Clinical Research in Cardiology (Clin Res Cardiol)

Publications in this journal

• Article: Pickering syndrome: high-risk stenting of a renal artery stenosis in a multimorbid patient presenting with progressive congestive heart failure.

  Thomas Demming, Norbert Frey, Christoph Langer
  Clinical Research in Cardiology 05/2013;
• Article: Recommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran and rivaroxaban.

  T Steiner, M Böhm, M Dichgans, H-C Diener, C Ell, M Endres, C Epple, M Grond, U Laufs, G Nickenig, H Riess, J Röther, P D Schellinger, M Spannagl, R Veltkamp
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  ABSTRACT: Dabigatran, apixaban, and rivaroxaban have been approved for primary and secondary stroke prevention in patients with atrial fibrillation. However, questions have arisen about how to manage emergency situations, such as when thrombolysis would be required for acute ischemic stroke or for the managing intracranial or gastrointestinal bleedings. We summarize the current literature and provide recommendations for the management of these situations. Peak plasma levels of the direct oral anticoagulants (DOACs) apixaban, dabigatran, or rivaroxaban are observed about 2-4 h after intake. Elimination of dabigatran is mainly dependent on renal function. Consequently, if renal function is impaired, there is a risk of drug accumulation that is highest for dabigatran followed by rivaroxaban and then apixaban and thus dosing recommendations are different. To date, no bedside tests are available that reliably assess the anticoagulatory effect of DOACs, nor are specific antidotes available. We recommend performing the following tests if DOAC intake is unknown: dabigatran-associated bleeding risk is minimized or can be neglected if thrombin time, Hemoclot test, or Ecarin clotting time is normal. Apixaban and rivaroxaban effects can be ruled out if findings from the anti-factor Xa activity test are normal. High plasma levels of DOAC are also mostly excluded if PTT and PTZ are normal four or more hours after DOAC intake. However, normal values of global coagulation tests are not sufficient if thrombolysis is indicated for treating acute stroke. The decision for or against thrombolysis is an individual decision; in these cases, thrombolysis use is off-label. In case of bleeding, prothrombin complex concentrates seems to be the most plausible treatment. For severe gastrointestinal bleeding with life-threatening blood loss, the bleeding source needs to be identified and treated by invasive measures. Use of procoagulant drugs (antifibrinolytics) might also be considered. However, there is very limited clinical experience with these products in conjunction with DOAC.
  Clinical Research in Cardiology 05/2013;
• Article: Safety and efficacy of the subclavian access route for TAVI in cases of missing transfemoral access.

  Andrea Muensterer, Domenico Mazzitelli, Hendrik Ruge, Anke Wagner, Ina Hettich, Nicolo Piazza, Ruediger Lange, Sabine Bleiziffer
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  ABSTRACT: OBJECTIVE: We retrospectively analysed our experience with the subclavian access transcatheter aortic valve implantation (TAVI) with the self-expandable CoreValve prosthesis and compared the results with transfemorally treated patients. BACKGROUND: For TAVI, a subclavian access is alternatively used when the femoral arteries are diseased or very small. METHODS: Between June 2007 and February 2011, 341 patients underwent CoreValve implantation in the German Heart Center, Munich through either transfemoral (n = 301) or subclavian (n = 40) approach. The subclavian approach was chosen where transfemoral approach was not possible. RESULTS: There was no difference in baseline characteristics between the groups. There were no significant differences between groups for parameters potentially related to improved valve positioning (contrast medium, fluoroscopy time, implantation of a second valve, post-implantation balloon dilatation, valve dislocation, pacemaker implantation, aortic regurgitation), while the procedure duration was longer (105 ± 40 vs. 82 ± 33 min, p = 0.001). With the Kaplan-Meier estimate, survival was not different among groups. Strokes, myocardial ischaemia, and access vessel complications occurred in 2.5, 0, and 7.5 % (subclavian group) vs. 4.3, 2.0, 10.6 % (transfemoral group), ns. CONCLUSIONS: Our results demonstrate the safety of the subclavian access for TAVI and comparability with the transfemoral approach. With longer duration of the procedure and no significant advantages in clinical outcome, the subclavian access will have an indication for selected patients, while transfemoral TAVI should be considered first choice.
  Clinical Research in Cardiology 05/2013;
• Article: Detection of left ventricular hypertrophy by the R-wave voltage in lead aVL: population-based study.

