Publications by authors named "Jens Hellermann"

23 Publications

  • Page 1 of 1

Right ventricle and outcome in left ventricular non-compaction cardiomyopathy.

J Cardiol 2020 01 4;75(1):20-26. Epub 2019 Oct 4.

Department of Cardiology, University Heart Center Zurich, Zurich, Switzerland. Electronic address:

Background: The risk of adverse events in patients with left ventricular non-compaction cardiomyopathy (LVNC) is substantial. Information on prognostic factors, however, is limited. This study was designed to assess the prognostic value of right ventricular (RV) size and function in LVNC patients.

Methods: Cox regression analyses were used to determine the association of indexed RV end-diastolic area (RV-EDAI), indexed end-diastolic diameter (RV-EDDI), fractional area change (FAC), and tricuspid annular systolic excursion (TAPSE) with the occurrence of death or heart transplantation (composite endpoint).

Results: Out of 127 patients (53.2 ± 17.8 years; 61% males, median follow-up time was 7.7 years), 17 patients reached the endpoint. In a univariate analysis, RV-EDAI was the strongest predictor of outcome [HR 1.48 (1.24-1.77) per cm/m; p < 0.0001]. FAC was predictive as well [HR 1.44 (1.16-1.83) per 5% decrease; p = 0.0009], while TAPSE was not (p=ns). RV-EDAI remained an independent predictor in a bivariable analysis with indexed left ventricular ED volume [HR 1.41 (1.18-1.70) per cm/m; p = 0.0002], while analysis of FAC and left ventricular ejection fraction demonstrated that FAC was not independent [HR 1.20 (0.98-1.52); per 5% decrease; p = 0.0721]. RV-EDAI 11.5 cm/m was the best cut-off value for separating patients in terms of outcome. Patients with RV-EDAI >11.5 cm/m had a survival rate of 18.5% over 12 years as compared to 93.8% in patients with RV-EDAI <11.5 cm/m (p < 0.0001).

Conclusion: Increased end-diastolic RV size and decreased systolic RV function are predictors of adverse outcome in patients with LVNC. Patients with RV-EDAI >11.5 cm/m exhibit a significantly lower survival than those <11.5 cm/m.
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http://dx.doi.org/10.1016/j.jjcc.2019.09.003DOI Listing
January 2020

Long-term durability and haemodynamic performance of a self-expanding transcatheter heart valve beyond five years after implantation: a prospective observational study applying the standardised definitions of structural deterioration and valve failure.

EuroIntervention 2018 Jul 20;14(4):e390-e396. Epub 2018 Jul 20.

Heart Center, Segeberger Kliniken, Bad Segeberg, Germany.

Aims: Long-term results of transcatheter aortic valve implantation (TAVI), in particular the incidence of bioprosthetic valve failure (BVF), are uncertain. This study presents data derived from a long-term, structured follow-up programme of the self-expanding CoreValve device utilising standardised definitions and core lab adjudication of valve performance.

Methods And Results: The study prospectively included all 152 patients who had undergone TAVI with the self-expanding CoreValve up to December 2011 at the Heart Center, Bad Segeberg, Germany. Late BVF (>30 days) was defined as either: 1) severe structural valve deterioration (transprosthetic mean pressure gradient ≥40 mmHg and/or ≥20 mmHg rise from baseline OR severe intraprosthetic aortic regurgitation), OR 2) bioprosthetic valve dysfunction leading to death or reintervention. Echocardiographic follow-up at 6.3±1.0 years (range: 5.0-8.9 years) was 88% complete (60 out of 68 survivors beyond five years) and all echocardiograms were analysed by an independent core laboratory. The all-cause mortality rate at 1, 2, 5, 6, 7 and 8 years was 14%, 20%, 50%, 60%, 65%, and 73%, respectively. Among survivors beyond five years, effective orifice area was 1.60±0.46 cm2, and transvalvular mean pressure gradient was 6.7±3.1 mmHg; no cases showed evidence of structural valve deterioration. Five patients (3.3%) had undergone redo TAVI (n=4) or surgery (n=1) 0.6 to 5.2 years after the index procedure, all due to paravalvular leakage. The estimated rate of BVF at eight years was 7.9% for the actuarial and 4.5% for the actual analysis.

Conclusions: Long-term follow-up up to 8.9 years after TAVI documents favourable performance of the self-expanding CoreValve with low rates of BVF.
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http://dx.doi.org/10.4244/EIJ-D-18-00041DOI Listing
July 2018

Tissue Factor Expression Does Not Predict Mortality in Breast Cancer Patients.

Anticancer Res 2017 06;37(6):3259-3264

Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland

Background: Tissue factor (TF), the trigger of coagulation, not only initiates thrombus formation, but also elicits tumor growth and invasion in breast cancer. However, the characterization of TF expression in breast cancer tissue and its prognostic value remain unclear.

Materials And Methods: Three hundred and three primary breast cancer specimens from the local tumor tissue database were immunostained for TF expression and evaluated semiquantitatively. Tumor characteristics (size, grade, nodal status, and ER expression) as well as patient's survival were assessed.

Results: Expression of TF was detected in 99% of specimens with higher expression in invasive lobular than ductal carcinoma (p=0.008). TF expression correlated with ER expression (p<0.0001) and inversely with tumor grade (p=0.006). Survival analysis did not reveal any prognostic impact of TF expression (p=0.966).

