Of 14 171 patients, 14% were hospitalized at least once. Of 2614 total hospitalizations, 41% were cardiovascular including 4% for AF; of the remaining, 12% were for bleeding. Compared with patients not hospitalized, hospitalized patients were older (74 vs. 72 years), and more frequently had diabetes (46 vs. 39%), prior MI (23 vs. 16%), and paroxysmal AF (19 vs. 17%), but less frequently had prior transient ischaemic attack/stroke (49 vs. 56%). After multivariable adjustment, lung disease [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.29-1.66], diabetes [1.22, (1.11-1.34)], prior MI [1.27, (1.13-1.42)], and renal dysfunction [HR 1.07 per 5 unit GFR < 65 mL/min, (1.04-1.10)] were associated with increased hospitalization risk. Treatment assignment was not associated with differential rates of hospitalization. CONCLUSION: Nearly 1 in 7 of the moderate-to-high-risk patients with AF enrolled in this trial was hospitalized within 2 years, and both AF and bleeding were rare causes of hospitalization. Further research is needed to determine whether care pathways directed at comorbid conditions among AF patients could reduce the need for and costs associated with hospitalization.


Subject(s)
Atrial Fibrillation/therapy , Hospitalization/statistics & numerical data , Aged , Comorbidity , Double-Blind Method , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Female , Geography , Hemorrhage/chemically induced , Humans , International Cooperation , Male , Multivariate Analysis , Proportional Hazards Models , Risk Factors , Rivaroxaban/administration & dosage , Rivaroxaban/adverse effects , Stroke/prevention & control , Treatment Outcome , Warfarin/administration & dosage , Warfarin/adverse effects
9.
Eur Heart J ; 35(15): 979-88, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24558113

ABSTRACT

AIMS: Recent guidelines on acute myocardial infarction (AMI) are based on randomized clinical trials (RCTs) and registries with selected patients, and may therefore not represent 'real-life'. This analysis shows for the first time nationwide trends in AMI from Germany. METHODS AND RESULTS: We were provided with data on all in-patient hospitalizations by the Federal Statistical Office. All hospitalized cases with AMI (onset of symptoms <28 days) from the years 2005, 2007, and 2009 were analysed regarding morbidity, in-hospital mortality, treatments, and costs. Analysis of a total of 16.1, 16.6, and 17.2 million hospitalizations showed the proportion of coded AMI to remain relatively constant (1276, 1272, and 1181 per 100 000 hospitalizations in 2005, 2007, and 2009). The proportion of ST-elevation AMI decreased over time (STEMI; 631, 546, and 454 per 100 000 hospitalizations),while non-ST-elevation AMI increased (NSTEMI; 645, 726, and 727 per 100 000 hospitalizations). The proportion of older patients >75 years (+4.6%), of comorbidities such as hypertension (+5.8%), diabetes (+17.7%), left ventricular failure (+19.8%), peripheral artery disease (+13.3%), and chronic kidney disease (+165.4%) increased as well. In-hospital mortality remained relatively stable during this period in AMI cases overall (11.1, 10.7, 10.8%) but changed slightly in STEMI (11.2, 11.9, 12.2%) and NSTEMI (11.0, 9.9, 9.9%). Causing about 1.2% of hospitalizations, AMI accounted for 2.5% (1.2 billion €) of in-hospital health expenses. CONCLUSION: This hospitalization-based analysis revealed a marked increase of NSTEMI among constant AMI frequency. Despite all current efforts, in-hospital mortality was stagnating on a high level compared with data of RCTs.


Subject(s)
Myocardial Infarction/therapy , Aged , Coronary Artery Bypass/trends , Costs and Cost Analysis , Female , Germany , Hospital Mortality/trends , Hospitalization/economics , Hospitalization/trends , Humans , Male , Middle Aged , Myocardial Infarction/economics , Myocardial Infarction/mortality , Percutaneous Coronary Intervention/trends , Practice Patterns, Physicians'/economics , Practice Patterns, Physicians'/trends , Randomized Controlled Trials as Topic , Stents/trends , Thrombolytic Therapy/trends
10.
J Electrocardiol ; 45(5): 433-42, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22920782