  Sérgio Lamêgo Rodrigues, Lílian Cláudia Souza Angelo, Marcelo Perim Baldo, Eduardo Miranda Dantas, Alexandre Maulaz Barcelos, Alexandre C Pereira, José Eduardo Krieger, José Geraldo Mill
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  ABSTRACT: BACKGROUND: According to hypertension guidelines, the recommended electrocardiographic (ECG) diagnostic criteria for left ventricular hypertrophy (LVH) are the Sokolow-Lyon and Cornel voltage criteria, both with general acceptance by primary care physicians. However, it was recently reported that the R-wave voltage in lead aVL (RaVL) was as good as other more complicated and time-consuming ECG criteria to detect LVH in hypertensive patients. Therefore, our aim was to investigate if the ability of the RaVL to identify echocardiographic left ventricular hypertrophy (ECHO-LVH) could be translated to the general population, a more realistic assessment of its utility in a nonreferral setting. METHODS: 682 participants (43.5 % males), aged between 27 and 72 years from the urban population of Vitoria, ES, Brazil, were enrolled. We investigated the association of ECHO-LVH (LV mass >51 g/Ht(2.7)) with several ECG voltage measurements: Sokolow-Lyon and Cornel criteria, S-wave voltage in lead V3 (SV3) and RaVL. RESULTS: The RaVL showed the best positive correlation with LV mass indexed to Ht(2.7), superior to both Cornell and Sokolow-Lyon criteria and was not influenced by gender. Analysis of the ROC curves showed that the RaVL depicted a significant superior performance in relation to all the other measurements in the ability to detect ECHO-LVH. SV3 was not correlated with LV mass. Thus, it seems that most of Cornell's performance depends on its simplified version, that is, RaVL. CONCLUSION: We have shown that the simple and single assessment of RaVL presented a greater diagnostic ability in detecting ECHO-LVH in the general population, signaling its value mainly as a screening tool.
  Clinical Research in Cardiology 05/2013;
• Article: Door-to-implantation time of extracorporeal life support systems predicts mortality in patients with out-of-hospital cardiac arrest.

  Jürgen Leick, Christoph Liebetrau, Sebastian Szardien, Ulrich Fischer-Rasokat, Matthias Willmer, Arnaud van Linden, Johannes Blumenstein, Holger Nef, Andreas Rolf, Matthias Arlt, Thomas Walther, Christian Hamm, Helge Möllmann
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  ABSTRACT: OBJECTIVE: This study aimed to identify predictors of mortality in patients with out-of-hospital cardiac arrest (OHCA) undergoing in-hospital extracorporeal life support system (ECLS) treatment. METHODS: We retrospectively studied the characteristics and clinical outcomes of 28 patients (January 2010 and December 2011) with OHCA and veno-arterial ECLS implemented during ongoing cardiopulmonary resuscitation (CPR) upon admission to the cath lab. Baseline left ventricular ejection fraction (LVEF) was determined after ECLS implantation and then every 24 h during and after successful weaning from ECLS. RESULTS: Overall 30-day survival rate was 39.3 % (11 of 28 patients). Baseline characteristics, initial laboratory measurements, and LVEF on admission were not significantly different between survivors and non-survivors. There was no difference regarding median CPR duration [survivors 44.0 min (IQR 31.0-45.0) vs. non-survivors 53.0 min (IQR 40.0-61.3); P = 0.23]. Door-to-ECLS implantation time was significantly longer in non-survivors [42.5 min (IQR 28.0-56.5) vs. 25.0 min (IQR 21.0-30.0); P < 0.01]. ECLS treatment duration was not significantly different between the two groups [survivors: 4.0 days (IQR 1.5-7.5) vs. non-survivors 6.5 days (IQR 1.0-8.0); P = 0.69]. LVEF significantly improved in survivors during ECLS treatment (mean ± SD survivor 47.5 ± 14.7 % vs. non-survivor 23.3 ± 14.9 %; P < 0.01). The door-to-ECLS implantation time was the only significant and independent predictor of 30-day mortality in multivariate Cox regression analysis (P = 0.04). Kaplan-Meier survival analysis showed a benefit favouring patients with a door-to-ECLS implantation time <30 min (log rank 6.29; P = 0.01). CONCLUSION: A door-to-ECLS implantation time <30 min significantly improves 30-day outcomes in patients with OHCA.
  Clinical Research in Cardiology 05/2013;
• Article: Outcomes of correcting hyponatremia in patients with myocardial infarction.

