Journal: Clin Res Cardiol

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Abstract

Prognostic value of changes in high-sensitivity cardiac troponin T beyond biological variation in stable outpatients with cardiovascular disease: a validation study.

Biener M, Giannitsis E, Hogrefe K, Mueller-Hennessen M, ... Frankenstein L, Täger T
Objective
To evaluate the prognostic implications of longitudinal long-term changes beyond the biological variation of high-sensitivity cardiac troponin T (hs-cTnT) in outpatients with stable or asymptomatic cardiovascular disease (CV) and to assess possible differences in the prognostic value while using reference change value (RCV) and minimal important differences (MID) as metric for biological variation.
Methods
Hs-cTnT was measured at index visit and after 12 months in outpatients presenting for routine follow-up. The prognostic relevance of a concentration change of hs-cTnT values exceeding the biological variation defined by RCV and MID of a healthy population within the next 12 months following the stable initial period was determined regarding three endpoints: all-cause mortality (EP1), a composite of all-cause mortality, non-fatal myocardial infarction and stroke (EP2), and a composite of all-cause mortality, non-fatal myocardial infarction, stroke, hospitalization for acute coronary syndrome (ACS) or decompensated heart failure, and planned and unplanned percutaneous coronary interventions (PCI, EP3).
Results
Change in hs-cTnT values exceeding the biovariability defined by MID but not by RCV discriminated a group with a higher cardiovascular risk profile. Changes within MID were associated with uneventful course (NPV 91.6-99.7%) while changes exceeding MID were associated with a higher occurrence of all endpoints within the next 365 days indicating a 5.5-fold increased risk for EP 1 (p = 0.041) a 2.4-fold increased risk for EP 2 (p = 0.049) and a 1.9-fold increased risk for EP 3 (p < 0.0001).
Conclusions
In stable outpatients MID calculated from hs-cTnT changes measured 365 ± 120 days apart are helpful to predict an uneventful clinical course.
Clinical trials identifier
NCT01954303.

© 2021. The Author(s).

Clin Res Cardiol: 24 Oct 2021; epub ahead of print
Biener M, Giannitsis E, Hogrefe K, Mueller-Hennessen M, ... Frankenstein L, Täger T
Clin Res Cardiol: 24 Oct 2021; epub ahead of print | PMID: 34694435
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Abstract

Controlling my genome with my smartphone: first clinical experiences of the PROMISE system.

Amr A, Hinderer M, Griebel L, Deuber D, ... Frey N, Meder B
Background
The development of Precision Medicine strategies requires high-dimensional phenotypic and genomic data, both of which are highly privacy-sensitive data types. Conventional data management systems lack the capabilities to sufficiently handle the expected large quantities of such sensitive data in a secure manner. PROMISE is a genetic data management concept that implements a highly secure platform for data exchange while preserving patient interests, privacy, and autonomy.
Methods
The concept of PROMISE to democratize genetic data was developed by an interdisciplinary team. It integrates a sophisticated cryptographic concept that allows only the patient to grant selective access to defined parts of his genetic information with single DNA base-pair resolution cryptography. The PROMISE system was developed for research purposes to evaluate the concept in a pilot study with nineteen cardiomyopathy patients undergoing genotyping, questionnaires, and longitudinal follow-up.
Results
The safety of genetic data was very important to 79%, and patients generally regarded the data as highly sensitive. More than half the patients reported that their attitude towards the handling of genetic data has changed after using the PROMISE app for 4 months (median). The patients reported higher confidence in data security and willingness to share their data with commercial third parties, including pharmaceutical companies (increase from 5 to 32%).
Conclusion
PROMISE democratizes genomic data by a transparent, secure, and patient-centric approach. This clinical pilot study evaluating a genetic data infrastructure is unique and shows that patient\'s acceptance of data sharing can be increased by patient-centric decision-making.

© 2021. The Author(s).

Clin Res Cardiol: 24 Oct 2021; epub ahead of print
Amr A, Hinderer M, Griebel L, Deuber D, ... Frey N, Meder B
Clin Res Cardiol: 24 Oct 2021; epub ahead of print | PMID: 34694434
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Abstract

Initial in-hospital heart rate is associated with long-term survival in patients with acute ischemic stroke.

Lee JD, Kuo YW, Lee CP, Huang YC, Lee M, Lee TH
Aims
Increased heart rate has been associated with stroke risk and outcomes. The purpose of this study was to explore the long-term prognostic value of initial in-hospital heart rate in patients with acute ischemic stroke (AIS).
Methods
We analyzed data from 21,655 patients with AIS enrolled (January 2010-September 2018) in the Chang Gung Research Database. Mean initial in-hospital heart rates were averaged and categorized into 10-beat-per-minute (bpm) increments. The primary and secondary outcomes were all-cause mortality and cardiovascular death. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable adjusted Cox proportional hazard models, using the heart rate < 60 bpm subgroup as the reference.
Results
The adjusted HRs for all-cause mortality were 1.23 (95% CI 1.08-1.41) for heart rate 60-69 bpm, 1.74 (95% CI 1.53-1.97) for heart rate 70-79 bpm, 2.16 (95% CI 1.89-2.46) for heart rate 80-89 bpm, and 2.83 (95% CI 2.46-3.25) for heart rate ≥ 90 bpm compared with the reference group. Likewise, heart rate ≥ 60 bpm was also associated with an increased risk of cardiovascular death (adjusted HR 1.18 [95% CI 0.95-1.46] for heart rate 60-69 bpm, 1.57 [95% CI 1.28-1.93] for heart rate 70-79 bpm, 1.98 [95% CI 1.60-2.45] for heart rate 80-89 bpm, and 2.36 [95% CI 1.89-2.95] for heart rate ≥ 90 bpm).
Conclusions
High initial in-hospital heart rate is an independent predictor of all-cause mortality and cardiovascular death in patients with AIS.

© 2021. The Author(s).

Clin Res Cardiol: 22 Oct 2021; epub ahead of print
Lee JD, Kuo YW, Lee CP, Huang YC, Lee M, Lee TH
Clin Res Cardiol: 22 Oct 2021; epub ahead of print | PMID: 34687320
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Abstract

Early response of right-ventricular function to percutaneous mitral valve repair.

Sugiura A, Shamekhi J, Goto T, Spieker M, ... Becher MU, of the Heart Failure Network Rhineland
Background
The change in right-ventricular function (RVF) after transcatheter mitral valve repair is still poorly understood. We assessed the early response of RVF to the MitraClip procedure and its clinical relevance.
Methods
We analyzed consecutive patients who underwent a MitraClip procedure to treat MR between August 2010 and March 2019 in the Heart Failure Network Rhineland registry. RVF was assessed before and after the procedure. Impaired RVF was defined as an RV fractional area change (RVFAC) < 35% or tricuspid annular plane systolic excursion (TAPSE) < 16 mm.
Results
816 eligible patients (77 ± 9 years, 58.5% male) were included in the analysis. Baseline values of RVF were: RVFAC 38.6 (IQR 29.7-46.7) % and TAPSE 17.0 (IQR 14.0-21.0) mm. At a median time of 3 (IQR 2-5) days after the procedure, the RVF remained normal in 34% (n = 274), normalized in 17% (n = 140), deteriorated in 15% (n = 125), and was persistently impaired in 34% (n = 277) of patients. The RVF response was significantly associated with a composite outcome of all-cause mortality and hospitalization due to heart failure within a 2-year follow-up. Compared to stable/normal RVF, the adjusted hazard ratios for the outcome were 1.78 (95% CI 1.10-2.86) for normalized RVF, 1.89 (95% CI 1.34-3.15) for deteriorated RVF, and 2.25 (95% CI 1.47-3.44) for persistently impaired RVF. Changes in TAPSE and RVFAC as continuous variables were significantly correlated with the outcome.
Conclusion
An early change in RVF following transcatheter mitral valve repair is predictive of mortality and hospitalization due to heart failure during follow-up. Early response of RVF after MitraClip and its clinical significance. An acute, early change in RVF can be observed following the MitraClip procedure, which is associated with the risk of mortality and hospitalization for HF.

© 2021. The Author(s).

Clin Res Cardiol: 19 Oct 2021; epub ahead of print
Sugiura A, Shamekhi J, Goto T, Spieker M, ... Becher MU, of the Heart Failure Network Rhineland
Clin Res Cardiol: 19 Oct 2021; epub ahead of print | PMID: 34669015
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Abstract

Left atrial appendage closure with the watchman device reduces atrial fibrillation management costs.

D Ancona G, Safak E, Weber D, Arslan F, ... Kugler J, Ince H
Aims
To report hospitalization costs of patients with non-valvular atrial fibrillation (AF) submitted to percutaneous left atrial appendage closure (LAAC) with the Watchman device.
Methods
Pre- and post-procedural hospitalization AF-related costs were calculated using the DRG system (diagnosis-related groups) and compared.
Results
Between 2012 and 2016, 677 non-valvular AF patients underwent LAAC. Median time from first cardiac hospitalization to LAAC was 5.9 years (IQR 1.6-9.1) and median follow-up after LAAC was 4.8 years (IQR 3.6-5.6). LAAC mortality was 1.3% and follow-up mortality 16.9%. Median pre-LAAC hospitalization cost was € 17,867 (IQR € 7512-35,08) and post-LAAC € 8772 (IQR € 1183-25,159) (p < 0.0001). Annualized cost pre-LAAC was 3773 € (IQR € 1644-8,493) and post-LAAC 2,001 € (IQR € 260-6913) (p < 0.0001). Follow-up survivors had significantly lower post-LAAC costs (p < 0.0001) and after a survival cut-off time of 4.6 years LAAC procedural and post-procedural hospitalization costs achieved parity with pre-LACC costs (AUC 0.64; p = 0.02). CHA2DS2-VASc score (B = 0.04; p = 0.02; 95% CI 0.006-0.08), and HAS-BLED score (B = 0.08; p = 0.004; 95% CI 0.02-0.14) were independent determinants for annualized hospitalization costs post-LAAC. At Cox-regression analysis the DRG mean clinical complexity level (CCL) was the only independent determinant for follow-up mortality (OR = 2.2; p < 0.0001; 95% CI 1.6-2.8) with a cut-off value of 2.25 to predict follow-up mortality (AUC 0.72; p < 0.0001; Spec. 70%; Sens. 70%).
Conclusion
Hospitalization costs pre-LAAC are consistent, and after LAAC, they are significantly reduced. Costs seem related to the patient\'s risk profile at the time of the procedure. With the increase in post-LAAC survival time, the procedure becomes economically more profitable.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 14 Oct 2021; epub ahead of print
D Ancona G, Safak E, Weber D, Arslan F, ... Kugler J, Ince H
Clin Res Cardiol: 14 Oct 2021; epub ahead of print | PMID: 34652527
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Abstract

Drug overdose and the risk of cardiovascular diseases: a nested case-control study.

Gan WQ, Buxton JA, Palis H, Janjua NZ, ... Desai R, Slaunwhite AK
Background
North America has been experiencing an unprecedented epidemic of drug overdose. This study investigated the associations of drug overdose with the risk of cardiovascular disease (CVD) and 11 major CVD subtypes.
Methods
This nested case-control study was based on a cohort of 20% random sample of residents in British Columbia, Canada, who were aged 18-80 years and did not have known CVD at baseline (n = 617,863). During a 4-year follow-up period, persons who developed incident CVD were identified as case subjects, and the onset date of CVD was defined as the index date. For each case subject, we used incidence density sampling to randomly select up to five control subjects from the cohort members who were alive and did not have known CVD by the index date, were admitted to an emergency department or hospital on the index date for non-CVD causes, and were matched on age, sex, and region of residence. Overdose exposure on the index date and each of the previous 5 days was examined for each subject.
Results
This study included 16,113 CVD case subjects (mean age 53 years, 59% male) and 66,875 control subjects. After adjusting for covariates, overdose that occurred on the index date was strongly associated with CVD [odds ratio (OR), 2.9; 95% confidence interval (CI), 2.4-3.5], especially for arrhythmia (OR, 8.6; 95% CI, 6.2-12.0), ischemic stroke (OR, 5.3; 95% CI, 2.0-14.1), hemorrhagic stroke (OR, 3.1; 95% CI, 1.2-8.3), and myocardial infarction (OR, 3.0; 95% CI, 1.5-5.8). The CVD risk was decreased but remained significantly elevated for overdose that occurred on the previous day, and was not observed for overdose that occurred on each of the previous 2-5 days.
Conclusions
Drug overdose appears to be associated with increased risk of cardiovascular diseases.

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.

Clin Res Cardiol: 14 Oct 2021; epub ahead of print
Gan WQ, Buxton JA, Palis H, Janjua NZ, ... Desai R, Slaunwhite AK
Clin Res Cardiol: 14 Oct 2021; epub ahead of print | PMID: 34654963
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Abstract

Growth differentiation factor 15 predicts poor prognosis in patients with heart failure and reduced ejection fraction and anemia: results from RED-HF.

Ueland T, Gullestad L, Kou L, Young JB, ... Anand IS, Aukrust P
Aims
We aimed to assess the value of GDF-15, a stress-responsive cytokine, in predicting clinical outcomes in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and anemia METHODS AND
Results:
Serum GDF-15 was assessed in 1582 HFrEF and mild-to-moderate anemia patients who where followed for 28 months in the Reduction of Events by Darbepoetin alfa in Heart Failure (RED-HF) trial, an overall neutral RCT evaluating the effect darbepoetin alfa on clinical outcomes in patients with systolic heart failure and mild-to-moderate anemia. Association between baseline and change in GDF-15 during 6 months follow-up and the primary composite outcome of all-cause death or HF hospitalization were evaluated in multivariable Cox-models adjusted for conventional clinical and biochemical risk factors. The adjusted risk for the primary outcome increased with (i) successive tertiles of baseline GDF-15 (tertile 3 HR 1.56 [1.23-1.98] p < 0.001) as well as with (ii) a 15% increase in GDF-15 levels over 6 months of follow-up (HR 1.68 [1.38-2.06] p < 0.001). Addition of change in GDF-15 to the fully adjusted model improved the C-statistics (p < 0.001). No interaction between treatment and baseline or change in GDF-15 on outcome was observed. GDF-15 was inversely associated with several indices of anemia and correlated positively with ferritin.
Conclusions
In patients with HF and anemia, both higher baseline serum GDF-15 levels and an increase in GDF-15 during follow-up, were associated with worse clinical outcomes. GDF-15 did not identify subgroups of patients who might benefit from correction of anemia but was associated with several indices of anemia and iron status in the HF patients.

© 2021. The Author(s).

Clin Res Cardiol: 04 Oct 2021; epub ahead of print
Ueland T, Gullestad L, Kou L, Young JB, ... Anand IS, Aukrust P
Clin Res Cardiol: 04 Oct 2021; epub ahead of print | PMID: 34611778
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Abstract

Ten-year all-cause death following percutaneous or surgical revascularization in patients with prior cerebrovascular disease: insights from the SYNTAX Extended Survival study.

Wang R, Takahashi K, Garg S, Thuijs DJFM, ... Holmes DR, Serruys PW
Background
Coronary bypass artery grafting (CABG) has a higher procedural risk of stroke than percutaneous coronary intervention (PCI), but may offer better long-term survival. The optimal revascularization strategy for patients with prior cerebrovascular disease (CEVD) remains unclear.
Methods and results
The SYNTAXES study assessed the vital status out to 10 year of patients with three-vessel disease and/or left main coronary artery disease enrolled in the SYNTAX trial. The relative efficacy of PCI vs. CABG in terms of 10 year all-cause death was assessed according to prior CEVD. The primary endpoint was 10 year all-cause death. The status of prior CEVD was available in 1791 (99.5%) patients, of whom 253 patients had prior CEVD. Patients with prior CEVD were older and had more comorbidities (medically treated diabetes, insulin-dependent diabetes, metabolic syndrome, peripheral vascular disease, chronic obstructive pulmonary disease, impaired renal function, and congestive heart failure), compared with those without prior CEVD. Prior CEVD was an independent predictor of 10 year all-cause death (adjusted HR: 1.35; 95% CI: 1.04-1.73; p = 0.021). Patients with prior CEVD had a significantly higher risk of 10 year all-cause death (41.1 vs. 24.1%; HR: 1.92; 95% CI: 1.54-2.40; p < 0.001). The risk of 10 year all-cause death was similar between patients receiving PCI or CABG irrespective of the presence of prior CEVD (p-interaction = 0.624).
Conclusion
Prior CEVD was associated with a significantly increased risk of 10 year all-cause death which was similar in patients treated with PCI or CABG. These results do not support preferential referral for PCI rather than CABG in patients with prior CEVD.
Trial registration
SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.

© 2021. The Author(s).

Clin Res Cardiol: 29 Sep 2021; 110:1543-1553
Wang R, Takahashi K, Garg S, Thuijs DJFM, ... Holmes DR, Serruys PW
Clin Res Cardiol: 29 Sep 2021; 110:1543-1553 | PMID: 33517534
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Abstract

Heart failure re-hospitalizations and subsequent fatal events in coronary artery disease: insights from COMMANDER-HF, EPHESUS, and EXAMINE.

Ferreira JP, Cleland JG, Lam CSP, Anker SD, ... Greenberg B, Zannad F
Background
Patients with coronary artery disease (CAD) are at increased risk of developing and being hospitalised for heart failure (HFH). However, the risk of HFH versus ischemic events may vary among patients with CAD, depending on whether acute myocardial infarction (MI), left ventricular dysfunction or decompensated HF is present at baseline.
Aims
We aim to explore the risk of non-fatal events (HFH, MI, stroke) and subsequent death in 3 landmark trials, COMMANDER-HF, EPHESUS and EXAMINE that, together, included patients with CAD with and without reduced ejection fraction and acute MI.
Methods
Events, person-time metrics and time-updated Cox models.
Results
In COMMANDER-HF the event-rate for the composite of AMI, stroke or all-cause death was 13.5 (12.8-14.3) events/100 py. Rates for AMI and stroke were much lower (2.2 [2.0-2.6] and 1.3 [1.1-1.6] events/100 py, respectively) than the rate of HFH (16.9 [16.1-17.9] events/100 py). In EPHESUS, the rates of MI and stroke were also lower than the rate of HFH: 7.2 (6.7-7.8), 1.9 (1.7-2.3), and 10.6 (9.9-11.3) events/100 py, but this was not true for EXAMINE with 4.4 (4.0-4.9), 0.7 (0.6-0.9), and 2.4 (2.0-2.7) events/100 py, respectively. In all 3 trials, a non-fatal event (HFH, MI or stroke) during follow-up doubled the risk of subsequent mortality. This most commonly followed a HFH.
Conclusions
A first or recurrent HFH is common in patients with CAD and AMI or HFrEF and indicates a poor prognosis. Preventing the development of heart failure after AMI and control of congestion in patients with CAD and HFrEF are key unmet needs and therapeutic targets.
Registration
ClinicalTrials.gov Identifier: NCT01877915. URL: https://clinicaltrials.gov/ct2/show/NCT01877915 .

© 2021. Springer-Verlag GmbH, DE part of Springer Nature.

Clin Res Cardiol: 29 Sep 2021; 110:1554-1563
Ferreira JP, Cleland JG, Lam CSP, Anker SD, ... Greenberg B, Zannad F
Clin Res Cardiol: 29 Sep 2021; 110:1554-1563 | PMID: 33686472
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Abstract

Colchicine in ischemic heart disease: the good, the bad and the ugly.

