Evaluation of a multiplex PCR screening approach to identify community-acquired bacterial co-infections in COVID-19: a multicenter prospective cohort study of the German competence network of community-acquired pneumonia (CAPNETZ).

PURPOSE: Thorough knowledge of the nature and frequency of co-infections is essential to optimize treatment strategies and risk assessment in cases of coronavirus disease 2019 (COVID-19). This study aimed to evaluate the multiplex polymerase chain reaction (PCR) screening approach for community-acquired bacterial pathogens (CABPs) at hospital admission, which could facilitate identification of bacterial co-infections in hospitalized COVID-19 patients. METHODS: Clinical data and biomaterials from 200 hospitalized COVID-19 patients from the observational cohort of the Competence Network for community-acquired pneumonia (CAPNETZ) prospectively recruited between March 17, 2020, and March 12, 2021 in 12 centers in Germany and Switzerland, were included in this study. Nasopharyngeal swab samples were analyzed on hospital admission using multiplex real-time reverse transcription (RT)-PCR for a broad range of CABPs. RESULTS: In total of 200 patients Staphylococcus aureus (27.0%), Haemophilus influenzae (13.5%), Streptococcus pneumoniae (5.5%), Moraxella catarrhalis (2.5%), and Legionella pneumophila (1.5%) were the most frequently detected bacterial pathogens. PCR detection of bacterial pathogens correlated with purulent sputum, and showed no correlation with ICU admission, mortality, and inflammation markers. Although patients who received antimicrobial treatment were more often admitted to the ICU and had a higher mortality rate, PCR pathogen detection was not significantly related to antimicrobial treatment. CONCLUSION: General CABP screening using multiplex PCR with nasopharyngeal swabs may not facilitate prediction or identification of bacterial co-infections in the early phase of COVID-19-related hospitalization. Most patients with positive PCR results appear to be colonized rather than infected at that time, questioning the value of routine antibiotic treatment on admission in COVID-19 patients.

Anxiety, depression and quality of life in acute high risk cardiac disease patients eligible for wearable cardioverter defibrillator: Results from the prospective multicenter CRED-registry.

BACKGROUND: Psychological distress is common in patients with cardiovascular disease and negatively impacts outcome. HYPOTHESIS: Psychological distress is high in acute high risk cardiac patients eligible for a WCD, and associated with low quality of life. Distress is aggravated by WCD. METHODS: Consecutive patients eligible for a WCD were included in the prospective, multicenter "Cologne Registry of External Defibrillator" registry. Quality of life (Short Form-12), depressive symptoms (Beck-Depression Inventory II) and anxiety (State Trait Anxiety Inventory) were assessed at enrollment and 6-weeks, and associations with WCD prescription were analyzed. RESULTS: 123 patients (mean [SD] age 59 [± 14] years, 75% male) were included, 85 (69%) of whom received a WCD. At enrollment 21% showed clinically significant depressive symptoms and 52% anxiety symptoms, respectively. At 6 weeks, depressive and anxious symptoms significantly decreased to 7% and 25%, respectively. Depressive symptoms at enrollment and changes at 6 weeks showed significant associations with health-related quality of life, whereas anxious symptoms did not. There was a trend for better improvement of depression scores in patients with WCD (mean [SD] change in score points: -4.1 [6.1] vs -1.8 [3.9]; p = 0.09), whereas change of the anxiousness score was not different (-4.6 [9.5]) vs -3.7 [9.1], p = 0.68). CONCLUSION: In patients eligible for a WCD, depressive and anxiety symptoms were initially common and depressive symptoms showed a strong association with reduced health-related quality of life contributing to their clinical relevance. WCD recipients showed at least similar improvement of depression and anxiety at 6 weeks when compared to non recipients.

INvestigation on Routine Follow-up in CONgestive HearT FAilure Patients with Remotely Monitored Implanted Cardioverter Defibrillators SysTems (InContact).

