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Funding Acknowledgements Type of funding sources: None. Background Over the last years, the concept of multidisciplinary pulmonary embolism response teams (PERTs) has emerged to encounter the increasing variety and complexity in the management of acute pulmonary embolism (PE). Purpose To investigate the composition and added clinical value of PERT in our city. Methods Over a 5-year period (01/2017-09/2022), patients with confirmed PE were enrolled in a prospective single-centre cohort study (PERT). We investigated the composition of PERT and compared, after propensity score matching, patients with acute PE prior and after the formation of PERT at our institution. The primary outcome was in-hospital PE-related mortality before and after the formation of PERT. Results During the period from 2017 to 2022, 88 patients with acute PE with a PERT decision were registered. Of those, 13 (14.8%) patients died during the in-hospital stay. Patients evaluated by a PERT had a mean age of 68 years; among these 48.9% were females, and 21.7% suffered from malignancy. Right ventricular dysfunction was present in 84.9% of the patients. In total, 42.0% were classified as intermediate-risk PE and 11.6% as high-risk PE. First PERT contact originated mostly by emergency departments (33.3 %) and intensive care unit (30.0%), followed by chest pain unit (21.3%) and regular ward (12.0%) (Figure 1a). The participation rate of specialties demonstrated that cardiologists (100%) or cardiac/vascular surgeons (98.6%) were included in almost all PERT activations followed by radiologist (95.9%) or anesthesiologist (87.8%). Further disciplines were present in few cases as summarized in Figure 1b. When comparing patients characteristics of the pre-PERT era with the PERT era, more patients were classified as sPESI ≥1 and as high-risk according to ESC 2019 guidelines in the pre-PERT era (78.4% and 18.2%) opposed to the PERT era (71.6 and 11.4%) (Figure 2). A considerable higher all-cause mortality (31.8% vs. 14.8%) and PE-related mortality rate (22.7% vs. 13.6%) was observed in patients in the pre-PERT era compared to the PERT era. After propensity matching (1:1) by including parameters as age, sex, sPESI and ESC risk classes, an univariate regression analyses demonstrated, that the PE management based on a PERT-decision was associated with lower risk of all-cause mortality (OR, 0.37 [95%CI 0.18-0.77]; p=0.009) and PE-related mortality (OR, 0.54 [95%CI 0.24-1.18]; p=0.121) compared to patients without a PERT-decision. Conclusion PERT implementation tended to reduce the mortality rate in patients with acute PE. Large prospective studies are needed to further explore the impact of PERTs on clinical outcomes.

Background Over the last years, the concept of multidisciplinary pulmonary embolism response teams (PERTs) has been developed to encounter the increasing variety and complexity in the management of acute pulmonary embolism (PE), but data on the use and the benefit of PERT are sparse. Purpose We aimed to systematically investigate the composition of PERT and its clinical value in clinical routine across different countries. Methods We searched PubMed, CENTRAL and Web of Science until January 2022 for full-text, prospective and retrospective observational studies, which included patients with acute PE who were evaluated by a PERT. Eligible articles were designed to either describe the structure and function of PERTs and/or to investigate outcomes related to the implementation of PERT. We performed a random-effects meta-analysis of controlled studies (PERT vs. pre-PERT era) to investigate the impact of PERTs on clinical outcomes and use of advanced therapies. Results We included 22 original studies and four surveys. Overall, 31.5% of patients with PE were evaluated by PERT referred mostly by emergency departments (59.4%). In total, PERT involved a median of 6 (range 2–10) specialties for guiding further diagnostic and treatment modalities. Patients evaluated by a PERT had a mean age of 60 years; of them, 48.7% were females, and 23.5% suffered from malignancy. Right ventricular dysfunction was present in 55% of the patients. In total, 74.5% were classified as intermediate-risk PE and 16% as high-risk PE. In eleven single-arm studies, 1,532 patients with intermediate- and high-risk PE were evaluated by PERT with a mortality rate of 10% and a bleeding rate of 9%. The mean length of stay was 7.3 days and the use of advanced therapy was reported in 30% of all cases. From these, catheter-directed treatment (CDT) was performed in 22% and inferior vena cava filter was inserted in 15%, while systemic thrombolysis was administered in only 6%, surgical thrombectomy in 2% and ECMO in 3% of all cases. When comparing PERT and pre-PERT era no difference in mortality (risk ratio [RR] 0.89, 95% confidence interval [CI] 0.67–1.19, I2=63%) was observed based on nine controlled studies, while mortality tended to be lower when including only intermediate and high-risk patients in the analysis (RR 0.71, 95% CI 045–1.12) (Figure 1). The use of advanced therapies was more common (RR 2.67, 95% CI 1.29–5.50) and the in-hospital stay as well as the duration of treatment in intensive care unit was shorter (mean difference −1.6 days and −1.8 days, respectively) in the PERT era. Conclusion PERT implementation tended to reduce the mortality rate in patients with intermediate- and high-risk PE and resulted in a shorter in-hospital stay. Large prospective studies are needed to further explore the impact of PERTs on clinical outcomes. Funding Acknowledgement Type of funding sources: None.