  Waqas Qureshi, Syed Hassan, Fatima Khalid, Mohamed Faher Almahmoud, Bhavik Shah, Ra'ad Tashman, Nikhil Ambulgekar, Mostafa El-Refai, Chetan Mittal, Zaid Alirhayim
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  ABSTRACT: BACKGROUND: Hyponatremia has significant prognostic implications in patients with heart, failure. However, little data are available regarding its significance in patients presenting with myocardial infarction. In addition, it is not known if correction of hyponatremia impacts outcomes in these patients. The aim of this study was to evaluate the prognostic value of hyponatremia in patients with myocardial infarction and the effect of its correction on all-cause mortality. METHODS: Patients with the discharge diagnosis of myocardial infarction at our institution between 2000 and 2010 with serum sodium levels measured within 24 h of admission were included in this retrospective analysis. Multivariate analysis was used to determine the predictors of all-cause mortality. Cox proportional hazard model was applied to determine the adjusted survival. RESULTS: A total of 11,562 patients (67.15 ± 14.6 years, males 56.3 %) were included in the analysis. There were a total of 1,535 (13.3 %) deaths within mean follow-up duration of 5.5 ± 3.3 years. There were 425 (27.9 %) deaths in patients with corrected hyponatremia and 155 (55.3 %) deaths in persistent hyponatremia patients. Multivariate analysis indicated that corrected hyponatremia and persistent hyponatremia were independent predictors of all cause mortality (p < 0.0001). When analyzing short-term (30 days) and long-term mortality, corrected hyponatremia group did not have associated long term mortality. Various methods to correct hyponatremia were also analyzed and use of vaptans was associated with decrease in mortality in patients with hyponatremia from 115 to 125 (HR 0.45; 95 % CI 0.26-0.78, p = 0.005). CONCLUSION: Our analysis showed that corrected and persistent hyponatremia in patients presenting with myocardial infarction is a predictor of all-cause mortality, major adverse cardiac events and heart failure related 30 day rehospitalization. In certain cases, correction of hyponatremia may actually improve survival of the patients.
  Clinical Research in Cardiology 05/2013;
• Article: Invasive versus non-invasive cooling after in- and out-of-hospital cardiac arrest: a randomized trial.

  Undine Pittl, Alexandra Schratter, Steffen Desch, Raluca Diosteanu, Denise Lehmann, Katharina Demmin, Jacqueline Hörig, Gerhard Schuler, Thorsten Klemm, Meinhard Mende, Holger Thiele
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  ABSTRACT: INTRODUCTION: Mild induced hypothermia (MIH) is indicated for comatose survivors of sudden cardiac arrest (SCA) to improve clinical outcome. In this study, we compared the efficacy of two different cooling devices for temperature management in SCA survivors. METHODS: Between April 2008 and August 2009, 80 patients after survived in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) were included in this prospective, randomized, single center study. Hypothermia was induced after randomization by either invasive Coolgard(®) cooling or non-invasive ArcticSun(®) surface cooling at 33.0 °C core body temperature for 24 h followed by active rewarming. The primary endpoint was defined as the efficacy of both cooling systems, measured by neuron-specific enolase (NSE) levels as a surrogate parameter for brain damage. Secondary efficacy endpoints were the clinical and neurological outcome, time to start of cooling and reaching the target temperature, target temperature-maintenance and hypothermia-associated complications. RESULTS: NSE at 72 h did not differ significantly between the 2 groups with 16.5 ng/ml, interquartile range 11.8-46.5 in surface-cooled patients versus 19.0 ng/ml, interquartile range 11.0-42.0 in invasive-cooled patients, p = 0.99. Neurological and clinical outcome was similar in both groups. Target temperature of 33.0 °C was maintained more stable in the invasive group (33.0 versus 32.7 °C, p < 0.001). Bleeding complications were more frequent with invasive cooling (n = 17 [43.6 %] versus n = 7 [17.9 %]; p = 0.03). CONCLUSION: Invasive cooling has advantages with respect to temperature management over surface cooling; however, did not result in different outcome as measured by NSE release in SCA survivors. Bleeding complications were more frequently encountered by invasive cooling.
  Clinical Research in Cardiology 05/2013;
• Article: Persistent angina: highly prevalent and associated with long-term anxiety, depression, low physical functioning, and quality of life in stable angina pectoris.

