Publications by authors named "Uzair Ansari"

59 Publications

Prediction of cardiac events with non-contrast magnetic resonance feature tracking in patients with ischaemic cardiomyopathy.

ESC Heart Fail 2021 Nov 24. Epub 2021 Nov 24.

1st Department of Medicine, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, Heidelberg, D-68167, Germany.

Aims: The aim of this study was to evaluate the prognostic value of feature tracking (FT) derived cardiac magnetic resonance (CMR) strain parameters of the left ventricle (LV)/right ventricle (RV) in ischaemic cardiomyopathy (ICM) patients treated with an implantable cardioverter-defibrillator (ICD). Current guidelines suggest a LV-ejection fraction ≤35% as major criterion for ICD implantation in ICM, but this is a poor predictor for arrhythmic events. Supplementary parameters are missing.

Methods And Results: Ischaemic cardiomyopathy patients (n = 242), who underwent CMR imaging prior to primary and secondary implantation of ICD, were classified depending on EF ≤ 35% (n = 188) or >35% (n = 54). FT parameters were derived from steady-state free precession cine views using dedicated software. The primary endpoint was a composite of cardiovascular mortality (CVM) and/or appropriate ICD therapy. There were no significant differences in FT-function or LV-/RV-function parameters in patients with an EF ≤ 35% correlating to the primary endpoint. In patients with EF > 35%, standard CMR functional parameters, such as LV-EF, did not reveal significant differences. However, significant differences in most FT parameters correlating to the primary endpoint were observed in this subgroup. LV-GLS (left ventricular-global longitudinal strain) and RV-GRS (right ventricular-global radial strain) revealed the best diagnostic performance in ROC curve analysis. The combination of LV-GLS and RV-GRS showed a sensitivity of 85% and a specificity of 76% for the prediction of future events.

Conclusions: The impact of FT derived measurements in the risk stratification of patients with ICM depends on LV function. The combination of LV-GLS/RV-GRS seems to be a predictor of cardiovascular mortality and/or appropriate ICD therapy in patients with EF > 35%.
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http://dx.doi.org/10.1002/ehf2.13712DOI Listing
November 2021

Clinical outcome of out-of-hospital vs. in-hospital cardiac arrest survivors presenting with ventricular tachyarrhythmias.

Heart Vessels 2021 Nov 16. Epub 2021 Nov 16.

First Department of Medicine, Faculty of Medicine Mannheim, University Medical Centre Mannheim (UMM), European Centre for AngioSience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Limited data regarding the prognostic impact of ventricular tachyarrhythmias related to out-of-hospital (OHCA) compared to in-hospital cardiac arrest (IHCA) is available. A large retrospective single-center observational registry with all patients admitted due to ventricular tachyarrhythmias was used including all consecutive patients with ventricular tachycardia (VT) and fibrillation (VF) on admission from 2002 to 2016. Survivors discharged after OHCA were compared to those after IHCA using multivariable Cox regression models and propensity-score matching for evaluation of the primary endpoint of long-term all-cause mortality at 2.5 years. Secondary endpoints were all-cause mortality at 6 months and cardiac rehospitalization at 2.5 years. From 2.422 consecutive patients with ventricular tachyarrhythmias, a total of 524 patients survived cardiac arrest and were discharged from hospital (OHCA 62%; IHCA 38%). In about 50% of all cases, acute myocardial infarction was the underlying disease leading to ventricular tachyarrhythmias with consecutive aborted cardiac arrest. Survivors of IHCA were associated with increased long-term all-cause mortality compared to OHCA even after multivariable adjustment (28% vs. 16%; log rank p = 0.001; HR 1.623; 95% CI 1.002-2.629; p = 0.049) and after propensity-score matching (28% vs. 19%; log rank p = 0.045). Rates of cardiac rehospitalization rates at 2.5 years were equally distributed between OHCA and IHCA survivors. In patients presenting with ventricular tachyarrhythmias, survivors of IHCA were associated with increased risk for all-cause mortality at 2.5 years compared to OHCA survivors.
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http://dx.doi.org/10.1007/s00380-021-01976-yDOI Listing
November 2021

Galectin-3 reflects the echocardiographic quantification of right ventricular failure.

Scand Cardiovasc J 2021 Dec 5;55(6):362-370. Epub 2021 Nov 5.

First Department of Medicine, University Medical Center Mannheim, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.

. Galectin-3 (gal-3) is a mediator of extracellular matrix metabolism and reflects an ongoing cardiac fibrotic process. The aim of this study was to determine the potential use of gal-3 in evaluating the structural and functional parameters of the right ventricle as determined by echocardiography. Ninety-one patients undergoing routine echocardiography were prospectively enrolled in this monocentric study. Serum samples for gal-3 and aminoterminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 h of echocardiographic examination. Patients were arbitrarily divided into subgroups based on right ventricular function as measured by tricuspid annular plane systolic excursion (TAPSE) and these included TAPSE >24 mm ( = 23); TAPSE 18-24 mm ( = 55); TAPSE ≤17 mm ( = 13); permitting the detailed statistical analysis of derived data. Serum levels of gal-3 in all patients correlated with age ( = 0.36.  < .001), creatinine ( = 0.60,  < .001), NT-proBNP ( = 0.53,  < .001), RA area ( = 0.38,  < .001) and TAPSE ( = -0.3.  < .01). The distribution of echocardiographic indices according to TAPSE subgroups revealed an association between gal-3 and its ability to identify patients with right ventricular failure (RVF) as diagnosed by a TAPSE ≤17 mm ( = 0.04,  < .001). The multivariable logistic regression model with adjusted odds ratio showed the ability of gal-3 to identify RVF when adjusted to age and gender (adjusted odds ratio 3.60, 95% CI 1.055-12.282,  < .05). Gal-3 correlated with echocardiographic indices of RVF and could effectively diagnose these patients. The supplementary use of NT-proBNP strengthened the diagnostic capability of each biomarker. The 'Cardiovascular Imaging and Biomarker Analyses' (CIBER Study), clinicaltrials.gov identifier: NCT03074253. Registered 3/8/2017. https://www.clinicaltrials.gov/ct2/show/NCT03074253.
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http://dx.doi.org/10.1080/14017431.2021.1995036DOI Listing
December 2021

Impact of Chronobiological Variation in Takotsubo Syndrome: Prognosis and Outcome.

Front Cardiovasc Med 2021 26;8:676950. Epub 2021 Aug 26.

University of Mannheim, Mannheim, Germany.

A considerable amount of evidence has shown that acute cardiovascular diseases exhibit specific temporal patterns in their onset. This study was performed to determine if takotsubo syndrome (TTS) shows chronobiological variations with short and long-term impacts on adverse events. Our institutional database constituted a collective of 114 consecutive TTS patients between 2003 and 2015. Patients were divided into groups defined by the onset of TTS as per time of the day, day of the week, month and quarter of year. TTS events were most common afternoon and least common in the night, indicating a wave-like pattern ( = 0.001) of manifestation. The occurrence of TTS events was similar among days of the week and weeks of the month. TTS patients diagnosed in the month of November and subsequently in the fourth quarter showed a significantly longer QTc interval. These patients also revealed a significantly lower event-free-survival over a 1-year follow-up. In a multivariate Cox regression analysis, TTS events occurring in the fourth quarter of year (HR 6.8, 95%CI: 1.3-35.9; = 0.02) proved to be an independent predictor of lower event-free-survival. TTS seems to exhibit temporal preference in its onset, but nevertheless this possibly coincidental result needs to be analyzed in a large multicenter registry.
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http://dx.doi.org/10.3389/fcvm.2021.676950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427492PMC
August 2021

Impact of a standardised parenteral nutrition protocol: a quality improvement experience from a NICU of a developing country.