Background Unselected data of nationwide studies of hospitalized patients with COVID-19 is still sparse, but these data are of outstanding interest not to exceed hospital capacities and to avoid overloading of national health-care systems. Purpose Thus, we sought to analyze seasonal/regional trends, predictors of in-hospital case-fatality and mechanical ventilation (MV) in patients with COVID-19 in Germany. Methods We used the German nationwide inpatient sample to analyze all hospitalized patients with confirmed COVID-19 diagnosis in Germany between January 1st and December 31st in 2020 (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2020, own calculations). Covid-19-inpatients with MV vs. without MV and survivors vs. non-survivors were compared. Logistic regression models were calculated to investigate associations between patients' characteristics as well as adverse events and i) necessity of MV and ii) in-hospital death. Results We analyzed data of 176,137 hospitalizations of patients with confirmed COVID-19-infection. Among those, 31,607 (17.9%) died, whereby in-hospital case-fatality grew exponentially with age. Cardiovascular comorbidities were common in hospitalized patients with confirmed COVID-19-infections: Overall, almost half of the patients (46.8%; n=82,480) had arterial hypertension and 25,574 (14.4%) had a diagnosis of coronary artery disease. In 60.7% (n=106,913) of the hospitalizations, pneumonia was reported, 8.6% (n=15,061) had an acute infection of the upper or lower airways other than pneumonia, and 6.6% (n=11,594) suffered from an acute respiratory distress syndrome (ARDS) during hospitalization Age ≥70 years (OR 5.91, 95% CI 5.70–6.13, P Conclusion The results of our study indicate seasonal and regional variations concerning number of COVID-19-patients, necessity of MV and case-fatality in Germany. These findings may help to ensure flexible allocation of intensive care (human) resources, which is essential for managing enormous societal challenges worldwide to avoid overloaded regional health-care systems. Funding Acknowledgement Type of funding sources: None.

Background Pulmonary embolism (PE) is responsible for considerable personal and societal costs. Detailing this burden would support an efficient public health resource allocation. However, cost estimates so far have failed to account for both resource utilization and excess costs in its long-term management beyond the acute phase. Purpose To provide estimates for the economic and disease burden of PE in the European Union (EU) also accounting for long-term healthcare utilization and costs beyond the acute phase. Methods This is a cost-of-illness analysis, from a societal perspective, with a bottom-top approach and a time horizon of 12 months based on data from the PREFER in VTE registry. We calculated direct and indirect costs of an acute PE event and its 12-month follow-up. We used cost inputs derived from the literature and as directly reported in the PREFER in VTE registry and we adjusted them for inflation and purchasing power parity to 2020 Euros (€). Total average costs per PE patient comprised six general categories: costs for the index PE hospitalization; costs for clinical events during follow-up; costs for anticoagulation after the index event; costs for ambulatory visits during follow-up; the patient's own contribution; and costs related to productivity loss (using the friction cost method). A stratified analysis was performed according to the presence of active cancer, non-cancer provoked PE, and unprovoked PE. In addition, we used the EQ-5D health questionnaire to derive a disability weight for the post-PE state 12 months after the index event and the corresponding disability adjusted life years (DALYs) presumably due to PE. Results Annual disease-specific costs for each incident PE case ranged between 9,135 € and 10,620 €. Costs for patients with cancer (8,274 to 9,752 €) and patients with unprovoked PE (8,695 to 9,612 €) were lower than costs for non-cancer patients with provoked PE (10,423 to 11,307 €), mainly due to differences in productivity loss. The indirect costs were mainly driven by productivity losses and their proportion to total costs was 42–49% for the overall population (28–33% for cancer, 52–56% for non-cancer provoked PE and 43–47% for unprovoked PE) (Figure 1). Anticoagulation accounted for 18–21% of total costs for cancer patients (while only 5–6% for non-cancer patients) and was primarily driven by the use of low-molecular-weight heparins and fondaparinux (Figure 2). The calculated disability weight for cancer-free survivors of PE 12 months after the index event was 0.017 (bootstrapped 95% CI 0.0002–0.0344) and the estimated annual DALYs per incident case were 1.17 (bootstrapped 95% CI 0.75–1.59). Conclusion PE imposes a significant annual economic burden, for which productivity loss is the main driver. Total costs in the EU could range between 0.5 and 3.8 billion €. The disease burden from PE is notable and translates to the loss of roughly 1.2 years of healthy life per incident PE case per year. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This study was supported by an unrestricted grant from Daiichi Sankyo (Title: “Filling the gaps of knowledge on healthcare outcomes during long-term anticoagulant treatment of pulmonary embolism”, grant number DSE-DE-CV-20001).