  Lasse Jespersen, Steen Z Abildstrøm, Anders Hvelplund, Eva Prescott
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  ABSTRACT: AIMS: To evaluate persistent angina in stable angina pectoris with no obstructive coronary artery disease (CAD) compared to obstructive CAD and its relation to long-term anxiety, depression, quality of life (QOL), and physical functioning. METHODS AND RESULTS: We invited 357 patients (men = 191; women = 166; response rate 83 %) with no prior cardiovascular disease who had a first-time coronary angiography (CAG) in 2008-2009 due to suspected stable angina to participate in a questionnaire survey in 2011 with the Seattle Angina Questionnaire and the Hospital Anxiety and Depression Scale as key elements. Long-term persistent angina (i.e., symptoms at least once a month) was present in 64 % of patients with diffuse non-obstructive CAD (1-49 % stenosis), 49 % of patients with normal coronary arteries (0 % stenosis), and 41 % of patients with obstructive CAD (≥50 % stenosis) (P = 0.01). Depression and anxiety were more common in patients with persistent angina: 24 versus 7 % (P < 0.001) reported HADS-Depression-scores >7 and 42 versus 21 % (P < 0.001) reported HADS-Anxiety-scores >7. In multivariate regression models, persistent angina was associated with depression (OR 4.3, 95 % confidence interval (CI) 1.9-9.6, P < 0.001), anxiety (OR 2.9, 95 % CI 1.6-5.1, P < 0.001), the severity of persistent angina with impaired physical functioning (P < 0.001), and QOL (P < 0.001); whereas outcomes were not related to age, gender, or degree of CAD. CONCLUSIONS: The study indicates higher prevalence of persistent angina in patients with diffuse non-obstructive CAD or normal coronary arteries than in patients with obstructive CAD. Persistent angina symptoms were associated with long-term anxiety, depression, impaired physical functioning, and QOL irrespective of the degree of CAD. Contrary to common perception, excluding obstructive CAD in stable angina does not ensure a favorable disease course, and further risk stratification and treatment strategies are warranted.
  Clinical Research in Cardiology 05/2013;
• Article: Heart rate differentiates urgency and emergency in hypertensive crisis.

  Rashed Al Bannay, Michael Böhm, Aysha Husain
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  ABSTRACT: OBJECTIVE: To study the clinical significance of presenting blood pressure parameters and heart rate in patients with hypertensive crisis. METHODS: In patients admitted with hypertensive crisis between January 2011 and May 2011, demography, mode of presentation, co-morbidities, blood pressure readings, and heart rate at presentation were documented. Further clustering of hypertensive crisis into emergency or urgency was based on the presence or absence of target organ involvement. The relationship between blood pressure parameters, heart rate, and other variables was analyzed. RESULTS: 189 patients in sinus rhythm were enrolled in this pilot study. The rate of hypertensive urgency was 56 %, whereas the rate of hypertensive emergency was 44 %, respectively. Subjects with hypertensive emergency had a higher mean heart rate (93 ± 22.7 bpm) than those with urgency (81 ± 11.5 bpm) (P = 0.015). Women had higher heart rates (92 ± 18.5 bpm) than men (86 ± 17.6 bpm) (P = 0.014). Heart rates below 100 bpm had a specificity of 94 %, classifying patients as hypertensive urgency. Tachycardia had a powerful statistical association with hypertensive left ventricular failure (P < 0.0001). Other hemodynamic parameters, including systolic blood pressure, diastolic blood pressure, pulse pressure, and mean blood pressure relates neither to urgency nor to emergency. Diabetic patients with HBA1c levels of more than 53 mmol/mol had a heart rate of more than 100 bpm (P = 0.015) during hypertensive crisis. CONCLUSIONS: Normal heart rate is characteristic of hypertensive urgency. Tachycardia in this setting is an ominous sign and denotes hypertensive complications in particular left ventricular failure. Among diabetics, elevated heart rate is associated with poor glycemic control.
  Clinical Research in Cardiology 04/2013;
• Article: Heart rate before ICU discharge: a simple and readily available predictor of short- and long-term mortality from critical illness.