D\'Amario D, Cappetta D, Cappannoli L, Princi G, ... Liuzzo G, Crea F
Inflammation is the main pathophysiological process involved in atherosclerotic plaque formation, progression, instability, and healing during the evolution of coronary artery disease (CAD). The use of colchicine, a drug used for decades in non-ischemic cardiovascular (CV) diseases and/or systemic inflammatory conditions, stimulated new perspectives on its potential application in patients with CAD. Previous mechanistic and preclinical studies revealed anti-inflammatory and immunomodulatory effects of colchicine exerted through its principal mechanism of microtubule polymerization inhibition, however, other pleiotropic effects beneficial to the CV system were observed such as inhibition of platelet aggregation and suppression of endothelial proliferation. In randomized double-blinded clinical trials informing our clinical practice, low doses of colchicine were associated with the significant reduction of cardiovascular events in patients with stable CAD and chronic coronary syndrome (CCS) while in patients with a recent acute coronary syndrome (ACS), early initiation of colchicine treatment significantly reduced major adverse CV events (MACE). On the other hand, the safety profile of colchicine and its potential causal relationship to the observed increase in non-CV deaths warrants further investigation. For these reasons, postulates of precision medicine and patient-tailored approach with regards to benefits and harms of colchicine treatment should be employed at all times due to potential toxicity of colchicine as well as the currently unresolved signal of harm concerning non-CV mortality. The main goal of this review is to provide a balanced, critical, and comprehensive evaluation of currently available evidence with respect to colchicine use in the setting of CAD.

© 2021. The Author(s).

Clin Res Cardiol: 29 Sep 2021; 110:1531-1542
D'Amario D, Cappetta D, Cappannoli L, Princi G, ... Liuzzo G, Crea F
Clin Res Cardiol: 29 Sep 2021; 110:1531-1542 | PMID: 33713178
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Abstract

Physical activity, sedentary behavior and risk of coronary artery disease, myocardial infarction and ischemic stroke: a two-sample Mendelian randomization study.

Bahls M, Leitzmann MF, Karch A, Teumer A, ... Baumeister SE, Baurecht H
Aims
Observational evidence suggests that physical activity (PA) is inversely and sedentarism positively related with cardiovascular disease risk. We performed a two-sample Mendelian randomization (MR) analysis to examine whether genetically predicted PA and sedentary behavior are related to coronary artery disease, myocardial infarction, and ischemic stroke.
Methods and results
We used single nucleotide polymorphisms (SNPs) associated with self-reported moderate to vigorous PA (n = 17), accelerometer based PA (n = 7) and accelerometer fraction of accelerations > 425 milli-gravities (n = 7) as well as sedentary behavior (n = 6) in the UK Biobank as instrumental variables in a two sample MR approach to assess whether these exposures are related to coronary artery disease and myocardial infarction in the CARDIoGRAMplusC4D genome-wide association study (GWAS) or ischemic stroke in the MEGASTROKE GWAS. The study population included 42,096 cases of coronary artery disease (99,121 controls), 27,509 cases of myocardial infarction (99,121 controls), and 34,217 cases of ischemic stroke (404,630 controls). We found no associations between genetically predicted self-reported moderate to vigorous PA, accelerometer-based PA or accelerometer fraction of accelerations > 425 milli-gravities as well as sedentary behavior with coronary artery disease, myocardial infarction, and ischemic stroke.
Conclusions
These results do not support a causal relationship between PA and sedentary behavior with risk of coronary artery disease, myocardial infarction, and ischemic stroke. Hence, previous observational studies may have been biased.

© 2021. The Author(s).

Clin Res Cardiol: 29 Sep 2021; 110:1564-1573
Bahls M, Leitzmann MF, Karch A, Teumer A, ... Baumeister SE, Baurecht H
Clin Res Cardiol: 29 Sep 2021; 110:1564-1573 | PMID: 33774696
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Abstract

Influence of sex, age and race on coronary and heart failure events in patients with diabetes and post-acute coronary syndrome.

Rossello X, Ferreira JP, Caimari F, Lamiral Z, ... White WB, Zannad F
Background
Women, older patients and non-White ethnic groups experience a substantial proportion of acute coronary syndromes (ACS), although they have been historically underrepresented in ACS randomized clinical trials (RCTs). To assess the influence of sex, age and race on major adverse cardiovascular events (MACE) and on heart failure events, we studied patients with type 2 diabetes in a large post-ACS trial (EXAMINE).
Methods
Differences in baseline characteristics and the respective composite endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE) and cardiovascular death or heart failure hospitalization (HF events) were evaluated by subgroups in a cohort of post-ACS patients with diabetes, using unadjusted and adjusted Cox regression modelling.
Results
The EXAMINE trial enrolled 5380 patients with 35% aged > 65, 32% female and 27% non-White. The risk of MACE was higher in non-White compared to White patients after adjustment for potential confounding (HR = 1.35; 95% CI 1.04-1.75), but there were no significant differences by sex and age (HR = 1.03; 95% CI 0.87-1.22 for women; HR = 1.14; 95% CI 0.96-1.35 for patients ≥ 65 years). The risk of HF events was higher in non-White patients (HR = 1.56; 95% CI 1.13-2.14), and in patients aged > 65 (HR = 1.33; 95% CI 1.07-1.66) and nominally so in women (HR = 1.23; 95% CI 0.99-1.52). The additive risk of each demographic factor (women, older age and non-White race) was greater for HF events in comparison with MACE. Moreover, non-White elderly patients consistently had poorer prognosis regardless of sex.
Conclusions
Older adults, women and non-White patients with diabetes who are post-ACS are often underrepresented in RCTs. The risk for HF events was higher in older and non-White patients, with a trend towards significance in women, whereas only non-White patients (and not women and older patients) were at higher risk for MACE. Future trials should enrich enrollment of these persons at risk.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 29 Sep 2021; 110:1612-1624
Rossello X, Ferreira JP, Caimari F, Lamiral Z, ... White WB, Zannad F
Clin Res Cardiol: 29 Sep 2021; 110:1612-1624 | PMID: 33929598
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Abstract

Outcomes of patients treated with a biodegradable-polymer sirolimus-eluting stent versus durable-polymer everolimus-eluting stents after rotational atherectomy.

Mankerious N, Hemetsberger R, Traboulsi H, Toelg R, ... Richardt G, Allali A
Objective
To compare Orsiro biodegradable-polymer sirolimus-eluting stent (Orsiro BP-SES) with durable-polymer everolimus-eluting stent (DP-EES) regarding target lesion failure (TLF) after rotational atherectomy (RA), with a focus on small stents (diameter ≤ 3 mm) where Orsiro BP-SES has 60 µm strut thickness, while DP-EES remains with 81 µm strut thickness.
Background
New-generation drug-eluting stent (DES) is superior to early-generation DES in all percutaneous coronary intervention (PCI) settings including RA. Recently, the Orsiro BP-SES was superior to a DP-EES in an all comer\'s population.
Methods
Among patients who underwent RA at a single center, 121 were treated with Orsiro BP-SES and 164 with DP-EES (Promus and Xience). Those treated with other stent types, presenting with acute myocardial infarction or had a chronic total occlusion were excluded. Incidence of TLF was assessed.
Results
After 2 years, the TLF rate in Orsiro BP-SES and DP-EES groups was 10% and 18%, respectively (adjusted HR 0.55, 95%CI 0.26-1.16, p = 0.115). The rate of TLF was significantly lower in small Orsiro BP-SES with ultra-thin struts as compared to DP-EES with the same diameters (adjusted HR 0.19, 95% CI 0.04-0.87, p = 0.032), driven by lower rates of clinically driven target lesion revascularization (log-rank p = 0.022). Age (p = 0.035), total stent length (p = 0.007) and diabetes mellitus (p = 0.011) emerged as independent predictors of TLF in the whole population.
Conclusion
In the whole cohort, Orsiro BP-SES and DP-EES had comparable rates of long-term TLF after RA. In the small stent subgroup, the Orsiro BP-SES with ultra-thin struts showed significant lower rate of TLF at 2 years.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 29 Sep 2021; 110:1574-1585
Mankerious N, Hemetsberger R, Traboulsi H, Toelg R, ... Richardt G, Allali A
Clin Res Cardiol: 29 Sep 2021; 110:1574-1585 | PMID: 33861369
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Abstract

Global longitudinal strain improves risk assessment after ST-segment elevation myocardial infarction: a comparative prognostic evaluation of left ventricular functional parameters.

Holzknecht M, Reindl M, Tiller C, Reinstadler SJ, ... Metzler B, Mayr A
Aim
We aimed to investigate the comparative prognostic value of left ventricular ejection fraction (LVEF), mitral annular plane systolic excursion (MAPSE), fast manual long-axis strain (LAS) and global longitudinal strain (GLS) determined by cardiac magnetic resonance (CMR) in patients after ST-segment elevation myocardial infarction (STEMI).
Methods and results
This observational cohort study included 445 acute STEMI patients treated with primary percutaneous coronary intervention (pPCI). Comprehensive CMR examinations were performed 3 [interquartile range (IQR): 2-4] days after pPCI for the determination of left ventricular (LV) functional parameters and infarct characteristics. Primary endpoint was the occurrence of major adverse cardiac events (MACE) defined as composite of death, re-infarction and congestive heart failure. During a follow-up of 16 [IQR: 12-49] months, 48 (11%) patients experienced a MACE. LVEF (p = 0.023), MAPSE (p < 0.001), LAS (p < 0.001) and GLS (p < 0.001) were significantly related to MACE. According to receiver operating characteristic analyses, only the area under the curve (AUC) of GLS was significantly higher compared to LVEF (0.69, 95% confidence interval (CI) 0.64-0.73; p < 0.001 vs. 0.60, 95% CI 0.55-0.65; p = 0.031. AUC difference: 0.09, p = 0.020). After multivariable analysis, GLS emerged as independent predictor of MACE even after adjustment for LV function, infarct size and microvascular obstruction (hazard ratio (HR): 1.13, 95% CI 1.01-1.27; p = 0.030), as well as angiographical (HR: 1.13, 95% CI 1.01-1.28; p = 0.037) and clinical parameters (HR: 1.16, 95% CI 1.05-1.29; p = 0.003).
Conclusion
GLS emerged as independent predictor of MACE after adjustment for parameters of LV function and myocardial damage as well as angiographical and clinical characteristics with superior prognostic validity compared to LVEF.

© 2021. The Author(s).

Clin Res Cardiol: 29 Sep 2021; 110:1599-1611
Holzknecht M, Reindl M, Tiller C, Reinstadler SJ, ... Metzler B, Mayr A
Clin Res Cardiol: 29 Sep 2021; 110:1599-1611 | PMID: 33884479
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Impact:
Abstract

The impact of epicardial adipose tissue in patients with acute myocardial infarction.

Fisser C, Colling S, Debl K, Hetzenecker A, ... Buchner S, Arzt M
Aims
Epicardial adipose tissue (EAT) has been linked to impaired reperfusion success after percutaneous coronary intervention (PCI). Whether EAT predicts myocardial damage in the early phase after acute myocardial infarction (MI) is unclear. Therefore, we investigated whether EAT in patients with acute MI is associated with more microvascular obstruction (MVO), greater ST-deviation, larger infarct size and reduced myocardial salvage index (MSI).
Methods and results
This retrospective analysis of a prospective observational study including patients with acute MI (n = 54) undergoing PCI and 12 healthy matched controls. EAT, infarct size and MSI were analyzed with cardiac magnetic resonance imaging, conducted 3-5 days and 12 weeks after MI. Patients with acute MI showed higher EAT volume than healthy controls (46 [25.;75. percentile: 37;59] vs. 24 [15;29] ml, p < 0.001). The high EAT group (above median) showed significantly more MVO (2.22 [0.00;5.38] vs. 0.0 [0.00;2.18] %, p = 0.004), greater ST-deviation (0.38 [0.22;0.55] vs. 0.15 [0.03;0.20] mV×10-1, p = 0.008), larger infarct size at 12 weeks (23 [17;29] vs. 10 [4;16] %, p < 0.001) and lower MSI (40 [37;54] vs. 66 [49;88] %, p < 0.001) after PCI than the low EAT group. After accounting for demographic characteristics, body-mass index, heart volume, infarct location, TIMI-flow grade as well as apnea-hypopnea index, EAT was associated with infarct size at 12 weeks (B = 0.38 [0.11;0.64], p = 0.006), but not with MSI.
Conclusions
Patients with acute MI showed higher volume of EAT than healthy individuals. High EAT was linked to more MVO and greater ST-deviation. EAT was associated with infarct size, but not with MSI.

© 2021. The Author(s).

Clin Res Cardiol: 29 Sep 2021; 110:1637-1646
Fisser C, Colling S, Debl K, Hetzenecker A, ... Buchner S, Arzt M
Clin Res Cardiol: 29 Sep 2021; 110:1637-1646 | PMID: 33978815
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Impact:
Abstract

Sex-specific differences and long-term outcome of patients with coronary artery disease and chronic kidney disease: the Coronary Artery Disease and Renal Failure (CAD-REF) Registry.

Engelbertz C, Pinnschmidt HO, Freisinger E, Reinecke H, ... Pavenstädt H, Brand E
Background
Cardiovascular morbidity and mortality are closely linked to chronic kidney disease (CKD). Sex-specific long-term outcome data of patients with coronary artery disease (CAD) and CKD are scarce.
Methods
In the prospective observational multicenter Coronary Artery Disease and REnal Failure (CAD-REF) Registry, 773 (23.1%) women and 2,579 (76.9%) men with angiographically documented CAD and different stages of CKD were consecutively enrolled and followed for up to 8 years. Long-term outcome was evaluated using survival analysis and multivariable Cox-regression models.
Results
At enrollment, women were significantly older than men, and suffered from more comorbidities like CKD, hypertension, diabetes mellitus, and multivessel coronary disease. Regarding long-term mortality, no sex-specific differences were observed (Kaplan-Meier survival estimates: 69% in women vs. 69% in men, plog-rank = 0.7). Survival rates decreased from 89% for patients without CKD at enrollment to 72% for patients with CKD stages 1-2 at enrollment and 49% for patients with CKD stages 3-5 at enrollment (plog-rank < 0.001). Cox-regression analysis revealed that sex or multivessel coronary disease were no independent predictors of long-term mortality, while age, CKD stages 3-5, albumin/creatinine ratio, diabetes, valvular heart disease, peripheral artery disease, and left-ventricular ejection fraction were predictors of long-term mortality.
Conclusions
Sex differences in CAD patients mainly exist in the cardiovascular risk profile and the extent of CAD. Long-term mortality was not depended on sex or multivessel disease. More attention should be given to treatment of comorbidities such as CKD and peripheral artery disease being independent predictors of death. Clinical Trail Registration ClinicalTrials.gov Identifier: NCT00679419.

© 2021. The Author(s).

Clin Res Cardiol: 29 Sep 2021; 110:1625-1636
Engelbertz C, Pinnschmidt HO, Freisinger E, Reinecke H, ... Pavenstädt H, Brand E
Clin Res Cardiol: 29 Sep 2021; 110:1625-1636 | PMID: 34036426
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Impact:
Abstract

Ten-year clinical outcomes of polymer-free versus durable polymer new-generation drug-eluting stent in patients with coronary artery disease with and without diabetes mellitus : Results of the Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol- and Zotarolimus-Eluting Stents (ISAR-TEST 5) trial.

Koch T, Lenz T, Joner M, Xhepa E, ... Kufner S, Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus- Eluting Stents (ISAR-TEST 5) Investigators
Background
Very long-term outcomes according to diabetic status of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DES) are scant. Both, the durable polymer zotarolimus-eluting stent (DP-ZES), the first DES to gain FDA-approval for specific use in patients with diabetes mellitus, and the polymer-free sirolimus- and probucol-eluting stent (PF-SES), with a unique design that enables effective drug release without the need of a polymer offer the potential to enhance clinical long-term outcomes especially in patients with diabetes mellitus.
Methods
We investigate 10-year clinical outcomes of the prespecified subgroups of patients with and without diabetes mellitus, randomly assigned to treatment with PF-SES versus DP-ZES in the ISAR-TEST 5 trial. The primary endpoint of interest was major adverse cardiac events (MACE), defined as the composite of all-cause death, any myocardial infarction or any revascularization. Further endpoints of interest were cardiac death, myocardial infarction related to the target vessel and target lesion revascularization as well as the individual components of the primary composite endpoint and the incidence of definite or probable stent thrombosis at 10 years.
Results
This analysis includes a total of 3002 patients randomly assigned to PF-SES (n = 2002) or DP-ZES (n = 1000). Prevalence of diabetes mellitus was high and comparable, 575 Patients (28.7%) in PF-SES group and 295 patients (29.5%) in DP-ZES group (P = 0.66). At 10 years 53.5% of patients with diabetes mellitus and 68.5% of patients without diabetes mellitus were alive. Regarding major adverse cardiac events, PF-SES as compared to DP-ZES showed comparable event rates in patients with diabetes mellitus (74.8% vs. 79.6%; hazard ratio 0.86; 95% CI 0.73-1.02; P = 0.08) and in patients without diabetes (PF-SES 62.5% vs. DP-ZES 62.2%; hazard ratio 0.99; 95% CI 0.88-1.11; P = 0.88).
Conclusion
At 10 years, both new-generation DES show comparable clinical outcome irrespective of diabetic status or polymer strategy. Event rates after PCI in patients with diabetes mellitus are considerable higher than in patients without diabetes mellitus and continue to accrue over time.
Trial registration
ClinicalTrials.gov, NCT00598533, Registered 10 January 2008, https://clinicaltrials.gov/ct2/show/NCT00598533?term=NCT00598533 Kaplan-Meier estimates of endpoints of interest for patients with vs. without diabetes mellitus treated with PF-SES vs. DP-ZES. Bar graphs: Kaplan-Meier estimates as percentages. PF-SES: polymer-free sirolimus-eluting stent; DP-ZES: durable polymer zotarolimus-eluting stent; DM: diabetes mellitus. Comparison of event rates of individual endpoints in patients with and without diabetes mellitus treated with PF-SES vs. DP-ZES all without statistically significant differences. Comparison of event rates of individual endpoints in overall patients with vs. without diabetes mellitus significantly different (P ≤ 0.01 for all comparisons).

© 2021. The Author(s).

Clin Res Cardiol: 29 Sep 2021; 110:1586-1598
Koch T, Lenz T, Joner M, Xhepa E, ... Kufner S, Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus- Eluting Stents (ISAR-TEST 5) Investigators
Clin Res Cardiol: 29 Sep 2021; 110:1586-1598 | PMID: 34156521
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Abstract

Prevalence and clinical characteristics of prediabetes and diabetes mellitus in young patients with ST-segment elevation myocardial infarction.

Mata Marín LA, Schmucker J, Fach A, Osteresch R, ... Hambrecht R, Wienbergen H
Background
Only few data on the prevalence of DM in young patients with ST-elevation myocardial infarction (STEMI) exist. Aim of the present study was to analyse this prevalence, its association to other cardiovascular risk factors and its impact on severity of CAD. In a substudy, consecutive HbA1c measurements in each patient were evaluated.
Methods
All patients ≤ 45 years old, admitted with STEMI to an overregional German Heart Centre and treated with primary coronary intervention between 2006 and 2019, entered analysis. Since 2015 HbA1c measurements were performed to detect unknown dysglycaemia.
Results
Out of 776 young patients of the total cohort, 88 patients (11.4%) had a DM, while 688 (88.6%) did not. Diabetics were more likely to be obese (BMI ≥ 30 kg/m2, OR 2.4, 95%CI 1.4-4.0, p < 0.01) and very obese (BMI ≥ 40 kg/m2, OR 5.1, 95%CI 2.1-12.2, p < 0.01). In diabetics, a higher likelihood of subacute STEMI (OR 2.2, 95% CI 1.1-4.5, p < 0.05) and more advanced CAD (OR 1.6, 95% CI 1.0-2.6, p < 0.05) compared to non-diabetics was observed. 208 patients were included in the substudy with HbA1c measurements. Out of those, 26 patients (12%) had known DM, while 17 patients (8%) had newly diagnosed DM and 49 patients (24%) preDM. The combined prevalence of any type of dysglycaemia was 44%.
Conclusion
DM in young patients with STEMI was associated with (severe) obesity, a higher likelihood of subacute STEMI and more advanced CAD compared to non-diabetics. Measurement of HbA1c in every consecutive STEMI-patient increased the rate of detected dysglycaemias more than three times higher than in general population.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 29 Sep 2021; 110:1647-1658
Mata Marín LA, Schmucker J, Fach A, Osteresch R, ... Hambrecht R, Wienbergen H
Clin Res Cardiol: 29 Sep 2021; 110:1647-1658 | PMID: 34216252
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Impact:
Abstract

Quantitative flow ratio (QFR) identifies functional relevance of non-culprit lesions in coronary angiographies of patients with acute myocardial infarction.