Conclusion: This study - by analyzing TF expression in the largest cohort of breast cancer patients so far - does not support a prognostic impact of TF expression.
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http://dx.doi.org/10.21873/anticanres.11689DOI Listing
June 2017

Accuracy of smartphone apps for heart rate measurement.

Eur J Prev Cardiol 2017 08 2;24(12):1287-1293. Epub 2017 May 2.

5 Heart Clinic Zurich, Switzerland.

Background Smartphone manufacturers offer mobile health monitoring technology to their customers, including apps using the built-in camera for heart rate assessment. This study aimed to test the diagnostic accuracy of such heart rate measuring apps in clinical practice. Methods The feasibility and accuracy of measuring heart rate was tested on four commercially available apps using both iPhone 4 and iPhone 5. 'Instant Heart Rate' (IHR) and 'Heart Fitness' (HF) work with contact photoplethysmography (contact of fingertip to built-in camera), while 'Whats My Heart Rate' (WMH) and 'Cardiio Version' (CAR) work with non-contact photoplethysmography. The measurements were compared to electrocardiogram and pulse oximetry-derived heart rate. Results Heart rate measurement using app-based photoplethysmography was performed on 108 randomly selected patients. The electrocardiogram-derived heart rate correlated well with pulse oximetry ( r = 0.92), IHR ( r = 0.83) and HF ( r = 0.96), but somewhat less with WMH ( r = 0.62) and CAR ( r = 0.60). The accuracy of app-measured heart rate as compared to electrocardiogram, reported as mean absolute error (in bpm ± standard error) was 2 ± 0.35 (pulse oximetry), 4.5 ± 1.1 (IHR), 2 ± 0.5 (HF), 7.1 ± 1.4 (WMH) and 8.1 ± 1.4 (CAR). Conclusions We found substantial performance differences between the four studied heart rate measuring apps. The two contact photoplethysmography-based apps had higher feasibility and better accuracy for heart rate measurement than the two non-contact photoplethysmography-based apps.
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http://dx.doi.org/10.1177/2047487317702044DOI Listing
August 2017

Reduction of falls and fractures after permanent pacemaker implantation in elderly patients with sinus node dysfunction.

Europace 2017 Jul;19(7):1220-1226

Cardiology/Electrophysiology, University of Basel, Basel, Switzerland.

Aims: Elderly patients with sinus node dysfunction (SND) are at increased risk of falls with possible injuries. However, the incidence of these adverse events and its reduction after permanent pacemaker (PPM) implantation are not known.

Methods And Results: Eighty-seven patients (mean [SD] age 75.4 [8.3] years, 51% women) with SND and an indication for cardiac pacing were included and were examined by a standardized interview targeting fall history. The incidence and total number of falls, falls with injury, falls requiring treatment, and falls resulting in a fracture were assessed for the time period of 12 months before (retrospectively) and after PPM implantation (prospectively). Furthermore, symptoms such as syncope, dizziness, and dyspnea were evaluated before and after PPM implantation. The implantation of a PPM was associated with a reduced proportion of patients experiencing at least one fall by 71% (from 53 to 15%, P < 0.001) and a reduction of the absolute number of falls by 90% (from 127 to 13, P < 0.001) during the 12 months before vs. after PPM implant. Falls with injury (28 vs. 10%, P = 0.005), falls requiring medical attention (31 vs. 8%, P < 0.001), and falls leading to fracture (8 vs. 0%, P = 0.013) were similarly reduced. Notably, fewer patients had syncope (4 vs. 45%, P < 0.001) and dizziness after PPM implantation (12 vs. 45%, P < 0.001).

Conclusion: Falls, fall-related injuries, and fall-related fractures are frequent in SND patients. Permanent pacemaker implantation is associated with a significantly reduced risk of these adverse events, although no causal relationship could be established due to the study design.
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http://dx.doi.org/10.1093/europace/euw156DOI Listing
July 2017

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy.

N Engl J Med 2015 Sep;373(10):929-38

From University Heart Center, Department of Cardiology (C. Templin, J.R.G., J.D., D.R.B., M.J., V.L.C., V.G., C.A.N., M.S., P.E., F.R., T.F.L.), and Department of Psychiatry and Psychotherapy (K. Eisenhardt, J.J.), University Hospital Zurich, and Division of Biostatistics, Epidemiology, Biostatistics, and Prevention Institute, University of Zurich (B.S.), Zurich, Spitalregion Rheintal Werdenberg Sarganserland, Altstätten (J.H.), Department of Cardiology, Kantonsspital Lucerne, Lucerne (F. Cuculi, P.E.), Department of Cardiology, Kantonsspital Winterthur, Winterthur (T.A.F.), and Department of Cardiology, University Hospital Basel, Basel (C.K., S.O.) - all in Switzerland; Department of Cardiology and Angiology, Hannover Medical School, Hannover (L.C.N., J.B.), Department of Cardiology, Heidelberg University Hospital, Heidelberg (J.F., H.A.K.), Deutsches Herzzentrum München, Technische Universität München (C.B., H.S., W.K.), and DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance (H.S., W.K.), Munich, University Heart Center Lübeck, Medical Clinic II, Department of Cardiology, Angiology and Intensive Care Medicine, Lübeck (C.M., H.T.), DZHK, partner site Hamburg/Kiel/Lübeck (C.M., H.T., M.K.), Division of Cardiology, Asklepios Clinics St. Georg Hospital (A.C., K.-H.K.), and Department of General and Interventional Cardiology, University Heart Center Hamburg (M.K.), Hamburg, Department of Cardiology, Charité, Campus Rudolf Virchow, Berlin (C. Tschöpe, H.-P.S.), Department of Internal Medicine III, Heart Center University of Cologne, Cologne (G.M., R.P.), Department of Internal Medicine III, Cardiology, Angiology, and Intensive Care Medicine, Saarland University, Homburg (C.U., M.B.), Department of Cardiology, University Hospital Essen, Essen (R.E.), Clinic for Cardiology and Pneumology, Georg August University Göttingen (C.J., G.H.), and DZHK, partner site Göttingen (C.J., G.H.), Göttingen, Department of Internal Medicine II

