Improving Clostridioides difficile Infectious Disease Treatment Response via Adherence to Clinical Practice Guidelines.

Clostridioides difficile (C. difficile) is a predominant nosocomial infection, and guidelines for improving diagnosis and treatment were published in 2017. We conducted a single-center, retrospective 10-year cohort study of patients with primary C. difficile infectious disease (CDID) at the largest referral Lithuanian university hospital, aiming to evaluate the clinical and laboratory characteristics of CDID and their association with the outcomes, as well as implication of concordance with current Clinical Practice Guidelines. The study enrolled a total of 370 patients. Cases with non-concordant CDID treatment resulted in more CDID-related Intensive Care Unit (ICU) admissions (7.5 vs. 1.8%) and higher CDID-related mortality (13.0 vs. 1.8%) as well as 30-day all-cause mortality (61.0 vs. 36.1%) and a lower 30-day survival compared with CDID cases with concordant treatment (p < 0.05). Among cases defined by two criteria for severe CDID, only patients with non-concordant metronidazole treatment had refractory CDID (68.8 vs. 0.0%) compared with concordant vancomycin treatment. In the presence of non-concordant metronidazole treatment for severe CDID, only cases defined by two severity criteria had more CDID-related ICU admissions (18.8 vs. 0.0%) and higher CDID-related mortality (25.0 vs. 2.0%, p < 0.05) compared with cases defined by one criterion. Severe comorbidities and the continuation of concomitant antibiotics administered at CDID onset reduced (p < 0.05) the 30-day survival and increased (p = 0.053) 30-day all-cause mortality, with 57.6 vs. 10.7% and 52.0 vs. 25.0%, respectively. Conclusions: CDID treatment non-concordant with the guidelines was associated with various adverse outcomes. In CDID with leukocytes ≥ 15 × 109/L and serum creatinine level > 133 µmol/L (>1.5 mg/dL), enteral vancomycin should be used to avoid refractory response, as metronidazole use was associated with CDID-related ICU admission and CDID-related mortality. Severe comorbidities worsened the outcomes as they were associated with reduced 30-day survival. The continuation of concomitant antibiotic therapy increased 30-day all-cause mortality; thus, it needs to be reasonably justified, deescalated or stopped.

Decongestion in Acute Heart Failure-Time to Rethink and Standardize Current Clinical Practice?

Most episodes of acute heart failure (AHF) are characterized by increasing signs and symptoms of congestion, manifested by edema, pleura effusion and/or ascites. Immediately and repeatedly administered intravenous (IV) loop diuretics currently represent the mainstay of initial therapy aiming to achieve adequate diuresis/natriuresis and euvolemia. Despite these efforts, a significant proportion of patients have residual congestion at discharge, which is associated with a poor prognosis. Therefore, a standardized approach is needed. The door to diuretic time should not exceed 60 min. As a general rule, the starting IV dose is 20-40 mg furosemide equivalents in loop diuretic naïve patients or double the preexisting oral home dose to be administered via IV. Monitoring responses within the following first hours are key issues. (1) After 2 h, spot urinary sodium should be ≥50-70 mmol/L. (2) After 6 h, the urine output should be ≥100-150 mL/hour. If these target measures are not reached, the guidelines currently recommend a doubling of the original dose to a maximum of 400-600 mg furosemide per day and in patients with severely impaired kidney function up to 1000 mg per day. Continuous infusion of loop diuretics offers no benefit over intermittent boluses (DOSE trial). Emerging evidence by recent randomized trials (ADVOR, CLOROTIC) supports the concept of an early combination diuretic therapy, by adding either acetazolamide (500 mg IV once daily) or hydrochlorothiazide. Acetazolamide is particularly useful in the presence of a baseline bicarbonate level of ≥27 mmol/L and remains effective in the presence of preexisting/worsening renal dysfunction but should be used only in the first three days to prevent severe metabolic disturbances. Patients should not leave the hospital when they are still congested and/or before optimized long-term guideline-directed medical therapy has been initiated. Special attention should be paid to AHF patients during the vulnerable post-discharge period, with an early follow-up visit focusing on up-titrate treatments of recommended doses within 2 weeks (STRONG-HF).

Visualization of the SyncAV® Algorithm for CRT Optimization by Non-invasive Imaging of Cardiac Electrophysiology: NICE-CRT Trial.