Background The COVID-19 pandemic caused a large number of excess deaths. COVID-19 emerged as a prothrombotic disease often complicated by pulmonary embolism (PE). In light of this, we hypothesized that PE-related mortality rates (stable before the pandemic) would be characterized by an increasing trend following the COVID-19 outbreak. Purpose To investigate the mortality rates associated with PE among deaths with or without COVID-19 during the 2020 pandemic in the United States (US). Methods For this retrospective epidemiological study, we analyzed public medically certified vital registration data (death certificates encompassing underlying and multiple causes of death) from the Mortality Multiple Cause-of-Death database provided by the Division of Vital Statistics of the US Centers for Disease Control and Prevention (CDC; US, 2018–20). We investigated the time trends in monthly PE-related crude mortality rates for 2018–2019 and for 2020 (the latter associated vs. not associated with COVID-19), utilizing annual national population totals from the US Census Bureau. Second, we calculated the PE-related proportionate mortality among COVID-19 deaths (overall and limited to autopsy-based diagnosis). We performed subgroup analyses based on age groups, sex and race. Results During 2020, 49,423 deaths in association with PE were reported, vs. 39,450 in 2019 and 38,215 in 2018. The crude PE-related mortality rate without COVID-19 was 13.3 per 100,000 population in 2020 compared to 11.7 in 2018 and 12.0 in 2019 (Figure 1A). The PE-related mortality rate with COVID-19 was 1.6 per 100,000 population in 2020. Among non-COVID-19-related deaths, the crude PE-related mortality rate was higher in women; among COVID-19-related deaths, it was higher in men. PE-related mortality rates were approximately two-fold higher among black (vs. white) general population irrespective of COVID-19 status (Figures 1B and 1C). Among COVID-19 deaths, PE-related deaths corresponded to 1.4% of total; the value rose to 6.0% when an autopsy was performed. This figure was higher in men and its time evolution is depicted in Figure 2A. The proportionate mortality of PE in COVID-19 deaths was higher for younger age groups (15–44 years) compared to non-COVID-19-related deaths (Figure 2B). Conclusion In 2020, an overall 20%-increase in PE-related mortality was reported, not being limited to patients with COVID-19. Our findings could be interpreted in the context of undiagnosed COVID-19 cases, uncounted late sequelae, and possibly sedentary lifestyle and avoidance of healthcare facilities during the pandemic that may have prevented timely diagnosis and treatment of other diseases. Whether vaccination programs had an impact on PE-associated mortality in the year 2021, remains to be determined. Funding Acknowledgement Type of funding sources: None.

Aims: Despite the existence of many studies, there are still limited data about the characteristics of myocarditis in Greece. This led to the creation of the Greek Myocarditis Registry aiming to document the different symptoms and treatment of myocarditis, assess possible prognostic factors, and find similarities and differences to what is already published in literature. This paper is a preliminary descriptive analysis of this Registry. Methods and results: We analysed data for the hospitalization period of all patients included in the Registry from December 2015 until November 2017. Statistics are reported as frequency (%) or median and inter-quartile range (IQR) as appropriate. In total, 146 patients were included; 83.3% of the patients reported an infection during the last 3 months. The most common symptom, regardless of the underlying infection, was chest pain (82.2%) followed by dyspnoea (18.5%), while the most common finding in clinical examination was tachycardia (26.7%). Presentation was more frequent in the winter months. ECG findings were not specific, with the repolarization abnormalities being the most frequent (60.3%). Atrial fibrillation was observed in two patients, both of whom presented with a reduced ventricular systolic function. Left ventricular ejection fraction changed significantly during the hospitalization [55% (IQR: 50–60%) on admission vs. 60% (IQR: 55–60%) on discharge, P = 0.0026]. Cardiac magnetic resonance was performed in 88 patients (61%), revealing mainly subepicardial and midcardial involvement of the lateral wall. Late gadolinium enhancement was present in all patients, while oedema was found in 39 of them. Only 11 patients underwent endomyocardial biopsy. Discharge medication consisted mainly of beta-blockers (71.9%) and angiotensin-converting enzyme inhibitors (41.8%), while 39.7% of the patients were prescribed both. Conclusions: This preliminary analysis describes the typical presentation of myocarditis patients in Greece. It is a first step in developing a better prognostic model for the course of the disease, which will be completed after the incorporation of the patients' follow-up data. © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology

ZusammenfassungDie Thrombolyse ist eine längst etablierte Therapie des akuten Myokardinfarktes mit persistierender ST-Elevation (STEMI). Von dieser Therapieform profitieren jedoch überwiegend Patienten, die innerhalb der ersten zwei Stunden nach Beginn der Symptomatik behandelt werden. Im Gegensatz zur Thrombolyse ist die Effektivität der mechanischen Rekanalisation (PCI) in Bezug auf die komplette Reperfusion sehr hoch und unabhängig von der Dauer der Symptomatik. Nach den Ergebnissen kürzlich veröffentlichter Untersuchungen scheinen Patienten mit STEMI mehr von einer sofortigen Verlegung in ein PCI-Zentrum als von einer Thrombolyse vor Ort zu profitieren. Diese Strategie wird daher grundsätzlich in den aktualisierten Leitlinien deutscher und internationaler Fachgesellschaften befürwortet. Der transportbedingte Zeitverlust darf allerdings nicht länger als 60 bis 90 Minuten betragen.

Die venose Thromboembolie bleibt weiterhin eines der haufigsten und gefahrlichsten akuten kardiovaskularen Syndrome. Ihre Inzidenz ist in den vergangenen Jahren sowohl in Europa als auch in den USA konstant geblieben und betragt ca. 1,5 Falle/1000 Einwohner/Jahr [24, 29]. Jedes Jahr erfolgen ca. 100 Krankenhauseinweisungen/100.000 Einwohner wegen venoser Thromboembolie, und 10% dieser Patienten versterben wahrend des Krankenhausaufenthalts. Besonders alarmierend ist schlieslich die Tatsache, dass bei 50–70% aller Patienten, die an akuter Lungenembolie versterben, die Diagnose erst nach dem Tod gestellt wird [28]. Diese Fakten unterstreichen nicht nur die epidemiologische Relevanz des Problems „akute Lungenembolie“, sondern auch die Notwendigkeit einer Optimierung der aktuellen diagnostischen und therapeutischen Strategie. Dabei erweist sich die rasche Erkennung eines akuten Cor pulmonale mittels Echokardiographie und kardialer Biomarker als besonders hilfreich.

This position paper summarises current developments in chronic thromboembolic pulmonary hypertension (CTEPH) including diagnostic approaches and treatment options. Based on the guidelines of the task force of CTEPH experts at the 5th World Symposium on Pulmonary Hypertension in Nice 2013. Open questions arising during the treatment of patients with CTEPH are addressed. Patients with suspected CTEPH should undergo echocardiography and cardiopulmonary exercise testing. A ventilation/perfusion scan is the recommended imaging test for screening in the diagnostic algorithm for the evaluation of CTEPH. CTEPH-patients should be discussed in an expert center with an interdisciplinary team and an experienced PEA surgeon to decide the further treatment. Pulmonary endarterectomy (PEA) is the treatment of choice for patients with CTEPH. Medical therapy with PH-targeted medications for inoperable CTEPH and residual disease after PEA should only be initiated if evaluation reveals that the patient is no candidate for a PEA. Current data suggest that CTEPH patients treated with PEA have a better long-term survival rate and quality of life than patients treated with medical therapy.