Arch Dis Child 2021 Jul 13. Epub 2021 Jul 13.

Department of Paediatrics and Child Health, Aga Khan University Hospital, Karachi, Pakistan

Objective: Nutrition societies recommend using standardised parenteral nutrition (SPN) solutions. We designed evidence-based SPN formulations for neonates admitted to our neonatal intensive care unit (NICU) and evaluated their outcomes.

Design: This was a quality improvement initiative. Data were collected retrospectively before and after the intervention.

Setting: A tertiary-care level 3 NICU at the Aga Khan University in Karachi, Pakistan.

Patients: All NICU patients who received individualised PN (IPN) from December 2016 to August 2017 and SPN from October 2017 to June 2018.

Interventions: A team of neonatologists and nutrition pharmacists collaborated to design two evidence-based SPN solutions for preterm neonates admitted to the NICU.

Main Outcome Measures: We recorded mean weight gain velocity from days 7 to 14 of life. The other outcomes were change in weight expressed as z-scores, metabolic abnormalities, PN-associated liver disease (PNALD), length of NICU stay and episodes of sepsis during hospital stay.

Results: Neonates on SPN had greater rate of change in weight compared with IPN (β=13.40, 95% CI: 12.02 to 14.79) and a smaller decrease in z-scores (p<0.001). Neonates in the SPN group had fewer hyperglycemic episodes (IPN: 37.5%, SPN: 6.2%) (p<0.001), electrolyte abnormalities (IPN: 56.3%, SPN: 21%) (p<0.001), PNALD (IPN: 52.5%, SPN: 18.5%) (p<0.001) and sepsis (IPN: 26%, SPN: 20%) (p<0.05). The median length of stay in NICU was 14.0 (IQR 12.0-21.0) for the IPN and 8.0 (IQR 5.0-13.0) days for the SPN group.

Conclusions: We found that SPN was associated with shorter NICU stay and greater weight gain. In-house preparation of SPN can be used to address the nutritional needs in resource-limited settings where commercially prepared SPN is not available.
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http://dx.doi.org/10.1136/archdischild-2021-321552DOI Listing
July 2021

Atrial fibrillation increases the risk of recurrent ventricular tachyarrhythmias in implantable cardioverter defibrillator recipients.

Arch Cardiovasc Dis 2021 Jun-Jul;114(6-7):443-454. Epub 2021 May 7.

First Department of Medicine, University Medical Centre Mannheim (UMM), Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.

Background: Data regarding recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) recipients according to atrial fibrillation is limited.

Objective: To assess the prognostic impact of atrial fibrillation on recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator recipients.

Methods: A large retrospective registry was used, including all ICD recipients with episodes of ventricular tachycardia or fibrillation from 2002 to 2016. Patients with atrial fibrillation were compared to those without atrial fibrillation. The primary endpoint was first recurrence of ventricular tachyarrhythmias at 5 years. Secondary endpoints comprised recurrences of ICD-related therapies, first cardiac rehospitalization and all-cause mortality at 5 years. Cox regression, Kaplan-Meier and propensity score-matching analyses were applied.

Results: A total of 592 consecutive ICD recipients were included (33% with atrial fibrillation). Atrial fibrillation was associated with reduced freedom from recurrent ventricular tachyarrhythmias (42% vs. 50%, log-rank P=0.004; hazard ratio 1.445, 95% confidence interval 1.124-1.858), mainly attributable to recurrent ventricular fibrillation in secondary-preventive ICD recipients. Accordingly, atrial fibrillation was associated with reduced freedom from first appropriate ICD therapies (31% vs. 42%, log-rank P=0.001; hazard ratio 1.598, 95% confidence interval 1.206-2.118). Notably, the primary endpoint of freedom from first episode of recurrent ventricular tachyarrhythmias was still reduced in those with atrial fibrillation compared to those without atrial fibrillation after propensity score matching. Regarding secondary endpoints, patients with atrial fibrillation still showed a trend towards reduced freedom from appropriate ICD therapies.

Conclusions: Atrial fibrillation was associated with increased rates of recurrent ventricular tachyarrhythmias and appropriate device therapies in ICD recipients with ventricular tachyarrhythmias.
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http://dx.doi.org/10.1016/j.acvd.2020.12.010DOI Listing
September 2021

Determinants of short birth intervals among married women: a cross-sectional study in Karachi, Pakistan.

BMJ Open 2021 04 26;11(4):e043786. Epub 2021 Apr 26.

Pediatrics & Child Health, Aga Khan University, Karachi, Pakistan

Introduction: Birth spacing is a critical pathway to improving reproductive health. WHO recommends a minimum of 33-month interval between two consecutive births to reduce maternal, perinatal, infant morbidity and mortality. Our study evaluated factors associated with short birth intervals (SBIs) of less than 33 months between two consecutive births, in Karachi, Pakistan.

Methods: We used data from a cross-sectional study among married women of reproductive age (MWRA) who had at least one live birth in the 6 years preceding the survey (N=2394). Information regarding their sociodemographic characteristics, reproductive history, fertility preferences, family planning history and a 6-year reproductive calendar were collected. To identify factors associated with SBIs, we fitted simple and multiple Cox proportional hazards models and computed HRs with their 95% CIs.

Results: The median birth interval was 25 months (IQR: 14-39 months), with 22.9% (833) of births occurring within 33 months of the index birth. Women's increasing age (25-30 years (aHR 0.63 (0.53 to 0.75), 30+ years (aHR 0.29, 95% CI 0.22 to 0.39) compared with 20-24 years; secondary education (aHR 0.75, 95% CI 0.63 to 0.88), intermediate education (aHR 0.62, 95% CI 0.48 to 0.80), higher education (aHR 0.69, 95% CI 0.51 to 0.92) compared with no education, and a male child of the index birth (aHR 0.81, 95% CI 0.70 to 0.94) reduced the likelihood of SBIs. Women's younger age <20 years (aHR 1.24, 95% CI 1.05 to 1.24) compared with 20-24 years, and those who did not use contraception within 9 months of the index birth had a higher likelihood for SBIs for succeeding birth compared with those who used contraception (aHR 2.23, 95% CI 1.93 to 2.58).

Conclusion: Study shows that birth intervals in the study population are lower than the national average. To optimise birth intervals, programmes should target child spacing strategies and counsel MWRA on the benefits of optimal birth spacing, family planning services and contraceptive utilisation.
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http://dx.doi.org/10.1136/bmjopen-2020-043786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076934PMC
April 2021

Electrical storm reveals worse prognosis compared to myocardial infarction complicated by ventricular tachyarrhythmias in ICD recipients.

Heart Vessels 2021 Nov 26;36(11):1701-1711. Epub 2021 Apr 26.