Milzi A, Dettori R, Marx N, Reith S, Burgmaier M
Introduction
In patients with acute myocardial infarction (AMI) and multivessel coronary disease, revascularization of non-culprit lesions guided by proof of ischemia usually requires staged ischemia testing. Quantitative flow ratio (QFR) has been shown to be effective in assessing the hemodynamic relevance of lesions in stable coronary disease. However, its suitability in AMI patients is unknown. In this study, we tested the diagnostic value of QFR based on acute angiograms (aQFR) during AMI to assess the hemodynamic relevance of non-culprit lesions.
Methods
We retrospectively assessed the diagnostic efficiency of aQFR in 280 vessels from 220 patients, comparing it with staged ischemia testing using elective coronary angiography with FFR (n = 47), stress cardiac MRI (n = 200) or SPECT (n = 33).
Results
aQFR showed a very good diagnostic efficiency (AUC = 0.887, 95% CI 0.832-0.943, p < 0.001) in predicting ischemia of non-culprit lesions, significantly superior to coronary lesion\'s geometry as assessed by quantitative coronary angiography. The optimal cut-off for aQFR to predict ischemia was 0.80 (sensitivity = 83.7%, specificity = 86.1%). Maintaining a predefined level of 95% sensitivity and specificity, we created a decision model based on aQFR: lesions with aQFR ≤ 0.75 should be treated, lesions with aQFR ≥ 0.92 do not yield any hemodynamic relevance, and lesions in the \"grey zone\" (aQFR 0.75-0.92) benefit from further ischemia testings. This model would allow to reduce staged ischemia tests by 46.8% without a relevant loss in diagnostic efficiency.
Conclusion
Our data demonstrate that aQFR allows an effective assessment of hemodynamic relevance of non-culprit lesions in AMI and may guide interventions of non-culprit coronary lesions.

© 2021. The Author(s).

Clin Res Cardiol: 29 Sep 2021; 110:1659-1667
Milzi A, Dettori R, Marx N, Reith S, Burgmaier M
Clin Res Cardiol: 29 Sep 2021; 110:1659-1667 | PMID: 34251507
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Impact:
Abstract

Feasibility and safety of minimal-contrast IVUS-guided rotational atherectomy for complex calcified coronary artery disease.

Allali A, Traboulsi H, Sulimov DS, Abdel-Wahab M, ... Toelg R, Richardt G
Objectives
To assess the feasibility and safety of minimal-contrast percutaneous coronary intervention (PCI) using rotational atherectomy (RA) in patients with severe coronary calcification at high-risk of contrast-associated acute kidney injury (AKI).
Methods
Twenty-six patients with advanced chronic kidney disease undergoing PCI with RA at three high-volume centres were included. Baseline intravascular ultrasound (IVUS) was performed to assess lesion morphology, and to guide burr-, balloon-, and stent-selection. Final result was assessed by IVUS and angiographically. Feasibility and safety were determined by procedural and in-hospital complications, and efficacy was assessed by freedom from contrast-associated AKI after PCI. Procedural and in-hospital outcome was compared to a propensity-matched population of standard RA PCI.
Results
Mean glomerular filtration rate was 32 ± 17 ml/min/1.73 m2. In seven cases PCI was performed in the setting of acute coronary syndrome. The left main coronary artery was treated in 27.8% and a two-stent bifurcation technique in 44.4%. RA was more often performed electively compared to the standard RA cohort (92.3 vs. 50%; p = 0.0016). Angiographic success was achieved in 100% and documented with a median contrast amount of 12.5 ml [Range 4-43]. No in-hospital death or myocardial infarction was reported. Contrast-associated AKI occurred in one patient versus five patients in standard RA group (p = 0.19). Shorter fluoroscopy time and lower radiation dose were achieved as compared to standard RA.
Conclusion
A minimal-contrast RA approach with IVUS-guidance for treatment of complex calcified coronary lesions is feasible and safe with high success rate.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 29 Sep 2021; 110:1668-1679
Allali A, Traboulsi H, Sulimov DS, Abdel-Wahab M, ... Toelg R, Richardt G
Clin Res Cardiol: 29 Sep 2021; 110:1668-1679 | PMID: 34255133
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Impact:
Abstract

Impact of established cardiovascular disease on 10-year death after coronary revascularization for complex coronary artery disease.

Wang R, Garg S, Gao C, Kawashima H, ... Onuma Y, Serruys PW
Aims
To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD).
Methods
The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD.
Results
Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08-1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83-1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p-interaction = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11-4.23, p < 0.001) compared to those without CVD.
Conclusions
The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization.
Trial registration
SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.

© 2021. The Author(s).

Clin Res Cardiol: 29 Sep 2021; 110:1680-1691
Wang R, Garg S, Gao C, Kawashima H, ... Onuma Y, Serruys PW
Clin Res Cardiol: 29 Sep 2021; 110:1680-1691 | PMID: 34432113
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Impact:
Abstract

Immunothrombosis and new-onset atrial fibrillation in the general population: the Rotterdam Study.

Tilly MJ, Geurts S, Donkel SJ, Ikram MA, ... de Maat MPM, Kavousi M
Background
Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia. The etiology underlying AF is still largely unknown. At the intersection of the innate immune system and hemostasis, immunothrombosis may be a possible cause of atrial remodeling, and therefore be an underlying cause of AF.
Methods
From 1990 to 2014, we followed participants aged 55 and over, free from AF at inclusion. Immunothrombosis factors fibrinogen, von Willebrand factor, ADAMTS13, and neutrophil extracellular traps (NETs) levels were measured at baseline. Participants were followed until either onset of AF, loss-to-follow-up, or reaching the end-date of 01-01-2014. Cox proportional hazard modelling was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for cardiovascular risk factors.
Results
We followed 6174 participants (mean age 69.1 years, 57% women) for a median follow-up time of 12.8 years. 364 men (13.7%, incidence rate 13.0/1000 person-years) and 365 women (10.4%, incidence rate 8.9/1000 person-years) developed AF. We found no significant association between markers of immunothrombosis and new-onset AF after adjusting for cardiovascular risk factors [HR 1.00 (95% CI 0.93-1.08) for fibrinogen, 1.04 (0.97-1.12) for von Willebrand factor, 1.00 (1.00-1.01) for ADAMTS13, and 1.01 (0.94-1.09) for NETs]. In addition, we found no differences in associations between men and women.
Conclusion
We found no associations between markers of immunothrombosis and new-onset AF in the general population. Inflammation and immunothrombosis may be associated with AF through other cardiovascular risk factors or predisposing conditions of AF. Our findings challenge the added value of biomarkers in AF risk prediction.

© 2021. The Author(s).

Clin Res Cardiol: 23 Sep 2021; epub ahead of print
Tilly MJ, Geurts S, Donkel SJ, Ikram MA, ... de Maat MPM, Kavousi M
Clin Res Cardiol: 23 Sep 2021; epub ahead of print | PMID: 34559294
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Impact:
Abstract

In-hospital outcomes of self-expanding and balloon-expandable transcatheter heart valves in Germany.

Stachon P, Hehn P, Wolf D, Heidt T, ... von Zur Mühlen C, Kaier K
Introduction
The effect of valve type on outcomes in transfemoral transcatheter aortic valve replacement (TF-TAVR) has recently been subject of debate. We investigate outcomes of patients treated with balloon-expanding (BE) vs. self-expanding (SE) valves in in a cohort of all these procedures performed in Germany in 2018.
Methods
All patients receiving TF-TAVR with either BE (N = 9,882) or SE (N = 7,413) valves in Germany in 2018 were identified. In-hospital outcomes were analyzed for the endpoints in-hospital mortality, major bleeding, stroke, acute kidney injury, postoperative delirium, permanent pacemaker implantation, mechanical ventilation > 48 h, length of hospital stay, and reimbursement. Since patients were not randomized to the two treatment options, logistic or linear regression models were used with 22 baseline patient characteristics and center-specific variables as potential confounders. As a sensitivity analysis, the same confounding factors were taken into account using the propensity score methods (inverse probability of treatment weighting).
Results
Baseline characteristics differed substantially, with higher EuroSCORE (p < 0.001), age (p < 0.001) and rate of female sex (p < 0.001) in SE treated patients. After risk adjustment, no marked differences in outcomes were found for in-hospital mortality [risk adjusted odds ratio (aOR) for SE instead of BE 0.94 (96% CI 0.76;1.17), p = 0.617] major bleeding [aOR 0.91 (0.73;1.14), p = 0.400], stroke [aOR 1.13 (0.88;1.46), p = 0.347], acute kidney injury [OR 0.97 (0.85;1.10), p = 0.621], postoperative delirium [aOR 1.09 (0.96;1.24), p = 0.184], mechanical ventilation > 48 h [aOR 0.98 (0.77;1.25), p = 0.893], length of hospital stay (risk adjusted difference in days of hospitalization (SE instead of BE): - 0.05 [- 0.34;0.25], p = 0.762) and reimbursement [risk adjusted difference in reimbursement (SE instead of BE): - €72 (- €291;€147), p = 0.519)] There is, however, an increased risk of PPI for SE valves (aOR 1.27 [1.15;1.41], p < 0.001). Similar results were found after application of propensity score adjustment.
Conclusions
We find broadly equivalent outcomes in contemporary TF-TAVR procedures, regardless of the valve type used. Incidence of major complications is very low for both types of valve.

© 2021. The Author(s).

Clin Res Cardiol: 20 Sep 2021; epub ahead of print
Stachon P, Hehn P, Wolf D, Heidt T, ... von Zur Mühlen C, Kaier K
Clin Res Cardiol: 20 Sep 2021; epub ahead of print | PMID: 34546428
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Impact:
Abstract

Pre-medication with oral anticoagulants is associated with better outcomes in a large multinational COVID-19 cohort with cardiovascular comorbidities.

Rieder M, Gauchel N, Kaier K, Jakob C, ... Rieg S, Duerschmied D
Aims
Coagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients.
Methods and results
We analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056).
Conclusions
Pre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease.

© 2021. The Author(s).

Clin Res Cardiol: 20 Sep 2021; epub ahead of print
Rieder M, Gauchel N, Kaier K, Jakob C, ... Rieg S, Duerschmied D
Clin Res Cardiol: 20 Sep 2021; epub ahead of print | PMID: 34546427
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Impact:
Abstract

Mobile health solutions for atrial fibrillation detection and management: a systematic review.

Hermans ANL, Gawalko M, Dohmen L, van der Velden RMJ, ... Pluymaekers NAHA, Linz D
Aim
We aimed to systematically review the available literature on mobile Health (mHealth) solutions, including handheld and wearable devices, implantable loop recorders (ILRs), as well as mobile platforms and support systems in atrial fibrillation (AF) detection and management.
Methods
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The electronic databases PubMed (NCBI), Embase (Ovid), and Cochrane were searched for articles published until 10 February 2021, inclusive. Given that the included studies varied widely in their design, interventions, comparators, and outcomes, no synthesis was undertaken, and we undertook a narrative review.
Results
We found 208 studies, which were deemed potentially relevant. Of these studies included, 82, 46, and 49 studies aimed at validating handheld devices, wearables, and ILRs for AF detection and/or management, respectively, while 34 studies assessed mobile platforms/support systems. The diagnostic accuracy of mHealth solutions differs with respect to the type (handheld devices vs wearables vs ILRs) and technology used (electrocardiography vs photoplethysmography), as well as application setting (intermittent vs continuous, spot vs longitudinal assessment), and study population.
Conclusion
While the use of mHealth solutions in the detection and management of AF is becoming increasingly popular, its clinical implications merit further investigation and several barriers to widespread mHealth adaption in healthcare systems need to be overcome. Mobile health solutions for atrial fibrillation detection and management: a systematic review.

© 2021. The Author(s).

Clin Res Cardiol: 20 Sep 2021; epub ahead of print
Hermans ANL, Gawalko M, Dohmen L, van der Velden RMJ, ... Pluymaekers NAHA, Linz D
Clin Res Cardiol: 20 Sep 2021; epub ahead of print | PMID: 34549333
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Impact:
Abstract

Early arrhythmia recurrence after catheter ablation for persistent atrial fibrillation: is it predictive for late recurrence?

Popa MA, Kottmaier M, Risse E, Telishevska M, ... Hessling G, Bourier F
Background
Early recurrence of atrial tachyarrhythmia (ERAT) is common after radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF), but its clinical significance in patients with persistent AF remains unclear. We sought to determine the predictive value of ERAT for rhythm outcome after RFCA for persistent AF.
Methods
The study included 207 consecutive patients (mean age 66.4 ± 10.7 years, male 66.2%) with persistent and long-standing persistent AF undergoing de novo pulmonary vein isolation (± atrial substrate ablation). All patients remained off antiarrhythmic drugs. ERAT was defined as any atrial arrhythmia ≥ 30 s occurring within the first 30 days. Late recurrence (LR) was determined during follow-up visits scheduled 1, 3, 6 and 12 months post-ablation using 7-day Holter ECGs.
Results
ERAT occurred in 143/207 (69.1%) patients as AF (60%) or atrial tachycardia (40%) and was persistent in 82% of cases. During a median follow-up of 22.2 months, LR occurred significantly more often in patients with ERAT than in patients without ERAT (92.3 vs. 43.8%, P < 0.001). The only independent predictors for LR were ERAT (OR 16.8, 95% CI 6.184-45.797, P < 0.001) and intraprocedural termination to sinus rhythm (OR 0.052, 95% CI 0.003-0.851, P = 0.038). Extending the blanking period from 30 to 90 days did not impact LR rates.
Conclusion
ERAT following ablation of persistent AF is strongly associated with late arrhythmia recurrence, which challenges the assumption that ERAT represents merely a transient phenomenon. While limiting the blanking period to 30 days seems justified, the benefit of early re-ablations remains to be addressed in future studies.

© 2021. The Author(s).

Clin Res Cardiol: 13 Sep 2021; epub ahead of print
Popa MA, Kottmaier M, Risse E, Telishevska M, ... Hessling G, Bourier F
Clin Res Cardiol: 13 Sep 2021; epub ahead of print | PMID: 34519875
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Impact:
Abstract

Pregnancy-related acute myocardial infarction: a review of the recent literature.

Merlo AC, Rosa GM, Porto I
Pregnancy-related acute myocardial infarction is a rare and potentially life-threatening cardiovascular event, the incidence of which is growing due to the heightened prevalence of several risk factors, including increased maternal age. Its main aetiology is spontaneous coronary artery dissection, which particularly occurs in pregnancy and may engender severe clinical scenarios. Therefore, despite frequently atypical and deceptive presentations, early recognition of such a dangerous complication of gestation is paramount. Notwithstanding diagnostic and therapeutic improvements, pregnancy-related acute myocardial infarction often carries unfavourable outcomes, as emergent management is difficult owing to significant limitations in the use of ionising radiation-e.g. during coronary angiography, potentially harmful to the foetus even at low doses. Notably, however, maternal mortality has steadily decreased in recent decades, indicating enhanced awareness and major medical advances in this field. In our paper, we review the recent literature on pregnancy-related acute myocardial infarction and highlight the key points in its management.

© 2021. The Author(s).

Clin Res Cardiol: 11 Sep 2021; epub ahead of print
Merlo AC, Rosa GM, Porto I
Clin Res Cardiol: 11 Sep 2021; epub ahead of print | PMID: 34510263
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Impact:
Abstract

Safety and efficacy of minimalist transcatheter aortic valve implantation using a new-generation balloon-expandable transcatheter heart valve in bicuspid and tricuspid aortic valves.

Michel JM, Frangieh AH, Giacoppo D, Alvarez-Covarrubias HA, ... Joner M, Kasel AM
Background
Bicuspid aortic valve may be associated with increased complications during transcatheter aortic valve implantation (TAVI).
Aims
Compare balloon-expandable transcatheter heart valve (THV) safety and efficacy in severe tricuspid (TAV) and bicuspid (BAV) aortic stenosis.
Methods
Transfemoral TAVI was performed in 743 patients (Jan 2014-June 2019) using the SAPIEN 3 THV. Aortic valve morphology was determined using computed tomography. Valve Academic Research Consortium-2 (VARC-2) derived safety and efficacy endpoints at 1 year were evaluated.
Results
BAV patients (n = 78), were younger (77 [72, 81] vs. 81 [78, 85] years, p < 0.001) with lower surgical risk (EuroSCORE II 2.96% vs. 4.51% p < 0.001). Bicuspid valves were more calcified (BAV 1308mm3, TAV 848mm3 p < 0.001) with more asymmetric calcification (BAV 63/78 (81%), TAV 239/665 (36%), p < 0.001). Device success (BAV 94%, TAV 90%, p = 0.45) and major vascular complications (BAV 6%, TAV 9%, p = 0.66) were comparable. At 1 year, there was a trend toward lower combined all-cause mortality and rehospitalization for congestive heart failure in BAV patients (BAV 7%, TAV 13%, p = 0.08) with significantly lower all-cause mortality in this cohort (BAV 1%, TAV 9%, p = 0.020). VARC-2 time-related valve safety (BAV 22%, TAV 20%, p = 0.60) was comparable; however, bioprosthetic valve thrombosis remained more common in BAV patients (BAV 7%, TAV 2%, p = 0.010, Hazard ratio 3.57 [95% confidence interval 1.26, 10.10]). After propensity score matching, only bioprosthetic valve thrombosis remained significantly different.
Conclusions
Safety and efficacy of the SAPIEN 3 balloon-expandable THV in BAV is comparable with TAV. Higher rates of bioprosthetic valve thrombosis require further investigation.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 08 Sep 2021; epub ahead of print
Michel JM, Frangieh AH, Giacoppo D, Alvarez-Covarrubias HA, ... Joner M, Kasel AM
Clin Res Cardiol: 08 Sep 2021; epub ahead of print | PMID: 34505192
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Abstract

Influence of receptor selectivity on benefits from SGLT2 inhibitors in patients with heart failure: a systematic review and head-to-head comparative efficacy network meta-analysis.

Täger T, Frankenstein L, Atar D, Agewall S, ... Cleland JGF, Fröhlich H
Background
Receptor selectivity of sodium-glucose cotransporter-2 inhibitors (SGLT2i) varies greatly between agents. The overall improvement of cardiovascular (CV) outcomes in heart failure (HF) patients varies between trials. We, therefore, evaluated the comparative efficacy of individual SGLT2i and the influence of their respective receptor selectivity thereon.
Methods
We identified randomized controlled trials investigating the use of SGLT2i in patients with HF-either as the target cohort or as a subgroup of it. Comparators included placebo or any other active treatment. The primary endpoint was the composite of hospitalization for HF or CV death. Secondary outcomes included all-cause mortality, CV mortality, hospitalization for HF, worsening renal function (RF), and the composite of worsening RF or CV death. Evidence was synthesized using network meta-analysis. In addition, the impact of receptor selectivity on outcomes was analysed using meta-regression.
Results
We identified 18,265 patients included in 22 trials. Compared to placebo, selective and non-selective SGLT2i improved fatal and non-fatal HF events. Head-to-head comparisons suggest superior efficacy with sotagliflozin as compared to dapagliflozin, empagliflozin or ertugliflozin. No significant difference was found between canagliflozin and sotagliflozin. Meta-regression analyses show a decreasing benefit on HF events with increasing receptor selectivity of SGLT2i. In contrast, receptor selectivity did not affect mortality and renal endpoints and no significant difference between individual SGLT2i was noted.
Conclusion
Our data point towards a class-effect of SGLT2i on mortality and renal outcomes. However, non-selective SGLT2i such as sotagliflozin may be superior to highly selective SGLT2i in terms of HF outcomes.

© 2021. The Author(s).

