D-dimer levels for Risk Stratification in Patients with Suspected COVID-19 - A Prospective Observational Study.

BACKGROUND: Elevated D-dimer levels have been observed in COVID-19 and are of prognostic value, but have not been compared to an appropriate control group. METHODS: Observational cohort study including emergency patients with suspected or confirmed COVID-19. Logistic regression defined the association of D-dimer levels, COVID-19 positivity, age, and gender with 30-day-mortality. RESULTS: 953 consecutive patients (median age 58, 43% women) presented with suspected COVID-19: 12 (7.4%) patients with confirmed SARS-CoV-2-infection died, compared with 28 (3.5%) patients without SARS-CoV-2-infection. Overall, most (56%) patients had elevated D-dimer levels (≥0.5mg/l). Age (OR 1.07, CI 1.05-1.10), D-dimer levels ≥0.5mg/l (OR 2.44, CI 0.98-7.39), and COVID-19 (OR 2.79, CI 1.28-5.80) were associated with 30-day-mortality. CONCLUSION: D-dimer levels are effective prognosticators in both patient groups.

Prognostic significance of present atrial fibrillation on a single office electrocardiogram in patients with atrial fibrillation.

BACKGROUND: Evidence for the association of atrial fibrillation (AF) present on the ECG and cardiovascular outcomes in AF patients is limited. OBJECTIVE: To investigate the prognostic significance of AF on a single surface ECG for cardiovascular outcomes in AF patients. METHODS: A total of 3642 AF patients were prospectively enrolled. Main exclusion criteria were rhythms other than sinus rhythm (SR) or AF. The primary end-point was a composite of all-cause death and hospitalizations for congestive heart failure (CHF). Secondary end-points were all-cause death, CHF hospitalizations, cardiovascular death, myocardial infarction, any stroke and stroke subtypes. Associations were assessed with multivariable Cox proportional hazards models. RESULTS: Mean age was 71 years, 28% were female, and mean follow-up was 3.4 years. Patients with SR on the ECG at study enrolment (56%) were younger (69 vs. 74 years, P < 0.0001), had more often paroxysmal AF (73 vs. 18%, P < 0.0001) and fewer comorbidities. The incidence of the primary end-point was 1.8 and 3.1 per 100 person-years in patients with SR and AF, respectively. The multivariable-adjusted hazard ratio was 1.4 (95% confidence intervals 1.1; 1.7; P = 0.001) for patients with AF on the ECG compared to patients with SR. The hazard ratios (95% confidence intervals) were 1.4 (1.1; 1.8; P = 0.006) for all-cause death, 1.5 (1.2; 1.9; P = 0.001) for CHF and 1.6 (1.1; 2.2; P = 0.006) for cardiovascular death. None of the other associations were statistically significant. CONCLUSIONS: The presence of AF in a single office ECG had significant prognostic implications with regard to mortality and CHF hospitalizations in patients with AF. These patients present a high-risk group and might benefit from intensified treatment.

Circadian rhythm of cardiac troponin I and its clinical impact on the diagnostic accuracy for acute myocardial infarction.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) blood concentrations were shown to exhibit a diurnal rhythm, characterized by gradually decreasing concentrations throughout daytime, rising concentrations during nighttime and peak concentrations in the morning. We aimed to investigate whether this also applies to (h)s-cTnI assays and whether it would affect diagnostic accuracy for acute myocardial infarction (AMI). METHODS: Blood concentrations of cTnI were measured at presentation and after 1 h using four different cTnI assays: three commonly used sensitive (s-cTnI Architect, Ultra and Accu) and one experimental high-sensitivity assay (hs-cTnI Accu) in a prospective multicenter diagnostic study of patients presenting to the emergency department with suspected AMI. These concentrations and their diagnostic accuracy for AMI (quantified by the area under the curve (AUC)) were compared between morning (11 p.m. to 2 p.m.) and evening (2 p.m. to 11 p.m.) presenters. RESULTS: Among 2601 patients, AMI was the final diagnosis in 17.6% of patients. Concentrations of (h)s-cTnI as measured using all four assays were comparable in patients presenting in the morning versus patients presenting in the evening. Diagnostic accuracy for AMI of all four (h)s-cTnI assays were high and comparable between patients presenting in the morning versus presenting in the evening (AUC at presentation: 0.90 vs 0.93 for s-cTnI Architect; 0.91 vs 0.94 for s-cTnI Ultra; 0.89 vs 0.94 for s-cTnI Accu; 0.91 vs 0.94 for hs-cTnI Accu). CONCLUSIONS: Cardiac TnI does not seem to express a diurnal rhythm. Diagnostic accuracy for AMI is very high and does not differ with time of presentation. CLINICAL TRIAL REGISTRATION: NCT00470587, http://clinicaltrials.gov/show/NCT00470587.