(1) Background: Periodic repetitive AV interval optimization using a device-based algorithm in cardiac resynchronization therapy (CRT) devices may improve clinical outcomes. There is an unmet need to successfully transform its application into clinical routine. (2) Methods: Non-invasive imaging of cardiac electrophysiology was performed in different device programming settings of the SyncAV® algorithm in 14 heart failure patients with left bundle branch block and a PR interval ≤ 250 milliseconds to determine the shortest ventricular activation time. (3) Results: the best offset time (to be manually programmed) permitting automatic dynamic adjustment of the paced atrioventricular interval after every 256 heart beats was found to be 30 and 50 milliseconds, decreasing mean native QRS duration from 181.6 ± 23.9 milliseconds to 130.7 ± 10.0 and 130.1 ± 10.5 milliseconds, respectively (p = 0.01); this was followed by an offset of 40 milliseconds (decreasing QRS duration to 130.1 ± 12.2 milliseconds; p = 0.08). (4) Conclusions: The herein presented NICE-CRT study supports the current recommendation to program an offset of 50 milliseconds as default in patients with left bundle branch block and preserved atrioventricular conduction after implantation of a CRT device capable of SyncAV® optimization. Alternatively, offset programming of 30 milliseconds may also be applied as default programming. In patients with no or poor CRT response, additional efforts should be spent to individualize best offset programming with electrocardiographic optimization techniques.

Clinical Features and Outcomes of VAP Due to Multidrug-Resistant Klebsiella spp.: A Retrospective Study Comparing Monobacterial and Polybacterial Episodes.

VAP due to multidrug-resistant (MDR) bacteria is a frequent infection among patients in ICUs. Patient characteristics and mortality in mono- and polybacterial cases of VAP may differ. A single-centre, retrospective 3-year study was conducted in the four ICUs of a Lithuanian referral university hospital, aiming to compare both the clinical features and the 60-day ICU all-cause mortality of monobacterial and polybacterial MDR Klebsiella spp. VAP episodes. Of the 86 MDR Klebsiella spp. VAP episodes analyzed, 50 (58.1%) were polybacterial. The 60-day mortality was higher (p < 0.05) in polybacterial episodes: overall (50.0 vs. 27.8%), in the sub-group with less-severe disease (SOFA < 8) at VAP onset (45.5 vs. 15.0%), even with appropriate treatment (41.7 vs. 12.5%), and the sub-group of extended drug-resistant (XDR) Klebsiella spp. (46.4 vs. 17.6%). The ICU mortality (44.0 vs. 22.5%) was also higher in the polybacterial episodes. The monobacterial MDR Klebsiella spp. VAP was associated (p < 0.05) with prior hospitalization (61.1 vs. 40.0%), diabetes mellitus (30.6 vs. 5.8%), obesity (30.6 vs. 4.7%), prior antibiotic therapy (77.8 vs. 52.0%), prior treatment with cephalosporins (66.7 vs. 36.0%), and SOFA cardiovascular ≥ 3 (44.4 vs. 10.0%) at VAP onset. Patients with polybacterial VAP were more likely (p < 0.05) to be comatose (22.2 vs. 52.0%) and had a higher SAPS II score (median [IQR] 45.0 [35.25-51.1] vs. 50.0 [40.5-60.75]) at VAP onset. Polybacterial MDR Klebsiella spp. VAP had distinct demographic and clinical characteristics compared to monobacterial, and was associated with poorer outcomes.

A Soccer Shot with Lengthy Consequences-Case Report & Current Literature Review of Commotio Cordis.

(1) Background: Commotio cordis, caused by objects being directly delivered to the chest, may cause cardiac arrest in young athletes, even without identifiable structural damage to the sternum, ribs or heart itself. Its prevention and management often remain suboptimal, resulting in dismal outcomes. (2) Case summary: A 32-year semi-professional goalkeeper suffered from a non-penetrating blunt thoracic trauma after being struck by a high-velocity shot during a regional league soccer game. He immediately lost consciousness, collapsed, and was successfully resuscitated through early defibrillation of ventricular fibrillation. After an uneventful follow-up for approximately 6 years, recurrent episodes of ventricular tachycardia occurred, which could ultimately only be prevented by epicardial ablation. (3) Conclusion: Very late recurrences of ventricular tachyarrhythmias may occur after ventricular fibrillation due to blunt chest trauma, even in the primary absence of evident structural myocardial damage.