BACKGROUND: In heart failure (HF) patients with implantable cardioverter defibrillators (ICD) or cardiac resynchronisation therapy defibrillators (CRT-D), remote monitoring has been shown to result in at least non-inferior outcomes relative to in-clinic visits. We aimed to provide further evidence for this effect, and to assess whether adding telephone follow-ups to remote follow-ups influenced outcomes. METHODS: InContact was a prospective, randomised, multicentre study. Subjects receiving quarterly automated follow-up only (telemetry group) were compared to those receiving personal physician contact. Personal contact patients were further divided into those receiving automated follow-up plus a telephone call (remote+phone subgroup) or in-clinic visits only. RESULTS: Two hundred and ten patients underwent randomisation (telemetry n = 102; personal contact n = 108 [remote+phone: n = 53; visit: n = 55]). Baseline characteristics were comparable between groups and subgroups. Over 12 months, 34.8% of patients experienced deterioration of their Packer Clinical Composite Response, with no significant difference between the telemetry group and personal care (p > 0.999), remote+phone (p = 0.937) or visit (p = 0.940) patients; predefined non-inferiority criteria were met. Mortality rates (5.2% overall) were comparable between groups and subgroups (p = 0.832/p = 0.645), as were HF-hospitalisation rates (11.0% overall; p = 0.605/p = 0.851). The proportion of patients requiring ≥1 unscheduled follow-up was nominally higher in telemetry and remote+phone groups (42.2 and 45.3%) compared to the visit group (29.1%). Overall, ≥ 1 ICD therapy was delivered to 15.2% of patients. CONCLUSION: In HF patients with ICDs/CRT-Ds, quarterly remote follow-up only over 12 months was non-inferior to regular personal contact. Addition of quarterly telephone follow-ups to remote monitoring does not appear to offer any clinical advantage. TRIAL REGISTRATION: clinicaltrials.gov: NCT01200381 (retrospectively registered on September 13th 2010).

Reduction of inappropriate ICD therapies in patients with primary prevention of sudden cardiac death: DECREASE study.

BACKGROUND: A significant number of patients with an implantable cardioverter/defibrillator (ICD) for primary prevention receive inappropriate shocks. Previous studies have reported a reduction of inappropriate therapies with simple modifications of ICD detection settings, however, inclusion criteria and settings varied markedly between studies. Our aim was to investigate the effect of raising the ICD detection zone in the entire primary prevention ICD population. METHODS AND RESULTS: 543 patients receiving an ICD for primary prevention were randomized to either conventional or progressive ICD programming. The detection rate was programmed at 171 bpm for ventricular tachycardia (VT) and 214 bpm for ventricular fibrillation (VF) in the Conventional group and 187 bpm for VT and 240 bpm for VF in the Progressive group. 43 % of patients received single-chamber and 57 % dual-chamber detection devices (DDD-ICD 19 %; CRT-D 38 %). The primary endpoint consisted of inappropriate therapies and untreated VT/VF. The primary endpoint was reached in 35 patients (13 %) in the Conventional group and 17 patients (6 %) in the Progressive group (p = 0.004). Progressive ICD programming led to significantly fewer amount of patients with ICD therapies (26 vs. 14 %; p < 0.001) and shocks (11 vs. 5 %; p = 0.023) compared to conventional ICD programming. Sub-analyses showed the greatest reduction of inappropriate therapies and shocks in dual-chamber detection devices with progressive compared to single-chamber detection devices with conventional ICD programming (p < 0.001). CONCLUSIONS: Progressive ICD programming reduces the number of inappropriate therapies and shocks in a broad primary prevention ICD population particularly in combination with dual-chamber detection algorithms. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov ; ClinicalTrials.gov identifier NCT01217528.

Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial.