First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Both acute myocardial infarction complicated by ventricular tachyarrhythmias (AMI-VTA) and electrical storm (ES) represent life-threatening clinical conditions. However, a direct comparison of both sub-groups regarding prognostic endpoints has never been investigated. All consecutive implantable cardioverter-defibrillator (ICD) recipients were included retrospectively from 2002 to 2016. Patients with ES apart from AMI (ES) were compared to patients with AMI accompanied by ventricular tachyarrhythmias (AMI-VTA). The primary endpoint was all-cause mortality at 3 years, secondary endpoints were in-hospital mortality, rehospitalization rates and major adverse cardiac event (MACE) at 3 years. A total of 198 consecutive ICD recipients were included (AMI-VTA: 56%; ST-segment elevation myocardial infarction (STEMI): 22%; non-ST-segment myocardial infarction (NSTEMI) 78%; ES: 44%). ES patients were older and had higher rates of severely reduced left ventricular ejection fraction (LVEF) < 35%. ES was associated with increased all-cause mortality at 3 years (37% vs. 19%; p = 0.001; hazard ratio [HR] = 2.242; 95% CI 2.291-3.894; p = 0.004) and with increased risk of first cardiac rehospitalization (44% vs. 12%; p = 0.001; HR = 4.694; 95% CI 2.498-8.823; p = 0.001). This worse prognosis of ES compared to AMI-VTA was still evident after multivariable adjustment (long-term all-cause mortality: HR = 2.504; 95% CI 1.093-5.739; p = 0.030; first cardiac rehospitalization: HR = 2.887; 95% CI 1.240-6.720; p = 0.014). In contrast, the rates of MACE (40% vs. 32%; p = 0.326) were comparable in both groups. At long-term follow-up of 3 years, ES was associated with higher rates of all-cause mortality and rehospitalization compared to patients with AMI-VTA.
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http://dx.doi.org/10.1007/s00380-021-01844-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481166PMC
November 2021

Incomplete neo-endothelialization of left atrial appendage closure devices is frequent after 6 months: a pilot imaging study.

Int J Cardiovasc Imaging 2021 Jul 5;37(7):2291-2298. Epub 2021 Mar 5.

First Department of Medicine, University Medical Center Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Purpose: To bridge neo-endothelialization (NE) of implanted left atrial appendage closure (LAA/LAAC) devices, dual antiplatelet therapy is prescribed. Cardiac computed tomography angiography (cCTA) has been proposed for the evaluation of interventional LAAC. This prospective longitudinal observational study applied a standardized imaging protocol to detect progression of NE of LAAC devices 6 months after implantation.

Methods: Consecutive cCTA datasets of patients six months after LAAC were acquired and the standardized multi-planar reconstruction LAA occluder view for post-implantation evaluation (LOVE) algorithm was used. Residual flow of contrast agent inside the LAA without a peri-device leak (PDL) was defined as incomplete neo-endothelialization. Absence of residual flow was defined as complete neo-endothelialization. Since PDL allows residual flow in the LAA, irrespective of neoendothelialization, PDL were excluded from this study. Diabetes mellitus, liver disease, body-mass-index, age, device sizes and type will be assessed as predictors for incomplete NE.

Results: 53 consecutive patients were recruited for cCTA imaging. 36 (68%) showed no PDL and were included in the study (median age 77 years, 19% female). At median follow-up of 6 months (median 180 days, IQR 178-180), 44% of patients showed complete NE compared to 56% with NE still incomplete. Age, BMI, device type and size as well as prevalence of diabetes mellitus and liver disease did not show significant correlation with the completeness of NE.

Conclusion: This pilot study showed that neo-endothelialization is still incomplete in a majority of patients at mid-term follow-up of 6 months after successful LAAC therapy. Further investigation on the consequences of incomplete endothelialization is needed to guide antiplatelet therapy schedules.
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http://dx.doi.org/10.1007/s10554-021-02192-5DOI Listing
July 2021

Chronic kidney disease impairs prognosis in electrical storm.

J Interv Card Electrophysiol 2021 Jan 23. Epub 2021 Jan 23.

First Department of Medicine, University Medical Centre Mannheim, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, 68167, Deutschland.

Background: The study sought to assess the prognostic impact of chronic kidney disease (CKD) in patients with electrical storm (ES). ES represents a life-threatening heart rhythm disorder. In particular, CKD patients are at risk of suffering from ES. However, data regarding the prognostic impact of CKD on long-term mortality in ES patients is limited.

Methods: All consecutive ES patients with an implantable cardioverter-defibrillator (ICD) were included retrospectively from 2002 to 2016. Patients with CKD (MDRD-GFR < 60 ml/min/1.73 m) were compared to patients without CKD. The primary endpoint was all-cause mortality at 3 years. Secondary endpoints were in-hospital mortality, cardiac rehospitalization, recurrences of electrical storm (ES-R), and major adverse cardiac events (MACE) at 3 years.

Results: A total of 70 consecutive ES patients were included. CKD was present in 43% of ES patients with a median glomerular filtration rate (GFR) of 43.3 ml/min/1.73 m. CKD was associated with increased all-cause mortality at 3 years (63% vs. 20%; p = 0.001; HR = 4.293; 95% CI 1.874-9.836; p = 0.001) and MACE (57% vs. 30%; p = 0.025; HR = 3.597; 95% CI 1.679-7.708; p = 0.001). In contrast, first cardiac rehospitalization (43% vs. 45%; log-rank p = 0.889) and ES-R (30% vs. 20%; log-rank p = 0.334) were not affected by CKD. Even after multivariable adjustment, CKD was still associated with increased long-term mortality (HR = 2.397; 95% CI 1.012-5.697; p = 0.047), as well as with the secondary endpoint MACE (HR = 2.520; 95% CI 1.109-5.727; p = 0.027).

Conclusions: In patients with ES, the presence of CKD was associated with increased long-term mortality and MACE.
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http://dx.doi.org/10.1007/s10840-020-00924-6DOI Listing
January 2021

Copeptin reliably reflects longitudinal right ventricular function.

Ann Clin Biochem 2021 07 11;58(4):270-279. Epub 2021 Feb 11.

First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.

Background: Data is limited evaluating novel biomarkers in right ventricular dysfunction. Normal right heart function improves the prognosis of patients with heart failure. Therefore, this study investigates the association between the novel biomarker copeptin and right heart function compared to NT-proBNP.

Methods: Patients undergoing routine echocardiography were enrolled prospectively. Right ventricular function was assessed by tricuspid annular plane systolic excursion (TAPSE) and further right ventricular and atrial parameters. Exclusion criteria were age under 18 years, left ventricular ejection fraction < 50% and moderate to severe valvular heart disease. Blood samples were taken for biomarker measurements within 72 h of echocardiography.

Results: Ninety-one patients were included. Median values of copeptin increased significantly according to decreasing values of TAPSE ( = 0.001; right heart function grade I: tricuspid annular plane systolic excursion; TAPSE > 24 mm: 5.20 pmol/L; grade II: TAPSE 18-24 mm: 8.10 pmol/L; grade III: TAPSE < 18 mm: 26.50 pmol/L). Copeptin concentrations were able to discriminate patients with decreased right heart function defined as TAPSE < 18 mm (area under the curves [AUC]: copeptin: 0.793;  = 0.001; NT-proBNP: 0.805;  = 0.0001). Within a multivariable linear regression model, copeptin was independently associated with TAPSE (copeptin: T: -4.43;  = 0.0001; NT-proBNP: T: -1.21;  = 0.23). Finally, copeptin concentrations were significantly associated with severely reduced right heart function (TAPSE < 18 mm) within a multivariate logistic regression model (copeptin: odds ratio: 0.94; 95% confidence interval: 0.911-0.975;  = 0.001).