Ungeachtet der Schwierigkeiten bei der Bestatigung einer paradoxen Embolie konnte der Zusammenhang zwischen dem Vorliegen eines ventiloffenen Foramen ovale (PFO) und zerebraler Ischamie-Ereignisse unklarer Ursache wiederholt nachgewiesen werden. Daruber hinaus wurde berichtet, das das Risiko von Embolie-Rezidiven bei diesen Patienten 3–4% pro Jahr betragt. Eine zuverlassige Risikostratifikation der Patienten mit PFO auf der Basis klinischer oder echokardiographischer Befunde ist bisher – mit Ausnahme der hamodynamisch wirksamen Lungenembolie – in der Regel nicht moglich. Das Vorliegen eines Vorhofseptumaneurysmas und eine weite Offnung des PFO wahrend des Herzzyklus oder ein groser interatrialer Shunt bei der transosophagealen Kontrast-Echokardiographie werden jedoch von manchen Autoren als Risikofaktoren angesehen. Die sekundare Pravention paradoxer Embolien mittels oraler Antikoagulanzen (Warfarin) beinhaltet das Risiko einer signifikanten Blutung (Inzidenzrate 2–5% pro Jahr) und mangelhaften Compliance der Patienten. Auserdem scheint diese Therapieform wenig effektiv zu sein. Der chirurgische Verschlus des PFO ist ein technisch ausgereifter, sicherer Eingriff. Erste Berichte bestatigen seine hohe Effektivitat hinsichtlich der Rezidivprophylaxe, weitere prospektive Studien sind jedoch erforderlich, um die fur eine chirurgische Behandlung geeigneten Patienten festzulegen. Kathetertechnische Verfahren zum PFO-Verschlus stehen ebenfalls zur Verfugung und befinden sich derzeit in der Phase der klinischen Erprobung. Weitere technische Verbesserungen erscheinen jedoch erforderlich, um den Ablauf des interventionellen Eingriffes zu vereinfachen, die Stabilitat dieser Systeme zu erhohen und die Komplikationsgefahr zu minimieren.

Die akute Lungenembolie ist in den vergangenen 30 Jahren eine der haufigsten Todesursachen bei hospitalisierten Patienten geblieben. Diese Feststellung weist auf die Notwendigkeit einer effektiveren diagnostischen und therapeutischen Strategie bei klinischem Verdacht auf Lungenembolie hin. Insbesondere gilt dies fur Patienten, die aufgrund akuter Rechtsherzinsuffizienz und/oder hamodynamischer Instabilitat einer intensivmedizinischen Behandlung bedurfen. Die klinischen und radiologischen Befunde dieser Patienten sind oft unspezifisch und die EKG-Veranderungen im Sinne einer Rechtsherzbelastung nur vorubergehend zu beobachten. Die traditionellen bildgebenden Verfahren (Pulmonalisangiographie, Ventilations-Perfusions-Szintigraphie der Lunge) konnen zwar das thromboembolische Ereignis in der Regel zuverlassig bestatigen oder ausschliesen, sind jedoch mit einem erheblichen zeitlichen Aufwand verbunden und daher fur klinisch instabile Patienten einer Intensiv- bzw. Notaufnahmestation eher nicht geeignet. Auserdem konnen invasive angiographische Untersuchungen zu lebensbedrohlichen Blutungskomplikationen bei thrombolytisch behandelten Patienten fuhren. Dagegen erlaubt die Echokardiographie eine nicht-invasive und am Krankenbett durchfuhrbare Untersuchung, die sofortige Feststellung einer akuten Rechtsherzbelastung und somit die Diagnose einer hamodynamisch wirksamen Lungenembolie. In diesem Fall ist aufgrund des erhohten Todes- und Komplikationsrisikos zusatzlich zur konventionellen Heparin-Antikoagulation eine thrombolytische Behandlung auch bei fehlenden klinischen Zeichen einer Kreislaufinstabilitat zu empfehlen. Andererseits sollten Patienten mit echokardiographischem Nachweis frei flottierender intrakardialer Thromben sofort operativ behandelt werden.

Acute venous thromboembolism is a common cardiovascular emergency. Acute pulmonary embolism (PE) is present in one third of these patients. With an average lethality rate of 11% within the first two weeks following diagnosis, approximately 40,000 patients in Germany die annually as a result of PE; therefore, their diagnosis and therapy is of particular importance. For this reason, the European Society of Cardiology published guidelines on diagnosis and therapy in 2000. The current article presents and discusses the points as updated and extended in the 2008 version of the guidelines, including: (1) initial risk stratification--when PE is already suspected; (2) diagnostic procedures and algorithms; (3) further risk stratification; (4) therapeutic strategies in the acute phase; (5) further management and (6) long-term anticoagulation and secondary prophylaxis.