Clin Res Cardiol: 07 Sep 2021; epub ahead of print
Täger T, Frankenstein L, Atar D, Agewall S, ... Cleland JGF, Fröhlich H
Clin Res Cardiol: 07 Sep 2021; epub ahead of print | PMID: 34498169
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Impact:
Abstract

Impact of implantation depth on outcomes of new-generation balloon-expandable transcatheter heart valves.

Kim WK, Renker M, Doerr O, Hofmann S, ... Choi YH, Hamm CW
Background
Little is known about the impact of the ID on outcomes and device success using balloon-expandable devices. This study sought to analyze the impact of implantation depth (ID) on procedural outcomes.
Methods
In consecutive patients (n = 969) undergoing transfemoral TAVR with new-generation balloon-expandable prostheses, the mean ID (IDMean) was determined by aortography and categorized into low, correct, and high device position. Outcomes of interest were device success (VARC-2), paravalvular regurgitation (PVR) ≥ moderate, severe prosthesis-patient mismatch (PPM), permanent pacemaker implantation (PPI), and the composite of the three latter outcome measures (COMPPPP).
Results
IDMean was greater among patients with PPI (median 4.0 [interquartile range 2.0; 4.0] vs. 3.5 [1.5; 5.5] mm; p = 0.002), severe PPM (3.5 [1.5; 5.0] vs. 4.0 [2.0; 6.0] mm; p = 0.028), and COMPPPP (4.0 [2.0; 6.0] vs. 3.0 [1.5; 5.5] mm; p < 0.001) when compared with the respective groups without these complications. There was no significant association between IDMean and device success or PVR ≥ moderate. Categorization into low (7.3%), correct (90.7%), and high (2.0%) device position showed significant discrimination with an increase of severe PPM, PPI, and COMPPPP with lower position, whereas device success was not significantly affected by position. Only PVR ≥ moderate showed an asymmetric distribution with highest rates in the high and low position group, which was non-significant. However, among patients without correct position the rate of device success was 45.6%.
Conclusions
A higher device position was associated with improved outcomes. Malpositioning without functional impairment should not be classified as device failure. The odds ratio of IDMean was calculated by univariate logistic regression for each outcome variable, showing that with higher values of IDMean (i.e., low implantation depth), the risk of severe PPM, PPI, and COMPPPP increases. The bar charts under the heading \"Position category\" denote the frequency of each outcome measure across patients with high, correct, and low device position. The p values are derived from chi-squared test.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 01 Sep 2021; epub ahead of print
Kim WK, Renker M, Doerr O, Hofmann S, ... Choi YH, Hamm CW
Clin Res Cardiol: 01 Sep 2021; epub ahead of print | PMID: 34476559
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Impact:
Abstract

Response to beta-blockers and natriuretic peptide level in acute heart failure: analysis of data from the Korean acute heart failure registry.

Park CS, Park JJ, Mebazaa A, Lee HY, ... Oh BH, Choi DJ
Background
To investigate the effect of beta-blockers according to NP levels and HF phenotypes because natriuretic peptide (NP) level can be used to risk-stratify HF patients regardless of left ventricular ejection fraction (LVEF).
Methods
Of 5,625 patients in the Korean acute heart failure registry, we included patients with LVEF and NP levels. HF phenotypes were defined as HF with reduced ejection fraction (HFrEF) (EF ≤ 40%), HF with midrange ejection fraction (HFmrEF) (40% < EF < 50%), and HF with preserved EF (HFpEF) (EF ≥ 50%). Patients were further stratified by NP tertiles. Primary outcome was 5-year all-cause mortality according to beta-blocker use at discharge.
Results
Both B-type NP (BNP) (r = -0.279, P < 0.001) and N-terminal pro-BNP (r = -0.186, P < 0.001) levels correlated inversely with LVEF. During a median follow-up duration of 961 days, 1560 (35.3%) patients died. In HFrEF, patients taking beta-blockers showed better survival regardless of NP levels. Regarding HFmrEF, there was no mortality difference between those taking and not taking beta-blockers. In HFpEF, beta-blocker use demonstrated lower mortality in those in the 3rd NP tertile (log-rank P = 0.041) but not in those in the 1st and 2nd NP tertiles (log-rank P > 0.05). After adjusting covariates, the use of beta-blockers was associated with a 38%-reduced mortality (hazard ratio: 0.62; 95% confidence interval: 0.39-0.98; P = 0.040) in HFpEF patients in the 3rd NP tertile but not in those in 1st and 2nd tertiles.
Conclusions
We confirm that the use of beta-blockers is beneficial in patients with HFrEF. Furthermore, we extend the benefits of beta-blockers to patients with HFpEF and high NP levels.
Clinical trial registration
ClinicalTrial.gov identifier: NCT01389843 URL: https://clinicaltrials.gov/ct2/show/NCT01389843.

© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 30 Aug 2021; 110:1392-1403
Park CS, Park JJ, Mebazaa A, Lee HY, ... Oh BH, Choi DJ
Clin Res Cardiol: 30 Aug 2021; 110:1392-1403 | PMID: 32588127
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Impact:
Abstract

Thromboembolic complications in adult congenital heart disease: the knowns and the unknowns.

Karsenty C, Waldmann V, Mulder B, Hascoet S, Ladouceur M
Despite impressive improvement in long-term survival, adults with congenital heart disease (CHD) remain exposed to a significant cardiovascular morbidity over lifetime. Thromboembolic events (TE) are a major issue. Specific anatomic groups have been shown a particular high risk of TE, including cyanotic heart disease and Fontan circulation. Many intercurrent clinical factors add a substantial risk such as intracardiac medical devices, atrial arrhythmia, endocarditis, or pregnancy. Nevertheless, what is unknown exceeds what is known, especially regarding the management of this heterogenous patient population. Anticoagulation decision should always be individualized weighing balanced with the alternative risk of hemorrhagic complications. In this review, we aim to synthetize existing literature on TE in adults with CHD, discuss management issues, highlight gaps in knowledge, and intend to suggest high priority research.

© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 30 Aug 2021; 110:1380-1391
Karsenty C, Waldmann V, Mulder B, Hascoet S, Ladouceur M
Clin Res Cardiol: 30 Aug 2021; 110:1380-1391 | PMID: 33037501
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Impact:
Abstract

Comparison of mechanical circulatory support with venoarterial extracorporeal membrane oxygenation or Impella for patients with cardiogenic shock: a propensity-matched analysis.

Karatolios K, Chatzis G, Markus B, Luesebrink U, ... Jerrentrup A, Schieffer B
Background
Percutaneous mechanical circulatory devices are increasingly used in patients with cardiogenic shock (CS). As evidence from randomized studies comparing these devices are lacking, optimal choice of the device type is unclear. Here we aim to compare outcomes of patients with CS supported with either Impella or vaECMO.
Methods
Retrospective single-center analysis of patients with CS, from September 2014 to September 2019. Patients were assisted with either Impella 2.5/CP or vaECMO. Patients supported ultimately with both devices were analyzed according to the first device implanted. Primary outcomes were hospital and 6-month survival. Secondary endpoints were complications. Survival outcomes were compared using propensity-matched analysis to account for differences in baseline characteristics between both groups.
Results
A total of 423 patients were included (Impella, n = 300 and vaECMO, n = 123). Survival rates were similar in both groups (hospital survival: Impella 47.7% and vaECMO 37.3%, p = 0.07; 6-month survival Impella 45.7% and vaECMO 35.8%, p = 0.07). There was no significant difference in survival rates, even after adjustment for baseline differences (hospital survival: Impella 50.6% and vaECMO 38.6%, p = 0.16; 6-month survival Impella 45.8% and vaECMO 38.6%, p = 0.43). Access-site bleeding and leg ischemia occurred more frequently in patients with vaECMO (17% versus 7.3%, p = 0.004; 17% versus 7.7%, p = 0.008).
Conclusions
In this retrospective analysis of patients with CS, treatment with Impella 2.5/CP or vaECMO was associated with similar hospital and 6-month survival rates. Device-related access-site vascular complications occurred more frequently in the vaECMO group. A randomized trial is warranted to examine the effects of these devices on outcomes and to determine the optimal device choice in patients with CS.

© 2020. The Author(s).

Clin Res Cardiol: 30 Aug 2021; 110:1404-1411
Karatolios K, Chatzis G, Markus B, Luesebrink U, ... Jerrentrup A, Schieffer B
Clin Res Cardiol: 30 Aug 2021; 110:1404-1411 | PMID: 33185749
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Impact:
Abstract

Outcome of patients treated with extracorporeal life support in cardiogenic shock complicating acute myocardial infarction: 1-year result from the ECLS-Shock study.

Lackermair K, Brunner S, Orban M, Peterss S, ... Hagl C, Guenther SPW
Background
Treatment with extracorporeal life support (ECLS) in acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) fell short of improving myocardial recovery measured by 30 day ejection fraction in the ECLS-SHOCK trial. However, to date, no data regarding impact of ECLS on long-term outcomes exist.
Methods
In this randomized, controlled, prospective, open-label trial, 42 patients with CS complicating AMI were randomly assigned to ECLS (ECLS group, n = 21) or no ECLS (control group, n = 21). The primary endpoint was left ventricular ejection fraction (LVEF) after 30 days. Secondary endpoints included mortality and neurological outcome after 12 months. Evaluation of neurological outcome used the modified Rankin Scale.
Results
The 12-month all-cause mortality was 19% in the ECLS group versus 38% in the control group (p = 0.31). Only one patient (control group) died after the initial 30 days. Three patients underwent elective percutaneous coronary intervention (PCI) during follow-up (one in the control and two in the ECLS group). Favorable neurological outcome (modified Rankin Score ≤ 2) was seen in 61.9% of patients in the ECLS group versus 57.1% in the control group (p = 1).
Conclusion
This pilot study showed that randomized studies with ECLS in CS patients are feasible and safe. Small numbers of included patients impede meaningful conclusions about mortality and neurological outcome. Our findings of numerical differences in mortality and survival with severe neurological impairment give an urgent call for larger multi-centric randomized trials assessing the endpoint of all-cause mortality but also considering the effects on neurological outcome measures.

© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 30 Aug 2021; 110:1412-1420
Lackermair K, Brunner S, Orban M, Peterss S, ... Hagl C, Guenther SPW
Clin Res Cardiol: 30 Aug 2021; 110:1412-1420 | PMID: 33180150
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Impact:
Abstract

Cardiogenic shock: incidence, survival and mechanical circulatory support usage 2007-2017-insights from a national registry.

Lang CN, Kaier K, Zotzmann V, Stachon P, ... Wengenmayer T, Staudacher DL
Background
A central element in the management of cardiogenic shock (CS) comprises mechanical circulatory support (MCS) systems to maintain cardiac output (CO). This study aims to quantify incidence, outcome and influence of MCS in CS over the last decade.
Methods
All patients hospitalized with CS in a tertiary university hospital in Germany between 2007 and 2017 were identified utilizing the international coding system ICD-10 with code R57.0. Application of MCS was identified via German procedure classification codes (OPS).
Results
383,983 cases of cardiogenic shock were reported from 2007 to 2017. Patients had a mean age of 71 years and 38.5% were female. The incidence of CS rose by 65.6% from 26,828 cases in 2007 (33.1 per 100,000 person-years, hospital survival 39.2%) to 44,425 cases in 2017 (53.7 per 100,000 person-years, survival 41.2%). In 2007, 16.0% of patients with CS received MCS (4.6 per 100,000 person-years, survival 46.6%), dropping to 13.9% in 2017 (6.6 per 100,000 person-years, survival 38.6%). Type of MCS changed over the years, with decreasing use of the intra-aortic balloon pump (IABP), an increase in extracorporeal membrane oxygenation (VA-ECMO) and percutaneous ventricular assist device (pVAD) usage. Significant differences regarding in-hospital survival were observed between the devices (survival: overall: 40.2%; medical treatment = 39.5%; IABP = 49.5%; pVAD = 36.2%; VA-ECMO = 30.5%; p < 0.001).
Conclusions
The incidence of CS is increasing, but hospital survival remains low. MCS was used in a minority of patients, and the percentage of MCS usage in CS has decreased. The use rates of the competing devices change over time.

© 2020. The Author(s).

Clin Res Cardiol: 30 Aug 2021; 110:1421-1430
Lang CN, Kaier K, Zotzmann V, Stachon P, ... Wengenmayer T, Staudacher DL
Clin Res Cardiol: 30 Aug 2021; 110:1421-1430 | PMID: 33258007
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Impact:
Abstract

Outcomes in patients with acute myocardial infarction and new atrial fibrillation: a nationwide analysis.

Fauchier L, Bisson A, Bodin A, Herbert J, ... Danchin N, Cottin Y
Background
In patients with acute myocardial infarction (AMI), history of atrial fibrillation (AF) and new onset AF during the early phase may be associated with a worse prognosis. Whether both conditions are associated with similar outcomes is a matter of debate.
Methods
We collected information for all patients with AMI seen in French hospitals between 2010 and 2019. Among 797,212 patients seen with STEMI or NSTEMI, 75,701 (9.5%) had history of AF, and 34,768 (4.4%) had new AF diagnosed between day 1 and day 30 after AMI.
Results
Patients with new AF were older and had more comorbidities than those with no AF but were younger and had less comorbidities than those with history of AF. During follow-up [mean (SD) 1.8 (2.4) years, median (interquartile range) 0.7 (0.1-3.1) years], 163,845 deaths and 30,672 ischemic strokes were recorded. Using Cox multivariable analysis, compared to patients with no AF, history of AF was associated with a higher risk of death during follow-up (adjusted hazard ratio HR 1.17, 95% CI 1.16-1.19) and this was also the case for patients with new AF (adjusted HR 2.11, 2.07-2.15). Both history of AF and new AF were associated with a higher risk of ischemic stroke compared to patients with no AF: adjusted HR 1.19 (1.15-1.23) for history of AF, adjusted HR 1.78 (1.68-1.88) for new AF. New AF was associated with a higher risk of death and of ischemic stroke than history of AF: adjusted HR 1.74 (1.70-1.79) and 1.32 (1.23-1.42), respectively.
Conclusions
In a large and systematic nationwide analysis, AF first recorded in the first 30 days after AMI was independently associated with higher risks of death and ischemic stroke than those in patients with no AF or previously known AF.

© 2021. Springer-Verlag GmbH, DE part of Springer Nature.

Clin Res Cardiol: 30 Aug 2021; 110:1431-1438
Fauchier L, Bisson A, Bodin A, Herbert J, ... Danchin N, Cottin Y
Clin Res Cardiol: 30 Aug 2021; 110:1431-1438 | PMID: 33507390
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Impact:
Abstract

Acute chest pain with ST-segment elevation in lead V1-V3: when you hear hoofbeats, also look for zebras.

Pascale P, Pavon AG, Bogaert J, Bennett J, ... Schwitter J, Masci PG
ST-segment elevation (STE) in the anterior precordial leads is the hallmark of anterior myocardial infarction. In rare cases, this ECG pattern may be due to isolated infarction of the right ventricle since leads V1-V3 directly overlie the right ventricular free wall. Herein, we aimed to provide clues to recognize and understand this diagnostic pitfall through a series of 4 patients presenting with STE in the anterior leads.

© 2021. Springer-Verlag GmbH, DE part of Springer Nature.

Clin Res Cardiol: 30 Aug 2021; 110:1516-1522
Pascale P, Pavon AG, Bogaert J, Bennett J, ... Schwitter J, Masci PG
Clin Res Cardiol: 30 Aug 2021; 110:1516-1522 | PMID: 33547960
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Impact:
Abstract

Prognostic impact of mean heart rate by Holter monitoring on long-term outcome in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention.

Shen J, Liu G, Yang Y, Li X, ... Huang B, Luo S
Background
Previous studies have shown elevated admission heart rate (HR) was associated with worse outcome in patients with myocardial infarction (MI). However, the prognostic value of mean heart rate (MHR) with Holter monitoring remains unclear.
Objectives
Our present study aims to evaluate the impact of MHR by Holter monitoring on long-term mortality in patients with ST-segment elevation myocardial infarction (STEMI).
Methods
1013 STEMI patients were divided into four groups according to the quartiles of MHR by Holter monitoring, Q1 (< 66 bpm), Q2 66-72 bpm), Q3 (73-78 bpm), and Q4 (> 78 bpm). The endpoint was long-term all-cause mortality. The predictive value of admission HR, discharge HR, and MHR was compared with receiver operating characteristic (ROC) curves.
Results
Patients in Q4 were more likely to present with anterior MI, high Killip class, relatively lower admission blood pressure, significantly increased troponin I, B-type natriuretic peptide, and decreased left ventricular ejection fraction. During a median of 28.3 months follow up period, 91 patients (8.9%) died. The mortality in Q4 was significantly higher than in the other three groups (P < 0.001). After multivariate adjustment, Q4 was associated with a 1.0-fold increased risk of long-term all-cause mortality (HR = 2.096, 95% CI 1.190-3.691, P = 0.010). ROC analysis shows MHR with Holter (AUC = 0.672) was superior to admission HR (AUC = 0.556) or discharge HR (AUC = 0.578).
Conclusions
MHR based on Holter monitoring provided important prognostic value and MHR > 78 bpm was independently associated with increased risk of long-term all-cause mortality in patients with STEMI, and its predictive validity was superior to admission or discharge HR.

© 2021. Springer-Verlag GmbH, DE part of Springer Nature.

Clin Res Cardiol: 30 Aug 2021; 110:1439-1449
Shen J, Liu G, Yang Y, Li X, ... Huang B, Luo S
Clin Res Cardiol: 30 Aug 2021; 110:1439-1449 | PMID: 33547959
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Impact:
Abstract

Critical appraisal of the 2020 ESC guideline recommendations on diagnosis and risk assessment in patients with suspected non-ST-segment elevation acute coronary syndrome.

Giannitsis E, Blankenberg S, Christenson RH, Frey N, ... Wollert KC, Huber K
Multiple new recommendations have been introduced in the 2020 ESC guidelines for the management of acute coronary syndromes with a focus on diagnosis, prognosis, and management of patients presenting without persistent ST-segment elevation. Most recommendations are supported by high-quality scientific evidence. The guidelines provide solutions to overcome obstacles presumed to complicate a convenient interpretation of troponin results such as age-, or sex-specific cutoffs, and to give practical advice to overcome delays of laboratory reporting. However, in some areas, scientific support is less well documented or even missing, and other areas are covered rather by expert opinion or subjective recommendations. We aim to provide a critical appraisal on several recommendations, mainly related to the diagnostic and prognostic assessment, highlighting the discrepancies between Guideline recommendations and the existing scientific evidence.

© 2021. The Author(s).

Clin Res Cardiol: 30 Aug 2021; 110:1353-1368
Giannitsis E, Blankenberg S, Christenson RH, Frey N, ... Wollert KC, Huber K
Clin Res Cardiol: 30 Aug 2021; 110:1353-1368 | PMID: 33635437
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Impact:
Abstract

Prognostic benefit from an early invasive strategy in patients with non-ST elevation acute coronary syndrome (NSTEACS): evaluation of the new risk stratification in the NSTEACS European guidelines.