Conclusions: This study demonstrates that the novel biomarker copeptin reflects longitudinal right heart function assessed by standardized transthoracic echocardiography compared with NT-proBNP.
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http://dx.doi.org/10.1177/0004563221989364DOI Listing
July 2021

Simulator-based ultrasound training for identification of endotracheal tube placement in a neonatal intensive care unit using point of care ultrasound.

BMC Med Educ 2020 Nov 7;20(1):409. Epub 2020 Nov 7.

Pediatric Emergency Medicine, McMaster Children's Hospital, Hamilton, Canada.

Background: Simulators are an extensively utilized teaching tool in clinical settings. Simulation enables learners to practice and improve their skills in a safe and controlled environment before using these skills on patients. We evaluated the effect of a training session utilizing a novel intubation ultrasound simulator on the accuracy of provider detection of tracheal versus esophageal neonatal endotracheal tube (ETT) placement using point-of-care ultrasound (POCUS). We also investigated whether the time to POCUS image interpretation decreased with repeated simulator attempts.

Methods: Sixty neonatal health care providers participated in a three-hour simulator-based training session in the neonatal intensive care unit (NICU) of Aga Khan University Hospital (AKUH), Karachi, Pakistan. Participants included neonatologists, neonatal fellows, pediatric residents and senior nursing staff. The training utilized a novel low-cost simulator made with gelatin, water and psyllium fiber. Training consisted of a didactic session, practice with the simulator, and practice with intubated NICU patients. At the end of training, participants underwent an objective structured assessment of technical skills (OSATS) and ten rounds of simulator-based testing of their ability to use POCUS to differentiate between simulated tracheal and esophageal intubations.

Results: The majority of the participants in the training had an average of 7.0 years (SD 4.9) of clinical experience. After controlling for gender, profession, years of practice and POCUS knowledge, linear mixed model and mixed effects logistic regression demonstrated marginal improvement in POCUS interpretation over repeated simulator testing. The mean time-to-interpretation decreased from 24.7 (SD 20.3) seconds for test 1 to 10.1 (SD 4.5) seconds for Test 10, p < 0.001. There was an average reduction of 1.3 s (β = - 1.3; 95% CI: - 1.66 to - 1.0) in time-to-interpretation with repeated simulator testing after adjusting for the covariates listed above.

Conclusion: We found a three-hour simulator-based training session had a significant impact on technical skills and performance of neonatal health care providers in identification of ETT position using POCUS. Further research is needed to examine whether these skills are transferable to intubated newborns in various health settings.

Trial Registration: ClinicalTrials.gov Identifier: NCT03533218 . Registered May 2018.
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http://dx.doi.org/10.1186/s12909-020-02338-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648944PMC
November 2020

Prognostic impact of coronary chronic total occlusion on recurrences of ventricular tachyarrhythmias and ICD therapies.

Clin Res Cardiol 2021 Feb 4;110(2):281-291. Epub 2020 Nov 4.

First Department of Medicine, Faculty of Medicine Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, DZHK (German Center for Cardiovascular Research) Partner Site Heidelberg/Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Background: Despite a few studies evaluating the prognostic impact of coronary chronic total occlusion (CTO) in implantable cardioverter defibrillator (ICD) recipients, the impact of CTO on different types of recurrences of ventricular tachyarrhythmias, as well as their predictors has not yet been investigated in CTO patients.

Methods: A large retrospective registry was used including all consecutive patients with ventricular tachyarrhythmias undergoing coronary angiography at index from 2002 to 2016. Only ICD recipients with CTO were compared to patients without (non-CTO). Kaplan-Meier and Cox regression analyses were applied for the primary end point of first recurrence of ventricular tachyarrhythmias at 5 years. Secondary end points comprised of the different types of recurrences, first appropriate ICD therapy and all-cause mortality at 5 years.

Results: From a total of 422 consecutive ICD recipients with ventricular tachyarrhythmias at index, at least one CTO was present in 25%. CTO was associated with the primary end point of first recurrence of ventricular tachyarrhythmias at 5 years (55% vs. 39%; log rank p = 0.001; HR = 1.665; 95% CI 1.221-2.271; p = 0.001), as well as increased risk of first appropriate ICD therapy (40% vs. 31%; log rank p = 0.039; HR = 1.454; 95% CI 1.016-2.079; p = 0.041) and all-cause mortality at 5 years (26% vs. 16%; log rank p = 0.011; HR = 1.797; 95% CI 1.133-2.850; p = 0.013). Less developed collaterals (i.e., either ipsi- or contralateral compared to bilateral) and a J-CTO score ≥ 3 were strongest predictors of recurrences in CTO patients at 5 years.

Conclusion: A coronary CTO even in the presence of less developed collaterals and more complex CTO category is associated with increasing risk of recurrent ventricular tachyarrhythmias at 5 years in consecutive ICD recipients.
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http://dx.doi.org/10.1007/s00392-020-01758-yDOI Listing
February 2021

Mechanistic Insights of Astrocyte-Mediated Hyperactive Autophagy and Loss of Motor Neuron Function in SOD1 Linked Amyotrophic Lateral Sclerosis.

Mol Neurobiol 2020 Oct 16;57(10):4117-4133. Epub 2020 Jul 16.

System Toxicology & Health Risk assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226001, India.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with no cure. The reports showed the role of nearby astrocytes around the motor neurons as one among the causes of the disease. However, the exact mechanistic insights are not explored so far. Thus, in the present investigations, we employed the induced pluripotent stem cells (iPSCs) of Cu/Zn-SOD1 linked ALS patient to convert them into the motor neurons (MNs) and astrocytes. We report that the higher expression of stress granule (SG) marker protein G3BP1, and its co-localization with the mutated Cu/Zn-SOD1 protein in patient's MNs and astrocytes are linked with AIF1-mediated upregulation of caspase 3/7 and hyper activated autophagy. We also observe the astrocyte-mediated non-cell autonomous neurotoxicity on MNs in ALS. The secretome of the patient's iPSC-derived astrocytes exerts significant oxidative stress in MNs. The findings suggest the hyperactive status of autophagy in MNs, as witnessed by the co-distribution of LAMP1, P62 and LC3 I/II with the autolysosomes. Conversely, the secretome of normal astrocytes has shown neuroprotection in patient's iPSC-derived MNs. The whole-cell patch-clamp assay confirms our findings at a physiological functional level in MNs. Perhaps for the first time, we are reporting that the MN degeneration in ALS triggered by the hyper-activation of autophagy and induced apoptosis in both cell-autonomous and non-cell autonomous conditions.
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http://dx.doi.org/10.1007/s12035-020-02006-0DOI Listing
October 2020

Impact of conflict on maternal and child health service delivery: a country case study of Afghanistan.

Confl Health 2020 10;14:38. Epub 2020 Jun 10.

Center of Excellence in Women and Child Health, Aga Khan University, Karachi, Pakistan.