[Atrial fibrillation in athletes : Prevalence, diagnosis, and treatment]. / Vorhofflimmern beim Sportler : Häufigkeit, Diagnose und Therapie.

BACKGROUND: The incidence of atrial fibrillation (AF) is increased by an average of approximately 2.5-fold in recreational and elite athletes, depending on the intensity of exercise. It is, however, difficult to determine the exact duration or intensity of exercise that increases the risk of AF. The pathophysiological mechanisms of AF in athletes are a combination of pulmonary vein ectopy as a trigger, myocardial changes such as fibrosis and remodeling processes, and modulators such as changes in the autonomic nervous system. However, gastroesophageal reflux also seems to play an important role. MATERIAL AND METHODS: The classic AF diagnosis is performed by means of 12-lead or Holter ECG; arrhythmia recordings via chest belts and pulse watches are not sufficient for the differentiation of the arrhythmia. However, wearables with the capability of ECG recording can also be used for AF screening. The first AF documentation in an athlete should be followed by cessation of physical exercise and initiation of detailed cardiac diagnostics. Thereafter, evaluation of oral anticoagulation is important. Long-term antiarrhythmic therapies are usually not tolerated or desired by athletes. Thus, valuable therapeutic options are either a "pill in the pocket" therapy with antiarrhythmic drugs or catheter ablation.

Limbic Responses to Aversive Visual Stimuli during the Acute and Recovery Phase of Takotsubo Syndrome.

The role of the limbic system in the acute phase and during the recovery of takotsubo syndrome needs further clarification. In this longitudinal study, anatomical and task-based functional magnetic resonance imaging of the brain was performed during an emotional picture paradigm in 19 postmenopausal female takotsubo syndrome patients in the acute and recovery phases in comparison to sex- and aged-matched 15 healthy controls and 15 patients presenting with myocardial infarction. Statistical analyses were performed based on the general linear model where aversive and positive picture conditions were included in order to reveal group differences during encoding of aversive versus positive pictures and longitudinal changes. In the acute phase, takotsubo syndrome patients showed a lower response in regions involved in affective and cognitive emotional processes (e.g., insula, thalamus, frontal cortex, inferior frontal gyrus) while viewing aversive versus positive pictures compared to healthy controls and patients presenting with myocardial infarction. In the recovery phase, the response in these brain regions normalized in takotsubo syndrome patients to the level of healthy controls, whereas patients 8-12 weeks after myocardial infarction showed lower responses in the limbic regions (mainly in the insula, frontal regions, thalamus, and inferior frontal gyrus) compared to healthy controls and takotsubo syndrome patients. In conclusion, compared to healthy controls and patients suffering from acute myocardial infarction, limbic responses to aversive visual stimuli are attenuated during the acute phase of takotsubo syndrome, recovering within three months. Reduced functional brain responses in the recovery phase after a myocardial infarction need further investigation.

Clinical Features and Outcomes of Monobacterial and Polybacterial Episodes of Ventilator-Associated Pneumonia Due to Multidrug-Resistant Acinetobacter baumannii.

Multidrug-resistant A. baumannii (MDRAB) VAP has high morbidity and mortality, and the rates are constantly increasing globally. Mono- and polybacterial MDRAB VAP might differ, including outcomes. We conducted a single-center, retrospective (January 2014−December 2016) study in the four ICUs (12−18−24 beds each) of a reference Lithuanian university hospital, aiming to compare the clinical features and the 30-day mortality of monobacterial and polybacterial MDRAB VAP episodes. A total of 156 MDRAB VAP episodes were analyzed: 105 (67.5%) were monomicrobial. The 30-day mortality was higher (p < 0.05) in monobacterial episodes: overall (57.1 vs. 37.3%), subgroup with appropriate antibiotic therapy (50.7 vs. 23.5%), and subgroup of XDR A. baumannii (57.3 vs. 36.4%). Monobacterial MDRAB VAP was associated (p < 0.05) with Charlson comorbidity index ≥3 (67.6 vs. 47.1%), respiratory comorbidities (19.0 vs. 5.9%), obesity (27.6 vs. 9.8%), prior hospitalization (58.1 vs. 31.4%), prior antibiotic therapy (99.0 vs. 92.2%), sepsis (88.6 vs. 76.5%), septic shock (51.9 vs. 34.6%), severe hypoxemia (23.8 vs. 7.8%), higher leukocyte count on VAP onset (median [IQR] 11.6 [8.4−16.6] vs. 10.9 [7.3−13.4]), and RRT need during ICU stay (37.1 vs. 17.6%). Patients with polybacterial VAP had a higher frequency of decreased level of consciousness (p < 0.05) on ICU admission (29.4 vs. 14.3%) and on VAP onset (29.4 vs. 11.4%). We concluded that monobacterial MDRAB VAP had different demographic/clinical characteristics compared to polybacterial and carried worse outcomes. These important findings need to be validated in a larger, prospective study, and the management implications to be further investigated.