Martinón-Martínez J, Álvarez Álvarez B, González Ferrero T, García-Rodeja Arias F, ... Gude Sampedro F, González Juanatey JR
Objectives
The objective of our work is to evaluate the prognostic benefit of an early invasive strategy in patients with high-risk NSTACS according to the recommendations of the 2020 clinical practice guidelines during long-term follow-up.
Methods
This retrospective observational study included 6454 consecutive NSTEACS patients. We analyze the effects of early coronary angiography (< 24 h) in patients with: (a) GRACE risk score > 140 and (b) patients with \"established NSTEMI\" (non ST-segment elevation myocardial infarction defined by an increase in troponins) or dynamic ST-T-segment changes with a GRACE risk score < 140.
Results
From 2003 to 2017, 6454 patients with \"new high-risk NSTEACS\" were admitted, and 6031 (93.45%) of these underwent coronary angiography. After inverse probability of treatment weighting, the long-term cumulative probability of being free of all-cause mortality, cardiovascular mortality and MACE differed significantly due to an early coronary intervention in patients with NSTEACS and GRACE > 140 [HR 0.62 (IC 95% 0.57-0.67), HR 0.62 (IC 95% 0.56-0.68), HR 0.57 (IC 95% 0.53-0.61), respectively]. In patients with NSTEACS and GRACE < 140 with established NSTEMI or ST/T-segment changes, the benefit of the early invasive strategy is only observed in the reduction of MACE [HR 0.62 (IC 95% 0.56-0.68)], but not for total mortality [HR 0.96 (IC 95% 0.78-1.2)] and cardiovascular mortality [HR 0.96 (IC 95% 0.75-1.24)].
Conclusions
An early invasive management is associated with reduced all-cause mortality, cardiovascular mortality and MACE in NSTEACS with high GRACE risk score. However, this benefit is less evident in the subgroup of patients with a GRACE score < 140 with established NSTEMI or ST/T-segment changes.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 30 Aug 2021; 110:1464-1472
Martinón-Martínez J, Álvarez Álvarez B, González Ferrero T, García-Rodeja Arias F, ... Gude Sampedro F, González Juanatey JR
Clin Res Cardiol: 30 Aug 2021; 110:1464-1472 | PMID: 33687519
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Impact:
Abstract

Incidence and outcomes of perioperative myocardial infarction/injury diagnosed by high-sensitivity cardiac troponin I.

Gualandro DM, Puelacher C, Lurati Buse G, Glarner N, ... Mueller C, BASEL-PMI Investigators
Background
 Perioperative myocardial infarction/injury (PMI) diagnosed by high-sensitivity troponin (hs-cTn) T is frequent and a prognostically important complication of non-cardiac surgery. We aimed to evaluate the incidence and outcome of PMI diagnosed using hs-cTnI, and compare it to PMI diagnosed using hs-cTnT.
Methods
We prospectively included 2455 patients at high cardiovascular risk undergoing 3111 non-cardiac surgeries, for whom hs-cTnI and hs-cTnT concentrations were measured before surgery and on postoperative days 1 and 2. PMI was defined as a composite of perioperative myocardial infarction (PMIInfarct) and perioperative myocardial injury (PMIInjury), according to the Fourth Universal Definition of Myocardial Infarction. All-cause mortality was the primary endpoint.
Results
Using hs-cTnI, the incidence of overall PMI was 9% (95% confidence interval [CI] 8-10%), including PMIInfarct 2.6% (95% CI 2.0-3.2) and PMIInjury 6.1% (95% CI 5.3-6.9%), which was lower versus using hs-cTnT: overall PMI 15% (95% CI 14-16%), PMIInfarct 3.7% (95% CI 3.0-4.4) and PMIInjury 11.3% (95% CI 10.2-12.4%). All-cause mortality occurred in 52 (2%) patients within 30 days and 217 (9%) within 1 year. Using hs-cTnI, both PMIInfarct and PMIInjury were independent predictors of 30-day all-cause mortality (adjusted hazard ratio [aHR] 2.5 [95% CI 1.1-6.0], and aHR 2.8 [95% CI 1.4-5.5], respectively) and, 1-year all-cause mortality (aHR 2.0 [95% CI 1.2-3.3], and aHR 1.8 [95% CI 1.2-2.7], respectively). Overall, the prognostic impact of PMI diagnosed by hs-cTnI was comparable to the prognostic impact of PMI using hs-cTnT.
Conclusions
Using hs-cTnI, PMI is less common versus using hs-cTnT. Using hs-cTnI, both PMIInfarct and PMIInjury remain independent predictors of 30-day and 1-year mortality.

© 2021. The Author(s).

Clin Res Cardiol: 30 Aug 2021; 110:1450-1463
Gualandro DM, Puelacher C, Lurati Buse G, Glarner N, ... Mueller C, BASEL-PMI Investigators
Clin Res Cardiol: 30 Aug 2021; 110:1450-1463 | PMID: 33768367
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Impact:
Abstract

Impact of pulse pressure on clinical outcome in extracorporeal cardiopulmonary resuscitation (eCPR) patients.

Rilinger J, Riefler AM, Bemtgen X, Jäckel M, ... Staudacher DL, Wengenmayer T
Background
Hemodynamic response to successful extracorporeal cardiopulmonary resuscitation (eCPR) is not uniform. Pulse pressure (PP) as a correlate for myocardial damage or recovery from it, might be a valuable tool to estimate the outcome of these patients.
Methods
We report retrospective data of a single-centre registry of eCPR patients, treated at the Interdisciplinary Medical Intensive Care Unit at the Medical Centre, University of Freiburg, Germany, between 01/2017 and 01/2020. The association between PP of the first 10 days after eCPR and hospital survival was investigated. Moreover, patients were divided into three groups according to their PP [low (0-9 mmHg), mid (10-29 mmHg) and high (≥ 30 mmHg)] at each time point.
Results
One hundred forty-three patients (age 63 years, 74.1% male, 40% OHCA, average low flow time 49 min) were analysed. Overall hospital survival rate was 28%. A low PP both early after eCPR (after 1, 3, 6 and 12 h) and after day 1 to day 8 was associated with reduced hospital survival. At each time point (1 h to day 5) the classification of patients into a low, mid and high PP group was able to categorize the patients for a low (5-20%), moderate (20-40%) and high (50-70%) survival rate. A multivariable analysis showed that the mean PP of the first 24 h was an independent predictor for survival (p = 0.008).
Conclusion
In this analysis, PP occurred to be a valuable parameter to estimate survival and maybe support clinical decision making in the further course of patients after eCPR.

© 2021. The Author(s).

Clin Res Cardiol: 30 Aug 2021; 110:1473-1483
Rilinger J, Riefler AM, Bemtgen X, Jäckel M, ... Staudacher DL, Wengenmayer T
Clin Res Cardiol: 30 Aug 2021; 110:1473-1483 | PMID: 33779810
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Impact:
Abstract

Admission blood glucose level and outcome in patients requiring venoarterial extracorporeal membrane oxygenation.

Bemtgen X, Rilinger J, Jäckel M, Zotzmann V, ... Lother A, Staudacher DL
Background
Patients with cardiogenic shock or cardiac arrest undergoing venoarterial extracorporeal membrane oxygenation (V-A ECMO) frequently present with blood glucose levels out of normal range. The clinical relevance of such findings in the context of V-A ECMO is unknown. We therefore investigated the prognostic relevance of blood glucose at time of cannulation for V-A ECMO.
Methods
We conducted a single-center retrospective registry study. All patients receiving V-A ECMO from October 2010 to January 2020 were included if blood glucose level at time of cannulation were documented. Patients were divided in five groups according to the initial blood glucose level ranging from hypoglycemic (< 80 mg/dl), normoglycemic (80-140 mg/dl), to mild (141-240 mg/dl), moderate (241-400 mg/dl), and severe (> 400 mg/dl) hyperglycemia, respectively. Clinical presentation, arterial blood gas analysis, and survival were compared between the groups.
Results
392 patients met inclusion criteria. Median age was 62 years (51.5-70.0), SAPS II at admission was 54 (43.5-63.0), and 108/392 (27.6%) were female. 131/392 were discharged alive (hospital survival 33.4%). At time of cannulation, survivors had higher pH, hemoglobin, calcium, bicarbonate but lower potassium and lactate levels compared to non-survivors (all p < 0.01). Outcome of patients diagnosed with particularly high (> 400 mg/dl) and low (< 80 mg/dl) blood glucose at time of V-A ECMO cannulation, respectively, was worse compared to patients with normoglycemic, mildly or moderately elevated values (p = 0.02). Glucose was independently associated with poor outcome after adjustment for other predictors of survival and persisted in all investigated subgroups.
Conclusion
Arterial blood glucose at time of V-A ECMO cannulation predicts in-hospital survival of patients with cardiac shock or after ECPR. Whether dysglycemia represents a potential therapeutic target requires further evaluation in prospective studies.

© 2021. The Author(s).

Clin Res Cardiol: 30 Aug 2021; 110:1484-1492
Bemtgen X, Rilinger J, Jäckel M, Zotzmann V, ... Lother A, Staudacher DL
Clin Res Cardiol: 30 Aug 2021; 110:1484-1492 | PMID: 33944987
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Impact:
Abstract

New challenges in cardiac intensive care units.

Lüsebrink E, Kellnar A, Scherer C, Krieg K, ... Massberg S, Orban M
Critical care cardiology is a steadily and rapidly developing sub-specialization within cardiovascular medicine, since the first emergence of a coronary care unit in the early 1960s. Today, modern cardiac intensive care units (CICU) serve a complex patient population with a high burden of cardiovascular and non-cardiovascular critical illnesses. Treatment of these patients requires a multidisciplinary approach, with a combination of highly specialized knowledge and skills in cardiovascular diseases, as well as emergency, critical-care and internal medicine. The CICU has always posed special challenges to both experienced intensivists as well as fellows-in-training (FIT) and is certainly one of the most demanding training phases. In recent years, these challenges have grown significantly owing to technological innovations, with new and steadily rising numbers of complex interventional procedures and new options for temporary circulatory support for critically ill patients, such as venoarterial extracorporeal membrane oxygenation (VA-ECMO). Herein, we focus on the successful CICU management of these special patient cohorts, which must become an integral part of critical-care training.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 30 Aug 2021; 110:1369-1379
Lüsebrink E, Kellnar A, Scherer C, Krieg K, ... Massberg S, Orban M
Clin Res Cardiol: 30 Aug 2021; 110:1369-1379 | PMID: 33966127
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Impact:
Abstract

Clopidogrel vs. prasugrel vs. ticagrelor in patients with acute myocardial infarction complicated by cardiogenic shock: a pooled IABP-SHOCK II and CULPRIT-SHOCK trial sub-analysis.

Orban M, Kleeberger J, Ouarrak T, Freund A, ... Thiele H, Hausleiter J
Aims
The aim of this pooled sub-analysis of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) and Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial was to compare the clinical outcome of patients with acute myocardial infarction complicated by cardiogenic shock treated either with clopidogrel or the newer, more potent ADP-receptor antagonists prasugrel or ticagrelor.
Methods and results
For the current analysis the primary endpoint was 1-year mortality and the secondary safety endpoint was moderate or severe bleedings until hospital discharge with respect to three different ADP-receptor antagonists. 856 patients were eligible for analysis. Of these, 507 patients (59.2%) received clopidogrel, 178 patients (20.8%) prasugrel and 171 patients (20.0%) ticagrelor as acute antiplatelet therapy. The adjusted rate of mortality after 1-year did not differ significantly between prasugrel and clopidogrel (hazard ratio [HR]: 0.81, 95% confidence interval [CI] 0.60-1.09, padj = 0.17) or between ticagrelor and clopidogrel treated patients (HR: 0.86, 95% CI 0.65-1.15, padj = 0.31). In-hospital bleeding events were significantly less frequent in patients treated with ticagrelor vs. clopidogrel (HR: 0.37, 95% CI 0.20 -0.69, padj = 0.002) and not significantly different in patients treated with prasugrel vs. clopidogrel (HR: 0.73, 95% CI 0.43 -1.24, padj = 0.24).
Conclusion
This pooled sub-analysis is the largest analysis on safety and efficacy of three oral ADP-receptor antagonists and shows that acute therapy with either clopidogrel, prasugrel or ticagrelor is no independent predictor of 1-year mortality. Treatment with ticagrelor seems independently associated with less in-hospital moderate and severe bleeding events compared to clopidogrel. This finding might be due to selection bias and should be interpreted with caution.

© 2021. The Author(s).

Clin Res Cardiol: 30 Aug 2021; 110:1493-1503
Orban M, Kleeberger J, Ouarrak T, Freund A, ... Thiele H, Hausleiter J
Clin Res Cardiol: 30 Aug 2021; 110:1493-1503 | PMID: 33999281
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Impact:
Abstract

Left ventricular function recovery after ST-elevation myocardial infarction: correlates and outcomes.

Dauw J, Martens P, Deferm S, Bertrand P, ... Dupont M, Mullens W
Background
Contemporary data on left ventricular function (LVF) recovery in patients with left ventricular dysfunction after ST-elevation myocardial infarction (STEMI) are scarce and to date, no comparison has been made with patients with a baseline normal LVF. This study examined predictors of LVF recovery and its relation to outcomes in STEMI.
Methods
Patients presenting with STEMI between January 2010 and December 2016 were categorized in three groups after 3 months according to left ventricular ejection fraction (EF): (i) baseline normal LVF (EF ≥ 50% at baseline); (ii) recovered LVF (EF < 50% at baseline and ≥ 50% after 3 months); and (iii) reduced LVF (EF < 50% at baseline and after 3 months). Heart failure hospitalization, all-cause mortality and cardiovascular mortality were compared between the three groups.
Results
Of 577 patients, 341 (59%) patients had a baseline normal LVF, 112 (19%) had a recovered LVF and 124 (22%) had a reduced LVF. Independent correlates of LVF recovery were higher baseline EF, lower peak troponin and cardiac arrest. After median 5.8 years, there was no difference in outcomes between patients with LVF recovery and baseline normal LVF. In contrast, even after multivariate adjustment, patients with persistently reduced LVF had a higher risk for heart failure hospitalization (HR 5.00; 95% CI 2.17-11.46) and all-cause mortality (HR 1.87; 95% CI 1.11-3.16).
Conclusion
In contemporary treated STEMI patients, prognosis is significantly worse in those with a persistently reduced LVF after 3 months, compared with patients with a baseline normal LVF and those with LVF recovery.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 30 Aug 2021; 110:1504-1515
Dauw J, Martens P, Deferm S, Bertrand P, ... Dupont M, Mullens W
Clin Res Cardiol: 30 Aug 2021; 110:1504-1515 | PMID: 34091698
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Impact:
Abstract

Remote proctoring for high-risk coronary interventions with mechanical circulatory support during COVID-19 pandemic and beyond.

Woitek FJ, Haussig S, Mierke J, Linke A, Mangner N
Remote proctoring by advanced digital technologies may help to overcome pandemic, geographic, and resource-related constraints for mentoring and educating interventional cardiology skills. We present a case series of patients undergoing high-risk percutaneous coronary intervention (HR-PCI) with mechanical circulatory support (MCS) guided by remote proctoring to gain insights into a streaming technology platform with regard to video/audio quality, visibility of all structural and imaging details, and delay in transmission. According to our experience, remote proctoring appears to be a reliable, quick, and resource-conserving way to disseminate, educate and improve MCS-supported HR-PCI with implications far beyond the COVID-19 pandemic.

© 2021. The Author(s).

Clin Res Cardiol: 30 Aug 2021; 110:1525-1530
Woitek FJ, Haussig S, Mierke J, Linke A, Mangner N
Clin Res Cardiol: 30 Aug 2021; 110:1525-1530 | PMID: 34156523
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Impact:
Abstract

Echocardiography-derived total atrial conduction time (PA-TDI duration): risk stratification and guidance in atrial fibrillation management.

Müller P, Weijs B, Bemelmans NMAA, Mügge A, ... Linz D, den Uijl DW
Atrial fibrillation (AF) is a major cause of cardiovascular morbidity and mortality. To early detect and to avoid AF-related complications, several cardiac imaging modalities and approaches aim to quantify the severity of the underlying atrial cardiomyopathy (i.e., the extent of atrial remodeling). However, most established cardiac imaging modalities just incorporate single components of atrial remodeling and do not reflect the complete multifactorial process, which may contribute to their limited predictive value. Echocardiography-derived PA-TDI duration is a sophisticated echocardiographic parameter to assess total atrial conduction time and directly reflects both electrical and structural changes to the atria. Therefore, PA-TDI duration provides a more comprehensive quantification of the extent of atrial remodeling than other imaging modalities. In this article we review the role of PA-TDI duration as a marker of atrial remodeling and summarize the available data on PA-TDI duration to identify patients at risk for AF, as well as to guide AF management. Moreover, we discuss how to assess PA-TDI duration and provide recommendations on the implementation of PA-TDI duration into routine clinical care.

© 2021. The Author(s).

Clin Res Cardiol: 27 Aug 2021; epub ahead of print
Müller P, Weijs B, Bemelmans NMAA, Mügge A, ... Linz D, den Uijl DW
Clin Res Cardiol: 27 Aug 2021; epub ahead of print | PMID: 34453577
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Impact:
Abstract

Coronary artery bypass grafting versus stent implantation in patients with chronic coronary syndrome and left main disease: insights from a register throughout Germany.

Stachon P, Kaier K, Hehn P, Peikert A, ... Bode C, von Zur Mühlen C
Background
Recent randomized controlled trials have sparked debate about the optimal treatment of patients suffering from left main coronary artery disease. The present study analyzes outcomes of left main stenting versus coronary bypass grafting (CABG) in a nationwide registry in patients with chronic coronary syndrome (CCS).
Methods
All cases suffering from CCS and left main coronary artery disease treated either with CABG or stent, were identified within the database of the German bureau of statistics. Logistic or linear regression models were used with 20 baseline patient characteristics as potential confounders to compare both regimens.
Results
In 2018, 1318 cases with left main stenosis were treated with CABG and 8,920 with stent. Patients assigned for stenting were older (72.58 ± 9.87 vs. 68.63 ± 9.40, p < 0.001) and at higher operative risk, as assessed by logistic EuroSCORE (8.77 ± 8.45 vs. 4.85 ± 4.65, p < 0.001). After risk adjustment, no marked differences in outcomes were found for in-hospital mortality and stroke (risk adjusted odds ratio (aOR) for stent instead of CABG: aOR mortality: 1.08 [95% CI 0.66; 1.78], p = 0.748; aOR stroke: 0.59 [0.27; 1.32], p = 0.199). Stent implantation was associated with a reduced risk of relevant bleeding (aOR 0.38 [0.24; 0.61], p < 0.001), reduced prolonged ventilation time (aOR 0.54 [0.37 0.79], p = 0.002), and postoperative delirium (aOR 0.16 [0.11; 0.22], p < 0.001). Furthermore, stent implantation was associated with shorter hospital stay (- 6.78 days [- 5.86; - 7.71], p < 0.001) and lower costs (- €10,035 [- €11,500; - €8570], p < 0.001).
Conclusion
Left main stenting is a safe and effective treatment option for CCS-patients suffering from left main coronary artery disease at reasonable economic cost. Coronary artery bypass grafting versus stent implantation in patients with chronic coronary syndrome and left main disease: insights from a register throughout Germany. All cases with chronic coronary syndrome and left main stenosis treated in 2018 in Germany either with left main stenting or coronary bypass grafting were extracted from a nation-wide database. In-hospital outcomes were compared after logistic regression analysis.

© 2021. The Author(s).

Clin Res Cardiol: 27 Aug 2021; epub ahead of print
Stachon P, Kaier K, Hehn P, Peikert A, ... Bode C, von Zur Mühlen C
Clin Res Cardiol: 27 Aug 2021; epub ahead of print | PMID: 34453576
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Impact:
Abstract

Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients: the Aldo-DHF randomized controlled trial.