ABSTRACT

Brugada syndrome is an inherited heart disease without structural abnormalities that is thought to arise as a result of accelerated inactivation of Na channels and predominance of transient outward K current (I(to)) to generate a voltage gradient in the right ventricular layers. This gradient triggers ventricular tachycardia/ventricular fibrillation possibly through a phase 2 reentrant mechanism. The Brugada electrocardiographic (ECG) pattern, which can be dynamic and is sometimes concealed, being only recorded in upper precordial leads, is the hallmark of Brugada syndrome. Because of limitations of previous consensus documents describing the Brugada ECG pattern, especially in relation to the differences between types 2 and 3, a new consensus report to establish a set of new ECG criteria with higher accuracy has been considered necessary. In the new ECG criteria, only 2 ECG patterns are considered: pattern 1 identical to classic type 1 of other consensus (coved pattern) and pattern 2 that joins patterns 2 and 3 of previous consensus (saddle-back pattern). This consensus document describes the most important characteristics of 2 patterns and also the key points of differential diagnosis with different conditions that lead to Brugada-like pattern in the right precordial leads, especially right bundle-branch block, athletes, pectus excavatum, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Also discussed is the concept of Brugada phenocopies that are ECG patterns characteristic of Brugada pattern that may appear and disappear in relation with multiple causes but are not related with Brugada syndrome.


Subject(s)
Brugada Syndrome/diagnosis , Brugada Syndrome/physiopathology , Electrocardiography/methods , Consensus , Diagnosis, Differential , Humans
11.
Int J Cardiol ; 149(2): 186-191, 2011 Jun 02.
Article in English | MEDLINE | ID: mdl-20156659

ABSTRACT

BACKGROUND: The number of adult congenital heart disease (ACHD) patients will be larger in the medium to long term than that of children and adolescents with congenital heart disease. The present structures for the medical care of ACHD patients are not sufficient and need to be improved. Therefore the Task Force aimed at developing recommendations for adult and paediatric cardiologists to acquire the additional qualification "Adults with Congenital Heart Disease" (ACDH). METHODS: The members of the interdisciplinary Task Force were selected on the basis of their special clinical, scientific and organisational expertise. The leading author submitted a draft version, which was revised by a sub-group of the interdisciplinary Task Force. It was subsequently agreed upon and re-circulated by all the members of the Task Force. The recommendations were then presented to the relevant committees of all participating associations and groups and approved following detailed discussion. RESULTS: A training programme for acquiring an additional qualification in the treatment of adults with congenital heart disease was created successfully. CONCLUSIONS: The medical care of adults with congenital heart disease is a sub-speciality in the border area between adult cardiology and paediatric cardiology. ACHD cardiologists are to be specially trained experts with appropriate knowledge and special skills and experience in the diagnosis and therapy of congenital heart disease in adults. ACHD cardiologists should be able to recognise and treat problems that occur in adulthood in connection with congenital heart disease.


Subject(s)
Advisory Committees/standards , Cardiology/standards , Heart Defects, Congenital/therapy , Pediatrics/standards , Physicians/standards , Practice Guidelines as Topic/standards , Cardiology/education , Health Services Needs and Demand/standards , Heart Defects, Congenital/diagnosis , Humans , Pediatrics/education , Workforce
12.
Am J Cardiol ; 106(10): 1436-42, 2010 Nov 15.
Article in English | MEDLINE | ID: mdl-21059433

ABSTRACT

Whether drug-eluting stents are effective and safe in patients with moderate renal insufficiency (RI) is unknown. We performed a pooled analysis of data from 3 blinded randomized trials of sirolimus-eluting stents (SESs) versus bare metal stents (BMSs; SIRIUS, C-SIRIUS, E-SIRIUS) that included 1,510 patients. Clinical and angiographic outcomes were stratified by the presence of RI defined by creatinine clearance calculated by the Cockcroft-Gault formula (normal ≥ 90, mild 60 to 89, moderate < 60 ml/min). Patients with baseline creatinine > 3.0 mg/dl were excluded from these trials. Baseline mild RI was present in 517 patients (34.7%, mean creatinine clearance 75.7 ml/min) and moderate RI in 228 patients (15.3%, mean creatinine clearance 47.2 ml/min). Treatment with SESs resulted in lower rates of 8-month angiographic restenosis rates in patients with RI (mild RI 6.7% vs 42.6%, p < 0.001; moderate RI 9.7% vs 39.7%, p < 0.001) and without baseline RI (7.7% vs 37.2%, p < 0.001). One-year target vessel revascularization rates were similarly decreased with SESs in patients with (mild RI 4.7% vs 24.2%, p < 0.001; moderate RI 5.5% vs 26.9%, p < 0.001) and without (8.1% vs 22.4%, p < 0.001) RI, and this benefit was maintained at 5 years. Compared to patients with normal or mild RI, patients with moderate RI had higher rates of overall mortality and cardiac death at 1 year and 5 years (death 2.6% vs 0.6%, p <0.01, and 17.5% vs 6.3%, p < 0.01, at 1 year and 5 years, respectively; cardiac death 1.3% vs 0.2%, p = 0.05, and 6.6% vs 3.4%, p = 0.04, at 1 year and 5 years, respectively). However, there was no differential effect of SESs versus BMSs on any safety end point. In conclusion, patients with moderate RI have a nearly threefold increase in 5-year mortality after percutaneous coronary intervention compared to patients without RI. The effectiveness of SESs in decreasing restenosis compared to BMSs in patients with moderate RI was preserved and rates of death and myocardial infarction were not adversely affected.