Management of venous thromboembolism has long been characterized by a high degree of complexity and a disappointing lack of both efficacy and efficiency. The non-specific clinical signs of acute pulmonary embolism (PE) and the limitations of earlier imaging procedures such as the lung scan and pulmonary angiography led to the development of numerous sophisticated, multi-step diagnostic algorithms which, however, have proved extremely difficult to implement in clinical practice. As a result, the diagnosis of potentially life-threatening PE was frequently missed in many patients who subsequently died of the disease without receiving appropriate treatment, while other patients unnecessarily underwent a battery of invasive, time consuming procedures due to a vague, poorly documented clinical suspicion. Recently, the development of structured models for assessment of clinical pre-test probability, the widespread use of D-dimer testing in the outpatient setting, and particularly the technical advances of multidetector-row CT scan, had an enormous impact on our strategy for approaching patients with suspected PE. Contemporary diagnostic algorithms based on the above modalities are not only efficient and reliable but also simple and practicable. Furthermore, the importance of right ventricular (RV) dysfunction, even in the absence of overt hemodynamic instability, was recognized, and a number of studies demonstrated the value of echocardiography and laboratory biomarkers for risk stratification of PE. At present, low molecular weight heparins are increasingly becoming established as the treatment of choice for hemodynamically stable patients without RV dysfunction (non-massive PE), while consensus exists that patients with massive PE and cardiogenic shock necessitate emergency removal of pulmonary thrombus using thrombolytic agents, surgical embolectomy, or catheter-based thrombus aspiration. On the other hand, the treatment of stable patients with RV dysfunction (submassive PE) remains the subject of debate, and a large randomized trial is urgently needed to address the possible clinical benefits of thrombolysis in this setting.

Thrombolysis is an established treatment of acute myocardial infarction with persistent ST elevation (STEMI). Thrombolytic agents are most effective in patients who can be treated within two hours of symptom onset. On the other hand, the efficacy of mechanical recanalization (PCI) was consistently shown to be superior to thrombolysis regardless of the duration of symptoms. Recent studies further suggest that it may be preferable for small hospitals to rapidly transfer patients with acute STEMI to a PCI center rather than perform on-site thrombolysis. Therefore, this novel strategy is principally recommended in the updated guidelines of German and international cardiac societies. However, it is emphasized that the transfer-related delay of treatment should not exceed 60-90 minutes.

Venous thromboembolism remains one of the most frequent and threatening acute cardiovascular syndromes. Its incidence has remained constant over the last several years, both in Europe and the United States, accounting for approximately 1.5 cases per 1000 inhabitants per year. Every year about 100 cases of venous thromboembolism per 100,000 inhabitants are admitted to the hospital, and 10% of these patients die during the hospital stay. Particularly alarming is the fact that in 50-70% of all patients who die from an acute pulmonary embolism the diagnosis is only made after death. These facts emphasize not only the relevance of the problem of "acute pulmonary embolism," but also the need for optimization of current diagnostic and therapeutic strategies. Rapid identification of acute cor pulmonale with echocardiography and cardiac biomarkers has recently proven to be especially helpful in this regard.

Notwithstanding the difficulties in definitely confirming paradoxical embolism, the association between patent foramen ovale (PFO) and cryptogenic stroke has repeatedly been demonstrated in clinical studies. Moreover, the recurrence rate of cerebral ischemia in patients with PFO and an unexplained stroke was found to be 3-4% per year in two recently published series. With the exception of right atrial pressure elevation in the setting of major pulmonary embolism, a reliable risk stratification of patients with PFO based on clinical or echocardiographic findings is not yet possible. The presence of atrial septal aneurysm, a wide opening of the defect during the cardiac cycle and a large atrial shunt have been implicated as risk factors by some investigators. Long-term prevention of paradoxical embolism with oral anticoagulants seems to be of questionable benefit. Besides, these agents are poorly tolerated and carry the risk of significant or fatal bleeding at a rate of 2-5% per year. Surgery of the atrial septum has been performed for many decades in patients with atrial septal defect and evidence accumulates that it is a safe and highly effective procedure in patients with PFO. At present, surgical closure of the PFO appears to be the treatment of choice for secondary prevention of paradoxical embolism. However, further studies are needed to define the appropriate candidates for surgical treatment. Devices for catheter-based sealing of PFO are also available and are currently being evaluated in clinical trials. However, experience with their use remains confined to specialized centers. Furthermore, further technical improvements of these systems are needed in order to optimize successful delivery and positioning, increase their long-term stability, and reduce periprocedural complications.