Background: The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood.

Methods: The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome.

Results: Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year.

Conclusions: Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).
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http://dx.doi.org/10.1056/NEJMoa1406761DOI Listing
September 2015

Gender disparities in acute coronary syndrome: a closing gap in the short-term outcome.

J Cardiovasc Med (Hagerstown) 2015 May;16(5):355-62

aDepartment of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland bUniversity of California Davis Medical Center, California, USA cAltstaetten Hospital, Department for Internal Medicine, Division of Cardiology, Altstaetten, Switzerland.

Aims: The aim of the present study was to analyze gender disparities in a large cohort of acute coronary syndrome (ACS) patients from the Zurich Acute Coronary Syndrome (Z-ACS) Registry.

Methods: Gender disparities in ACS were examined. The primary endpoint included in-hospital death rate, and the secondary endpoint major adverse cardiac and cerebrovascular events (MACCEs) at 30-day follow-up. Furthermore, independent predictors for MACCEs and death were identified.

Results: In total, 2612 patients with ACS were identified. Out of these, 23% were women. The mean age was higher in women (68.6 ± 12.2; P < 0.001). Troponin-T on admission (1.33 ± 4.64 vs. 1.19 ± 3.04 μg/l; P = 0.002) and N-terminal of the prohormone brain natriuretic peptide on admission (3456.2 ± 7286.7 vs. 1665.6 ± 4800.6 ng/l; P < 0.001) were higher in women compared with men. Single-vessel disease was more common in women (44.9 vs. 39.7%; P = 0.023) and, conversely, multivessel disease was more prevalent in male patients as compared with their female counterparts (59.4 vs. 54.4%; P = 0.029). At discharge, men were more likely prescribed statins (89.4 vs. 85.2%; P = 0.004). Overall mortality and MACCEs were similar for both genders. In women, peak creatine kinase and peak C-reactive protein emerged as independent predictors for MACCEs and SBP on admission, and maximal C-reactive protein and use of glycoprotein IIb/IIIa inhibitors (GPIIb/IIIa) as strong independent predictors for in-hospital death.

Conclusion: The present results suggest a closing gap in short-term outcome and improvement in cardiac care between women and men. Nonetheless, differences in treatment strategies continue to exist, particularly pertaining to statin regimens at discharge, which might potentially have a powerful impact on long-term outcomes and gender disparities.
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http://dx.doi.org/10.2459/JCM.0000000000000248DOI Listing
May 2015

Acute coronary syndromes in octogenarians referred for invasive evaluation: treatment profile and outcomes.

Clin Res Cardiol 2015 Jan 21;104(1):51-8. Epub 2014 Aug 21.

Department of Cardiology, University Heart Center, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland,

Background: With increasing life expectancy in the western world, the aging population will compose a significant portion of the demographic. Notably, cardiovascular disease is particularly prevalent in the elderly population. The aim of the present study is to investigate the outcomes of octogenarians referred for urgent coronary angiography in the setting of acute coronary syndromes (ACS).

Methods: Between June 2007 and June 2012, consecutive patients with ACS were referred for evaluation and percutaneous intervention. Subsequently, the in-hospital death and major adverse cardiovascular events (MACE) at 30 days were analyzed. Multivariate analysis was performed to identify the predictors for death and MACE.

Results: In patients ≥80 years (n = 296) ST-segment elevation myocardial infarction (STEMI) occurred in 46.6%, non-ST-segment elevation myocardial infarction (NSTEMI) in 45.9%, and 7.4% had unstable angina. On the other hand, in patients <80 years (n = 2,316) STEMI was observed in 53.4%, NSTEMI in 37.8% and unstable angina in 9.0%. The primary end-point of total mortality was significantly higher in octogenarians (7.4 vs. 4.5%, p = 0.026). Similarly, the secondary end-point comprising overall MACE rate was significantly higher among the elderly (12.5 vs. 7.3%, p = 0.002). Within the group of octogenarians, no relation between age and outcomes was noted (for death: OR 0.99, 95% CI 0.84-1.16, p = 0.915; and for MACE: OR 1.10, 95% CI 0.88-1.36, p = 0.412); however, in patients <80 years, age was related to outcomes (for death: OR 1.05, 95% CI, 1.02-1.08, p = 0.003; and for MACE: OR 1.03, 95% CI, 1.01-1.05, p = 0.011). In a multivariate analysis, systolic blood pressure (OR 0.97 95% CI 0.94-0.99, p = 0.0058), maximal value of creatine kinase (OR 1.00, 95% CI 1.00-1.00, p = 0.033), and maximal value of NT-proBNP (OR 1.00, 95% CI 1.00-1.00, p = 0.0225) were independent predictors for death, while systolic blood pressure (OR 0.98, 95% CI 0.96-0.99, p = 0.0384) and maximal value of C-reactive protein (OR 1.01, 95% CI 1.00-1.01, p = 0.0265) were associated with overall MACE.