Coronary Artery Dimensions in Endurance Athletes by Computed Tomography Angiography: A Quantitative Analysis.

(1) Background: The athlete's heart may develop permanent vessel enlargement. The purpose of our study was to define normal values for coronary artery dimensions of endurance athletes by coronary computed tomography angiography (CTA). (2) Methods: Ninety-eight individuals (56.2 ± 11 years) were included into this retrospective matched case-controlled-study. Endurance athletes had regular training volumes of ≥1 h per unit, ≥3-7 times per week (either cycling, running or mountain-endurance). Athletes were matched for age and gender with sedentary controls using propensity score. Quantitative CTA analysis included coronary vessel dimensions (two diameters and area) of the LM, LAD, CX and RCA for all AHA-16-segments. (3) Results: Proximal LAD area and diameter (p = 0.019); proximal/mid CX (diameter and area; p = 0.026 and p = 0.018/p = 0.008 and p = 0.009); mid RCA diameter and area; and proximal RCA diameter were significantly larger in endurance athletes (p < 0.05). The left main area (p = 0.708) and diameter (p = 0.809) as well as the mid LAD and distal segments were not different. We present the histograms and data for normal values ±1 and ± 2 SD. (4) Conclusions: Endurance athletes have larger proximal LAD, proximal/mid CX and RCA vessel dimensions, while LM and distal segments are similar. Hence, dilated coronary arteries in endurance athletes ("Athlete's arteries") have to be distinguished from diffuse ectatic segments developing during Kawasaki disease or multisystemic inflammation syndrome after COVID-19.

The Atherosclerotic Profile of a Young Symptomatic Population between 19 and 49 Years: Coronary Computed Tomography Angiography or Coronary Artery Calcium Score?

(1) Background: Whether coronary computed tomography angiography (CTA) or the coronary artery calcium score (CACS) should be used for diagnosis of coronary heart disease, is an open debate. The aim of our study was to compare the atherosclerotic profile by coronary CTA in a young symptomatic high-risk population (age, 19-49 years) in comparison with the coronary artery calcium score (CACS). (2) Methods: 1137 symptomatic high-risk patients between 19-49 years (mean age, 42.4 y) who underwent coronary CTA and CACS were stratified into six age groups. CTA-analysis included stenosis severity and high-risk-plaque criteria (3) Results: Atherosclerosis was more often detected based on CTA than based on CACS (45 vs. 27%; p < 0.001), 50% stenosis in 13.6% and high-risk plaque in 17.7%. Prevalence of atherosclerosis was low and not different between CACS and CTA in the youngest age groups (19-30 y: 5.2 and 6.4% and 30-35 y: 10.6 and 16%). In patients older than >35 years, the rate of atherosclerosis based on CTA increased (p = 0.004, OR: 2.8, 95%CI:1.45-5.89); and was higher by CTA as compared to CACS (34.9 vs. 16.7%; p < 0.001), with a superior performance of CTA. In patients older than 35 years, stenosis severity (p = 0.002) and >50% stenosis increased from 2.6 to 12.5% (p < 0.001). High-risk plaque prevalence increased from 6.4 to 26.5%. The distribution of high-risk plaque between CACS 0 and >0.1 AU was similar among all age groups, with an increasing proportion in CACS > 0.1 AU with age. A total of 24.9% of CACS 0 patients had coronary artery disease based on CTA, 4.4% > 50% stenosis and 11.5% had high-risk plaque. (4) Conclusions: In a symptomatic young high-risk population older than 35 years, CTA performed superior than CACS. In patients aged 19-35 years, the rate of atherosclerosis was similar and low based on both modalities. CACS 0 did not rule out coronary artery disease in a young high-risk population.