  Wilhelm Grander, Kathrin Müllauer, Bernhard Koller, Herbert Tilg, Martin Dünser
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  ABSTRACT: PURPOSE: A heart rate >90 bpm serves as one of four characteristics defining the systemic inflammatory response syndrome and is used in scoring systems to predict in-hospital mortality of intensive care unit (ICU) patients. Despite its central role in critical illness, specific data regarding the relationship between heart rate and outcome are rare. METHODS: In this post hoc analysis of a prospectively collected database, we analyzed the value of heart rate averaged from four predefined time points during the last 24 h before ICU discharge as a predictor of post-ICU in-hospital and post-hospital mortality in medical ICU patients. Furthermore, the relationship between heart rate and inflammation, as well as the influence of rate control medications on the association between heart rate and outcome were identified. RESULTS: Among the 702 ICU patients discharged from the ICU, 7.1 % died before hospital discharge. At 4 years of follow-up, post-hospital mortality was 14.4 %. Multivariate Cox proportional hazards models revealed heart rate before ICU discharge (HR 5.95; 95 % CI 1.24-28.63; p = 0.03) as an independent predictor of post-ICU in-hospital mortality. Both heart rate (HR 2.56; 95 % CI, 1.05-6.34; p = 0.04) and the C-reactive protein serum concentration before ICU discharge (HR, 1.26; 95 % CI, 1.09-1.46; p = 0.002) were independently associated with post-hospital mortality. Heart rate control therapy reduced the risk of post-ICU in-hospital (HR 0.38; 95 % CI, 0.18-0.81; p = 0.01) and post-hospital (HR, 0.47; 95 % CI, 0.22-1.00; p = 0.05) mortality. CONCLUSION: Heart rate evaluated 24 h before ICU discharge was independently associated with post-ICU in-hospital and post-hospital mortality. Pharmacological interventions to control heart rate may beneficially influence post-ICU mortality.
  Clinical Research in Cardiology 04/2013;
• Article: Environmental exposure to combustion-derived air pollution is associated with reduced functional capacity in apparently healthy individuals.

  Arie Steinvil, Hezzy Shmueli, Eyal Ben-Assa, Eran Leshem-Rubinow, Itzhak Shapira, Shlomo Berliner, Levana Kordova-Biezuner, Ori Rogowski
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  ABSTRACT: Prior toxicological exposure reports demonstrated the decremental effect of several air pollutants on the metabolic equivalents achieved during exercise testing (METs). There are no prior large scale epidemiological reports about the effect of environmental air pollution exposure on those parameters. We analyzed a cohort of apparently healthy individuals attending a screening survey program held between 2003 and 2009. Participants were included if residing within an 11 km radius from the nearest air pollution monitoring station. Linear regression models were fitted for the metabolic equivalents and adjusted to short- and long-term air pollutant exposure (particulate matter under 10 micron, sulfur dioxide, nitrogen dioxide, carbon monoxide and ozone). The models were adjusted for possible confounders that affect air pollution and stress testing measurements. The study population comprised 6,612 individuals (4,201 males and 2,411 females). We found a statistically significant short- and long-term negative correlation between air pollutants, mainly CO and NO2 and between the metabolic equivalents achieved. A similar short-term effect was found for SO2. We conclude that exposure to combustion-derived air pollutants has a short- and long-term decremental effect on cardiorespiratory fitness as measured by exercise stress testing. Our epidemiological data support previous toxicological reports.
  Clinical Research in Cardiology 04/2013;
• Article: Intracardiac fistula due to prosthetic aortic valve abscess causing acute heart failure.

  Daniel Lavall, Jan-Christian Reil, Michael Böhm
  Clinical Research in Cardiology 04/2013;
• Article: Impact of intracoronary reinfusion of bone marrow-derived mononuclear progenitor cells on cardiopulmonary exercise capacity in patients with chronic postinfarction heart failure.

  Joerg Honold, Ulrich Fischer-Rasokat, Florian H Seeger, David Leistner, Saskia Lotz, Stefanie Dimmeler, Andreas M Zeiher, Birgit Assmus
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  ABSTRACT: INTRODUCTION: Intracoronary infusion of bone marrow-derived progenitor cells (BMC) in patients with chronic ischaemic heart failure (CHF) is associated with improvement in left ventricular ejection fraction (LVEF), reduction of NT-proBNP levels and improved prognosis. However, effects of this therapy on cardiopulmonary exercise capacity have not been investigated separately so far. PATIENTS AND METHODS: One hundred and fifty-four patients with ischaemic heart failure (mean LVEF 40.3 ± 10.9 %, NT-proBNP 1,103 ± 1,436 pg/ml) underwent cardiopulmonary exercise capacity testing (CPX) before and 3 months after intracoronary infusion of autologous BMC. Thirty patients with a potential bias on the CPX course as concomitant coronary intervention, bypass surgery, new onset of arrhythmias or implantation of cardiac resynchronization devices were excluded from further analysis. RESULTS: The remaining 124 patients showed an increase in exercise time and peak workload by 16.8 and 6 %. Peak oxygen uptake and oxygen uptake efficiency slope also improved by 2.9 and 12.9 %, whereas other parameters like peak oxygen pulse and the slope of minute ventilation versus CO2 elimination remained unchanged. Analysis of patients with poor, moderate and conserved CPX results prior to cell therapy documented that patients in tertiles with lowest initial exercise capacity showed the largest improvements in CPX after therapy. The differences in response to cell therapy were detectable in all investigated CPX parameters and became significant for exercise time, peak oxygen uptake and peak oxygen pulse. These findings indicate that intracoronary BMC therapy improves exercise capacity in CHF patients with more advanced heart failure.
  Clinical Research in Cardiology 04/2013;
• Article: Mobile left ventricular thrombus in left ventricular dysfunction: case report and review of literature.