Conclusions: Here we confirm that in-hospital death and MACE rate remain significantly elevated in octogenarians in spite of implementation of modern therapies. However, our real-world registry strongly suggests that early revascularization appears safe and effective in elderly patients. Furthermore, we have identified that systolic blood pressure, creatine kinase, NT-proBNP, and C-reactive protein are strong predictors for outcomes in octogenarians.
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http://dx.doi.org/10.1007/s00392-014-0756-5DOI Listing
January 2015

Vascular lesions induced by renal nerve ablation as assessed by optical coherence tomography: pre- and post-procedural comparison with the Simplicity catheter system and the EnligHTN multi-electrode renal denervation catheter.

Eur Heart J 2013 Jul 25;34(28):2141-8, 2148b. Epub 2013 Apr 25.

Department of Cardiology, Cardiovascular Center, University Hospital Zurich, Raemistrasse 100, Zurich CH-8091, Switzerland.

Aims: Catheter-based renal nerve ablation (RNA) using radiofrequency energy is a novel treatment for drug-resistant essential hypertension. However, the local endothelial and vascular injury induced by RNA has not been characterized, although this importantly determines the long-term safety of the procedure. Optical coherence tomography (OCT) enables in vivo visualization of morphologic features with a high resolution of 10-15 µm. The objective of this study was to assess the morphological features of the endothelial and vascular injury induced by RNA using OCT.

Methods And Results: In a prospective observational study, 32 renal arteries of patients with treatment-resistant hypertension underwent OCT before and after RNA. All pre- and post-procedural OCT pullbacks were evaluated regarding vascular changes such as vasospasm, oedema (notches), dissection, and thrombus formation. Thirty-two renal arteries were evaluated, in which automatic pullbacks were obtained before and after RNA. Vasospasm was observed more often after RNA then before the procedure (0 vs. 42%, P < 0.001). A significant decrease in mean renal artery diameter after RNA was documented both with the EnligHTN (4.69 ± 0.73 vs. 4.21 ± 0.87 mm; P < 0.001) and with the Simplicity catheter (5.04 ± 0.66 vs. 4.57 ± 0.88 mm; P < 0.001). Endothelial-intimal oedema was noted in 96% of cases after RNA. The presence of thrombus formations was significantly higher after the RNA then before ablation (67 vs. 18%, P < 0.001). There was one evidence of arterial dissection after RNA with the Simplicity catheter, while endothelial and intimal disruptions were noted in two patients with the EnligHTN catheter.

Conclusion: Here we show that diffuse renal artery constriction and local tissue damage at the ablation site with oedema and thrombus formation occur after RNA and that OCT visualizes vascular lesions not apparent on angiography. This suggests that dual antiplatelet therapy may be required during RNA.
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http://dx.doi.org/10.1093/eurheartj/eht141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717310PMC
July 2013

Electrical activation in the coronary sinus branches as a guide to cardiac resynchronisation therapy: rationale for a coordinate system.

PLoS One 2011 8;6(8):e19914. Epub 2011 Aug 8.

Division of Pacing and Electrophysiology, Clinic for Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.

Background: For successful cardiac resynchronisation therapy (CRT) a spatial and electrical separation of right and left ventricular electrodes is essential. The spatial distribution of electrical delays within the coronary sinus (CS) tributaries has not yet been identified.

Objective: Electrical delays within the CS are described during sinus rhythm (SR) and right ventricular pacing (RVP). A coordinate system grading the mitral ring from 0° to 360° and three vertical segments is proposed to define the lead positions irrespective of individual CS branch orientation.

Methods: In 13 patients undergoing implantation of a CRT device 6±2.5, (median 5) lead positions within the CS were mapped during SR and RVP. The delay to the onset and the peak of the local signal was measured from the earliest QRS activation or the pacing spike. Fluoroscopic positions were compared to localizations on a nonfluoroscopic electrode imaging system.

Results: During SR, electrical delays in the CS were inhomogenous in patients with or without left bundle branch block (LBBB). During RVP, the delays increased by 44±32 ms (signal onset from 36±33 ms to 95±30 ms; p<0.001, signal peak from 105±44 ms to 156±30 ms; p<0.001). The activation pattern during RVP was homogeneous and predictable by taking the grading on the CS ring into account: (% QRS) = 78-0.002 (grade-162)(2), p<0.0001. This indicates that 78% of the QRS duration can be expected as a maximum peak delay at 162° on the CS ring.

Conclusion: Electrical delays within the CS vary during SR, but prolong and become predictable during RVP. A coordinate system helps predicting the local delays and facilitates interindividual comparison of lead positions irrespective of CS branch anatomy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019914PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152548PMC
February 2012

Predictors of appropriate implantable cardioverter-defibrillator therapy during long-term follow-up of patients with coronary artery disease.