Diagnosing pulmonary embolism (PE) remains a challenge due to the often confusing clinical presentation of the disease. Plasma D-dimer testing with ELISA is increasingly becoming part of the initial diagnostic work up. Due to the high specificity of the assay, a negative test can reliably exclude PE. Importantly, massive PE can be promptly diagnosed or excluded by echocardiography which is a particularly valuable noninvasive method for detection of right ventricular dysfunction at the bedside. High-risk patients can thus be identified and treated immediately without further time-consuming examinations. Confirmation of PE in patients with inconclusive or normal echocardiograms is often based on lung scans, but diagnostic uncertainty is common with this procedure. The popularity of pulmonary angiography is decreasing due to its invasiveness, whereas spiral CT appears to be a promising alternative. Search for (residual) deep vein thrombosis is useful for guiding therapy in stable patients with small pulmonary emboli, since their risk is determined by the potential for PE recurrence. Recent evidence confirmed that right ventricular dysfunction predicts an unfavorable prognosis and might therefore justify thrombolytic treatment of massive PE regardless of systemic hemodynamics. On the other hand, simplified anticoagulation regimens with low-molecular weight heparins have yielded very promising results in stable patients. These diagnostic and therapeutic principles based on cardiovascular risk stratification will hopefully result in a more effective approach to patients with venous thromboembolism in the future.

We are reporting on a 36 year-old woman who presented with recurrent cardiac myxomas over a period of nine years. Two of the tumors typically originated in the left atrium and one in the right atrium. Tumor embolization was the presenting symptom twice, leading to reversible cerebral ischemia and minor pulmonary embolism, respectively. The third tumor remained asymptomatic and was detected during routine echocardiographic examination. Based on a positive family history of cardiac tumors, a facially pronounced hyperpigmentation of the skin and the presence of a thyroid adenoma, the diagnosis of a "myxoma syndrome" was established. Patients with "myxoma syndrome" are generally younger than their counterparts with "sporadic myxoma" (mean age at diagnosis 25 vs. 56 years) and have a high frequency of unusual skin freckling (68%). Familial clustering of cardiac myxomas is also frequent (25%). The tumors may be located in any of the cardiac chambers (87% in the atrias, 13% in the ventricles, 50% at multiple sites simultaneously) and have relatively high (18%) 5-year recurrence rate after surgical excision. Since the clinical signs of cardiac tumors are non-specific, diagnosis essentially relies on cardiac imaging by echocardiography, computer tomography, or angiography. The superiority of transesophageal echocardiography is emphasized in this report.

Two-dimensional and Doppler echocardiography have been widely used for noninvasive determination of valve area in patients with mitral stenosis. Recent studies have indicated that the Doppler-echocardiographic pressure half-time method (PHT) does not accurately predict mitral orifice area (MOA). Therefore, applications of the continuity equation and the Gorlin formula have been used additionally to the PHT for Doppler-echocardiographic assessment of MOA. In a prospective study of 34 patients MOA determined by two-dimensional and Doppler echocardiography was compared with MOA measured by cardiac catheterization (range 0.40 to 1.90 cm2, mean 1.08 +/- 0.37 cm2). There was a moderate correlation between two-dimensional echocardiographic and invasive measurements (r = 0.65, SEE = 0.20 cm2). MOA calculated by the PHT showed only poor correlation with cardiac catheterization (r = 0.38 SEE = 0.37 cm2). We found better correlations for the continuity equation (r = 0.73, SEE = 0.35 cm2) and Doppler-echocardiographic application of the Gorlin formula (r = 0.81, SEe = 0.27 cm2). Doppler-echocardiographic use of the Gorlin formula yielded the best prediction of the severity of mitral valve stenosis (concordance with invasive measurement in 82%).Pressure half-time is only a poor predictor of the severity of mitral valve stenosis. More accurate results are obtained by Doppler-echocardiographic applications of the continuity equation and especially the Gorlin formula.

Transesophageal echocardiography is well established in detecting and diagnosing heart tumors. In contrast, its role in assessing presence, growth and evidence of malignancy of tumors originating from the mediastinal site remains widely uncertain. In a prospective and investigator-blind study, we evaluated 72 consecutive patients with cardiac and/or mediastinal tumor lesions to assess the diagnostic impact of transthoracic and transesophageal echocardiography in determining localization, growth and malignancy. All tumor lesions were diagnosed and carefully evaluated by computer tomography and/or magnetic resonance imaging prior to the study. Biopsy demonstrated a malignant tumor in 49 patients and a benign tumor in 23 patients. Transthoracic and transesophageal echocardiography were equally effective in visualizing tumors of the heart in 24 patients (92% vs 100%; N.S.). Tumors originating from the mediastinum were 2.9 times less likely to be detected by the transthoracic approach (p0.001). In these patients, transesophageal echocardiography was also superior in diagnosing myocardial infiltration (18 vs 4 patients, p0.001) and invasion or intracardiac growth of the tumor (13 vs 6 patients, p0.05). When compared to histological findings, transesophageal echocardiography predicted malignancy from the presence of tumor spread both in- and outside the heart, infiltration and invasion in 21/49 patients (43%), a false positive result was obtained in only 1/23 patients with a benign tumor. Conventional echocardiography predicted malignancy in only 4/49 patients (8%, p0.005). In conclusion, transesophageal echocardiography is increasingly used in patients with suspected mediastinal tumor lesions. Our study demonstrates, that transesophageal echocardiography is effective and superior to the conventional approach in predicting localization and growth of mediastinal tumors, as well as in accessing evidence of malignancy of the tumor.