  Jürgen Leick, Sebastian Szardien, Christoph Liebetrau, Matthias Willmer, Ulrich Fischer-Rasokat, Jörg Kempfert, Holger Nef, Andreas Rolf, Thomas Walther, Christian Hamm, Helge Möllmann
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  ABSTRACT: INTRODUCTION: Left ventricular (LV) thrombi carry a high risk of embolization. Therapeutic recommendations like treatment with low molecular heparin and intravenous unfractionated heparin (UFH), thrombolysis or surgical thrombectomy have failed to reach a consensus. CASE DESCRIPTION: A 56-year-old female patient presented in cardiogenic shock to the emergency department. Echocardiography demonstrated a dilated LV with a severely depressed global systolic function and a large LV apical thrombus. Treatment with UFH was initiated as well as a treatment with catecholamines for stabilizing the patient's hemodynamic situation. On the follow-up echocardiographic examination, extensive free-floating parts of the thrombus could be documented. Given the high risk of embolization in a now hemodynamically stable situation, emergency surgical embolectomy was performed. DISCUSSION: A conservative procedure might be useful for bridging till surgical treatment is available and/or the risk due to surgery is acceptable. CONCLUSION: In absence of evidence-based guidelines for the treatment of LV thrombi, individualized management options concerning surgical, embolization and bleeding risk must be taken into account.
  Clinical Research in Cardiology 04/2013;
• Article: Increased pericardial adipose tissue is correlated with atrial fibrillation and left atrial dilatation.

  Martin Greif, Franz von Ziegler, Reza Wakili, Janine Tittus, Christoph Becker, Susanne Helbig, Ruediger P Laubender, Wolfgang Schwarz, Melvin D'Anastasi, Jan Schenzle, Alexander W Leber, Alexander Becker
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  ABSTRACT: INTRODUCTION: Pericardial adipose tissue (PAT), a visceral fat depot surrounding the heart, serves as an endocrine active organ and is associated with inflammation. There is growing evidence that atrial fibrillation (AF) is linked with inflammation, which in turn can be a promoter of left atrial remodeling. The aim of this study was to evaluate a potential correlation of PAT to AF and left atrial structural remodeling represented by LA size. METHODS: PAT was measured in 1,288 patients who underwent coronary artery calcium-scanning for coronary risk stratification. LA size was determined by two independent readers. Patients were subdivided into patients without AF, patients with paroxysmal and persistent AF. RESULTS: PAT was independently correlated with AF, persistent AF, and LA size (all p values <0.001). No association could be observed between paroxysmal AF and PAT. These associations persisted after multivariate adjustment for AF risk factors such as age, hypertension, valvular disease, heart failure, and body mass index (AF: OR 1.52, 95 % CI 1.15-2.00, p = 0.003; persistent AF: OR 2.58, 95 % CI 1.69-3.99, p = 0.001; LA size: regression coefficient 0.15 with 95 % CI 0.10-0.20, p < 0.001). CONCLUSION: PAT is associated with AF, in particular with persistent AF and LA size. These findings suggest that PAT could be an independent risk factor for the development of AF and for LA remodeling.
  Clinical Research in Cardiology 04/2013;
• Article: Electrical myostimulation improves left ventricular function and peak oxygen consumption in patients with chronic heart failure: results from the exEMS study comparing different stimulation strategies.