Use of copeptin and high-sensitive cardiac troponin T for diagnosis and prognosis in patients with diabetes mellitus and suspected acute myocardial infarction.

BACKGROUND: Diabetes is a major risk factor for acute myocardial infarction (AMI). Assessment of diabetic patients is challenging due to an often atypical presentation of symptoms. We aimed to evaluate the two novel biomarkers copeptin and high-sensitive cardiac troponin (hs-TnT) for the improvement of early diagnosis and risk-stratification in patients with diabetes and suspected AMI. METHODS: In this prospective international multicenter study we evaluated 379 patients with diabetes in a cohort of 1991 patients presenting with symptoms suggestive of AMI. The measurement of biomarkers was performed at presentation. RESULTS: Among the 379 diabetic patients, 32.7% had AMI, and in the 1621 patients without diabetes, 18.8% had AMI. The additional use of copeptin improved the diagnostic accuracy provided by conventional troponin alone (AUC 0.86 vs. 0.79, p=0.004). During a median follow-up of 814 days, 49 (13.1%) diabetic patients died. Cumulative 2-year survival rate for patients with copeptin levels below 9 pmol/l was 96.6% compared to 82.8% in patients above that level (p<0.001). The same was observed for hs-TnT with a cutoff level of 14 ng/l (97.7% vs. 82.0%, p<0.001) respective of cTnT with a cutoff level of 10 ng/l (93.5% vs. 75.6%, p<0.001). In multivariate Cox analysis, copeptin, hs-TnT and cTnT were strong and independent predictors of 24-month-mortality. Using the dual marker strategy (copeptin and troponin) identified two groups of high-risk patients where 22.5% of the group with hs-cTnT and copeptin above the cutoff and 28.6% with cTnT and copeptin above the cutoff died. CONCLUSION: In diabetic patients, copeptin only slightly improves the early diagnosis of AMI provided by hs-cTnT. However, both markers (copeptin and troponin) predict long-term mortality accurately and independently of each other.

Adjustments of heart failure medication after implantation of a cardiac resynchronization therapy defibrillator.

AIM: "Optimal" medical therapy is mandatory before implantation of a cardiac resynchronization therapy (CRT) device, but "optimal" is not further specified. We determined the number of patients on a specific drug, the percentages of recommended target doses of the drugs the patients were on and their evolution over time. METHODS: Drug therapy (ACE-inhibitors (ACE-I), AT-receptor antagonists (ARBs), betablockers) of 140 patients with a follow-up of at least one year was studied. Response to CRT was defined as reduction in NYHA class ≥1. RESULTS: Age was 66±9 years, follow-up 43±25 months during which 28 patients (20%) had died. At baseline, 81 % of patients were on a betablocker compared to 95% after 3 years (P-value 0.02). Percentages of target doses were 55±34% and increased to 68±41% after 3 years (P-value <0.02). Percentages were increased in responders (58±40% to 72±32%, P-value 0.01 after 3 years), but not in non-responders (57±31% to 56±38%). At baseline, 97% of patients were on ACE-Is/ARBs and 100% after 3 years. Mean percentages of target doses were 78±43% at implant and between 73±40% and 79±49% during follow-up. Percentages were stable both in responders (83% at implant, 78% after 3 years) and in non-responders (80%/87%, both P-value n.s.). CONCLUSION: Even though quantity and quality of drug therapy at baseline was on an acceptable (betablockers) or high (ACE-Is/ARBs) level, physicians must be very observant on therapy during long-term follow-up, especially on target doses of betablockers in non-responders.

Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial.