Identifying the Location of an Accessory Pathway in Pre-Excitation Syndromes Using an Artificial Intelligence-Based Algorithm.

(1) Background: The exact anatomic localization of the accessory pathway (AP) in patients with Wolff-Parkinson-White (WPW) syndrome still relies on an invasive electrophysiologic study, which has its own inherent risks. Determining the AP localization using a 12-lead ECG circumvents this risk but is of limited diagnostic accuracy. We developed and validated an artificial intelligence-based algorithm (location of accessory pathway artificial intelligence (locAP AI)) using a neural network to identify the AP location in WPW syndrome patients based on the delta-wave polarity in the 12-lead ECG. (2) Methods: The study included 357 consecutive WPW syndrome patients who underwent successful catheter ablation at our institution. Delta-wave polarity was assessed by four independent electrophysiologists, unaware of the site of successful catheter ablation. LocAP AI was trained and internally validated in 357 patients to identify the correct AP location among 14 possible locations. The AP location was also determined using three established tree-based, ECG-based algorithms (Arruda, Milstein, and Fitzpatrick), which provide limited resolutions of 10, 5, and 8 AP locations, respectively. (3) Results: LocAP AI identified the correct AP location with an accuracy of 85.7% (95% CI 79.6-90.5, p < 0.0001). The algorithms by Arruda, Milstein, and Fitzpatrick yielded a predictive accuracy of 53.2%, 65.6%, and 44.7%, respectively. At comparable resolutions, the locAP AI achieved a predictive accuracy of 95.0%, 94.9%, and 95.6%, respectively (p < 0.001 for differences). (4) Conclusions: Our AI-based algorithm provided excellent accuracy in predicting the correct AP location. Remarkably, this accuracy is achieved at an even higher resolution of possible anatomical locations compared to established tree-based algorithms.

Smoking and obesity predict high-risk plaque by coronary CTA in low coronary artery calcium score (CACS).

BACKGROUND: The AHA recommends statins in patients with CACS>100 AU. However in patients with low CACS (1-99 AU), no clear statement is provided, leaving the clinician in a grey-zone. High-risk plaque (HRP) criteria by coronary CTA are novel imaging biomarkers indicating a higher a-priori cardiovascular (CV) risk, which could help for decision-making. Therefore the objective of our study was to identify which CV-risk factors predict HRP in patients with low CACS 1-99. METHODS: 1003 symptomatic patients with low-to-intermediate risk, a clinical indication for coronary computed tomography angiography (CCTA) and who had a coronary artery calcium score (CACS) between 1 and 99 AU, were enrolled. CCTA analysis included: stenosis severity and HRP-criteria: low-attenuation plaque (LAP <30HU, <60HU and <90HU) napkin-ring-sign, spotty calcification and positive remodeling. Multivariate regression models were created for predicting HRP-criteria by the major 5 cardiovascular risk factors (CVRF) (smoking, arterial hypertension, positive family history, dyslipidemia, diabetes) and obesity (BMI>25 â€‹kg/m2). RESULTS: 304 (33.5%) were smokers. 20.4% of smokers had HRP compared with only 14.9% of non-smokers (p â€‹= â€‹0.045). Male gender was associated with HRP (p â€‹< â€‹0.001). Smoking but not the other 5 CVRF had the most associations with HRP-criteria (LAP<60HU/≥2 criteria:OR 1.59; 95%CI:1.07-2.35), LAP<90HU (OR 1.57; 95%CI:1.01-2.43), Napkin-Ring-Sign (OR 1.78; 95%CI:1.02-3.1) and positive remodelling (OR 1.54; 95%CI:1.09-2.19). Smoking predicted fibrofatty LAP<90HU in males only. Obesity predicted LAP<60HU in both females and males. CONCLUSIONS: In patients with low CACS 1-99AU, male gender, smoking and obesity, but not the other CVRF predict HRP. These patients would rather benefit from intensification of primary CV-prevention measures such as statins.