Introduction: Since decades, the health system of Afghanistan has been in disarray due to ongoing conflict. We aimed to explore the direct effects of conflict on provision of reproductive, maternal, newborn, child and adolescent health and nutrition (RMNCAH&N) services and describe the contextual factors influencing these services.

Method: We conducted a quantitative analysis of secondary data on RMNCAH&N indicators and undertook a supportive qualitative study to help understand processes and contextual factors. For quantitative analysis, we stratified the various provinces of Afghanistan into minimal-, moderate- and severe conflict categories based on battle-related deaths from Uppsala Conflict Data Program (UCDP) and through accessibility of health services using a Delphi methodology. The coverage of RMNCAH&N indicators across the continuum of care were extracted from the Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Survey (MICS). The qualitative data was captured by conducting key informant interviews of multi-sectoral stakeholders working in government, NGOs and UN agencies.

Results: Comparison of various provinces based on the severity of conflict through Delphi process showed that the mean coverage of various RMNCAH&N indicators including antenatal care (OR: 0.42, 95%CI: 0.32-0.55), facility delivery (OR: 0.42, 95%CI: 0.32-0.56), skilled birth attendance (OR: 0.43, 95%CI: 0.33-0.57), DPT3 (OR: 0.26, 95% CI: 0.20-0.33) and oral rehydration therapy (OR: 0.37, 95% CI: 0.25-0.55) was significantly lower for severe conflict provinces when compared to minimal conflict provinces. The qualitative analysis identified various factors affecting decision making and service delivery including insecurity, cultural norms, unavailability of workforce, poor monitoring, lack of funds and inconsistent supplies. Other factors include weak stewardship, capacity gap at the central level and poor coordination at national, regional and district level.

Conclusion: RMNCAH&N service delivery has been significantly hampered by conflict in Afghanistan over the last several years. This has been further compromised by poor infrastructure, weak stewardship and poor capacity and collaboration at all levels. With the potential of peace and conflict resolution in Afghanistan, we would underscore the importance of continued oversight and integrated implementation of sustainable, grass root RMNCAH&N services with a focus on reaching the most marginalized.
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http://dx.doi.org/10.1186/s13031-020-00285-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288441PMC
June 2020

Impact of conflict on maternal and child health service delivery - how and how not: a country case study of conflict affected areas of Pakistan.

Confl Health 2020 27;14:32. Epub 2020 May 27.

Center of Excellence in Women and Child Health, Aga Khan University, Karachi, Pakistan.

Introduction: In conflict affected countries, healthcare delivery remains a huge concern. Pakistan is one country engulfed with conflict spanning various areas and time spans. We aimed to explore the effect of conflict on provision of reproductive, maternal, newborn, child and adolescent health and nutrition (RMNCAH&N) services and describe the contextual factors influencing the prioritization and implementation in conflict affected areas of Pakistan (Balochistan and FATA).

Method: We conducted a secondary quantitative and a primary qualitative analysis. For the quantitative analysis, we stratified the various districts/agencies of Balochistan and FATA into the conflict categories of minimal-, moderate- and severe based on accessibility to health services through a Delphi methodology with local stakeholders and implementing agencies and also based on battle-related deaths (BRD) information from Uppsala Conflict Data Program (UCDP). The coverage of RMNCAH&N indicators across the continuum of care were extracted from the demographic and health surveys (DHS) and district health information system (DHIS). We conducted a stratified descriptive analysis and multivariate analysis using STATA version 15. The qualitative data was captured by conducting key informant interviews of stakeholders working in government, NGOs, UN agencies and academia. All the interviews were audiotaped which were transcribed, translated, coded and analyzed on Nvivo software version 10.

Results: The comparison of the various districts based on the severity of conflict through Delphi process showed that the mean coverage of various RMNCAH&N indicators in Balochistan were significantly lower in severe- conflict districts when compared to minimal conflict districts, while there was no significant difference between moderate and severe conflict areas. There was no reliable quantitative data available for FATA. Key factors identified through qualitative analysis, which affected the prioritization and delivery of services included planning at the central level, lack of coordination amongst various hierarchies of the government and various stakeholders. Other factors included unavailability of health workforce especially female workers, poor quality of healthcare services, poor data keeping and monitoring, lack of funds and inconsistent supplies. Women and child health is set at a high priority but capacity gap at service delivery, resilience from health workers, insecurity and poor infrastructure severely hampers the delivery of quality healthcare services.

Conclusion: Conflict has severely hampered the delivery of health services and a wholesome effort is desired involving coordination amongst various stakeholders. The multiple barriers in conflict contexts cannot be fully mitigated, but efforts should be made to negate these as much as possible with good governance, planning, efficiency and transparency in utilization of available resources.
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http://dx.doi.org/10.1186/s13031-020-00271-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254751PMC
May 2020

The Use of Beta Blockers in Takotsubo Syndrome as Compared to Acute Coronary Syndrome.

Front Pharmacol 2020 14;11:681. Epub 2020 May 14.

First Department of Medicine, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.

Background: Takotsubo syndrome (TTS) and acute coronary syndrome (ACS) patients have a similar mortality rate. In this study, we sought to determine the short- and long-term outcome of TTS patients as compared to ACS patients both treated with beta-blockers.

Objectives: In the present study we described the data of 5 years of follow up of 103 TTS and 422 ACS patients both treated with beta-blockers.

Methods: Data from TTS patients were included retrospectively and prospectively, ACS patients were included retrospectively. All retrospectively included patients have been followed up for 5 years. The end point in this study was the occurrence of death.

Results: TTS affected significantly more women (87.4%) than ACS (34.6%) (p < 0.01). TTS patients suffered significantly more often from thromboembolic events (14.6% versus 2.1%; p < 0.01) and cardiogenic shock (11.9% versus 3.6%; p < 0.01) than the ACS group. TTS patients had a significantly higher long-term mortality (within 5 years) as compared to ACS patients (17.5% versus 3.6%) (p < 0.01). Patients of the TTS group compared to the ACS group did not benefit from combination of beta-blockers and ACE-inhibitors in terms of long-term mortality (p < 0.01). As we compare TTS patients who were treated with beta-blockers and ACE-inhibitors versus single use of beta-blockers there was no difference in long-term mortality (p = 0.918).

Conclusion: TTS patients had a significantly higher long-term mortality (within 5 years) than patients with an ACS.
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http://dx.doi.org/10.3389/fphar.2020.00681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240099PMC
May 2020

Optimal duration for dual antiplatelet therapy with COMBO dual therapy stent.

J Geriatr Cardiol 2019 Nov;16(11):840-843

First Department of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany.

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http://dx.doi.org/10.11909/j.issn.1671-5411.2019.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911800PMC
November 2019

Arrhythmic events in Brugada syndrome patients induced by fever.

Ann Noninvasive Electrocardiol 2020 05 20;25(3):e12723. Epub 2019 Nov 20.

First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany.

Introduction: The Brugada syndrome is associated with arrhythmic events, which may even lead to sudden cardiac death (SCD) as it causes arrhythmic events. A typical Brugada syndrome ECG type I can be triggered at fever situations. The aim of this pooled meta-analysis is to further explore the baseline characteristics and the association of fever to BrS-related arrhythmic events.

Methods: We compiled data from a search of databases (PubMed, Web of Science, Cochrane Library, and Google Scholar). We included 17 studies including 14 case reports and a total of 53 patients.