OBJECTIVE: To investigate whether there is an increased risk of cardiac events with a combined therapy of clopidogrel and proton pump inhibitors (PPIs) after percutaneous coronary intervention (PCI). DESIGN: In the BAsel Stent Kosten Effektivitäts Trial (BASKET), all patients undergoing PCI received 6 months of clopidogrel and were analysed for the use of PPI therapy. Endpoints were major adverse cardiac events (MACE), myocardial infarction (MI), death and target vessel revascularization (TVR) after 36 months. RESULTS: Of 801 patients with available discharge medication data, 109 (14%) received PPIs. Patients who received PPIs were older (66.5 ± 10.5 vs. 63.3 ± 11.3 years, P = 0.006), more likely to be woman (80% vs. 69%, P = 0.009) and have a history of diabetes (29.6% vs. 17.3%, P = 0.002) or gastrointestinal ulcer disease (8.3% vs. 3.3%, P = 0.015) and more often received nonsteroidal anti-inflammatory drugs (7.3% vs. 2.2%, P = 0.003) and corticosteroids (11% vs. 3.6%, P = 0.001) but not aspirin (91.7% vs. 97%, P = 0.008) compared with those who did not receive PPIs. Patients who received PPI therapy had higher rates of MACE (30.3% vs. 20.8%, P = 0.027) and MI (14.7% vs. 7.4%, P = 0.01) but similar rates of death (9.2% vs. 7.4%, P = 0.51) and TVR (20.2% vs. 15.3%, P = 0.2) compared with those who did not. By multivariate analysis, diabetes (hazard ratio 1.83, 95% confidence interval 1.07-3.15) and PPI use (hazard ratio 1.88, 95% confidence interval 1.05-3.37) were the only independent risk factors for MI. CONCLUSION: In a real-world PCI population, the combination of PPIs and clopidogrel was associated with a doubling of MI rates after 3 years. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of outcome emphasizing the clinical importance of this drug-drug interaction.

Characterization and financial impact of implantable cardioverter-defibrillator patients without interventions 5 years after implantation.

BACKGROUND: Implantable cardioverter defibrillators (ICD's) are increasingly used for primary and secondary prevention of sudden cardiac death. However, data on how many ICD patients indeed receive appropriate ICD therapy during long-term follow-up is scarce. AIM: The aim of our study was to determine the number of patients without appropriate ICD therapy 5 years after ICD implantation, to identify predicting factors, to assess the occurrence of late first ICD therapy and to quantify the financial impact of ICD therapy in a real-world setting. DESIGN: Prospective observational study. METHODS: We prospectively enrolled 322 consecutive ICD patients. Baseline data were collected at implantation and patients were followed for a median of 7.3 years (IQR 5.8-9.2 years). Time to first appropriate ICD therapy (either antitachycardia pacing or cardioversion) was documented. RESULTS: Five years after implantation, 139 patients (43%) had not received appropriate ICD therapy. In multivariable analysis, a primary prevention indication and negative electrophysiological studies prior to ICD implantation were independent predictors of freedom from ICD therapy. Of the patients without ICD therapy, 5 years after implantation, 25% had experienced inappropriate ICD shocks. Two hundred and seven devices (1.5 devices per patient) were needed for the 139 patients without ICD intervention within 5 years, accounting for € 31,784 per patient. During an additional follow-up of 3 years, 12% of the patients with unused ICD received a late first appropriate ICD therapy. CONCLUSION: About half of the ICD patients receive appropriate ICD therapy within 5 years after implantation. Furthermore, there is a significant proportion of patients receiving late first shocks after five initially uneventful years.

Therapy with an implantable cardioverter defibrillator (ICD) in patients with coronary artery disease and dilated cardiomyopathy: benefits and disadvantages.