Lechner K, Scherr J, Lorenz E, Lechner B, ... Duvinage A, Edelmann F
Objectives
To evaluate associations of omega-3 fatty acid (O3-FA) blood levels with cardiometabolic risk markers, functional capacity and cardiac function/morphology in patients with heart failure with preserved ejection fraction (HFpEF).
Background
O3-FA have been linked to reduced risk for HF and associated phenotypic traits in experimental/clinical studies.
Methods
This is a cross-sectional analysis of data from the Aldo-DHF-RCT. From 422 patients, the omega-3-index (O3I = EPA + DHA) was analyzed at baseline in n = 404 using the HS-Omega-3-Index® methodology. Patient characteristics were; 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E/e\' 7.1 ± 1.5; median NT-proBNP 158 ng/L (IQR 82-298). Pearson\'s correlation coefficient and multiple linear regression analyses, using sex and age as covariates, were used to describe associations of the O3I with metabolic phenotype, functional capacity, echocardiographic markers for LVDF, and neurohumoral activation at baseline/12 months.
Results
The O3I was below (< 8%), within (8-11%), and higher (> 11%) than the target range in 374 (93%), 29 (7%), and 1 (0.2%) patients, respectively. Mean O3I was 5.7 ± 1.7%. The O3I was inversely associated with HbA1c (r = - 0.139, p = 0.006), triglycerides-to-HDL-C ratio (r = - 0.12, p = 0.017), triglycerides (r = - 0.117, p = 0.02), non-HDL-C (r = - 0.101, p = 0.044), body-mass-index (r = - 0.149, p = 0.003), waist circumference (r = - 0.121, p = 0.015), waist-to-height ratio (r = - 0.141, p = 0.005), and positively associated with submaximal aerobic capacity (r = 0.113, p = 0.023) and LVEF (r = 0.211, p < 0.001) at baseline. Higher O3I at baseline was predictive of submaximal aerobic capacity (β = 15.614, p < 0,001), maximal aerobic capacity (β = 0.399, p = 0.005) and LVEF (β = 0.698, p = 0.007) at 12 months.
Conclusions
Higher O3I was associated with a more favorable cardiometabolic risk profile and predictive of higher submaximal/maximal aerobic capacity and lower BMI/truncal adiposity in HFpEF patients. Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients. Higher O3I was associated with a more favorable cardiometabolic risk profile and aerobic capacity (left) but did not correlate with echocardiographic markers for left ventricular diastolic function or neurohumoral activation (right). An O3I-driven intervention trial might be warranted to answer the question whether O3-FA in therapeutic doses (with the target O3I 8-11%) impact on echocardiographic markers for left ventricular diastolic function and neurohumoral activation in patients with HFpEF. This figure contains modified images from Servier Medical Art ( https://smart.servier.com ) licensed by a Creative Commons Attribution 3.0 Unported License.

© 2021. The Author(s).

Clin Res Cardiol: 27 Aug 2021; epub ahead of print
Lechner K, Scherr J, Lorenz E, Lechner B, ... Duvinage A, Edelmann F
Clin Res Cardiol: 27 Aug 2021; epub ahead of print | PMID: 34453204
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Impact:
Abstract

Impact of HAS-BLED Score on outcome after percutaneous left atrial appendage closure: insights from the German Left Atrial Appendage Occluder Registry LAARGE.

Ledwoch J, Franke J, Brachmann J, Lewalter T, ... Krapivsky A, Sievert H
Aim
Percutaneous left atrial appendage (LAA) closure has been established as alternative stroke prophylaxis in patients with non-valvular atrial fibrillation (AF) and high bleeding risk. However, little is known regarding the outcome after LAA closure depending on the HAS-BLED score.
Methods
A sub-analysis of the prospective, multicenter, Left-Atrium-Appendage Occluder Register-GErmany (LAARGE) registry was performed assessing three different groups with respect to the HAS-BLED score (0-2 [group 1] vs. 3-4 [group 2] vs. 5-7 [group 3]).
Results
A total of 633 patients at 38 centers were enrolled. Of them, 9% (n = 59) were in group 1, 63% (n = 400) in group 2 and 28% (n = 174) in group 3. The Kaplan-Meier estimated 1-year composite of death, stroke and systemic embolism was 3.4% in group 1 vs. 10.4% in group 2 vs. 20.1% in group 3, respectively (p log-rank < 0.001). The difference was driven by death since stroke and systemic embolism did not show a significant difference between the groups. The rate of major bleeding at 1 year was 0% vs. 0% vs. 2.4%, respectively (p = 0.016).
Conclusion
The present data show that patients had similarly low rates of ischemic complications 1 year after LAA closure irrespective of the baseline bleeding risk. Higher HAS-BLED scores were associated with increased mortality due to higher age and more severe comorbidity of these patients.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 27 Aug 2021; epub ahead of print
Ledwoch J, Franke J, Brachmann J, Lewalter T, ... Krapivsky A, Sievert H
Clin Res Cardiol: 27 Aug 2021; epub ahead of print | PMID: 34455462
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Impact:
Abstract

Anticoagulants for stroke prevention in heart failure with reduced ejection fraction.

Schäfer A, Flierl U, Bauersachs J
Impaired left-ventricular ejection-fraction (LV-EF) is a known risk factor for ischemic stroke and systemic embolism in patients with heart failure (HF) even in the absence of atrial fibrillation. While stroke risk is inversely correlated with LV-EF in HF patients with sinus rhythm, strategies using anticoagulation with Vitamin-K antagonists (VKA) were futile as the increase in major bleedings outweighed the potential benefit in stroke reduction. Non-Vitamin K oral anticoagulants (NOACs) proved to be an effective and in general safer approach for stroke prevention in patients with atrial fibrillation and may also have a favourable risk-benefit profile in HF patients. In HF patients with sinus rhythm, the COMPASS trial suggested a potential benefit for rivaroxaban, whereas the more dedicated COMMANDER-HF trial remained neutral on overall ischemic benefit owed to a higher mortality which was not influenced by anticoagulation. More recent data from subgroups in the COMMANDER-HF trial, however, suggest that there might be a benefit of rivaroxaban regarding stroke prevention under certain circumstances. In this article, we review the existing evidence for NOACs in HF patients with atrial fibrillation, elaborate the rationale for stroke prevention in HF patients with sinus rhythm, summarise the available data from anticoagulation trials in HF with sinus rhythm, and describe the patient who might eventually profit from an individualised strategy aiming to reduce stroke risk.

© 2021. The Author(s).

Clin Res Cardiol: 26 Aug 2021; epub ahead of print
Schäfer A, Flierl U, Bauersachs J
Clin Res Cardiol: 26 Aug 2021; epub ahead of print | PMID: 34448932
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Impact:
Abstract

Real-world applicability and impact of early rhythm control for European patients with atrial fibrillation: a report from the ESC-EHRA EORP-AF Long-Term General Registry.

Proietti M, Vitolo M, Harrison SL, Lane DA, ... Lip GYH, ESC-EHRA EORP-AF Long-Term General Registry Investigators
Background
Use of rate/rhythm control is essential to control symptoms in patients with atrial fibrillation (AF). Recently, the EAST-AFNET 4 trial described how early rhythm control strategy was associated with a lower risk of adverse clinical outcomes.
Objectives
The aim was to evaluate the real-world applicability and impact of an early rhythm control strategy in patients with AF.
Methods
Use of an early rhythm control strategy was assessed in a European cohort of AF patients derived from the EHRA-ESC EORP-AF General Long-Term Registry. Early rhythm control was defined as use of antiarrhythmic drugs or cardioversion/catheter ablation. The primary outcome included cardiovascular death, stroke, acute coronary syndrome, and worsening of heart failure. Quality of life and health-care resource usage were also assessed as outcomes.
Results
Among the 10,707 patients evaluated for eligibility to EAST-AFNET 4, a total of 3774 (34.0%) were included. Early rhythm control was associated with better quality of life, but with greater use of health-care resources. During follow-up, the primary outcome occurred less often in early rhythm control patients than in those with no rhythm control (13.6% vs. 18.5%, p < 0.001). In the multivariate adjusted Cox regression model, no significant difference was found between no rhythm control and early rhythm control, for the primary outcome. No difference in the primary outcome between early rhythm control and \'no rhythm control patients\' adherent to Atrial fibrillation Better Care (ABC) pathway\' was evident (p = 0.753)
Conclusions:
Use of an early rhythm control strategy was associated with a lower rate of major adverse events, but this difference was non-significant on multivariate analysis, being mediated by differences in baseline characteristics and clinical risk profile. Early rhythm control was associated with a higher use of health-care resources and risk of hospital admission, despite showing better quality of life.

© 2021. The Author(s).

Clin Res Cardiol: 26 Aug 2021; epub ahead of print
Proietti M, Vitolo M, Harrison SL, Lane DA, ... Lip GYH, ESC-EHRA EORP-AF Long-Term General Registry Investigators
Clin Res Cardiol: 26 Aug 2021; epub ahead of print | PMID: 34448931
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Impact:
Abstract

Short- and long-term outcome of patients with spontaneous echo contrast or thrombus in the left atrial appendage in the era of the direct acting anticoagulants.

Backhaus JF, Pflaumbaum A, Krogias C, Kreimer F, ... Gold R, Gotzmann M
Background
Thrombi and spontaneous echo contrast (SEC) in the left atrial appendage (LAA) are associated with thromboembolic events and poor prognosis. There are very few data on long-term outcome, especially with the use of direct acting anticoagulants (DOAC).
Methods
In this retrospective study, all transoesophageal echocardiographies performed at a tertiary care university hospital from 2015 to 2020 were analyzed. All patients with thrombus or SEC in the LAA were included. Medical history, laboratory, echocardiographic parameters and medication at discharge were documented. The primary endpoint of the study was a composite endpoint (all-cause mortality, non-fatal stroke or transient ischaemic attack [TIA], non-fatal systemic embolization, non-fatal major bleeding and non-fatal myocardial infarction).
Results
Of a total of 4062 transoesophageal echocardiographies, thrombi were detected in 51 patients (1.2%) and SEC in 251 patients (6.2%). These patients formed the final study cohort (n = 302). During a mean follow-up period of 956 ± 663 days, 87 patients (29%) suffered the primary point. The following baseline characteristics predicted the primary endpoint: age, haemoglobin, a previous coronary artery bypass grafting, dialysis and choice of anticoagulation. Prescription of apixaban at discharge was associated with lower rate of adverse events (hazard ratio 0.564, confidence interval 0.331-0.960; p = 0.035) while prescription of dabigatran was associated with higher rate of adverse events (hazard ratio 3.091, confidence interval 1.506-6.347; p = 0.002).
Conclusion
Even in the DOAC era, the occurrence of thrombus or SEC in the LAA is associated with a high rate of MACCE. Our study suggests that the choice of DOAC therapy may have an impact on long-term survival.

© 2021. The Author(s).

Clin Res Cardiol: 25 Aug 2021; epub ahead of print
Backhaus JF, Pflaumbaum A, Krogias C, Kreimer F, ... Gold R, Gotzmann M
Clin Res Cardiol: 25 Aug 2021; epub ahead of print | PMID: 34436659
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Impact:
Abstract

Non-invasive predictors for infranodal conduction delay in patients with left bundle branch block after TAVR.

Auberson C, Badertscher P, Madaffari A, Malushi M, ... Knecht S, Kühne M
Aims
Left bundle branch block (LBBB) is the most common conduction disorder after transcatheter aortic valve replacement (TAVR) with an increased risk of atrioventricular (AV) block. The aim of the current study was to identify non-invasive predictors for infranodal conduction delay in patients with LBBB.
Methods
We analyzed consecutive patients undergoing TAVR with pre-existing or new-onset LBBB between August 2014 and August 2020. His ventricular (HV) interval measurement was performed on day 1 after TAVR. Baseline, procedural, as well as surface and intracardiac electrocardiographic parameters were included. Infranodal conduction delay was defined as HV interval > 55 ms.
Results
Of 825 patients screened after TAVR, 151 patients (82 ± 6 years, 39% male) with LBBB were included. Among these, infranodal conduction delay was observed in 25%. ΔPR (difference in PR interval after and before TAVR), PR and QRS duration after TAVR were significantly longer in the group with HV prolongation. In a multivariate analysis in patients with sinus rhythm (n = 123), ΔPR (OR per 10 ms increase: 1.52; 95%CI: 1.19-2.01; p = 0.002) was the only independent factor associated with infranodal conduction delay. A change in PR interval by 20 ms yielded a specificity of 83% and a sensitivity of 46%, with a negative predictive value of 84% and a positive predictive value of 45% to predict HV prolongation.
Conclusions
Simple analysis of surface ECG and a calculated ΔPR < 20 ms can be used as predictor for the absence of infranodal conduction delay in post-TAVR patients with LBBB.

© 2021. The Author(s).

Clin Res Cardiol: 25 Aug 2021; epub ahead of print
Auberson C, Badertscher P, Madaffari A, Malushi M, ... Knecht S, Kühne M
Clin Res Cardiol: 25 Aug 2021; epub ahead of print | PMID: 34448041
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Impact:
Abstract

Clinical and cardiac magnetic resonance findings in post-COVID patients referred for suspected myocarditis.

Breitbart P, Koch A, Schmidt M, Magedanz A, ... Mehta RH, Eggebrecht H
Objectives
We assessed possible myocardial involvement in previously cardiac healthy post-COVID patients referred for persisting symptoms with suspected myocarditis.
Background
Prior studies suggested myocardial inflammation in patients with coronavirus-induced disease 2019 (COVID-19). However, the prevalence of cardiac involvement among COVID patients varied between 1.4 and 78%.
Methods
A total of 56 post-COVID patients without previous heart diseases were included consecutively into this study. All patients had positive antibody titers against SARS-CoV-2. Patients were referred for persistent symptoms such as chest pain/discomfort, shortness of breath, or intolerance to activity. All patients underwent standardized cardiac assessment including electrocardiogram (ECG), cardiac biomarkers, echocardiography, and cardiac magnetic resonance (CMR).
Results
56 Patients (46 ± 12 years, 54% females) presented 71 ± 66 days after their COVID-19 disease. In most patients, the course of COVID-19 was mild, with hospital treatment being necessary in five (9%). At presentation, patients most often reported persistent fatigue (75%), chest pain (71%), and shortness of breath (66%). Acute myocarditis was confirmed by T1/T2-weighed CMR and elevated NTpro-BNP levels in a single patient (2%). Left ventricular ejection fraction was 56% in this patient. Additional eight patients (14%) showed suspicious CMR findings, including myocardial edema without fibrosis (n = 3), or non-ischemic myocardial injury suggesting previous inflammation (n = 5). However, myocarditis could ultimately not be confirmed according to 2018 Lake Louise criteria; ECG, echo and lab findings were inconspicuous in all eight patients.
Conclusions
Among 56 post-COVID patients with persistent thoracic complaints final diagnosis of myocarditis could be confirmed in a single patient using CMR.

© 2021. The Author(s).

Clin Res Cardiol: 25 Aug 2021; epub ahead of print
Breitbart P, Koch A, Schmidt M, Magedanz A, ... Mehta RH, Eggebrecht H
Clin Res Cardiol: 25 Aug 2021; epub ahead of print | PMID: 34448040
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Impact:
Abstract

Outcomes of conduction system pacing compared to right ventricular pacing as a primary strategy for treating bradyarrhythmia: systematic review and meta-analysis.

Abdin A, Aktaa S, Vukadinović D, Arbelo E, ... Vernooy K, Gale CP
Background
Right ventricular pacing (RVP) may cause electrical and mechanical desynchrony leading to impaired left ventricular ejection fraction (LVEF). We investigated the outcomes of RVP with His bundle pacing (HBP) and left bundle branch pacing (LBBP) for patients requiring a de novo permanent pacemaker (PPM) for bradyarrhythmia.
Methods and results
Systematic review of randomized clinical trials and observational studies comparing HBP or LBP with RVP for de novo PPM implantation between 01 January 2013 and 17 November 2020 was performed. Random and fixed effects meta-analyses of the effect of pacing technology on outcomes were performed. Study outcomes included all-cause mortality, heart failure hospitalization (HFH), LVEF, QRS duration, lead revision, atrial fibrillation, procedure parameters, and pacing metrics. Overall, 9 studies were included (6 observational, 3 randomised). HBP compared with RVP was associated with decreased HFH (risk ratio [RR] 0.68, 95% confidence interval [CI] 0.49-0.94), preservation of LVEF (mean difference [MD] 0.81, 95% CI - 1.23 to 2.85 vs. - 5.72, 95% CI - 7.64 to -3.79), increased procedure duration (MD 15.17 min, 95% CI 11.30-19.04), and increased lead revisions (RR 5.83, 95% CI 2.17-15.70, p = 0.0005). LBBP compared with RVP was associated with shorter paced QRS durations (MD 5.6 ms, 95% CI - 6.4 to 17.6) vs. (51.0 ms, 95% CI 39.2-62.9) and increased procedure duration (MD 37.78 min, 95% CI 20.04-55.51).
Conclusion
Of the limited studies published, this meta-analysis found that HBP and LBBP were superior to RVP in maintaining physiological ventricular activation as an initial pacing strategy.

© 2021. The Author(s).

Clin Res Cardiol: 18 Aug 2021; epub ahead of print
Abdin A, Aktaa S, Vukadinović D, Arbelo E, ... Vernooy K, Gale CP
Clin Res Cardiol: 18 Aug 2021; epub ahead of print | PMID: 34410461
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Impact:
Abstract

Global longitudinal strain predicts atrial fibrillation in individuals without hypertension: A Community-based cohort study.

Olsen FJ, Biering-Sørensen SR, Reimer Jensen AM, Schnohr P, ... Møgelvang R, Biering-Sørensen T
Background
Global longitudinal strain (GLS) is a sensitive marker of myocardial dysfunction and atrial reservoir function. We sought to evaluate its value for predicting atrial fibrillation (AF) in the general population.
Methods
Participants from the Copenhagen City Heart Study examined with echocardiography, including speckle tracking analyses, were included. The endpoint was AF obtained through national registries. Proportional hazards Cox regression was applied, including multivariable adjustments made for CHADS2 and CHARGE-AF risk factors. Abnormal GLS was defined as >-18%.
Results
The data from 1,309 participants were analyzed. Of those, 153 (12%) developed AF during a median follow-up time of 15.9 years. The follow-up was 100%. The mean age was 57 years, 38% had hypertension, and GLS was  - 18%. In unadjusted analysis, GLS was a univariable predictor of outcome (1.08 (1.04-1.13), p < 0.001, per 1% absolute decrease), but did not remain an independent predictor after adjusting for neither CHADS2 nor CHARGE-AF risk factors. However, hypertension modified the relationship between GLS and AF (p for interaction = 0.010), such that GLS only predicted AF in subjects without hypertension. In participants without hypertension, GLS remained an independent predictor of AF after adjusting for CHADS2 and CHARGE-AF (HR = 1.11 (1.03-1.20) and HR = 1.09 (1.01-1.19), respectively). In these participants, an abnormal GLS was associated with a more than twofold increased risk of AF (HR = 2.16 (1.26-3.72). The incidence rate was 3.17 and 6.81 per 1000 person-years for normal vs. abnormal GLS, respectively.
Conclusion
Global longitudinal strain predicts AF in individuals without hypertension from the general population, independently of common risk scores.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 17 Aug 2021; epub ahead of print
Olsen FJ, Biering-Sørensen SR, Reimer Jensen AM, Schnohr P, ... Møgelvang R, Biering-Sørensen T
Clin Res Cardiol: 17 Aug 2021; epub ahead of print | PMID: 34406455
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Impact:
Abstract

Short- and long-term outcomes after heart transplantation in cardiac sarcoidosis and giant-cell myocarditis: a systematic review and meta-analysis.

Bobbio E, Björkenstam M, Nwaru BI, Giallauria F, ... Karason K, Bollano E
Heart transplantation (HTx) is a valid therapeutic option for end-stage heart failure secondary to cardiac sarcoidosis (CS) or giant-cell myocarditis (GCM). However, post-HTx outcomes in patients with inflammatory cardiomyopathy (ICM) have been poorly investigated. We searched PubMed, Scopus, Science Citation Index, EMBASE, and Google Scholar, screened the gray literature, and contacted experts in the field. We included studies comparing post-HTx survival, acute cellular rejection, and disease recurrence in patients with and without ICM. Data were synthesized by a random-effects meta-analysis. We screened 11,933 articles, of which 14 were considered eligible. In a pooled analysis, post-HTx survival was higher in CS than non-CS patients after 1 year (risk ratio [RR] 0.88, 95% confidence interval [CI] 0.60-1.17; I2 = 0%) and 5 years (RR 0.72, 95% CI 0.52-0.91; I2 = 0%), but statistically significant only after 5 years. During the first-year post-HTx, the risk of acute cellular rejection was similar for patients with and without CS, but after 5 years, it was lower in those with CS (RR 0.38, 95% CI 0.03-0.72; I2 = 0%). No difference in post-HTx survival was observed between patients with and without GCM after 1 year (RR 1.16, 95% CI 0.05-2.28; I2 = 0%) or 5 years (RR 0.98, 95% CI 0.42-1.54; I2 = 0%). During post-HTx follow-up, recurrence of CS and GCM occurred in 5% and 8% of patients, respectively. Post-HTx outcomes in patients with CS and GCM are comparable with cardiac recipients with other heart failure etiologies. Patients with ICM should not be disqualified from HTx.