Int Heart J 2009 May;50(3):313-21

Arrhythmia Service, Cardiovascular Division, University Hospital Zurich, Zurich, Switzerland.

Indications for implantable cardioverter defibrillators (ICDs) are expanding. Defining long-term predictors of ICD therapies might help to identify those patients who will benefit most from implantation of an ICD. The objective of this study was to examine long-term predictors of appropriate ICD therapy among patients with coronary disease at high risk of sudden cardiac death. An analysis of 245 patients with coronary disease, who had been implanted with an ICD for primary or secondary prevention of sudden cardiac death, was performed. Time to appropriate ICD therapy, defined as antitachycardia pacing or shock, was evaluated by the Kaplan-Meier method. Cox regression analysis was performed to determine hazard ratios for factors predicting appropriate ICD therapies. During a mean (SD) follow-up of 41 (33) months, 115 patients (53%) experienced appropriate ICD therapy. Independent predictors of appropriate ICD therapy included advanced age, left ventricular ejection fraction (LVEF) < 35%, and impaired renal function, with covariate-adjusted hazard ratios of 1.36 per 10 years (95% CI, 1.11 - 1.66; P = 0.003), 1.78 (95% CI, 1.21 - 2.63; P = 0.004), and 1.59 (95% CI, 1.00 - 2.54; P = 0.050), respectively. Remote myocardial infarction (> 6 months prior to ICD implantation) was associated with higher probability of appropriate ICD therapy among patients with LVEF > 35% (adjusted HR 2.68 [95% CI, 1.05 - 6.86; P = 0.04]), but not among patients with LVEF < 35% (adjusted HR 1.09 [95% CI, 0.58 - 2.04; P = 0.79]). Left ventricular ejection fraction, advanced age, and renal impairment are long-term predictors of appropriate ICD therapy in patients with coronary disease at high risk of sudden cardiac death. Patients with an ejection fraction above 35% have few arrhythmic events early after the myocardial infarction but appropriate therapies become more frequent late after the myocardial infarction, possibly due to progression of the disease.
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http://dx.doi.org/10.1536/ihj.50.313DOI Listing
May 2009

Upregulation of alpha-skeletal muscle actin and myosin heavy polypeptide gene products in degenerating rotator cuff muscles.

J Orthop Res 2008 Jul;26(7):1007-11

Laboratory for Orthopedic Research, Balgrist University Hospital, Zurich, Switzerland.

Impaired function of shoulder muscles, resulting from rotator cuff tears, is associated with abnormal deposition of fat in muscle tissue, but corresponding cellular and molecular mechanisms, likely reflected by altered gene expression profiles, are largely unknown. Here, an analysis of muscle gene expression was carried out by semiquantitative RT-PCR in total RNA extracts of supraspinatus biopsies collected from 60 patients prior to shoulder surgery. A significant increase of alpha-skeletal muscle actin (p = 0.0115) and of myosin heavy polypeptide 1 (p = 0.0147) gene transcripts was observed in parallel with progressive fat deposition in the muscle, assessed on parasagittal T1-weighted turbo-spin-echo magnetic resonance images according to Goutallier. Upregulation of alpha-skeletal muscle actin and of myosin heavy polypeptide-1 has been reported to be associated with increased muscle tissue metabolism and oxidative stress. The findings of the present study, therefore, challenge the hypothesis that increased fat deposition in rotator cuff muscle after injury reflects muscle degeneration.
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http://dx.doi.org/10.1002/jor.20577DOI Listing
July 2008

Electrocardiographic artifacts due to electrode misplacement and their frequency in different clinical settings.

Am J Emerg Med 2007 Feb;25(2):174-8

Wolfson Institute of Biomedical Research, University College London, WC1E 6BT London, UK.

Misplacement of electrodes can change the morphology of an electrocardiogram (ECG) in clinical important ways. To assess the frequency of these errors in different clinical settings, we collected ECGs routinely performed at the cardiology outpatient clinic and the intensive care unit. Lead misplacement was suspected when one of the following morphological changes occurred: QRS axis between 180 degrees and -90 degrees , positive P wave in lead aVR, negative P waves in lead I and/or II, very low (<0.1 mV) amplitude in an isolated peripheral lead, or abnormal R progression in the precordial leads. We analyzed 838 ECGs and identified 37 ECGs suspicious for electrode misplacement, from which 7 were confirmed. The frequency of ECG artifacts due to switched electrodes was 0.4% (3/739) at the outpatient clinic and 4.0% (4/99) at the intensive care unit (P = .005). In conclusion, errors in ECG performance do occur with an increasing frequency in an acute medical care setting.
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http://dx.doi.org/10.1016/j.ajem.2006.06.018DOI Listing
February 2007

Time trends in the epidemiology of renal transplant patients with type 1 diabetes mellitus over the last four decades.

Nephrol Dial Transplant 2006 Mar 9;21(3):770-5. Epub 2006 Jan 9.

Department of Nephrology, University Hospital, Zurich, Switzerland.

Background: Diabetes mellitus (DM) type 1 is an important contributor to end-stage renal disease (ESRD) among younger transplant recipients. However, little is known about the changes in epidemiological characteristics of this population. Especially, time to reach ESRD may have changed in type 1 diabetic patients referred for transplantation, resulting in higher age at time of grafting. Such time trends may allow anticipating future developments regarding the demand for organ replacement in this patient group.