  Frank van Buuren, Klaus Peter Mellwig, Christian Prinz, Britta Körber, Andreas Fründ, Dirk Fritzsche, Lothar Faber, Tanja Kottmann, Nicola Bogunovic, Johannes Dahm, Dieter Horstkotte
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  ABSTRACT: AIMS: Electromyostimulation (EMS) of thigh and gluteal muscles is a strategy to increase exercise capacity in patients with chronic heart failure (CHF). The aim of this non-randomised pilot study was to investigate the effects of different stimulation strategies in CHF patients using a newly developed stimulation suit also involving trunk and arm muscles [extended electromyostimulation (exEMS)] in comparison with EMS therapy limited to gluteal and leg muscles (limEMS). METHODS: 60 individuals joined the EMS training programme. Stable CHF patients (NYHA class II-III) received either exEMS (22 patients, 15 males, mean age 59.95 ± 13.16 years) or limEMS (12 patients, 9 males, 62.75 ± 8.77 years). 26 participants served as healthy control group (CG) receiving exEMS. Training was performed for 10 weeks twice weekly for 20 min, and the level of daily activity remained unchanged. Effects on exercise capacity, oxygen uptake, left ventricular function (EF) and biomarkers were evaluated. RESULTS: There was a significant increase of oxygen uptake at aerobic threshold in all groups (exEMS: 13.7 ± 3.9-17.6 ± 5.1 ml/kg/min (+28.46 %, p < 0.001); limEMS 13.6 ± 3.0-16.0 ± 3.8 ml/kg/min (+17.6 %, p = 0.003); CG 15.0 ± 4.9-17.0 ± 6.4 ml/kg/min (+13.3 %, p = 0.005). LVEF increased from 38.3 ± 8.4 to 43.4 ± 8.8 % (+13.3 %, p = 0.001) (limEMS 37.1 ± 3.0-39.5 ± 5.3 % (+6.5 %, p = 0.27); CG 53.9 ± 6.7-53.7 ± 3.9 % (-0.4 %, p = 0.18). In CHF patients changes in oxygen consumption and LVEF were higher in the exEMS group than in limEMS (not significant). Maximal workload improved in healthy controls (p = 0.002) but not in CHF patients. CONCLUSION: Extended EMS can improve oxygen uptake and EF in CHF. In patients with limited EMS and in control patients without heart failure but extended EMS, oxygen uptake can be improved but EF is unaltered. For all groups, NT proBNP is unaffected by EMS.
  Clinical Research in Cardiology 04/2013;
• Article: Portable recording for detecting sleep disorder breathing in patients under the care of a heart failure clinic.

  Peter Dolliner, Lindsay Brammen, Senta Graf, Martin Huelsmann, Leopold Stiebellehner, Andreas Gleiss, Philipp Ubl, Guenter Steurer
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  ABSTRACT: BACKGROUND: Sleep disordered breathing (SDB) has important clinical implications in patients with congestive heart failure (CHF). We performed portable recording in unselected CHF patients on contemporary therapy. Data on the interactions of SDB in patients supervised at heart failure clinics are rare and we illustrate diversities of obstructive sleep apnoea (OSA) and central sleep apnoea (CSA). METHODS: We studied 176 consecutive subjects on contemporary medical therapy with a median left ventricular ejection fraction of 25.0 % (range 7-35 %) and median NT-pro BNP levels of 3,413.0 pg/ml (range 305.1-35,000.0 pg/ml). Participants underwent prospective overnight portable recording. RESULTS: 50 % presented with an at least moderate form of nocturnal breathing disorder [apnoea-hypopnoea index (AHI) ≥15/h]. Only 15 patients (17.1 %) with AHI ≥15/h reported excessive daytime sleepiness. Irrespective of left ventricular ejection fraction, patients with CSA had higher levels of NT-pro BNP compared to patients with OSA (differences in medians = 2,639.0 pg/ml, p = 0.016), and compared to patients with an AHI <15/h (differences in medians = 2,710.0 pg/ml, p < 0.001). OSA affected 26 patients (14.8 %). CONCLUSIONS: Patients with severe stable CHF on contemporary therapy have a prevalence of 50.0 % of moderate to severe SDB. The natural cascade of the failing heart is initially characterised by absent SDB or OSA, whereas end-stage CHF is associated with CSA.
  Clinical Research in Cardiology 04/2013;
• Article: Intact skeletal muscle mitochondrial enzyme activity but diminished exercise capacity in advanced heart failure patients on optimal medical and device therapy.

  Holly R Middlekauff, M Anthony Verity, Tamara B Horwich, Gregg C Fonarow, Michele A Hamilton, Perry Shieh
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  ABSTRACT: BACKGROUND: A skeletal myopathy, perhaps attributable to neuro-endocrine excitation or disuse, has been described in heart failure (HF) patients, and is thought to contribute to their exercise limitation. Our purpose was to assess biochemical and morphometric characteristics of skeletal muscles of HF patients on optimal HF therapy. A secondary purpose was to explore the effects of clonidine, which interrupts the neuro-endocrine excitation, on these same muscle characteristics. METHODS AND RESULTS: Eleven HF patients (50.8 ± 3.4 years, peak VO2 11.6 ± 2.5 ml/kg/min) underwent two vastus lateralis biopsies (pre/post clonidine). Baseline values were compared to biopsies in 11 age-matched, healthy controls. Scatter plots of individual values for each mitochondrial enzyme revealed almost complete overlap between HF and control groups; mean values, although tending to be greater in controls versus HF patients, were not significantly different. The proportion of type 1 fibers was diminished in 10 of 11 patients. There was no difference in any of the variables after 3 months clonidine versus placebo. CONCLUSION: In HF patients treated with optimal medical and device therapy, characteristic abnormalities of mitochondrial enzyme activity are not found, but muscle fiber type shifts are present. The remaining severe impairment in exercise capacity cannot be attributed to mitochondrial abnormalities.
  Clinical Research in Cardiology 04/2013;
• Article: One-year outcome after CRT implantation in NYHA class IV in comparison to NYHA class III patients.