Gender Differences in the Atherosclerosis Profile by Coronary CTA in Coronary Artery Calcium Score Zero Patients.

Background: The coronary artery calcium score (CACS) is a powerful tool for cardiovascular risk stratification. Coronary computed tomography angiography (CTA) allows for a more distinct analysis of atherosclerosis. The aim of the study was to assess gender differences in the atherosclerosis profile of CTA in patients with a CACS of zero. Methods: A total of 1451 low- to intermediate-risk patients (53 ± 11 years; 51% females) with CACS <1.0 Agatston units (AU) who underwent CTA and CACS were included. Males and females were 1:1 propensity score-matched. CTA was evaluated for stenosis severity (Coronary Artery Disease - Reporting and Data System (CAD-RADS) 0-5: minimal <25%, mild 25-49%, moderate 50-69%, severe ≥70%), mixed-plaque burden (G-score), and high-risk plaque (HRP) criteria (low-attenuation plaque, spotty calcification, napkin-ring sign, and positive remodeling). All-cause mortality, cardiovascular mortality, and major cardiovascular events (MACEs) were collected. Results: Among the patients, 88.8% had a CACS of 0 and 11.2% had an ultralow CACS of 0.1-0.9 AU. More males than females (32.1% vs. 20.3%; p < 0.001) with a CACS of 0 had atherosclerosis, while, among those with an ultralow CACS, there was no difference (88% vs. 87.1%). Nonobstructive CAD (25.9% vs. 16.2%; p < 0.001), total plaque burden (2.2 vs. 1.4; p < 0.001), and HRP were found more often in males (p < 0.001). After a follow-up of mean 6.6 ± 4.2 years, all-cause mortality was higher in females (3.5% vs. 1.8%, p = 0.023). Cardiovascular mortality and MACEs were low (0.2% vs. 0%; p = 0.947 and 0.3% vs. 0.6%; p = 0.790) for males vs. females, respectively. Females were more often symptomatic for chest pain (70% vs. 61.6%; p = 0.004). (4) Conclusions: In patients with a CACS of 0, males had a higher prevalence of atherosclerosis, a higher noncalcified plaque burden, and more HRP criteria. Nonetheless, females had a worse long-term outcome and were more frequently symptomatic.

Long-Term Technical Performance of the Osypka QT-5® Ventricular Pacemaker Lead.

BACKGROUND: Lead-associated complications and technical issues in patients with cardiac implantable electronic devices are common but underreported in the literature. METHODS: All patients undergoing implantation of the Osypka QT-5® ventricular lead at the University Clinic St. Pölten between 1 January 2006 and 31 December 2012 were retrospectively analyzed (n = 211). Clinical data including pacemaker follow-up examinations and the need for lead revisions were assessed. Kaplan-Meier analysis to estimate the rate of lead dysfunction during long-term follow-up was conducted. RESULTS: Patients were followed for a median of 5.2 years (interquartile range (IQR) 2.0-8.7). R-wave sensing properties at implantation, compared to last follow-up, remained basically unchanged: 9.9 mV (IQR 6.8-13.4) and 9.6 mV (IQR 5.6-12.0), respectively). Ventricular pacing threshold significantly increased between implantation (0.5 V at 0.4 ms; IQR 0.5-0.8) and the first follow-up visit (1.0 V at 0.4 ms; IQR 0.8-1.3; p < 0.001) and this increase persisted throughout to the last check-up (0.9 V at 0.4 ms; IQR 0.8-1.2). Impedance significantly declined from 1142 Ω (IQR 955-1285) at implantation to 814 Ω (IQR 701-949; p < 0.001) at the first check-up, followed by a further decrease to 450 Ω (IQR 289-652; p < 0.001) at the last check-up. Overall, the Osypka QT-5® ventricular lead was replaced in 36 patients (17.1%). CONCLUSIONS: This report shows an unexpected high rate of technical issues of the Osypka QT-5® ventricular lead during long-term follow-up.

Central Sleep Apnea and Pacing-Induced Cardiomyopathy.