Methods: We retrospectively analysed 173 patients with type 1 DM undergoing renal transplantation at our institution, stratified into four groups according to year of reaching ESRD (A = 1973-1983, B = 1984-1990, C = 1991-1995 and D = 1996-2002). For each group we determined age at diagnosis of DM, age at time of reaching ESRD and age at time of transplantation. From these data, the interval from diagnosis of DM to ESRD and from ESRD to transplantation was calculated. The results were analysed in relation to gender, year of and age at onset of diabetes.

Results: Patients reaching ESRD in more recent years (group D) tended to be both younger at diagnosis of DM and older when reaching ESRD, resulting in higher mean age at transplantation (35.0, 37.5, 39.6 and 41.0 years in groups A, B, C and D, respectively). Accordingly, median duration to ESRD has significantly been prolonged over the last five decades in patients with type 1 DM undergoing renal transplantation (group A: 21.0, B: 20.7, C: 22.3 and D: 28.5 years; P < 0.0001), this finding being more pronounced in female patients.

Conclusions: The results of our analysis are compatible with a change in epidemiology in patients undergoing kidney transplantation. Older age at time of reaching ESRD may impact significantly on the demand for renal grafts, as patients are already clearly older nowadays when being transplanted. From our data it cannot be concluded whether this development is due to a change in the progression of diabetic nephropathy or may simply reflect a change in the selection of type 1 diabetic patients referred for transplantation.
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http://dx.doi.org/10.1093/ndt/gfi278DOI Listing
March 2006

Heart failure after myocardial infarction: clinical presentation and survival.

Eur J Heart Fail 2005 Jan;7(1):119-25

Division of Cardiovascular Diseases and Internal Medicine, Rochester, MN, USA.

Objectives: To characterize the presentation and outcome of patients with heart failure (HF) after myocardial infarction (MI) according to left ventricular ejection fraction (LVEF) and test the hypothesis that the outcome of HF did not change over time.

Background: Little is known about the presentation and outcome of HF post-MI and how these may have changed over time.

Methods: Using the Rochester Epidemiology Project, all residents of Olmsted County, Minnesota who experienced an incident MI between 1979 and 1998 were identified; MI and HF were validated using standardized criteria. Subjects were followed through their community medical record.

Results: Between 1979 and 1998, 1915 patients with incident MI and no prior history of HF were identified. Of these, 791(41%) experienced new onset HF as defined by Framingham criteria during 6.6+/-5.0 years of follow-up. Forty-seven percent were men, mean age was 73+/-12 years. Forty-four percent had impaired LVEF, 18% preserved LVEF and 38% had no LVEF measurement within 60 days after the HF event. Median survival after HF onset was 4 years and at 5 years after HF onset, only 45% were alive. Older age, male sex, comorbidity, hypertension and no LVEF assessment were associated with increased risk of death, however, patients with impaired LVEF had the worst outcome. Over time, survival did not improve (HR for year: 1.00; 95% CI 0.99, 1.02; P=0.919) even after adjustment for baseline characteristics.

Conclusion: In this geographically defined cohort of patients with MI, new onset HF after the MI was frequent. When measured, LVEF was most frequently reduced, consistent with systolic heart failure. Mortality was high and did not decline over time and death was independently associated with male sex, older age, hypertension and comorbidity. It also differed according to LVEF, which was inconsistently ascertained in this setting, potentially representing practice opportunities.
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http://dx.doi.org/10.1016/j.ejheart.2004.04.011DOI Listing
January 2005

Advantages of subclavian artery perfusion for repair of acute type A dissection.

Eur J Cardiothorac Surg 2004 Sep;26(3):592-8

Clinic for Cardiovascular Surgery, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.

Objective: Arterial perfusion through the right subclavian artery is proposed to avoid intraoperative malperfusion during repair of acute type A dissection. This study evaluated the clinical and neurological outcome of patients undergoing surgery of acute aortic type A dissection following subclavian arterial cannulation compared to femoral artery approach.

Methods: From 1/97 to 1/03, 122 consecutive patients underwent surgery for acute type A aortic dissection. Subclavian cannulation was performed in 62 versus femoral cannulation in 60 patients. Clinical characteristics in both groups were similar. Mean age was 61 years (SD+/-14 years, 72% male) and mean follow-up was 3 years (+/-2 years). Patient outcome was assessed as the prevalence of clinical complications, especially neurological deficits, mortality at 30 days, perioperative morbidity and time of body temperature cooling and analyzed by nominal logistic regression analysis for odds ratio calculation.

Results: Arterial subclavian cannulation was successfully performed without any occurrence of malperfusion in all cases. Patients undergoing subclavian cannulation showed an odds ratio of 1.98 (95% CI 1.15-3.51; P=0.0057) for an improved neurological outcome compared to patients undergoing femoral cannulation. Re-exploration rate for postoperative bleeding was significantly reduced in the subclavian group (P<0.0001), as well as occurrence of myocardial infarction (P<0.0001) and duration for body temperature cooling (P=0.004). The 30-day mortality of patients with femoral cannulation was significantly higher compared to patients with subclavian artery cannulation (24 versus 8%; P=0.0179).