INTRODUCTION: This phase III study compared efficacy and safety of topotecan-cisplatin (TP) versus topotecan-etoposide (TE) versus cisplatin-etoposide (PE) in chemo-naïve extensive disease small-cell lung cancer patients. METHODS: Seven hundred and ninety-five previously untreated patients were randomly assigned to TP (topotecan 1mg/m IV, d1-5; cisplatin 75 mg/m IV, d5; n = 358), PE (cisplatin 75 mg/m IV, d1; etoposide 100 mg/m IV, d1-3; n = 345) or TE (topotecan 1mg/m IV, d1-5; etoposide 80 mg/m IV, d3-5; n = 92). Primary endpoint was superiority of TP compared with PE, with the possibility to switch to a noninferiority test. RESULTS: The TE arm was closed after recommendations by the Independent Data Safety Monitoring Board. Median survival was similar and met the predefined endpoint of noninferiority of TP to PE (44.9 versus 40.9 weeks; p = 0.40). One-year survival rate showed 39.7% for TP versus 36.1% for PE (p = 0.29). Median time to progression was significantly longer with TP (27.4 versus 24.3 weeks, p = 0.01). Overall response rates were significantly higher for TP (55.5% versus 45.5%, p = 0.01).Hematologic toxicity was slightly higher for TP regarding G 3/4 neutropenia (35.7/35.8%), G 3/4 thrombocytopenia (18.7/4.8%), G 3/4 anemia (11.6/6.7%), febrile neutropenia (2.0/2.7%), sepsis (1.7/1.2%), and toxicity-related deaths (5.2/2.7%). CONCLUSION: TP is noninferior to PE in overall survival and superior in time to progression and overall response rates. Because of slightly worse toxicity profile TP is not a first-line standard treatment for patients with extensive disease small-cell lung cancer.

AV interval optimization using pressure volume loops in dual chamber pacemaker patients with maintained systolic left ventricular function.

BACKGROUND: Atrioventricular (AV) interval optimization is often deemed too time-consuming in dual-chamber pacemaker patients with maintained LV function. Thus the majority of patients are left at their default AV interval. OBJECTIVE: To quantify the magnitude of hemodynamic improvement following AV interval optimization in chronically paced dual chamber pacemaker patients. PATIENTS AND METHODS: A pressure volume catheter was placed in the left ventricle of 19 patients with chronic dual chamber pacing and an ejection fraction >45 % undergoing elective coronary angiography. AV interval was varied in 10 ms steps from 80 to 300 ms, and pressure volume loops were recorded during breath hold. RESULTS: The average optimal AV interval was 152 ± 39 ms compared to 155 ± 8 ms for the average default AV interval (range 100-240 ms). The average improvement in stroke work following AV interval optimization was 935 ± 760 mmHg/ml (range 0-2,908; p < 0.001), which translates into an average improvement of 14 ± 9 % (range 0-28). A 10 ms variation of the AV interval changes the average stroke work by 207 ± 162 mmHg/ml. AV interval optimization also leads to improved systolic dyssynchrony indices (17.7 ± 7.0 vs. 19.4 ± 7.1 %; p = 0.01). CONCLUSION: The overall hemodynamic effect of AV interval optimization in patients with maintained LV function is in the same range as for patients undergoing cardiac resynchronization therapy for several parameters. The positive effect of AV interval optimization also applies to patients who have been chronically paced for years.

The effect of biventricular pacing on cardiac function after weaning from cardiopulmonary bypass in patients with reduced left ventricular function: a pressure-volume loop analysis.

OBJECTIVE: Patients with severely reduced left ventricular function undergoing coronary artery bypass grafting have increased complication rates. We hypothesized that temporary postoperative atrial synchronous biventricular pacing would improve left ventricular function after cardiopulmonary bypass. METHODS: A left ventricular pressure-volume catheter was placed in 21 patients undergoing coronary artery bypass grafting (ejection fraction 29% +/- 5%). Pressure-volume loops were obtained after weaning from cardiopulmonary bypass with atrial synchronous biventricular, left ventricular, and right ventricular outflow tract pacing and atrial-only stimulation at 90 beats/min. RESULTS: Steady-state systolic and preload-independent parameters were superior for atrial synchronous biventricular and left ventricular pacing and atrial-only pacing relative to atrial synchronous right ventricular outflow tract pacing (P < .05). Diastolic parameters, excepting maximum negative rate of left ventricular pressure change, were unaffected. No significant differences were observed between atrial synchronous biventricular and left ventricular pacing and atrial-only pacing. Systolic dyssynchrony was significantly lower for atrial synchronous biventricular pacing (21% +/- 5%), atrial synchronous left ventricular pacing (20% +/- 6%), and atrial-only pacing (20% +/- 6%) versus atrial synchronous right ventricular outflow tract pacing (25% +/- 7%, P < .05). Atrioventricular interval during atrial-only stimulation was positively correlated with difference in stroke work between atrial synchronous biventricular pacing and atrial-only pacing (r(2) = 0.78, P > .001). CONCLUSION: Postoperative atrial synchronous biventricular and left ventricular pacing and atrial-only stimulation significantly improve systolic function relative to atrial synchronous right ventricular outflow tract pacing. If atrioventricular conduction is prolonged, atrial synchronous biventricular pacing is preferable to atrial-only pacing.