Subject(s)
Coronary Restenosis/etiology , Coronary Restenosis/prevention & control , Drug-Eluting Stents , Renal Insufficiency/complications , Sirolimus/administration & dosage , Aged , Angioplasty, Balloon, Coronary , Double-Blind Method , Female , Humans , Male , Middle Aged , Postoperative Complications/etiology , Severity of Illness Index , Stents
13.
Europace ; 11(3): 289-96, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19095687

ABSTRACT

AIMS: We sought to investigate the association of inducibility of polymorphic ventricular tachycardia or ventricular fibrillation (PVT/VF) or sustained monomorphic ventricular tachycardia (SMVT) at standardized programmed ventricular stimulation (PVS) with the long-term likelihood of sudden death and/or fast VT in a large cohort of patients with idiopathic non-ischaemic dilated cardiomyopathy (DCM) and implantable cardioverter defibrillator (ICD) for secondary prophylaxis. METHODS AND RESULTS: Between 1994 and 2007, 160 consecutive patients with DCM and spontaneous sustained VT/VF or cardiac arrest underwent PVS prior to ICD implantation. Outcome data, particularly probability of survival without (sudden) death or appropriate ICD therapies for fast VT, were assessed during long-term follow-up. PVT/VF was induced in 50 (31%) and SMVT in 30 (19%) patients. During a mean follow-up of 53 +/- 15 months, we observed 19/50 (38%), 10/30 (33%), and 14/80 (18%) deaths in the PVT/VF, SMVT, and non-inducible group, respectively. These deaths were sudden in 7/50 (14%), 2/30 (7%), and 0/80 (0%) of patients, respectively. At least one fast VT was treated by the ICD in 26/50 (52%), 6/30 (20%), and 22/80 (28%) patients, respectively. PVT/VF but not SMVT-inducible patients had a significantly worse overall survival (log-rank P = 0.013), survival without sudden cardiac death (P < 0.01), or survival without fast VT (P < 0.01) according to Kaplan-Meier method than non-inducible patients. Additionally, survival free of fast VT was significantly worse in PVT/VF vs. SMVT-inducible patients (P < 0.01). CONCLUSION: Inducibility of PVT/VF is a much stronger predictor of recurrences of fast VT as opposed to SMVT induction in DCM patients with ICD for secondary prevention.


Subject(s)
Cardiomyopathies/complications , Cardiomyopathies/prevention & control , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Electric Stimulation/instrumentation , Electric Stimulation/methods , Tachycardia, Ventricular/diagnosis , Ventricular Fibrillation/diagnosis , Clinical Trials as Topic , Defibrillators, Implantable , Female , Humans , Male , Middle Aged , Myocardial Ischemia/prevention & control , Secondary Prevention , Treatment Outcome
14.
FASEB J ; 22(4): 1021-31, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17984177

ABSTRACT

To identify proteins involved in cardiac regeneration, a proteomics approach was applied. A total of 26 proteins, which displayed aberrant expression in mouse hearts infarcted through ligation of the left anterior descending coronary artery, were identified. These included the intermediate filament protein nestin, which was up-regulated in the infarct border zone. Corresponding changes were observed for its mRNA. Nestin mRNA was also up-regulated in hearts from 17 of 19 patients with end-stage heart failure, including 4 with acute myocardial infarction in comparison with 8 donor hearts. Immunofluorescence confocal laser scanning microscopy revealed that nestin is expressed, on the one hand, in small proportions of cardiomyocytes, endothelial cells, smooth muscle cells, neuronal cells, and fibroblasts. On the other hand, it was found to be coexpressed with the stem cell markers c-kit, Sca-1, Mdr-1, and Abcg2 in small interstitial cells. In infarcted hearts from chimeric mice transplanted with bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice, less than 1% of nestin-positive cells coexpressed EGFP, although EGFP-positive cells were abundant in these. Consequently, enhanced expression of nestin in the injured myocardium might reflect spontaneous regenerative processes supposedly based on the differentiation of resident cardiac stem cells into diverse cardiac cell types.