Contemporary guidelines refer to ICD implantation in patients who experienced ventricular tachycardia or fibrillation as secondary prevention, and in well-defined high risk groups as primary prevention. Randomised studies were performed in patients with coronary artery disease and in non-ischaemic cardiopathies, chiefly dilated cardiomyopathy. After four years' follow-up the absolute risk reduction was some 10% in secondary prevention and 8-20% in primary prevention, depending on the patient population. As only approx. 50% of ICD patients will receive appropriate therapies during long-term follow-up, reasonable risk stratification is crucial. However, apart from ejection fraction of <35%, all other echo- or electrocardiographic factors studied have thus far failed to have significant impact to determine risk in advance. In a retrospective analysis comorbidities such as advanced age, renal failure and atrial fibrillation have been shown to influence the effect of an ICD. During long term follow-up inappropriate shocks, lead complications, premature battery depletion and anxiety are some of the most significant problems for an ICD patient.

Epidemiology of atrial fibrillation.

Atrial fibrillation is the most common sustained cardiac arrhythmia in the general population. Unfortunately, current treatment strategies aiming at the elimination of atrial fibrillation have limited long term success rates and significant risks. In this context, recent publications have provided many insights on potentially treatable risk factors for the occurrence of atrial fibrillation, such as alcohol, blood pressure, obesity, inflammation and nutritional factors. In this review, we summarise the current evidence on these risk factors and indicate areas in need of further investigation. The current evidence shows that blood pressure, hypertension and obesity seem to play a key role in the pathogenesis of atrial fibrillation. Preliminary evidence also suggests that inflammation is an important mediator of these associations. Knowledge of these interrelationships may eventually help to develop new treatment strategies and decrease the burden of atrial fibrillation in the general population.

Cardiological diagnostic work-up in stroke patients--a comprehensive study of test results and therapeutic implications.

BACKGROUND AND PURPOSE: In some Western countries, many stroke patients undergo routine tests including ECG, echocardiography, carotid ultrasound and Holter monitoring, even though they have been shown to express limited value in unselected patients. Comprehensive data on yield of tests, especially on consequences taken from positive test results, are scanty. METHODS: Consecutive stroke patients with evidence of ischaemic lesions by imaging techniques were included. Aetiology was determined using TOAST-classifications. Rates of positive test results and their impact on drug therapy, especially anticoagulation were evaluated. RESULTS: Two hundred and forty-one consecutive patients, age 69 +/- 13 years were included. Positive test results were documented in 19% with 12-lead ECG, 24% with carotid ultrasound, 24% with echocardiography and never with Holter monitoring. Overall, in 41% positive test results were present. Apart from echocardiography (37%), a change of therapy resulted in 51-56% of patients with a positive test result. CONCLUSIONS: Even though 12-lead ECG, carotid ultrasound and echocardiography only had relatively low incidences of positive findings, their impact on management in case of positive test results was quite high. Nevertheless, future studies to select patients more appropriately are needed. In contrast, Holter monitoring had no impact and should not be used in routine evaluation of stroke patients.

Holter monitoring for syncope: diagnostic yield in different patient groups and impact on device implantation.

BACKGROUND: Holter monitoring is routinely used in patients referred for the evaluation of syncope, but its diagnostic value in different patient groups is unclear, as is its impact on device implantation (pacemaker or cardioverter-defibrillator). AIM: To determine the diagnostic yield of Holter monitoring in the routine evaluation of syncope, and its impact on subsequent device implantation. DESIGN: Retrospective record review. METHODS: We reviewed all Holter studies in patients referred with syncope between 2000 and 2005. Strict criteria were applied to determine whether a study was diagnostic. The diagnostic value of Holter monitoring (overall and in five subgroups: age, gender, structural heart disease, ejection fraction, medication) and its impact on the implantation of devices, were determined. RESULTS: Of 4877 Holter studies, 826 were performed in patients with syncope (age 72 +/- 15 years): 71 (8.6%) were considered to explain the syncope. Structural heart disease, ejection fraction and age were significant predictors of a diagnostic study (all p < 0.01), whereas gender and cardiac medication were not. A device was implanted in 33 patients (4.4%) whose initial Holter did not explain their syncope, after mean 7 months, whereas 45 patients (5.4%) received a pacemaker based on the Holter results (p = 0.32). DISCUSSION: The overall diagnostic yield of Holter monitoring in the evaluation of syncope was 8.6%, with dramatic differences between subgroups. Our data suggest that the impact of Holter monitoring on device implantation is generally overestimated.

A randomized trial comparing two different approaches of pacemaker selection.