Conclusions: Arterial perfusion through the right subclavian artery provides an excellent approach for repair of acute type A dissection with optimized arterial perfusion body perfusion and allows for antegrade cerebral perfusion during circulatory arrest. The technique is safe and results in a significantly improved clinical and especially neurological outcome.
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http://dx.doi.org/10.1016/j.ejcts.2004.04.032DOI Listing
September 2004

Measurement of ejection fraction after myocardial infarction in the population.

Chest 2004 Feb;125(2):397-403

Department of Health Sciences Research, Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA.

Objectives: To assess the secular trends in left ventricular ejection fraction (LVEF) assessment after myocardial infarction (MI) and to identify the determinants of testing.

Design: A population-based MI incidence cohort.

Methods: The use of tests measuring LVEF (echocardiography, radionuclide, and left ventricular [LV] angiography) was examined among all consecutive residents of Olmsted County, MN, hospitalized for a validated incident MI between 1979 and 1998. Baseline characteristics and outcome were ascertained from community medical records.

Results: Among 2,317 patients with incident MI, LVEF assessment increased from 1979 to 1986 (22 to 85%; p value for trend = 0.0001) to stabilize thereafter until 1998. During the most recent decade, LVEF was measured during the hospital stay in 81% of the patients. Characteristics associated with lesser use of tests included older age and measurement of ejection fraction within 1 year prior to the index MI. Larger MI size, prolonged hospital stay, and involvement of a cardiologist as a care provider were positively associated with determination of LVEF.

Conclusions: Measurement of LVEF after MI increased in the last 2 decades, but there continues to be a group of patients in whom it is not done. Given the potential benefits of LVEF measurement, including knowledge for risk stratification and therapeutic choices as underscored in recent practice guidelines, there may be additional opportunities for improving outcomes by ensuring its more consistent use. However, as testing for LVEF differs according to patient characteristics, reliance on selected clinically performed LVEF measurements will result in biased estimates of the prevalence of LV dysfunction after MI.
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http://dx.doi.org/10.1378/chest.125.2.397DOI Listing
February 2004

Differential effects of selective cyclooxygenase-2 inhibitors on endothelial function in salt-induced hypertension.

Circulation 2003 Nov 3;108(19):2308-11. Epub 2003 Nov 3.

Cardiology, Cardiovascular Center, University Hospital Zürich, the Institute of Physiology, University of Zürich-Irchel, Germany.

Background: In view of the ongoing controversy about potential differences in cardiovascular safety of selective cyclooxygenase (COX)-2 inhibitors (coxibs), we compared the effects of 2 different coxibs and a traditional NSAID on endothelial dysfunction, a well-established surrogate of cardiovascular disease, in salt-induced hypertension.

Methods And Results: Salt-sensitive (DS) and salt-resistant (DR) Dahl rats were fed a high-sodium diet (4% NaCl) for 56 days. From days 35 to 56, diclofenac (6 mg x kg(-1) x d(-1); DS-diclofenac), rofecoxib (2 mg x kg(-1) x d(-1); DS-rofecoxib), celecoxib (25 mg x kg(-1) x d(-1); DS-celecoxib) or placebo (DS-placebo) was added to the chow. Blood pressure increased with sodium diet in the DS groups, which was more pronounced after diclofenac and rofecoxib treatment (P<0.005 versus DS-placebo) but was slightly decreased by celecoxib (P<0.001 versus DS-placebo). Sodium diet markedly reduced NO-mediated endothelium-dependent relaxations to acetylcholine (10-10-10-5 mol/L) in aortic rings of untreated hypertensive rats (P<0.005 versus DR-placebo). Relaxation to acetylcholine improved after celecoxib (P<0.005 versus DS-placebo and DS-rofecoxib) but remained unchanged after rofecoxib and diclofenac treatment. Vasoconstriction after nitric oxide synthase inhibition, indicating basal NO release, with N(omega)-nitro-L-arginine methyl ester (10-4 mol/L) was blunted in DS rats (P<0.05 versus DR-placebo), normalized by celecoxib, but not affected by rofecoxib or diclofenac. Indicators of oxidative stress, 8-isoprostane levels, were elevated in untreated DS rats on 4% NaCl (6.55+/-0.58 versus 3.65+/-1.05 ng/mL, P<0.05) and normalized by celecoxib only (4.29+/-0.58 ng/mL).

Conclusions: These data show that celecoxib but not rofecoxib or diclofenac improves endothelial dysfunction and reduces oxidative stress, thus pointing to differential effects of coxibs in salt-induced hypertension.
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http://dx.doi.org/10.1161/01.CIR.0000101683.30157.0BDOI Listing
November 2003

Incidence of heart failure after myocardial infarction: is it changing over time?

Am J Epidemiol 2003 Jun;157(12):1101-7

Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.