Subject(s)
Cell Differentiation , Intermediate Filament Proteins/genetics , Myocardial Infarction/metabolism , Myocardium/metabolism , Myocytes, Cardiac/cytology , Nerve Tissue Proteins/genetics , Stem Cells/cytology , Up-Regulation , Adult , Aged , Animals , Cell Lineage , Female , Humans , Intermediate Filament Proteins/metabolism , Male , Mice , Mice, Inbred C57BL , Middle Aged , Models, Animal , Myocardial Infarction/genetics , Myocytes, Cardiac/metabolism , Nerve Tissue Proteins/metabolism , Nestin
15.
N Engl J Med ; 355(26): 2744-51, 2006 Dec 28.
Article in English | MEDLINE | ID: mdl-17192539

ABSTRACT

BACKGROUND: Congenital long-QT syndrome is a disorder resulting in ventricular arrhythmias and sudden death. The most common forms of the long-QT syndrome, types 1 and 2, are caused by mutations in the potassium-channel genes KCNQ1 and KCNH2, respectively. Although inheritance of the long-QT syndrome is autosomal dominant, female predominance has often been observed and has been attributed to an increased susceptibility to cardiac arrhythmias in women. We investigated the possibility of an unbalanced transmission of the deleterious trait. METHODS: We investigated the distribution of alleles for the long-QT syndrome in 484 nuclear families with type 1 disease and 269 nuclear families with type 2 disease, all with fully genotyped offspring. The families were recruited in five European referral centers for the long-QT syndrome. Mutation segregation, sex ratio, and parental transmission were analyzed after correction for single ascertainment. RESULTS: Classic mendelian inheritance ratios were not observed in the offspring of either female carriers of the long-QT syndrome type 1 or male and female carriers of the long-QT syndrome type 2. Among the 1534 descendants, the proportion of genetically affected offspring was significantly greater than that expected according to mendelian inheritance: 870 were carriers of a mutation (57%), and 664 were noncarriers (43%, P<0.001). Among the 870 carriers, the allele for the long-QT syndrome was transmitted more often to female offspring (476 [55%]) than to male offspring (394 [45%], P=0.005). Increased maternal transmission of the long-QT syndrome mutations to daughters was also observed, possibly contributing to the excess of female patients with autosomal dominant long-QT syndrome. CONCLUSIONS: Positive selection of the mutated alleles that cause the long-QT syndrome leads to transmission distortion, with increased proportions of mutation carriers among the offspring of affected families. Alleles for the long-QT syndrome are more often transmitted to daughters than to sons.


Subject(s)
Inheritance Patterns , Long QT Syndrome/genetics , Sex Ratio , Chi-Square Distribution , Female , Genes, Dominant , Genotype , Heterozygote , Humans , Male , Mutation , Pedigree , Retrospective Studies
16.
Invest Radiol ; 38(10): 653-61, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14501493

ABSTRACT

RATIONALE AND OBJECTIVES: Electrocardiogram-gated 3D volume data from multidetector computed tomography coronary angiography (MDCT-CA) enable image reconstruction in any phase of the cardiac cycle. The objective was to determine left ventricular (LV) function parameters by MDCT in comparison to cine magnetic resonance imaging (MRI). METHOD: Thirty patients with known or suspected coronary artery disease (CAD) underwent MDCT-CA. From multiplanar reformations in short axis orientation end-diastolic and end-systolic LV volumes (LVEDV, LVESV) were determined to calculate LV stroke volume and ejection fraction (LVSV, LVEF) and compared with MRI measurements. RESULTS: LVEDV (147 +/- 27 mL) and LVESV (65 +/- 22 mL) determined by MDCT correlated well to the respective MRI measurements (LVEDV 133 +/- 27 mL, r = 0.80, P < 0.001; LVESV 48 +/- 19 mL, r = 0.89, P < 0.001). LVSV (MDCT 82 +/- 15 mL; MRI 85 +/- 17 mL; r = 0.77, P < 0.001) and LVEF (MDCT 56 +/- 9%; MRI 65 +/- 8%; r = 0.85, P < 0.001) showed a good correlation as well. LVEF was significantly underestimated by MDCT (-8.5 +/- 4.7%, P < 0.001). CONCLUSIONS: Initial experience in patients evaluated for CAD shows that spiral MDCT studies may provide LV functional data in good correlation to Cine MRI.


Subject(s)
Coronary Artery Disease/physiopathology , Magnetic Resonance Imaging, Cine , Tomography, X-Ray Computed/methods , Ventricular Dysfunction, Left/diagnosis , Adult , Aged , Electrocardiography , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Sensitivity and Specificity , Ventricular Dysfunction, Left/diagnostic imaging
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