The role of central sleep apnea (CSA) in pacing-induced cardiomyopathy (PICM) remains speculative. In a prospective trial entitled UPGRADE, the presence of CSA was assessed by single-night polysomnography (PSG) in 54 PICM patients within 1 month after left ventricular lead implantation (with biventricular stimulation still not activated). CSA was diagnosed in half of patients (n = 27). Patients with moderate or severe CSA were randomized to cardiac resynchronization therapy (CRT) versus right ventricular pacing (RVP) in a double-blinded cross-over design and re-scheduled for a follow-up PSG within 3 to 5 months. After crossing-over of stimulation mode another PSG was conducted 3 to 5 months later. CRT led to a significant increase in left ventricular ejection fraction and significant reduction in left ventricular end systolic volumes and N-terminal pro brain natriuretic peptide plasma levels, whereas no significant effects were observed with ongoing RVP. CSA was significantly improved after 3.9 (3.2 to 4.4) months of CRT: apnea-hypopnea index decreased from 39.1 (32.1 to 54.0) events per hour at baseline to 22.2/h (10.9 to 36.7) by CRT (p <0.001). Central apnea index decreased from 27.1/h (17.7 to 36.1) at baseline to 6.8/h (1.1 to 14.4) after CRT activation (p <0.001). Ongoing RVP yielded only a minor improvement in apnea-hypopnea index and central apnea index. Pre-existent CSA did not affect structural response rate and had no impact on mid-term follow-up (median 2.8 years). In conclusion, CSA is highly prevalent in patients with PICM. CRT upgrading significantly improves CSA leading to a similar outcome in PICM patients without pre-existent CSA.

Supplemental dataset on the influence of cardiac resynchronisation therapy in pacing-induced cardiomyopathy and concomitant central sleep Apnea.

This article contains supplemental data to the publication "Central Sleep Apnea and Pacing-Induced Cardiomyopathy" [1], which was the most recent publication of the "UPGRADE" study. It provides in-depth analysis of the effects of cardiac resynchronisation therapy (CRT) in patients suffering from pacing-induced cardiomyopathy (PICM) on cardiac remodeling as well as functional cardiac parameters in comparison to continuous right ventricular pacing (RVP). Furthermore, it also covers additional data on several sleep parameters, which were not presented in the main article including the index for obstructive sleep apnea (OSA), the index for mixed sleep apnea and the oxygen saturation measurements during polysomnography. Further, Kaplan-Meier curves are presented for major adverse cardiac events (MACE) and overall mortality by severity of sleep apnea. Generally, the "UGRADE" study was a single-center prospective double-blinded randomized controlled trial lasting from 2014 to 2020. The methodology included a cross-over design giving the possibility to detect differences while CRT was activated and while continuous RVP was applied. The presented data should aid clinicians in daily practice as upgrading to CRT is not limited to improvement in cardiac parameters, but also modifies sleep apnea in patients with PICM, a generally sparsely studied entity of heart failure.

Left Atrial Appendage Morphology and Left Atrial Wall Thickness Are Associated with Cardio-Embolic Stroke.

BACKGROUND: New markers for stroke risk stratification in patients with atrial fibrillation (AF) are on demand. Hence, we aimed to investigate the association of left atrial appendage (LAA) and left atrium (LA) morphological parameters in patients with cardio-embolic (CE) stroke due to AF in comparison to controls without stroke. METHODS: A retrospective analysis of cardiac computed tomography angiography (CTA) examinations performed between 2006 and 2017 for clinical indications in 158 patients (median age 65 (54-73) years, 48.7% females) was conducted: 56 patients with CE stroke were compared to 102 controls not differing in gender, body mass index (BMI) and CHA2DS2-VASc score. RESULTS: On multivariable regression analysis adjusted for CHA2DS2-VASc score and LA diameter CE stroke was independently associated with the following parameters: windsock LAA type (OR 2.55; CI: 1.04-6.26, p = 0.041), a greater lobe number (OR 1.54; CI: 1.13-2.10, p = 0.006), a greater LAA ostium area (OR 1.88; CI: 1.38-2.55, p < 0.001) and a greater left atrium wall thickness (LAWT) in the middle and right part, measured along the anterior LA wall in the axial plane (respectively, OR 1.94; CI: 1.26-3.0, p = 0.003 and OR 1.57; CI: 1.07-2.31, p = 0.021). CONCLUSIONS: The windsock LAA type, a greater LAA lobe number, a larger LAA ostium and a greater LAWT are associated with CE stroke. These CTA parameters could improve risk stratification for thromboembolic stroke.