Improved survival after myocardial infarction (MI) could result in MI survivors' contributing to the US heart failure epidemic. Conversely, since the severity of MI is declining over time, a decline in post-MI heart failure might also be anticipated. This study tested the hypothesis that the incidence of post-MI heart failure was declining over time in a geographically defined MI incidence cohort. Between 1979 and 1994, 1,537 patients with incident MI and no prior history of heart failure were hospitalized in Olmsted County, Minnesota. Framingham Heart Study criteria were used to ascertain the incidence of inpatient and outpatient heart failure over a mean follow-up period of 7.6 years (standard deviation 5.5). Overall, 36% of patients experienced heart failure. After adjustment for factors related to post-MI heart failure (age, hypertension, smoking, and biomarkers), the incidence of heart failure declined by 2% per year (relative risk = 0.98, 95% confidence interval: 0.96, 0.99; p = 0.01). The relative risk of developing heart failure among persons with MIs occurring in 1994 versus 1979 was 0.72 (95% confidence interval: 0.55, 0.93), indicating a 28% reduction in the incidence of heart failure. Administration of reperfusion therapy within 24 hours after MI was associated with lower risk of post-MI heart failure and accounted for most of the temporal decline in heart failure. This suggests that improved survival after MI is unlikely to be a major contributor to the heart failure epidemic.
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http://dx.doi.org/10.1093/aje/kwg078DOI Listing
June 2003

Heart failure after myocardial infarction: prevalence of preserved left ventricular systolic function in the community.

Am Heart J 2003 Apr;145(4):742-8

Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minn 55905, USA.

Background: Studies have reported that a large proportion of the cases of congestive heart failure (CHF) with mixed etiologies have preserved left ventricular systolic function. Whether this is the case in subjects with CHF after myocardial infarction (MI) is not known. This study was undertaken to examine the prevalence and characteristics associated with CHF in patients who had preserved ejection fraction (LVEF) after MI.

Methods: Clinical characteristics and LVEF were ascertained in a population-based cohort of patients with CHF after incident MI in Olmsted County, Minn. All MIs were validated by use of standardized epidemiological criteria, and all episodes of CHF were validated by use of Framingham criteria.

Results: Between 1979 and 1994, 1658 patients had an MI, and 644 of these patients (38%) had CHF during 7.4 +/- 5.4 years of follow-up. Of these patients, 395 (61%) underwent LVEF assessment. Preserved LVEF (ie, > or =50%) was present in 30% of cases, and this proportion did not change with time. The proportion of women with CHF and preserved LVEF (37%) was greater than the proportion of men (23%, P =.002). The positive association between female sex and preserved LVEF remained significant after adjustment (odds ratio 1.97, 95% CI 1.26-3.07, P =.003). The highest tertile of peak creatinine phosphokinase level was negatively associated with preserved LVEF (odds ratio 0.51, 95% CI 0.29-0.89).

Conclusion: A notable proportion of cases of CHF after MI have preserved LVEF. This underscores the burden of CHF with preserved LVEF in a well-defined group of patients with documented coronary disease. CHF with preserved LVEF after MI is associated with female sex and smaller MI size.
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http://dx.doi.org/10.1067/mhj.2003.187DOI Listing
April 2003

Heart failure after myocardial infarction: a review.

Am J Med 2002 Sep;113(4):324-30

Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.

Purpose: The effects of survival after myocardial infarction on the prevalence of chronic heart failure have not been well characterized. We reviewed studies of the incidence, mortality, and predictors of heart failure after myocardial infarction, and suggest directions for further research.

Methods And Results: We conducted a review of the literature from 1978 to 2000. Of 33 identified articles, 18 (55%) included heart failure as a primary endpoint. The mean in-hospital incidence of heart failure after myocardial infarction differed significantly by study design; it was highest in population-based studies and lowest in clinical trials (37% vs. 18%, P <0.01). Only 10 studies reported the incidence of subsequent heart failure. One-year mortality ranged from 16% to 39% and showed no improvement with time. Patients with in-hospital heart failure after myocardial infarction had a two- to sixfold greater in-hospital mortality and up to a fivefold increased 1-year mortality compared with patients without heart failure. The most consistent risk factors for the development of heart failure after myocardial infarction were advanced age, female sex, diabetes, and an increased heart rate at the time of admission.

Conclusions: The reported incidence of, and mortality from, heart failure after myocardial infarction varies by study design. Additional research on the etiology and prognosis of late heart failure after myocardial infarction is needed.
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http://dx.doi.org/10.1016/s0002-9343(02)01185-3DOI Listing
September 2002

Longitudinal trends in the severity of acute myocardial infarction: a population study in Olmsted County, Minnesota.

Am J Epidemiol 2002 Aug;156(3):246-53

Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.

The mechanisms of the decline in coronary heart disease mortality are not fully elucidated. In particular, little is known about the trends in severity of myocardial infarction, which may have contributed to the mortality decline. This study examines indicators of myocardial infarction severity including Killip class, electrocardiogram descriptors, and peak creatine kinase values in a population-based, myocardial infarction incidence cohort to test the hypothesis that the severity of myocardial infarction declined over time. Between 1983 and 1994, 1,295 incident cases of myocardial infarction (mean age, 67 (standard deviation, 6) years; 43% women) occurred in Olmsted County, Minnesota. The median time between the onset of symptoms and presentation was 1.9 (interquartile range, 3.9) hours and declined over time (p = 0.018), while the use of reperfusion therapy increased. Over time, the hemodynamic presentation of patients did not change appreciably, but the proportion of persons with ST-segment elevation declined as did the occurrence of Q waves and peak creatine kinase values. These secular trends, which were largely independent from the time to first electrocardiogram and reperfusion therapy, indicate a decline in the severity of myocardial infarction over time.
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http://dx.doi.org/10.1093/aje/kwf034DOI Listing
August 2002