AIMS: DDD-pacemakers are favoured in patients with sick-sinus-syndrome or AV-block. However, AAI-pacemakers for sick-sinus-syndrome or VDD-pacemakers for AV-block may provide similar benefit with lower costs. The aim is to show that a tailored approach (TA) with arrhythmia-specific pacemaker selection was equal to a standard approach (SA) regarding quality of life (QoL) at lower costs. METHODS AND RESULTS: The study was prospective and randomized with QoL as primary endpoint. Secondary endpoints were a combined endpoint of all-cause mortality, worsening heart failure or angina, atrial fibrillation (AF), stroke, these endpoints individually and costs. Of 198 patients (age 77 +/- 10 years, 43% female, ejection fraction 54 +/- 12%, follow-up 38 +/- 15 months), 94 were randomized to SA and 104 to TA. Thirty-two patients (34%) died in the SA group vs. 25 (24%) in the TA (P= ns). QoL showed no differences in all dimensions. The combined secondary endpoint was reached more frequently with SA (51%) compared to TA (37%, P = 0.045). There was no difference regarding all single secondary endpoints. Hardware costs were reduced by 15% (P < 0.0001). CONCLUSION: In long-term follow-up, a TA is equal to SA regarding the primary endpoint QoL and secondary endpoints as AF and mortality. Depending on the healthcare system, it may significantly reduce costs.

Impact of contemporary emergency percutaneous coronary angioplasty for acute myocardial infarction on length of hospital stay.

QUESTIONS UNDER STUDY: Compared to thrombolysis, acute percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) allows both immediate revascularisation and identification of additional relevant stenosis, so that subsequently no further risk stratification should be necessary and hospital stay shortened. Our aim was to evaluate the impact of PCI on outcome and length of hospital stay after MI compared to that in the thrombolysis era. METHODS: Retrospective evaluation in a Swiss tertiary referral centre of 105 patients with AMI undergoing emergency PCI, who initially were neither in cardiogenic shock nor transferred to another primary or secondary care hospital for further treatment. Main outcome measurement was length of overall hospital stay. Additional measurements included mortality, left ventricular function, and time point of the last major adverse cardiac event (MACE). RESULTS: Overall hospitalisation time was 11.1 +/- 6.8 days, thus being only 1.5 days shorter than in the thrombolysis era. Age above 70 or type of infarction did not influence hospitalisation time, but age below 60 years did. In-hospital mortality was 1%. Left-ventricular function was considerably impaired (<35%) in 6 patients. After the sixth hospital day, 97% of MACE had occurred. According to a validated risk score, 92% of patients belonged to a low risk group with a 30-day mortality risk of 1.4% or less and could have been discharged not later than day 6. CONCLUSIONS: Our data suggest that an early discharge strategy, although safe in low risk patients is not followed at the present time. This approach could further reduce costs without jeopardizing outcome.

What are the professional and logistic demands to appropriately follow patients with an implantable cardioverter-defibrillator?

OBJECTIVES: To determine events during follow-up of patients with implantable cardioverter-defibrillators (ICD) and the specific experience cardiologists need for trouble-shooting. DESIGN: Prospective evaluation of all patient visits in an outpatient clinic. SETTING: University hospital, single centre performing ICD controls in a region of 1.5 Mio inhabitants. SUBJECTS: A total of 351 patients with 1118 consecutive visits during 14 months. INTERVENTIONS: Classification of events according to predefined training levels. MAIN OUTCOME MEASUREMENTS: Skill levels A: simple visit, e.g. for switching the device 'off'. B: normal visit, no further measures taken (no device reprogramming), even though the patient might have experienced ICD interventions. C: complex visit, electrophysiologist actively involved. Correlation of these levels with timing (routine, emergency on/off office hours) and reason of visits. RESULTS: Seventy-six per cent of visits were scheduled routine visits, 5% performed within 24 h because of shocks, 19% performed for other reasons (shock tests; switching the device 'off/on'; reported dizziness, syncope, palpitations without ICD interventions). Required skill levels were A in 44 (4%), B in 796 (71%) and C in 278 (25%) visits. Emergency visits were more often classified as level C (60%) than regular visits (20%), Skill level C was more often encountered during emergency (30%) than during regular visits (6%) (both P = 0.001). CONCLUSIONS: Our study suggests that for standard follow-up in patients without obvious problems, a cardiologist might be sufficient, whereas presentations due to/with clinical problems most likely will need the expertise of an electrophysiologist.