The effect of biventricular pacing after coronary artery bypass grafting: a prospective randomized trial of different pacing modes in patients with reduced left ventricular function.

OBJECTIVES: Biventricular pacing acutely improves left ventricular function in patients with heart failure and left ventricular dyssynchrony. Pressure-volume loop analysis has shown acute perioperative hemodynamic benefits of biventricular pacing immediately after weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting, but whether these effects can be maintained for the early postoperative period is unclear. We hypothesized that biventricular pacing is superior to atrioventricular universal pacing at right ventricular outflowtract and atrial inhibited pacing in patients undergoing coronary artery bypass grafting. METHODS: Ninety-four patients (mean age, 67 +/- 9 years; mean ejection fraction, 35% +/- 4%) were prospectively randomized to undergo biventricular, atrioventricular universal, or atrial inhibited pacing at 90 beats/min for 96 postoperative hours. Clinical end points and postoperative hemodynamics, aminoterminal pro-brain natriuretic peptide, inotropic support, atrial fibrillation, ventricular arrhythmias, and renal function were evaluated. RESULTS: Diastolic pulmonary arterial pressure, mean arterial pressure, mixed venous saturation, cardiac index, and cardiac power index did not differ significantly among groups for all time points. Neither raw aminoterminal pro-brain natriuretic peptide nor differential from preoperative values differed significantly among groups at any time point. Median intensive care unit stay (19.5 hours) did not differ significantly by pacing mode. Incidences of postoperative atrial fibrillation were 40% for atrial inhibited, 29% for atrioventricular universal, and 37% for biventricular (differences not significant). Renal function was unaffected by pacing mode. CONCLUSION: Despite short-term hemodynamic benefits for patients with reduced left ventricular function, biventricular pacing did not lead to improved postoperative hemodynamics or clinical outcome.

Continuous positive airway pressure therapy decreases evening cortisol concentrations in patients with severe obstructive sleep apnea.

Patients with obstructive sleep apnea syndrome (OSAS) show recurrent episodes of nightly hypoxic stress. The purpose of this study is the detection of alterations of the hypothalamic-pituitary-adrenal stress axis in OSAS patients before and after continuous positive airway pressure (CPAP) therapy. An activation of the hypothalamic-pituitary-adrenal axis was proposed because of the nightly hypoxic stress in these patients, but previous studies were not conclusive. Here we hypothesize that CPAP therapy decreases salivary cortisol concentrations in patients with severe OSAS. We performed a clinical within-subject study including 50 patients with newly diagnosed OSAS and an apnea-hypopnea index greater than or equal to 40 h(-1). Diurnal profiles of salivary cortisol concentrations were compiled before and after 3 months of treatment with CPAP. Therefore, 6 cortisol samples were collected: before and after lunch, in the evening, the next morning after awakening, and before and after breakfast. Thirty-eight patients returned after 3 months of CPAP therapy for follow-up. According to the reference range for healthy subjects, cortisol values were not pathologically increased. Analysis of variance revealed a significant effect of CPAP therapy on diurnal cortisol profiles (P = .048). Subjects with severe OSAS showed a decrease (3.04 +/- 0.55 nmol L(-1) pre-CPAP vs 2.48 +/- 0.78 nmol L(-1) post-CPAP, P = .038) of evening cortisol levels after CPAP treatment, whereas prelunch levels were increased after CPAP therapy (7.18 +/- 0.83 nmol L(-1) pre-CPAP vs 10.22 +/- 1.10 nmol L(-1) post-CPAP, P = .044). Our results show that CPAP therapy decreases evening cortisol concentrations in patients with severe OSAS. These data suggest that OSAS may increase the cortisol nadir that is reversed after CPAP therapy.