© 2021. The Author(s).

Clin Res Cardiol: 16 Aug 2021; epub ahead of print
Bobbio E, Björkenstam M, Nwaru BI, Giallauria F, ... Karason K, Bollano E
Clin Res Cardiol: 16 Aug 2021; epub ahead of print | PMID: 34402927
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Impact:
Abstract

Transcatheter aortic valve implantation in patients with a small aortic annulus: performance of supra-, intra- and infra-annular transcatheter heart valves.

Voigtländer L, Kim WK, Mauri V, Goßling A, ... Sinning JM, Seiffert M
Background
A small aortic annulus is associated with increased risk of prosthesis-patient mismatch (PPM) after transcatheter aortic valve implantation (TAVI). Whether specific transcatheter heart valve (THV) designs yield superior hemodynamic performance in these small anatomies remains unclear.
Methods
Data from 8411 consecutive patients treated with TAVI from May 2012 to April 2019 at four German centers were retrospectively evaluated. A small aortic annulus was defined as multidetector computed tomography-derived annulus area < 400 mm2. TAVI was performed with a balloon-expanding intra-annular (Sapien-3, n = 288), self-expanding intra-annular (Portico, n = 110), self-expanding supra-annular (Evolut, n = 179 and Acurate-Neo, n = 428) and mechanically expanding infra-annular (Lotus, n = 64) THV according to local practice. PPM was defined as indexed effective orifice area ≤ 0.85cm2/m2.
Results
A small annulus was found in 1069 (12.7%) patients. PPM was detected in 38.3% overall with a higher prevalence after implantation of a balloon-expanding intra-annular or mechanically expanding infra-annular THV compared to self-expanding intra- and supra-annular THV. Multivariable analysis linked self-expanding THV (Evolut: Odds ratio [OR] 0.341, Acurate-Neo: OR 0.436, Portico: OR 0.291), postdilatation (OR 0.648) and age (OR 0.968) to lower rates of PPM, while aortic valve calcification was associated with an increased risk (OR 1.001). Paravalvular regurgitation > mild was more frequent after TAVI with self-expanding THV (p = 0.04).
Conclusion
In this large contemporary multicenter patient population, a substantial number of patients with a small aortic anatomy were left with PPM after TAVI. Self-expanding supra- and intra-annular THV demonstrated superior hemodynamics in these patients at risk, however at the cost of higher rates of residual paravalvular regurgitation.

© 2021. The Author(s).

Clin Res Cardiol: 12 Aug 2021; epub ahead of print
Voigtländer L, Kim WK, Mauri V, Goßling A, ... Sinning JM, Seiffert M
Clin Res Cardiol: 12 Aug 2021; epub ahead of print | PMID: 34387736
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Impact:
Abstract

Significance of myeloperoxidase plasma levels as a predictor for cardiac resynchronization therapy response.

Sultan A, Wörmann J, Lüker J, V D Bruck J-, ... Baldus S, Steven D
Objectives
This study aimed to determine if changes in myeloperoxidase (MPO) levels correlate with response to cardiac resynchronization therapy (CRT) and the potential role of MPO as a predictor of response to CRT.
Background
CRT is a well-established treatment option in chronic heart failure (CHF) with 50-80% of patients benefiting. Inflammation and oxidative stress play a key role in CHF pathophysiology. Previous studies have demonstrated increased levels of MPO in CHF patients, but the correlation with CRT response remains incompletely understood.
Methods
Fifty-three patients underwent CRT implantation. During follow-up, patients were divided into two groups, responders and non-responders to CRT, based on improved physical capacity and NYHA classification. Levels of MPO and NT-pro-brain-natriuretic-peptide (NT-proBNP) were determined prior to implantation, 30 and 90 days after. Physical capacity, including a 6-min walking-test, NYHA class, and LVEF were evaluated at baseline and during follow-up.
Results
Thirty-four patients (64%) responded to CRT, showing improved physical capacity and LVEF. All responders revealed a significant decrease of MPO levels (503.8 ng/ml vs. 188.4 ng/ml; p < 0.001). Non-responding patients did not show any significant changes in clinical parameters or MPO levels (119.6 ng/ml vs. 134.3 ng/ml; p = 0.672) during follow-up. At baseline, physical capacity and NYHA class, as well as MPO levels differed significantly between both groups (p < 0.001). A ROC analysis identified an MPO cut-off value for response to CRT of 242 ng/ml with a sensitivity of 93.5% and specificity of 71.4%. There was a strong correlation between MPO and improvement of LVEF (Spearman\'s rho: - 0.453; p = 0.005) and physical capacity (Spearman\'s rho: - 0.335; p = 0.042).
Conclusions
Response to CRT and course of MPO levels correlate significantly. MPO levels differ between responders and non-responders prior to CRT, which may indicate an additional value of MPO as a predictor for CRT response. Further randomized studies are required to confirm our data in larger patient cohorts.

© 2020. The Author(s).

Clin Res Cardiol: 30 Jul 2021; 110:1173-1180
Sultan A, Wörmann J, Lüker J, V D Bruck J-, ... Baldus S, Steven D
Clin Res Cardiol: 30 Jul 2021; 110:1173-1180 | PMID: 32564144
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Impact:
Abstract

Association between right-sided cardiac function and ultrasound-based pulmonary congestion on acutely decompensated heart failure: findings from a pooled analysis of four cohort studies.

Kobayashi M, Gargani L, Palazzuoli A, Ambrosio G, ... Coiro S, Girerd N
Background
Right ventricular (RV) dysfunction and RV-pulmonary artery (PA) uncoupling are associated with the development of pulmonary congestion during exercise. However, there is limited information regarding the association between these right-sided cardiac parameters and pulmonary congestion in acutely decompensated heart failure (HF).
Methods
We performed an individual patient meta-analysis from four cohort studies of hospitalized patients with HF who had available lung ultrasound (B-lines) data on admission and/or at discharge. RV function was assessed by tricuspid annular plane systolic excursion (TAPSE), RV-PA coupling was defined as the ratio of TAPSE to PA systolic pressure (PASP).
Results
Admission and discharge cohort included 319 patients (75.8 ± 10.1 years, 46% women) and 221 patients (77.9 ± 9.0 years, 47% women), respectively. Overall, higher TAPSE was associated with higher ejection fraction, lower PASP, b-type natriuretic peptide and B-line counts. By multivariable analysis, worse RV function or RV-PA coupling was associated with higher B-line counts on admission and at discharge, and with a less reduction in B-line counts from admission to discharge. Higher B-line counts at discharge were associated with a higher risk of the composite of all-cause mortality and/or HF re-hospitalization [adjusted-HR 1.13 (1.09-1.16), p < 0.001]. Furthermore, the absolute risk increase related to high B-line counts at discharge was higher in patients with lower TAPSE.
Conclusions
In patients with acutely decompensated HF, impaired RV function and RV-PA coupling were associated with severe pulmonary congestion on admission, and less resolution of pulmonary congestion during hospital stay. Worse prognosis related to residual pulmonary congestion was enhanced in patients with RV dysfunction. TAPSE, tricuspid annular plane systolic excursion; PASP, pulmonary artery systolic pressure.

© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 30 Jul 2021; 110:1181-1192
Kobayashi M, Gargani L, Palazzuoli A, Ambrosio G, ... Coiro S, Girerd N
Clin Res Cardiol: 30 Jul 2021; 110:1181-1192 | PMID: 32770373
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Impact:
Abstract

Six-minute walk test: prognostic value and effects of nebivolol versus placebo in elderly patients with heart failure from the SENIORS trial.

Shibata MC, Curl-Roper J, Van Veldhuisen DJ, Roughton M, Coats AJS, Flather M
Background
There is limited information about the 6-min walk test (6MWT) in elderly patients with heart failure. We evaluated 6MWT and the effect of nebivolol on 6MWT from the SENIORS trial.
Methods and results
The SENIORS trial evaluated nebivolol versus placebo on death and hospitalisation in patients aged ≥ 70 years with heart failure. A total of 1982 patients undertook a 6MWT at baseline and 1716 patients at 6 months. Patients were divided into tertiles (≤ 200 m, 201 to ≤ 300 m and > 300 m) and to change in distance walked between baseline and 6 months (< 0 m, 0 to < 30 m and ≥ 30 m). The primary outcome was all-cause mortality and cardiovascular hospital admission. Secondary endpoint was all-cause mortality. Baseline walk distance of ≤ 200 m incurred a greater risk of the primary and secondary outcomes (HR 1.41, CI 95% 1.17-1.69, p < 0.001) and (HR 1.37, CI 95% 1.05-1.78, p = 0.019). A decline in walk distance over 6 months was associated with increased risk of clinical events. Nebivolol had no influence on change in walk distance over 6 months.
Conclusions
The 6MWT has prognostic utility in elderly patients. Those who walked less than 200 m were at highest risk. Nebivolol had no effect on 6MWT.

© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 30 Jul 2021; 110:1193-1201
Shibata MC, Curl-Roper J, Van Veldhuisen DJ, Roughton M, Coats AJS, Flather M
Clin Res Cardiol: 30 Jul 2021; 110:1193-1201 | PMID: 33136223
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Impact:
Abstract

Intensification of pharmacological decongestion but not the actual daily loop diuretic dose predicts worse chronic heart failure outcome: insights from TIME-CHF.

Simonavičius J, Maeder MT, Eurlings CGMJ, Aizpurua AB, ... Kaufmann BA, Brunner-La Rocca HP
Background
Both loop diuretics (LDs) and congestion have been related to worse heart failure (HF) outcome. The relationship between the cause and effect is unknown. The aim of this study was to investigate the interaction between congestion, diuretic use and HF outcome.
Methods
Six hundred and twenty-two chronic HF patients from TIME-CHF were studied. Congestion was measured by means of a clinical congestion index (CCI). Loop diuretic dose was considered at baseline and month 6. Treatment intensification was defined as the increase in LD dose over 6 months or loop diuretic and thiazide or thiazide-like diuretic co-administration. The end-points were survival and HF hospitalisation-free survival.
Results
High-LD dose at baseline and month 6 (≥ 80 mg of furosemide per day) was not identified as an independent predictor of outcome. CCI at baseline remained independently associated with impaired survival [hazard ratio (HR) 1.34, (95% confidence interval) (95% CI) (1.20-1.50), p < 0.001] and HF hospitalisation-free survival [HR 1.09, 95% CI (1.02-1.17), p = 0.015]. CCI at month 6 was independently associated with HF hospitalisation-free survival [HR 1.24, 95% CI (1.11-1.38), p < 0.001]. Treatment intensification was independently associated with survival [HR 1.75, 95% CI (1.19-1.38), p = 0.004] and HF hospitalisation-free survival [HR 1.69, 95% CI (1.22-2.35), p = 0.002]. Patients undergoing treatment intensification resulting in decongestion had better outcome than patients with persistent (worsening) congestion despite LD dose up-titration (p < 0.001).
Conclusion
Intensification of pharmacological decongestion but not the actual LD dose was related to poor outcome in chronic HF. If treatment intensification translated into clinical decongestion, outcome was better than in case of persistent or worsening congestion.

© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 30 Jul 2021; 110:1221-1233
Simonavičius J, Maeder MT, Eurlings CGMJ, Aizpurua AB, ... Kaufmann BA, Brunner-La Rocca HP
Clin Res Cardiol: 30 Jul 2021; 110:1221-1233 | PMID: 33216179
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Impact:
Abstract

Developing and validating models to predict sudden death and pump failure death in patients with heart failure and preserved ejection fraction.

Shen L, Jhund PS, Anand IS, Carson PE, ... Zile MR, McMurray JJV
Background
Sudden death (SD) and pump failure death (PFD) are leading modes of death in heart failure and preserved ejection fraction (HFpEF). Risk stratification for mode-specific death may aid in patient enrichment for new device trials in HFpEF.
Methods
Models were derived in 4116 patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-Preserve), using competing risks regression analysis. A series of models were built in a stepwise manner, and were validated in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved and Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trials.
Results
The clinical model for SD included older age, men, lower LVEF, higher heart rate, history of diabetes or myocardial infarction, and HF hospitalization within previous 6 months, all of which were associated with a higher SD risk. The clinical model predicting PFD included older age, men, lower LVEF or diastolic blood pressure, higher heart rate, and history of diabetes or atrial fibrillation, all for a higher PFD risk, and dyslipidaemia for a lower risk of PFD. In each model, the observed and predicted incidences were similar in each risk subgroup, suggesting good calibration. Model discrimination was good for SD and excellent for PFD with Harrell\'s C of 0.71 (95% CI 0.68-0.75) and 0.78 (95% CI 0.75-0.82), respectively. Both models were robust in external validation. Adding ECG and biochemical parameters, model performance improved little in the derivation cohort but decreased in validation. Including NT-proBNP substantially increased discrimination of the SD model, and simplified the PFD model with marginal increase in discrimination.
Conclusions
The clinical models can predict risks for SD and PFD separately with good discrimination and calibration in HFpEF and are robust in external validation. Adding NT-proBNP further improved model performance. These models may help to identify high-risk individuals for device intervention in future trials.
Clinical trial registration
I-Preserve: ClinicalTrials.gov NCT00095238; TOPCAT: ClinicalTrials.gov NCT00094302; CHARM-Preserved: ClinicalTrials.gov NCT00634712.

© 2020. The Author(s).

Clin Res Cardiol: 30 Jul 2021; 110:1234-1248
Shen L, Jhund PS, Anand IS, Carson PE, ... Zile MR, McMurray JJV
Clin Res Cardiol: 30 Jul 2021; 110:1234-1248 | PMID: 33301080
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Impact:
Abstract

Effect of frailty on treatment, hospitalisation and death in patients with chronic heart failure.

Sze S, Pellicori P, Zhang J, Weston J, Squire IB, Clark AL
Background
Frailty is common in patients with chronic heart failure (CHF) and is associated with poor outcomes. The natural history of frail patients with CHF is unknown.
Methods
Frailty was assessed using the clinical frailty scale (CFS) in 467 consecutive patients with CHF (67% male, median age 76 years, median NT-proBNP 1156 ng/L) attending a routine follow-up visit. Those with CFS > 4 were classified as frail. We investigated the relation between frailty and treatments, hospitalisation and death in patients with CHF.
Results
206 patients (44%) were frail. Of 291 patients with HF with reduced ejection fraction (HeFREF), those who were frail (N = 117; 40%) were less likely to receive optimal treatment, with many not receiving a renin-angiotensin-aldosterone system inhibitor (frail: 25% vs. non-frail: 4%), a beta-blocker (16% vs. 8%) or a mineralocorticoid receptor antagonist (50% vs 41%). By 1 year, there were 56 deaths and 322 hospitalisations, of which 25 (45%) and 198 (61%), respectively, were due to non-cardiovascular (non-CV) causes. Most deaths (N = 46, 82%) and hospitalisations (N = 215, 67%) occurred in frail patients. Amongst frail patients, 43% of deaths and 64% of hospitalisations were for non-CV causes; 58% of cardiovascular (CV) deaths were due to advancing HF. Among non-frail patients, 50% of deaths and 57% of hospitalisations were for non-CV causes; all CV deaths were due to advancing HF.
Conclusion
Frailty in patients with HeFREF is associated with sub-optimal medical treatment. Frail patients are more likely to die or be admitted to hospital, but whether frail or not, many events are non-CV.

© 2021. The Author(s).

Clin Res Cardiol: 30 Jul 2021; 110:1249-1258
Sze S, Pellicori P, Zhang J, Weston J, Squire IB, Clark AL
Clin Res Cardiol: 30 Jul 2021; 110:1249-1258 | PMID: 33399955
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Impact:
Abstract

Energy intake during hospital stay predicts all-cause mortality after discharge independently of nutritional status in elderly heart failure patients.

Katano S, Yano T, Kouzu H, Ohori K, ... Katayose M, Miura T
Objective
Malnutrition is associated with an increased risk of mortality in heart failure (HF) patients. Here, we examined the hypothesis that assessment of energy intake in addition to nutritional status improves the stratification of mortality risk in elderly HF patients.
Methods
We retrospectively examined 419 HF patients aged ≥ 65 years (median 78 years, 49% female). Nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF), and daily energy intake was calculated from intake during 3 consecutive days before discharge.
Results
During a median 1.52-year period (IQR 0.96-2.94 years), 110 patients (26%) died. Kaplan-Meier survival curves showed that patients with low tertile of daily energy intake had a higher mortality rate than did patients with high or middle tertile of daily energy intake. In multivariate Cox regression analyses, low daily energy intake was independently associated with higher mortality after adjustment for the model including age, sex, BNP, Charlson Comorbidity Index, history of HF hospitalization, and cachexia in addition to MNA-SF. Inclusion of both MNA-SF and energy intake into the adjustment model improved the accuracy of prediction of the mortality after discharge (continuous net reclassification improvement, 0.355, p = 0.003; integrated discrimination improvement, 0.029, p = 0.003). Results of a fully adjusted dose-dependent association analysis showed that risk of all-cause mortality was lowest among HF patients who consumed 31.5 kcal/kg/day of energy.
Conclusions
Energy intake during hospital stay is an independent predictor of the mortality in elderly HF patients, and its assessment together with established predictors improves the mortality risk stratification.

© 2021. The Author(s).

Clin Res Cardiol: 30 Jul 2021; 110:1202-1220
Katano S, Yano T, Kouzu H, Ohori K, ... Katayose M, Miura T
Clin Res Cardiol: 30 Jul 2021; 110:1202-1220 | PMID: 33399954
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Impact:
Abstract

Estimated plasma volume status in heart failure: clinical implications and future directions.

Kobayashi M, Girerd N, Duarte K, Chouihed T, ... Zannad F, Rossignol P
Congestion is one of the main predictors of poor outcome in patients with heart failure (HF). Assessing and monitoring congestion is essential for optimizing HF therapy. Among the various available methods, serial measurements of estimated plasma volume (ePVS) using routine blood count and/or body weight (e.g., the Strauss, Duarte, Hakim formulas) may be useful in HF management. Further prospective study is warranted to determine whether ePVS can help optimize decongestion therapy (loop diuretics, mineralocorticoid receptor antagonists, SGLT2i) in various HF settings. This narrative review summarizes the recent evidence supporting the association of ePVS with clinical congestion and outcome(s) and discusses future directions for monitoring ePVS in HF.

© 2021. Springer-Verlag GmbH, DE part of Springer Nature.

Clin Res Cardiol: 30 Jul 2021; 110:1159-1172
Kobayashi M, Girerd N, Duarte K, Chouihed T, ... Zannad F, Rossignol P
Clin Res Cardiol: 30 Jul 2021; 110:1159-1172 | PMID: 33409701
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Impact:
Abstract

Prognostic value of NT-proBNP for myocardial recovery in peripartum cardiomyopathy (PPCM).

Hoevelmann J, Muller E, Azibani F, Kraus S, ... Sliwa K, Viljoen CA
Introduction
Peripartum cardiomyopathy (PPCM) is an important cause of pregnancy-associated heart failure worldwide. Although a significant number of women recover their left ventricular (LV) function within 12 months, some remain with persistently reduced systolic function.
Methods
Knowledge gaps exist on predictors of myocardial recovery in PPCM. N-terminal pro-brain natriuretic peptide (NT-proBNP) is the only clinically established biomarker with diagnostic value in PPCM. We aimed to establish whether NT-proBNP could serve as a predictor of LV recovery in PPCM, as measured by LV end-diastolic volume (LVEDD) and LV ejection fraction (LVEF).
Results
This study of 35 women with PPCM (mean age 30.0 ± 5.9 years) had a median NT-proBNP of 834.7 pg/ml (IQR 571.2-1840.5) at baseline. Within the first year of follow-up, 51.4% of the cohort recovered their LV dimensions (LVEDD < 55 mm) and systolic function (LVEF > 50%). Women without LV recovery presented with higher NT-proBNP at baseline. Multivariable regression analyses demonstrated that NT-proBNP of ≥ 900 pg/ml at the time of diagnosis was predictive of failure to recover LVEDD (OR 0.22, 95% CI 0.05-0.95, P = 0.043) or LVEF (OR 0.20 [95% CI 0.04-0.89], p = 0.035) at follow-up.
Conclusions
We have demonstrated that NT-proBNP has a prognostic value in predicting LV recovery of patients with PPCM. Patients with NT-proBNP of ≥ 900 pg/ml were less likely to show any improvement in LVEF or LVEDD. Our findings have implications for clinical practice as patients with higher NT-proBNP might require more aggressive therapy and more intensive follow-up. Point-of-care NT-proBNP for diagnosis and risk stratification warrants further investigation.