Added value of high-risk plaque criteria by coronary CTA for prediction of long-term outcomes.

BACKGROUND AND AIMS: Long-term data relating coronary computed tomography angiography (CTA) to coronary artery disease (CAD) prognosis including novel CTA-biomarkers ("high-risk plaque criteria") is scarce. The aim of this study was to define predictors of long-term outcomes. METHODS: 1430 low-to-intermediate risk patients (57.9 ± 11.1 years; 44.4% females) who underwent CTA and coronary calcium scoring (CCS) were prospectively enrolled. CTAs were evaluated for (1) stenosis severity CADRADS 0-4 (minimal <25%, mild 25-50%, moderate 50-70%, severe >70%), (2) mixed plaque burden weighted for non-calcified plaque (NCP), and (3) high-risk-plaque (HRP) criteria: low-attenuation-plaque (LAP), napkin-ring-sign, spotty calcifications <3 mm or remodeling index >1.1. Endpoints were all-cause and cardiovascular mortality, composite fatal and nonfatal major adverse cardiovascular events (MACE). RESULTS: Over a mean follow-up of 10.55 years ± 1.98, 106 patients (7.4%) died, 25 from cardiovascular events (1.75%). Composite MACE occurred in 57 (3.9%) patients. In patients with negative CTA, cardiovascular mortality and MACE rates were 0% and 0.2%. Stenosis severity by CTA predicted all 3 endpoints (p < 0.001) while CCS >100 AU predicted only all-cause mortality (p = 0.045) but not MACE. The high risk plaque criteria LAP <60HU (HR: 4.00, 95%CI 95% 1.52-10.52, p = 0.005) and napkin-ring (HR 4.11, CI 95% 1.77-9.52, p = 0.001) predicted MACE but not all-cause-mortality, after adjusting for risk factors, while spotty calcification and remodeling index did not. Similarly, mixed plaque burden predicted MACE (p < 0.0001). HRP criteria, if added to CADRADS + CCS for prediction of MACE, were superior to CCS (c = 0.816 vs 0.716, p < 0.001). In 33.5% of CCS zero patients, non-calcified fibroatheroma were found. CONCLUSIONS: Long-term prognosis is excellent if CTA is negative for CAD. The high-risk plaque criteria LAP<60HU and napkin-ring-sign were independent predictors of MACE while HRP criteria added incremental prognostic value.

Functional neuroimaging in the acute phase of Takotsubo syndrome: volumetric and functional changes of the right insular cortex.

BACKGROUND: A brain-heart interaction has been proposed in Takotsubo syndrome (TTS). Structural changes in the limbic system and hypoconnectivity between certain brain areas in the chronic phase of the disease have been reported, but little is known concerning functional neuroimaging in the acute phase. We hypothesized anatomical and functional changes in the central nervous system and investigated whole-brain volumetric and functional connectivity alterations in the acute phase TTS patients compared to controls. METHODS: Anatomical and resting-state functional magnetic resonance imaging were performed in postmenopausal females: thirteen in the acute TTS phase and thirteen healthy controls without evidence of coronary artery disease. Voxel-based morphometry and graph theoretical analysis were applied to identify anatomical and functional differences between patients and controls. RESULTS: Significantly lower gray matter volumes were found in TTS patients in the right middle frontal gyrus (p = 0.004) and right subcallosal cortex (p = 0.009) compared to healthy controls. When lower threshold was applied, volumetric changes were noted in the right insular cortex (p = 0.0113), the right paracingulate cortex (p = 0.012), left amygdala (p = 0.018), left central opercular cortex (p = 0.017), right (p = 0.013) and left thalamus (p = 0.017), and left cerebral cortex (p = 0.017). Graph analysis revealed significantly (p < 0.01) lower functional connectivity in TTS patients compared to healthy controls, particularly in the connections originating from the right insular cortex, temporal lobes, and precuneus. CONCLUSION: In the acute phase of TTS volumetric changes in frontal regions and the central autonomic network (i.e. insula, anterior cingulate cortex, and amygdala) were noted. In particular, the right insula, associated with sympathetic autonomic tone, had both volumetric and functional changes.