Results: Our population including 53 patients showed a male predominance of 92% with a mean age of 40.6 ± 17.7 years. 58% of patients had a family history of SCD or BrS. Genetic screening was performed in 14 patients (26%) and revealed a SCN5A mutation in 21% of the patients. ICD implantation was initiated in six patients. 75% (n = 39) of patients did not have symptoms before the fever event. Symptoms at fever included life-threatening arrhythmia such as ventricular fibrillation (VF) or ventricular tachycardia (VT; 17%), syncope (13%), and cardiac arrest or aborted SCD (13%). One patient developed electrical storm which led to not aborted SCD.

Conclusion: Fever is a great risk factor for arrhythmia events in BrS patients. Patients with known fever triggered Brugada syndrome should be surveilled closely during fever and be started on antipyretic therapy as soon as possible.
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http://dx.doi.org/10.1111/anec.12723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358877PMC
May 2020

Takotsubo syndrome and cardiac implantable electronic device therapy.

Sci Rep 2019 11 12;9(1):16559. Epub 2019 Nov 12.

First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany.

Recent studies have reported that takotsubo syndrome (TTS) patients are suffering from life-threatening arrhythmias. The aim of our study was to understand the short and long-term usefulness of cardiac implantable electronic devices in TTS patients.We constituted a collective of 142 patients in a bi-centric study diagnosed with TTS between 2003 and 2017. The patient groups, divided according to the treatment with (n = 9, 6.3%) or without cardiac devices (n = 133, 93.7%), were followed-up to determine the importance of devices and its complications. One patient was treated with a permanent pacemaker, five patients with a wearable cardioverter defibrillator, two patients with a subcutaneous defibrillator and one patient with a transvenous defibrillator. Regular device check-up was documented in all patients, presenting an ongoing high-degree AV-block. Neither device complications nor life-threatening tachyarrhythmias were documented after acute TTS event. However, patients comprising the device group suffered significantly more often from a highly reduced EF (30 ± 7.7% versus 39.1 ± 9.7%; p < 0.05), cardiogenic shock with use of inotropic agents (66.6% versus 16.6%; p < 0.05) and cardiopulmonary resuscitation (44.4% versus 5.3%; p < 0.05). Our data confirm the usefulness of pacemaker in TTS patients. However, the cardioverter defibrillator including wearable cardioverter defibrillator may not be recommended.
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http://dx.doi.org/10.1038/s41598-019-52929-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851377PMC
November 2019

Implantable cardioverter-defibrillator in Brugada syndrome: Long-term follow-up.

Clin Cardiol 2019 Oct 22;42(10):958-965. Epub 2019 Aug 22.

First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany.

Background: Brugada syndrome (BrS) is associated with sudden cardiac death (SCD). Although implantable cardioverter-defibrillator (ICD) implantation is recommended, the long-term outcomes and follow-up data with regard to ICD complications have led to controversy.

Hypothesis: In the present study, we described the data assimilated in a total of 11 studies, analyzing the outcome in 747 BrS patients receiving ICD.

Methods: Data were performed and analyzed after a systematic review of literature compiled from a thorough database search (PubMed, Web of Science, Cochrane Library, and Cinahl).

Results: The mean age of patients receiving ICD was (43.1 ± 13.4, 82.5% males, 46.6% spontaneous BrS type I). Around 15.3% of the patients were admitted due to SCD and 10.4% suffered from atrial arrhythmia. Appropriate shocks were documented in 18.1% of the patients over a mean follow-up period of 82.3 months (47.5-110.4). The following complications were recorded: lead failure and fracture (5.4%), lead perforation (0.7%), lead dislodgement (1.7%), infection (3.9%), pain (0.4%), subclavian vein thrombosis (0.3%), pericardial effusion (0.1%), endocarditis (0.1%), psychiatric problems (1.5%), pneumothorax (0.7%). Inappropriate shocks were documented in 18.1% of the patients. The management of inappropriate shocks was achieved by pulmonary vein isolation (0.5%), drug treatment with sotalol (1.3%) or sotalol with beta-blocker (0.3%) and hydroquinidine (0.1%).

Conclusions: ICD therapy in BrS is associated with relevant ICD-related complications including a substantial risk of inappropriate shocks more frequently in symptomatic BrS patients.
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http://dx.doi.org/10.1002/clc.23247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788474PMC
October 2019

Statin therapy is associated with improved survival in patients with ventricular tachyarrhythmias.

Lipids Health Dis 2019 May 24;18(1):119. Epub 2019 May 24.

First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, European Center for AngioScience (ECAS), and DZHK (German Center for Cardiovascular Research) partner site Heidelberg/Mannheim, Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Objectives: The study sought to assess the impact of statin therapy on survival in patients presenting with ventricular tachyarrhythmias.

Background: Data regarding the outcome of patients with statin therapy presenting with ventricular tachyarrhythmias is limited.

Methods: A large retrospective registry was used including all consecutive patients presenting with ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2016. Patients with statin were compared to patients without statin therapy (non-statin). The primary prognostic endpoint was long-term all-cause death at 3 years. Uni- and multivariable Cox regression analyses were applied in propensity-score matched cohorts.

Results: A total of 424 matched patients was included. The rates of VT and VF were similar in both groups (VT: statin 71% vs. non-statin 68%; VF: statin 29% vs. 32%; p = 0.460). Statin therapy was associated with lower all-cause mortality at long-term follow-up (mortality rates 16% versus 33%; log rank, p = 0.001; HR = 0.438; 95% CI 0.290-0.663; p = 0.001), irrespective of the underlying type of ventricular tachyarrhythmia (VT/VF), left ventricular ejection fraction (LVEF) > 35%, presence of an activated implantable cardioverter defibrillator (ICD), cardiogenic shock or cardiopulmonary resuscitation (CPR).

Conclusion: Statin therapy is independently associated with lower long-term mortality in patients presenting with ventricular tachyarrhythmias on admission.

Trial Registration: Clinicaltrials.gov, NCT02982473 , 11/29/2016, Retrospectively registered.
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http://dx.doi.org/10.1186/s12944-019-1011-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533673PMC
May 2019

The association of high-sensitivity cardiac troponin I and T with echocardiographic stages of heart failure with preserved ejection fraction.

Ann Clin Biochem 2019 07 21;56(4):431-441. Epub 2019 May 21.

1 First Department of Medicine, Faculty of Medicine Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, European Center for AngioScience (ECAS) and DZHK (German Center for Cardiovascular Research) partner site Heidelberg/Mannheim, Mannheim, Germany.

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http://dx.doi.org/10.1177/0004563219841644DOI Listing
July 2019

Short- and Long-Term Incidence of Thromboembolic Events in Takotsubo Syndrome as Compared With Acute Coronary Syndrome.

Angiology 2019 Oct 15;70(9):838-843. Epub 2019 Apr 15.