Posttraumatic and postoperative cardiac luxation: computed tomography findings in nine patients.

BACKGROUND: Posttraumatic and postoperative cardiac luxation represents a serious complication of pericardial rupture, and early diagnosis is important. The purpose of this study is to determine signs of left cardiac luxation on computed tomography (CT). METHODS: CT scans in nine patients with pericardial rupture and cardiac luxation after blunt chest trauma (n = 7) and postoperatively after extended left pneumectomy (n = 2) were reviewed for abnormalities. We analyzed the clinical history, clinical findings, and the imaging findings. RESULTS: Dislocation of the heart to the left and pneumopericardium were seen in nine patients. Five of these nine patients revealed "entrapment" of the left heart between the proximal ascending aorta and the descending aorta. All patients underwent a pneumopericardium. All patients with a history of trauma showed a left-sided pneumothorax but no pericardial effusion. CONCLUSIONS: CT plays a key role for early diagnosis of cardiac luxation. Dislodgment of the heart, entrapment of the left atrium and ventricle, and pneumopericardium associated with pneumothorax are the most important CT findings.

Morphology-enhanced atrial event classification improves sensing in pacemakers.

BACKGROUND: In atrial-based pacing, appropriate therapy and reliable diagnostics depend on detection and discrimination of atrial signals. Accurate classification of atrial events is mainly confounded by oversensing of ventricular far-field R-wave signals (FFRW), but attempts to reject FFRWs by manipulating atrial sensitivity and/or postventricular atrial blanking period (PVAB) may result in undersensing (especially of atrial fibrillation, AF) or in 2:1 atrial flutter detection. The objective of this study is therefore to evaluate if such methods can be improved by morphology-enhanced atrial event classification (MORPH). METHODS: Twenty-four-hour ambulatory atrial electrograms were recorded from continuous telemetry of digital pacemakers. Half of the recording was used for collecting two individual morphology parameters that discriminated P-waves from FFRWs in every patient (learning phase). The other half was used to test the MORPH algorithm against traditional methods (classification phase). RESULTS: In 44/48 patients, data were suitable for analysis. Average P and FFRW amplitudes were 1.96 mV versus 0.61 mV (P < 0.001). The interval between ventricular events and FFRW oversensing (VA interval) averaged at 14 ms during sensing and at 118 ms during pacing in the ventricle. Compared to nominal ("Factory") settings, the MORPH algorithm improved the sensitivity for P-wave recognition from 97.2% to 99.2%, the specificity from 91.9% to 99.96%, and the accuracy from 95.3% to 99.4% (P < 0.01 for all). CONCLUSIONS: By improving atrial signal discrimination, morphology analysis of atrial electrograms allows for high atrial sensitivity settings, and potentially improves the reliability of atrial arrhythmia diagnostics in heart rhythm devices.

Lack of agreement between thermodilution and electrical velocimetry cardiac output measurements.

OBJECTIVE: The modified algorithm for the non-invasive determination of cardiac output (CO) by electrical bioimpedance-electrical velocimetry (EV)-has been reported to give reliable results in comparison with echocardiography and pulmonary arterial thermodilution (PA-TD) in patients either before or after cardiac surgery. The present study was designed to determine whether EV-CO measurements reflect intraindividual changes in CO during cardiac surgery. DESIGN: Prospective, observational study. SETTING: Operating room (OR) and intensive care unit (ICU) of a university hospital. PATIENTS: Twenty-nine patients undergoing elective cardiac surgery. INTERVENTIONS: None. MEASUREMENTS: CO was determined simultaneously by PA-TD and EV after induction of anesthesia (t1) and 4.9+/-3.5 h after ICU admission (t2). RESULTS: TD-CO was 3.9+/-1.4 and 5.4+/-1.1 l/min at t1 and t2 (p < 0.0001). EV-CO was 4.3+/-1.1 and 4.9+/-1.5 l/min at t1 and t2 (p = 0.013). Bland-Altman analysis showed a bias of -0.4 l/min and 0.4 l/min and a precision of 3.2 and 3.6 l/min (34.3% and 67.4%) at t1 and t2, respectively. Analysis of the individual pre- to postoperative changes in CO with both methods revealed bidirectional changes in n = 12 patients and unidirectional changes with a difference greater than 50% and less than 50% in n = 9 and n = 8 patients, respectively. CONCLUSIONS: The disagreement between PA-TD and EV-CO measurements after anesthesia induction and after ICU admission, as well as the fact that thoracic bioimpedance did not adequately reflect pre- to postoperative changes in CO, questions the reliability of EV-CO measurements in cardiac surgery patients and contrasts sharply with previous studies.