  Andreas Schuchert, Carmine Muto, Themistoklis Maounis, Robert Frank, Rita Omega Ella, Alexander Polauck, Luigi Padeletti
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  ABSTRACT: BACKGROUND: The aim of the analysis was to compare the outcome of heart failure patients in New York Heart Association (NYHA) class IV to that of NYHA class III patients 1 year after implantation of a CRT device. METHODS: The analysis was based on the 405 CRT patients enrolled in the MASCOT trial. At enrollment, 350 patients (86 %) were in NYHA class III and 55 (14 %) were in NYHA class IV. RESULTS: At 1-year follow-up, the improvement of the ejection fraction was not statistically significantly different between NYHA class III (+7.6 ± 11.7 %) and NYHA class IV patients (+9.2 ± 14.2 %; p = 0.78). NYHA class IV patients had a better mean NYHA class reduction with -1.93 ± 0.83 than NYHA class III patients with -0.93 ± 0.70 (p < 0.0001). There was a greater mean quality of life improvement in NYHA class IV (-27.2 ± 20.9) compared to NYHA class III (-17.7 ± 23.9; p = 0.02). All-cause mortality as well as cardiac mortality remained higher in NYHA class IV with 25.5 and 16.4 % than in NYHA class III with 7.1 and 3.1 % (p < 0.0001). CONCLUSIONS: In this study, 14 % of all patients receiving a CRT device had NYHA class IV at implantation. The data support the concept to implant a CRT device in NYHA class IV patients, because at 1 year after implantation, they experienced better symptomatic improvement compared to NYHA class III patients. The higher cardiac as well as non-cardiac mortality resulted in a fivefold higher all-cause mortality compared to NYHA class III patients.
  Clinical Research in Cardiology 03/2013;
• Article: Comparing outcome of patients with coronary artery disease and dilated cardiomyopathy in ICD and CRT recipients: data from the German DEVICE-registry.

  Kristina Wasmer, Julia Köbe, Dietrich Andresen, Ralf Zahn, Stefan G Spitzer, Joachim Jehle, Johannes Brachmann, Christoph Stellbrink, Eimo Martens, Matthias Hochadel, Jochen Senges, Helmut Klein, Lars Eckardt
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  ABSTRACT: AIMS: The purpose of this study was to evaluate whether there are differences in use and outcome of implantable cardioverter defibrillator (ICD) therapy with or without cardiac resynchronization therapy (CRT) between patients with underlying coronary artery disease (CAD) and non-ischemic dilated cardiomyopathy (DCM). METHODS: A total of 2,263 consecutive patients from 44 German centers who underwent new ICD or CRT implantation between March 2007 and April 2010 were enrolled in the German DEVICE registry. Patients were followed for at least 1 year. RESULTS: Of 1,621 patients who received an ICD, 1,202 (74.2 %) had CAD and 419 (25.8 %) suffered from DCM. Patients who received CRT (n = 642) had CAD in 52.2 % and DCM in 47.8 %. The vast majority received CRT with ICD backup (CRT-D, 95 %). In both ICD and CRT groups, CAD patients were older and more often male. LV ejection fraction in ICD patients with CAD was significantly higher than in DCM patients. Heart failure classification and history of atrial fibrillation were similar in CAD and DCM in CRT patients. There was no significant difference in mortality and first ICD shock delivery between CAD and DCM after 1 year of follow-up. Heart failure symptoms showed significant improvement in CRT patients irrespective of the underlying disease. CONCLUSION: ICD and CRT patients in the DEVICE registry showed similar short-term outcome irrespective of their underlying disease etiology. Except older age and preponderance of males, clinical characteristics, device selection and outcome of ICD or CRT patients in the German DEVICE registry are comparable with patients from randomized trials.
  Clinical Research in Cardiology 03/2013;