1 First Department of Medicine, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.

Thromboembolic events are a common complication in Takotsubo syndrome (TTS). However, their long-term incidence compared with acute coronary syndrome (ACS) is lacking. In-hospital and long-term incidence of thromboembolic events of 138 consecutive patients with TTS were compared with 138 sex- and age-matched patients with ACS. Predictors of events were analyzed. The incidence of thromboembolic events in TTS was 2-fold higher than ACS (21% vs 9%; < .01) over a mean follow-up of 5 years. Although the left ventricular ejection fraction (LVEF) at event was significantly lower in TTS compared with ACS (38% [9%] vs 54% [11%]; < .01), the follow-up LVEF was comparable. Patients with TTS suffering from thromboembolic events were more often treated with anticoagulation compared with ACS (44.8% vs 8.3%, = .03). However, more patients presenting with ACS (100% vs 48.3%; < .01) were discharged on aspirin. Only elevated C-reactive protein was a predictor of thromboembolic events using multivariate analysis (hazard ratio 1.1, 95% confidence interval, 1.0-1.2; < .01). In conclusion, the risk of thromboembolic events in TTS was significantly higher than the risk of thromboembolic events in ACS over a mean follow-up of 5 years.
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http://dx.doi.org/10.1177/0003319719842682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716204PMC
October 2019

Comparable survival in ischemic and nonischemic cardiomyopathy secondary to ventricular tachyarrhythmias and aborted cardiac arrest.

Coron Artery Dis 2019 06;30(4):303-311

First Department of Medicine, University Medical Center Mannheim, Faculty of Medicine Mannheim, University of Heidelberg, European Center for AngioScience (ECAS), and DZHK (German Center for Cardiovascular Research) partner site Heidelberg/Mannheim.

Objectives: The study sought to assess the impact of ischemic cardiomyopathy (ICMP) and nonischemic cardiomyopathy (NICMP) on secondary survival in patients presenting with ventricular tachyarrhythmias and aborted sudden cardiac arrest (SCA).

Background: Data regarding the outcome of patients with ICMP or NICMP presenting with ventricular tachyarrhythmias or aborted SCA is limited.

Patients And Methods: A large retrospective registry was used including all consecutive patients presenting with ventricular tachycardia (VT), ventricular fibrillation (VF), or aborted SCA on admission from 2002 to 2016. ICMP and NICMP were compared applying univariable correlation models and propensity score matching for evaluation of the primary prognostic end point defined as long-term all-cause mortality at 2.5 years. Secondary end points were all-cause mortality at 30 days, at index hospitalization, and after discharge; the composite end point of recurrent ventricular tachyarrhythmias, cardiac death at 24 h, and appropriate implantable cardioverter defibrillator (ICD) therapy; and finally, rehospitalization related to ventricular tachyarrhythmias.

Results: A total of 276 matched patients were included. The rates of VT and VF were similar in both groups (VT: 75 vs. 73%; VF: 23 vs. 22%). At 2.5 years, no differences were found regarding the primary end point of all-cause mortality in both patients with ICMP and NICMP (mortality rate: 33 vs. 32%; log-rank P=0.898). Similar survival was present irrespective of the presence of acute myocardial infarction, underlying ventricular tachyarhythmia (VT/VF), left ventricular dysfunction, and an activated ICD. Furthermore, no significant differences could be seen regarding secondary end points of all-cause mortality at 30 days, at index hospitalization, and after discharge; the composite end point of recurrent ventricular tachyarrhythmias, cardiac death at 24 h, and appropriate ICD interrogation; and finally rehospitalization related to ventricular tachyarrhythmias.

Conclusion: Both ICMP and NICMP reveal comparable secondary survival after episodes of ventricular tachyarrhythmias or SCA on admission.
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http://dx.doi.org/10.1097/MCA.0000000000000738DOI Listing
June 2019

Long-term follow-up of implantable cardioverter-defibrillators in Short QT syndrome.

Clin Res Cardiol 2019 Oct 16;108(10):1140-1146. Epub 2019 Mar 16.

First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Background: Short QT syndrome (SQTS) is associated with sudden cardiac death and implantable cardioverter-defibrillator (ICD) implantation is recommended in this rare disease. However, only a few SQTS families have been reported in literature with limited follow-up data.

Objectives: In the recent study, we describe the outcome data of 57 SQTS patients receiving ICD implantation. This includes seven SQTS families consecutively admitted to our hospital between 2002 and 2017 as well as patients reported in published literature.

Methods: Seven SQTS patients admitted to our hospital were followed up. Additionally, 7 studies out of a total of 626 researched articles were identified through systematic database search (PubMed, Web of Science, Cochrane Library, and Cinahl) and their data analyzed according to our model.

Results: Complications during a median follow-up time of 67.4 months (IQR 6-162 months) were documented in 31 (54%) patients. Inappropriate shocks were seen in 33% due to T wave oversensing (8.7%), supraventricular tachycardia (19%), lead failure and fracture (21%). Further complications were infection (10%), battery depletion (7%) and psychological distress (3.5%). Appropriate shocks were documented in 19%. Three patients (5%) were treated with s-ICD due to recurrent complications of transvenous ICD.

Conclusion: ICD therapy is an effective therapy in SQTS patients. However, it is also associated with significant risk of device-related complications.
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http://dx.doi.org/10.1007/s00392-019-01449-3DOI Listing
October 2019

Impact of ST-segment elevation on the outcome of Takotsubo syndrome.

Ther Clin Risk Manag 2019 7;15:251-258. Epub 2019 Feb 7.

First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany,

Background: Recent studies have highlighted that Takotsubo syndrome (TTS), mimicking acute coronary syndrome (ACS), is associated with poor clinical outcome. TTS is associated with different repolarization disorders including ST-segment elevation. ST elevation myocardial infarction (STEMI) in ACS is associated with declined prognosis. However, the clinical and prognostic impact of ST-segment elevation on TTS remains lacking.

Aim: The aim of this study was to determine the short- and long-term prognostic impact of ST-segment elevation on TTS patients as compared with STEMI patients.

Patients And Methods: Our institutional database constituted a consecutive cohort of 138 TTS patients and 138 ACS patients matched for age and sex. TTS patients (n=41) with ST-segment elevation were compared with ACS patients with ST-segment elevation (n=64).

Results: Chest pain was significantly more documented in STEMI patients as compared with TTS patients (48.8% vs 78.1%; <0.01). Cardiovascular risk factors such as diabetes mellitus (12.2% vs 29.7%; =0.02) were significantly more presented in STEMI patients. Although the initial left ventricular ejection fraction (LVEF) was more declined in TTS patients (39%±9% vs 45%±16%; <0.01), the LVEF was more declined in STEMI patients at follow-up (54%±10% vs 45%±16%; =0.04). Inhospital complications such as respiratory failure were significantly more presented in TTS patients (68.3% vs 20.3%; <0.01). The short-term as well as the long-term morality was similar in both groups. In univariate analysis, male sex, ejection fraction (EF) <35%, glomerular filtration rate (GFR) <60 mL/min, cardiogenic shock, inotropic drugs, and history of cancer were predictors of 5-year mortality.

Conclusion: Rates of the long-term mortality in TTS patients with ST elevations are comparable with STEMI patients.
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http://dx.doi.org/10.2147/TCRM.S180170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369855PMC
February 2019

Prognostic impact of recurrences of ventricular tachyarrhythmias and appropriate ICD therapies in a high-risk ICD population.

Clin Res Cardiol 2019 Aug 12;108(8):878-891. Epub 2019 Feb 12.