Selection bias of elderly patients with chronic angina referred for catheterization.

BACKGROUND: Registry patients are generally older and more sick than patients enrolled in trials questioning the generalizability of trial results. We assessed whether such a selection bias also exists in elderly patients with chronic angina referred for catheterization. METHODS AND RESULTS: All 119 patients age>or=75 years with Trial of Invasive versus Medical Therapy in the Elderly (TIME) inclusion but no major exclusion criteria referred for catheterization during the TIME trial inclusion period in four TIME centers were registered and followed-up for one year. Registry patients differed from the 188 trial patients in the same hospitals in that they were younger, somewhat more frequently male, with less antianginal drugs and studied more often after acute chest pain at rest but with more comorbidities than study patients. Left ventricular ejection fraction and vessel disease were similar. One year mortality was 11.4% in registry and 9.6% in invasive TIME patients but differences disappeared after adjustment for baseline differences. Symptomatic status after one year was similar too. CONCLUSIONS: In elderly patients with chronic angina, a bias in the selection for invasive management exists which seems different from that reported in younger patient settings. After adjustment for these selection factors, however, one-year outcome was remarkably similar in registry and trial patients.

[Cardiac resynchronization therapy (CRT)--a new option for severe heart failure]. / Cardiac Resynchronization Therapy (CRT)--eine neue Option bei schwerer Herzinsuffizienz.

The increasing incidence of heart failure is an important issue in cardiovascular medicine. Apart from pump failure, conduction disturbances and arrhythmias may play a major role and must be considered when selecting the therapy. In addition to optimal drug therapy, cardiac resynchronization (CRT) with biventricular stimulation offers a new therapeutic option.

[Extraordinary findings after radiofrequency ablation]. / Aussergewöhnliche Befunde nach Radiofrequenzablation.

We report the successful treatment with Heparin and Phenprocoumon of a large, free-floating, right atrial thrombus that developed after radiofrequency ablation (RFA) of an accessory pathway in a 24 year old patient with Wolff-Parkinson-White (WPW) Syndrome. In addition, "T-wave memory", a relatively common phenomenon after RFA in WPW-Syndrome, is demonstrated.

Value of routine holter monitoring for the detection of paroxysmal atrial fibrillation in patients with cerebral ischemic events.

BACKGROUND AND PURPOSE: Holter monitoring for the detection of paroxysmal atrial fibrillation (PAF) is a routine procedure after cerebral ischemic events, although its value is unknown. The aim of this study was to evaluate the incidence of PAF and its impact on drug treatment modifications in this population. METHODS: Retrospective evaluation of all Holter ECGs in patients with cerebral ischemic events was done. Chart analysis with regard to drug treatment modification and cardiovascular drug therapy was performed in all patients. RESULTS: Between January 2000 and December 2002, 425 hospitalized patients (median age, 68 years) had routine Holter ECG after a cerebral ischemic event. PAF was diagnosed in 9 patients (2.1%): in 2, oral anticoagulation was contraindicated; 1 had severe carotid stenosis as an additional risk factor; 1 had PAF but was on oral anticoagulation for basilar thrombosis; 2 had had PAF before and were on aspirin; and 3 had a new diagnosis of PAF. The last 5 patients were put on oral anticoagulation. Thus, routine Holter ECG resulted in drug treatment modification in only 5 of 425 patients (1.2%). CONCLUSIONS: PAF in cerebral ischemic event patients has a low incidence and, if diagnosed, rarely leads to drug modification. Therefore, routine Holter monitoring for PAF screening is not recommended in this patient population.

Elevated troponin levels in absence of coronary artery disease after supraventricular tachycardia.

Generally speaking elevated troponin levels are consistent with the diagnosis of acute coronary syndrome and haemodynamically relevant coronary artery stenosis. However, they may also point to minor myocardial injury in other circumstances. Four patients with elevated troponin levels after supraventricular tachycardia without evidence of coronary artery disease and very low risk scores for acute coronary syndrome are described and discussed.