© 2021. The Author(s).

Clin Res Cardiol: 30 Jul 2021; 110:1259-1269
Hoevelmann J, Muller E, Azibani F, Kraus S, ... Sliwa K, Viljoen CA
Clin Res Cardiol: 30 Jul 2021; 110:1259-1269 | PMID: 33555408
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Abstract

Re-appraisal of the obesity paradox in heart failure: a meta-analysis of individual data.

Marcks N, Aimo A, Januzzi JL, Vergaro G, ... Emdin M, Brunner-La Rocca HP
Background
Higher body mass index (BMI) is associated with better outcome compared with normal weight in patients with HF and other chronic diseases. It remains uncertain whether the apparent protective role of obesity relates to the absence of comorbidities. Therefore, we investigated the effect of BMI on outcome in younger patients without co-morbidities as compared to older patients with co-morbidities in a large heart failure (HF) population.
Methods
In an individual patient data analysis from pooled cohorts, 5,819 patients with chronic HF and data available on BMI, co-morbidities and outcome were analysed. Patients were divided into four groups based on BMI (i.e. ≤ 18.5 kg/m2, 18.5-25.0 kg/m2; 25.0-30.0 kg/m2; 30.0 kg/m2). Primary endpoints included all-cause mortality and HF hospitalization-free survival.
Results
Mean age was 65 ± 12 years, with a majority of males (78%), ischaemic HF and HF with reduced ejection fraction. Frequency of all-cause mortality or HF hospitalization was significantly worse in the lowest two BMI groups as compared to the other two groups; however, this effect was only seen in patients older than 75 years or having at least one relevant co-morbidity, and not in younger patients with HF only. After including medications and N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin concentrations into the model, the prognostic impact of BMI was largely absent even in the elderly group with co-morbidity.
Conclusions
The present study suggests that obesity is a marker of less advanced disease, but does not have an independent protective effect in patients with chronic HF. Categories of BMI are only predictive of poor outcome in patients aged > 75 years or with at least one co-morbidity (bottom), but not in those aged < 75 years without co-morbidities (top). The prognostic effect largely disappears in multivariable analyses even for the former group. These findings question the protective effect of obesity in chronic heart failure (HF).

© 2021. The Author(s).

Clin Res Cardiol: 30 Jul 2021; 110:1280-1291
Marcks N, Aimo A, Januzzi JL, Vergaro G, ... Emdin M, Brunner-La Rocca HP
Clin Res Cardiol: 30 Jul 2021; 110:1280-1291 | PMID: 33704552
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Abstract

Iron deficiency and short-term adverse events in patients with decompensated heart failure.

Palau P, Llàcer P, Domínguez E, Tormo JP, ... Bayés-Genís A, Núñez J
Background
For patients with heart failure (HF), iron deficiency (ID) is a common therapeutic target. However, little is known about the utility of transferrin saturation (TSAT) or serum ferritin for risk stratification in decompensated HF (DHF) or the European Society of Cardiology\'s (ESC) current definition of ID (ferritin < 100 μg/L or TSAT < 20% if ferritin is 100-299 μg/L). We evaluated the association between these potential markers of ID and the risk of 30-day readmission for HF or death in patients with DHF.
Methods
We retrospectively included 1701 patients from a multicenter registry of DHF. Serum ferritin and TSAT were evaluated 24-72 h after hospital admission, and multivariable Cox regression was used to assess their association with the composite endpoint.
Results
Participants\' median (quartiles) age was 76 (68-82) years, 43.8% were women, and 51.7% had a left ventricular ejection fraction > 50%. Medians for NT-proBNP, TSAT, and ferritin were 4067 pg/mL (1900-8764), 14.1% (9.0-20.3), and 103 ug/L (54-202), respectively. According to the current ESC definition, 1,246 (73.3%) patients had ID. By day 30, there were 177 (10.4%) events (95 deaths and 85 HF readmission). After multivariable adjustment, lower TSAT was associated with outcome (p = 0.009) but serum ferritin was not (HR 1.00; 95% confidence interval 0.99-1.00, p = 0.347).
Conclusions
Lower TSAT, but not ferritin, was associated with a higher risk of short-term events in patients with DHF. Further research is needed to confirm these findings and the utility of serum ferritin as a marker of ID in DHF.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 30 Jul 2021; 110:1292-1298
Palau P, Llàcer P, Domínguez E, Tormo JP, ... Bayés-Genís A, Núñez J
Clin Res Cardiol: 30 Jul 2021; 110:1292-1298 | PMID: 33721056
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Abstract

Heart failure and atrial fibrillation in patients with an interatrial shunt.

Park JJ, Cho GY, Choi W, Hwang IC, ... Han MK, Bae HJ
Objective
Congenital interatrial shunt can unload the left atrium (LA) and may lower the risk of new-onset heart failure (HF) or atrial fibrillation (AF). We evaluated the risk of new-onset HF or AF in patients with and without interatrial shunt.
Methods
We enrolled 2660 consecutive patients with acute stroke or transient ischemic attack (TIA) who underwent transesophageal echocardiography at Seoul National University Bundang Hospital from January 1, 2006 to December 31, 2018. The primary outcomes were 10-year new-onset HF, new-onset AF, and new-onset HF or AF composite.
Results
Overall, 466 (17.5%) patients with an interatrial shunt had smaller E velocity (0.66 ± 0.21 vs. 0.69 ± 0.22 m/s, P = 0.037) and smaller E/e\' (9.1 ± 4.0 vs. 10.0 ± 5.0, P = 0.001) than 2194 (82.5%) patients without an interatrial shunt. The 10-year incidence of AF, HF, and AF or HF composite was lower in patients with an interatrial shunt (10-year AF, 11.2 vs. 17.8%, P < 0.001; 10-year HF, 6.2 vs. 10.4%, P = 0.005; 10-year AF or HF composite, 16.5 vs. 23.4%, P = 0.001). In multivariable analysis, the presence of an interatrial shunt was associated with a 38% (HR 0.62, 95% CI 0.40-0.96), 40% (HR 0.60; 95% CI 0.39-0.93), and 26% (HR 0.74; 95% CI 0.57-0.96) reduced risk for new-onset HF, AF, and new-onset HF or AF composite, respectively.
Conclusion
In patients with interatrial shunt, the risk of AF and HF was lower. Interatrial shunt may be beneficial, and the closure of an interatrial shunt should be performed only in carefully selected patients. An interatrial shunt can unload the left atrium. In patients with stroke or TIA, the presence of an interatrial shunt was associated with a reduced risk for new-onset HF and AF. AF atrial fibrillation, HF heart failure, HR hazard ratio, LA left atrium.

© 2021. Springer-Verlag GmbH, DE part of Springer Nature.

Clin Res Cardiol: 30 Jul 2021; 110:1270-1279
Park JJ, Cho GY, Choi W, Hwang IC, ... Han MK, Bae HJ
Clin Res Cardiol: 30 Jul 2021; 110:1270-1279 | PMID: 33649885
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Abstract

Intravenous iron for heart failure with evidence of iron deficiency: a meta-analysis of randomised trials.

Graham FJ, Pellicori P, Ford I, Petrie MC, Kalra PR, Cleland JGF
Background
The recent AFFIRM-AHF trial assessing the effect of intravenous (IV) iron on outcomes in patients hospitalised with worsening heart failure who had iron deficiency (ID) narrowly missed its primary efficacy endpoint of recurrent hospitalisations for heart failure (HHF) or cardiovascular (CV) death. We conducted a meta-analysis to determine whether these results were consistent with previous trials.
Methods
We searched for randomised trials of patients with heart failure investigating the effect of IV iron vs placebo/control groups that reported HHF and CV mortality from 1st January 2000 to 5th December 2020. Seven trials were identified and included in this analysis. A fixed effect model was applied to assess the effects of IV iron on the composite of first HHF or CV mortality and individual components of these.
Results
Altogether, 2,166 patients were included (n = 1168 assigned to IV iron; n = 998 assigned to control). IV iron reduced the composite of HHF or CV mortality substantially [OR 0.73; (95% confidence interval 0.59-0.90); p = 0.003]. Outcomes were consistent for the pooled trials prior to AFFIRM-AHF. Whereas first HHF were reduced substantially [OR 0.67; (0.54-0.85); p = 0.0007], the effect on CV mortality was uncertain but appeared smaller [OR 0.89; (0.66-1.21); p = 0.47].
Conclusion
Administration of IV iron to patients with heart failure and ID reduces the risk of the composite outcome of first heart failure hospitalisation or cardiovascular mortality, but this outcome may be driven predominantly by an effect on HHF. At least three more substantial trials of intravenous iron are underway.

© 2021. The Author(s).

Clin Res Cardiol: 30 Jul 2021; 110:1299-1307
Graham FJ, Pellicori P, Ford I, Petrie MC, Kalra PR, Cleland JGF
Clin Res Cardiol: 30 Jul 2021; 110:1299-1307 | PMID: 33755777
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Abstract

Diuretic therapy as prognostic enrichment factor for clinical trials in patients with heart failure with reduced ejection fraction.

Coiro S, Girerd N, McMurray JJV, Pitt B, ... Rossignol P, Zannad F
Background
Loop diuretics are the mainstay of congestion treatment in patients with heart failure (HF). We assessed the association between baseline loop diuretic use and outcome. We also compared the increment in risk related to diuretic dose with conventional prognostic enrichment criteria used in the EMPHASIS-HF trial, which included patients with systolic HF and mild symptoms, such as prior hospitalization and elevated natriuretic peptides.
Methods
Individual analyses were performed according to baseline loop diuretic usage (furosemide-equivalent dose > 40 mg, 1-40 mg, and no furosemide), and according to enrichment criteria adopted in the trial [i.e. recent hospitalization (< 30 days or 30 to 180 days prior to randomization) due to HF or other cardiovascular cause, or elevated natriuretic peptides]. The primary endpoint was a composite of cardiovascular death or HF hospitalization.
Results
Loop diuretic usage at baseline (HR for > 40 mg furosemide-equivalent dose = 3.16, 95% CI 2.43-4.11; HR for 1-40 mg = 2.06, 95% CI 1.60-2.65) was significantly associated with a higher risk for the primary endpoint in a stepwise manner when compared to no baseline loop diuretic usage. In contrast, the differences in outcome rates were more modest when using history of hospitalization and/or BNP: all HR ranged from 1 (reference, non-HF related CV hospitalization > 30 days) to 2.04 (HF hospitalization < 30 days). The effect of eplerenone on the primary endpoint was consistent across subgroups in both analyses (P for interaction ≥ 0.2 for all).
Conclusions
Loop diuretic usage (especially at doses > 40 mg) identified patients at higher risk than history of HF hospitalization and/or high BNP blood concentrations.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 30 Jul 2021; 110:1308-1320
Coiro S, Girerd N, McMurray JJV, Pitt B, ... Rossignol P, Zannad F
Clin Res Cardiol: 30 Jul 2021; 110:1308-1320 | PMID: 33956209
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Abstract

Timely and individualized heart failure management: need for implementation into the new guidelines.

Abdin A, Bauersachs J, Frey N, Kindermann I, ... Wintrich J, Böhm M
Due to remarkable improvements in heart failure (HF) management over the last 30 years, a significant reduction in mortality and hospitalization rates in HF patients with reduced ejection fraction (HFrEF) has been observed. Currently, the optimization of guideline-directed chronic HF therapy remains the mainstay to further improve outcomes for patients with HFrEF to reduce mortality and HF hospitalization. This includes established device therapies, such as implantable defibrillators and cardiac resynchronization therapies, which improved patients\' symptoms and prognosis. Over the last 10 years, new HF drugs have merged targeting various pathways, such as those that simultaneously suppress the renin-angiotensin-aldosterone system and the breakdown of endogenous natriuretic peptides (e.g., sacubitril/valsartan), and those that inhibit the If channel and, thus, reduce heart rate (e.g., ivabradine). Furthermore, the treatment of patient comorbidities (e.g., iron deficiency) has shown to improve functional capacity and to reduce hospitalization rates, when added to standard therapy. More recently, other potential treatment mechanisms have been explored, such as the sodium/glucose co-transporter inhibitors, the guanylate cyclase stimulators and the cardiac myosin activators. In this review, we summarize the novel developments in HFrEF pharmacological and device therapy and discuss their implementation strategies into practice to further improve outcomes.

© 2021. The Author(s).

Clin Res Cardiol: 30 Jul 2021; 110:1150-1158
Abdin A, Bauersachs J, Frey N, Kindermann I, ... Wintrich J, Böhm M
Clin Res Cardiol: 30 Jul 2021; 110:1150-1158 | PMID: 33983472
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Abstract

Development and external validation of prognostic models to predict sudden and pump-failure death in patients with HFrEF from PARADIGM-HF and ATMOSPHERE.

Shen L, Claggett BL, Jhund PS, Abraham WT, ... Solomon SD, McMurray JJV
Background
Sudden death (SD) and pump failure death (PFD) are the two leading causes of death in patients with heart failure and reduced ejection fraction (HFrEF).
Objective
Identifying patients at higher risk for mode-specific death would allow better targeting of individual patients for relevant device and other therapies.
Methods
We developed models in 7156 patients with HFrEF from the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, using Fine-Gray regressions counting other deaths as competing risks. The derived models were externally validated in the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure (ATMOSPHERE) trial.
Results
NYHA class and NT-proBNP were independent predictors for both modes of death. The SD model additionally included male sex, Asian or Black race, prior CABG or PCI, cancer history, MI history, treatment with LCZ696 vs. enalapril, QRS duration and ECG left ventricular hypertrophy. While LVEF, ischemic etiology, systolic blood pressure, HF duration, ECG bundle branch block, and serum albumin, chloride and creatinine were included in the PFD model. Model discrimination was good for SD and excellent for PFD with Harrell\'s C of 0.67 and 0.78 after correction for optimism, respectively. The observed and predicted incidences were similar in each quartile of risk scores at 3 years in each model. The performance of both models remained robust in ATMOSPHERE.
Conclusion
We developed and validated models which separately predict SD and PFD in patients with HFrEF. These models may help clinicians and patients consider therapies targeted at these modes of death.
Trial registration number
PARADIGM-HF: ClinicalTrials.gov NCT01035255, ATMOSPHERE: ClinicalTrials.gov NCT00853658.

© 2021. The Author(s).

Clin Res Cardiol: 30 Jul 2021; 110:1334-1349
Shen L, Claggett BL, Jhund PS, Abraham WT, ... Solomon SD, McMurray JJV
Clin Res Cardiol: 30 Jul 2021; 110:1334-1349 | PMID: 34101002
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Abstract

Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients.

Schramm R, Costard-Jäckle A, Rivinius R, Fischer B, ... Knabbe C, Gummert J
Aims
Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients.
Methods and results
A total of 50 transplant patients [1-3 years post heart (42), lung (7), or heart-lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness.
Conclusions
The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.

© 2021. The Author(s).

Clin Res Cardiol: 30 Jul 2021; 110:1142-1149
Schramm R, Costard-Jäckle A, Rivinius R, Fischer B, ... Knabbe C, Gummert J
Clin Res Cardiol: 30 Jul 2021; 110:1142-1149 | PMID: 34241676
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Abstract

Predicting survival in heart failure: a risk score based on machine-learning and change point algorithm.

Kim W, Park JJ, Lee HY, Kim KH, ... Kook W, Choi DJ
Objective
Machine learning (ML) algorithm can improve risk prediction because ML can select features and segment continuous variables effectively unbiased. We generated a risk score model for mortality with ML algorithms in East-Asian patients with heart failure (HF).
Methods
From the Korean Acute Heart Failure (KorAHF) registry, we used the data of 3683 patients with 27 continuous and 44 categorical variables. Grouped Lasso algorithm was used for the feature selection, and a novel continuous variable segmentation algorithm which is based on change-point analysis was developed for effectively segmenting the ranges of the continuous variables. Then, a risk score was assigned to each feature reflecting nonlinear relationship between features and survival times, and an integer score of maximum 100 was calculated for each patient.
Results
During 3-year follow-up time, 32.8% patients died. Using grouped Lasso, we identified 15 highly significant independent clinical features. The calculated risk score of each patient ranged between 1 and 71 points with a median of 36 (interquartile range: 27-45). The 3-year survival differed according to the quintiles of the risk score, being 80% and 17% in the 1st and 5th quintile, respectively. In addition, ML risk score had higher AUCs than MAGGIC-HF score to predict 1-year mortality (0.751 vs. 0.711, P < 0.001).
Conclusions
In East-Asian patients with HF, a novel risk score model based on ML and the new continuous variable segmentation algorithm performs better for mortality prediction than conventional prediction models.
Clinical trial registration
Unique identifier: INCT01389843 https://clinicaltrials.gov/ct2/show/NCT01389843 .

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 30 Jul 2021; 110:1321-1333
Kim W, Park JJ, Lee HY, Kim KH, ... Kook W, Choi DJ
Clin Res Cardiol: 30 Jul 2021; 110:1321-1333 | PMID: 34259921
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Abstract

Gender-specific differences in COPD symptoms and their impact for the diagnosis of cardiac comorbidities.

Trudzinski FC, Kellerer C, Jörres RA, Alter P, ... Bals R, Kahnert K
Background
In chronic obstructive pulmonary disease (COPD), gender-specific differences in the prevalence of symptoms and comorbidity are known.
Research question
We studied whether the relationship between these characteristics depended on gender and carried diagnostic information regarding cardiac comorbidities.
Study design and methods
The analysis was based on 2046 patients (GOLD grades 1-4, 795 women; 38.8%) from the COSYCONET COPD cohort. Assessments comprised the determination of clinical history, comorbidities, lung function, COPD Assessment Test (CAT) and modified Medical Research Council dyspnea scale (mMRC). Using multivariate regression analyses, gender-specific differences in the relationship between symptoms, single CAT items, comorbidities and functional alterations were determined. To reveal the relationship to cardiac disease (myocardial infarction, or heart failure, or coronary artery disease) logistic regression analysis was performed separately in men and women.
Results
Most functional parameters and comorbidities, as well as CAT items 1 (cough), 2 (phlegm) and 5 (activities), differed significantly (p < 0.05) between men and women. Beyond this, the relationship between functional parameters and comorbidities versus symptoms showed gender-specific differences, especially for single CAT items. In men, item 8 (energy), mMRC, smoking status, BMI, age and spirometric lung function was related to cardiac disease, while in women primarily age was predictive.
Interpretation
Gender-specific differences in COPD not only comprised differences in symptoms, comorbidities and functional alterations, but also differences in their mutual relationships. This was reflected in different determinants linked to cardiac disease, thereby indicating that simple diagnostic information might be used differently in men and women.
Clinical trial registration
The cohort study is registered on ClinicalTrials.gov with identifier NCT01245933 and on GermanCTR.de with identifier DRKS00000284, date of registration November 23, 2010. Further information can be obtained on the website http://www.asconet.net .

© 2021. The Author(s).

Clin Res Cardiol: 30 Jul 2021; epub ahead of print
Trudzinski FC, Kellerer C, Jörres RA, Alter P, ... Bals R, Kahnert K
Clin Res Cardiol: 30 Jul 2021; epub ahead of print | PMID: 34331588
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Impact:

This program is still in alpha version.