First Department of Medicine, Faculty of Medicine Mannheim, European Center for AngioScience (ECAS), and DZHK, University Medical Centre Mannheim (UMM), University of Heidelberg, German Center for Cardiovascular Research) partner site Heidelberg/Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Purpose: The study sought to evaluate the prognostic impact of recurrences of ventricular tachyarrhythmias in consecutive ICD recipients with ventricular tachyarrhythmias on admission.

Methods: All consecutive patients surviving at least one episode of ventricular tachyarrhythmias from 2002 to 2016 and discharged with an ICD (pre-existing ICD or ICD implantation at index hospitalization) were included. The primary endpoint was all-cause mortality according to the presence or absence of recurrences of ventricular tachyarrhythmias at 5 years. Secondary endpoints comprised the impact of different types of recurrences, appropriate ICD therapies, as well as predictors of recurrences and appropriate ICD therapies. Kaplan-Meier, multivariable Cox regression and propensity score matching analyses were applied.

Results: A total of 592 consecutive ICD recipients was included (44% with recurrences of ventricular tachyarrhythmias and 56% without). Recurrences of ventricular tachyarrhythmias were associated with increased all-cause mortality at 5 years (HR = 1.498; 95% CI = 1.052-2.132; p = 0.025). Worst survival was observed in patients with sustained VT or VF as first recurrences compared to non-sustained VT, as well as in patients with cumulative recurrences of non-sustained or sustained VT plus VF, whereas mortality was not affected by the number of recurrences of ventricular tachyarrhythmias (> 4 vs. ≤ 4). Moreover, appropriate ICD therapies were associated with increased all-cause mortality (HR = 1.874; 95% CI = 1.318-2.666; p = 0.001), mainly attributed to secondary preventive ICDs. Finally, atrial fibrillation, LVEF < 35% and non-ischemic cardiomyopathy were identified as predictors of recurrences of ventricular tachyarrhythmias and appropriate ICD therapies.

Conclusions: Recurrences of ventricular tachyarrhythmias and recurrent appropriate ICD therapies are associated with increased long-term all-cause mortality in consecutive ICD recipients. Non-ischemic cardiomyopathy, AF and LVEF < 35% revealed to be significant predictors of both endpoints.
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http://dx.doi.org/10.1007/s00392-019-01416-yDOI Listing
August 2019

Impact of T-inversion on the outcome of Takotsubo syndrome as compared to acute coronary syndrome.

Eur J Clin Invest 2019 Apr 25;49(4):e13078. Epub 2019 Feb 25.

First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany.

Background: Previous studies revealed that patients with Takotsubo syndrome (TTS) have a higher mortality rate than the general population and a comparable mortality to acute coronary syndrome (ACS). Repolarisation abnormalities, namely T-wave amplitude, may provide incremental prognostic information, in addition to traditional risk factors in ACS. This study was performed to determine the short- and long-term prognostic impact of inverted T-waves in TTS patients, as compared to ACS patients.

Methods And Results: Our institutional database constituted a collective of 138 patients diagnosed with TTS from 2003 to 2017, as well as 532 patients suffering from ACS. Patients with TTS or with ACS (n = 138 per group) were matched for age and sex and assessed retrospectively and prospectively and divided into two groups, TTS with inverted T-waves (n = 123) and ACS with inverted T-waves (n = 80). In-hospital complications such as respiratory failure with the need of respiratory support (60.2% vs 6.3%; P < 0.01), thromboembolic events (13.8% vs 2.5%; P < 0.01) and cardiogenic shock (18.9% vs 8.8%; P = 0.05) were significantly more presented in TTS as compared to ACS patients. Among cardiovascular risk factors diabetes mellitus (23.6% vs 45.0%; P < 0.01) and arterial hypertension (57.7% vs 78.8%; P < 0.01) were more presented in ACS patients as compared to TTS patients. Short-term mortality was similar, however the long-term mortality of 5 years was significantly higher in the TTS group (25.2% vs 7.5%; P < 0.01). In univariate analysis were male gender, EF < 35%, GFR < 60 mL/min, cardiogenic shock, inotropic drugs and history of cancer predictors of 5-year mortality. The multivariate analysis showed only male gender (HR 2.7, 95% CI 1.1-6.5; P = 0.02), GFR < 60 mL/min (HR 2.8, 95% CI 1.2-6.0; P = 0.01) and history of cancer (HR 3.6, 95% CI 1.4-9.3; P < 0.01) as independent predictors of 5-year mortality.

Conclusion: Rates of long-term mortality were significantly higher in TTS patients showing inverted T-waves compared with patients diagnosed with ACS with inverted T-waves. However, T-inversion was not an independent predictor of 5-year mortality in the multivariate analysis.
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http://dx.doi.org/10.1111/eci.13078DOI Listing
April 2019

Prognostic impact of chronic kidney disease and renal replacement therapy in ventricular tachyarrhythmias and aborted cardiac arrest.

Clin Res Cardiol 2019 Jun 21;108(6):669-682. Epub 2018 Dec 21.

First Department of Medicine, Faculty of Medicine Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, European Center for AngioScience (ECAS), and DZHK (German Center for Cardiovascular Research) Partner Site Heidelberg/Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Background: The study sought to assess the prognostic impact of chronic kidney disease (CKD) and renal replacement therapy (RRT) in patients with ventricular tachyarrhythmias and sudden cardiac arrest (SCA) on admission.

Methods: A large retrospective registry was used including all consecutive patients presenting with ventricular tachycardia (VT), fibrillation (VF) and SCA on admission from 2002 to 2016. Non-CKD vs. "CKD without RRT", and "CKD without RRT" vs. "CKD with RRT" were compared applying multivariable Cox regression models and propensity-score matching for evaluation of the primary prognostic endpoint defined as long-term all-cause mortality at 2 years. Secondary prognostic endpoints were cardiac death at 24 h, in-hospital death at index and the composite endpoint of recurrent ventricular tachyarrhythmias, appropriate ICD therapies and cardiac death at 24 h.

Results: In 2686 unmatched high-risk patients with ventricular tachyarrhythmias and SCA, non-CKD was present in 46%, "CKD without RRT" in 46% and "CKD with RRT" in 8%. Each, VT and VF occurred in about one-third of CKD patients. Multivariable Cox regression models revealed that "CKD without RRT" (HR = 2.118; p = 0.001) and "CKD with RRT" (HR = 3.043; p = 0.001) patients were associated with the primary endpoint of long-term mortality at 2 years, which was also proven after propensity-score matching (non-CKD vs. "CKD without RRT": 43% vs. 27%, log rank p = 0.001; HR = 1.847; "CKD without RRT" vs. "CKD with RRT": 74% vs. 51%, log rank p = 0.001; HR = 2.129). The rates of secondary endpoints were higher for cardiac death at 24 h, in-hospital death at index and the composite of recurrent ventricular tachyarrhythmias, appropriate ICD therapies and  cardiac death at 24 h, respectively, for "CKD without RRT" and "CKD with RRT" patients.  CONCLUSION: In patients presenting with ventricular tachyarrhythmias and aborted SCA on admission, the presence of CKD, especially combined with RRT, is independently associated with an increase of long-term all-cause mortality at 2 years, cardiac death at 24 h, in-hospital death and the composite of recurrent ventricular tachyarrhythmias, appropriate ICD therapies and  cardiac death at 24 h.
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http://dx.doi.org/10.1007/s00392-018-1396-yDOI Listing
June 2019
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