Incidence and significance of far-field R wave sensing in a VDD-implantable cardioverter defibrillator.

BACKGROUND: A VDD-implantable cardioverter-defibrillator (ICD) provides atrioventricular (AV) synchronous stimulation when necessary and incorporates the advantages of dual chamber arrhythmia discrimination algorithms both at potentially lower costs and less periprocedural complications than a DDD-ICD system. A prerequisite for correct dual chamber ICD function is reliable atrial sensing. METHODS: We evaluated atrial near- and ventricular far-field sensing and its impact on the dual-chamber detection algorithm in 106 patients with a single-lead VDD-ICD during a 12-month follow-up period. RESULTS: Six hundred and thirty-nine follow-ups were included. Mean near-field amplitude was 3.82 +/- 1.76 mV; mean far-field amplitude was 0.31 +/- 0.15 mV. 46% of patients had far-fields >0.35 mV and 35% of patients showed atrial EGM markers corresponding to a ventricular far-field in at least one follow-up. Six hundred and forty-five tachycardia episodes were evaluated. Due to far-field sensing, three of 66 episodes (4.5%) of sinus tachycardia were misclassified as ventricular tachycardia (VT), leading to antitachycardia therapies. Delayed detection of VT was seen in a 12 of 323 episodes (3.7%) in five of 62 patients (8%) having VT events (delay 6.4 +/- 6.0 seconds (range 2-24 seconds)). Stable far-field amplitudes <0.2 mV in a follow-up had a high negative predictive value for the occurrence of malfunction during tachycardia-conversely, high far-field amplitudes or a high incidence of far-field markers are only moderately correlated with malfunction. CONCLUSIONS: Ventricular far-field sensing in a VDD-ICD is not uncommon, however, tachycardia detection by the dual chamber algorithm is not seriously impaired by far-field sensing.

Modulation of cardiac autonomic nervous activity early after cardioversion of atrial fibrillation by biphasic waveform.

BACKGROUND: Imbalance of cardiac autonomic nervous modulation might prominently contribute to early relapses of atrial fibrillation (AF) after cardioversion (CV). The biphasic (Bi) waveform is more effective than the monophasic (Mo) waveform in CV of AF. Whether these waveforms have different effects on autonomic modulation early after CV is unknown. METHODS: We investigated 171 consecutive patients after successful electrical CV (mean age 65.4 years, 82% male, 80% structural heart disease). Bi waveform was used in 89, Mo waveform in 82. Heart rate variability (HRV) was analyzed from 24-hour Holter recordings, started directly after CV. RESULTS: Mean delivered total energy was significantly lower in the Bi group (Bi 223 +/- 163 W, Mo 355 +/- 211 W, P < 0.001). Mean RR interval decreased within 5 hours after CV and increased again within the remaining hours, without significant differences between Bi and Mo groups. Time courses of time domain parameters of HRV revealed Bi profiles with the lowest levels 6 hours after CV in both groups. However, the hourly values of HRV were significantly higher in the Bi subgroup. CONCLUSION: Our study indicates that waveform and total delivered energy significantly influence autonomic modulation of the sinus node in the early phase after CV of AF. In contrast to Bi CV, Mo CV is characterized by a significant decrease of cardiac vagal modulation, which may have an arrhythmic effect by increasing the degree of early electrical stunning after CV of AF.