Doppler echocardiography has been widely used as a noninvasive method to evaluate valvular heart diseases. However, the diagnostic impact of Doppler echocardiography in the evaluation of prosthetic valves is discussed controversially. Reasons are, on one hand, the high variabilities of transvalvular gradients observed for normal prosthetic devices and, on the other hand, results of experimental in vitro studies demonstrating an impressive discrepancy between Doppler-echocardiographic and invasive measurements of the transvalvular gradients in prosthetic valves. In a prospective study, we evaluated 11 out of 335 patients after aortic valve replacement who demonstrated an elevated transvalvular gradient over the prosthetic valve. Eight patients had a St. Jude medical prosthesis (19-23 mm), two patients had a Medtronic Hall prosthesis, and one patient a Björk-Shiley prosthesis. The maximal instantaneous gradient measured by Doppler-echocardiography was 74 +/- 15 mmHg, the mean gradient was 47 +/- 12 mmHg. The prosthetic orifice area calculated by the continuity equation using the left ventricular outflow tract diameter was 0.86 +/- 0.25 cm2, and that calculated by using the prosthetic ring diameter was 0.98 +/- 0.23 cm2. None of the patients had a severe aortic valve regurgitation. All patients were clinically asymptomatic. Transesophageal echocardiography and x-ray showed a normal prosthetic function. Angiographic examination performed in seven patients showed a peak-to-peak gradient of 26 +/- 9 mmHg, and demonstrated a marked discrepancy between Doppler-echocardiographic and invasive results. These results confirm the clinical limitations of Doppler echocardiography to distinguish between normal and disturbed prosthetic function.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of spontaneous multivessel coronary artery spasm documented by coronary arteriography is reported. The patient was also resistant to sublingual nitrates and nifedipine and required intracoronary nitroglycerine to alleviate the spasm.

Thirty-three patients with acute inferior myocardial infarction (MI), who were treated with intravenous streptokinase, were studied by serial 12-lead ECGs for 48 hours to determine the relationship between early changes in the sum of elevations above the baseline 40 ms after the end of the QRS complex in leads II, III and AFV (SumST), the sum of amplitude of R waves in leads II, III and AVF, the sum of the Q waves in leads II, III and AVF, the sum of ST-segment depression in leads V1-V4 as measured from the baseline to 80 ms after the J point (SumST (V1-V4] and the patency of the infarct-related artery at angiography after MI. Patients with patent arteries had a faster rate of decline in the SumST during the first 2.5 hours; reached the steady state earlier; had a more pronounced decrease in the SumST at 1.25 hours; a larger percentage drop in SumR at 4.5 hours and a more pronounced SumST (V1-V4) early on but resolution times similar to that of patients with closed arteries. Several ECG indices may indicate reperfusion of the infarct-related artery in patients with inferior MI.

The safety and efficacy of streptokinase (STK) (Kabikinase; Keatings) in restoring vessel patency in 70 patients with acute myocardial infarction are reported. Return of vessel patency occurred more frequently (76%) in patients receiving STK than in patients in a control group (12%) (P = 0.001). The main complication was bleeding, which invariably resulted from invasive procedures. Dangerous dysrhythmias were uncommon and no fatalities were caused by STK administration. It is recommended that thrombolytic therapy be started as early as possible in patients with acute myocardial infarction, who can then be referred to centres equipped for coronary angiography for further management. Unnecessary invasive procedures should be avoided.

Non-invasive estimation of pulmonary capillary wedge (PCW) pressure by an echophonocardiographic technique is reported. The ratio of time interval from the Q-wave to the C-point (echocardiogram) (Q-C) and from aortic closing (A2) to the E-point (A2-E) correlated well with the measured PCW pressure (r = 0.89; P = 0.001). When these two intervals were subtracted (A2-E)-(Q-C) the correlation was r = -0.90 (P = 0.001).

The problem of a sotalol-induced ventricular arrhythmia (torsade de pointes) is presented and the contributory role of hypokalaemia is emphasized. It is concluded that sotalol may not be a suitable beta-blocker to use with a diuretic.

Two cases of sudden cardiac death during ambulatory ECG monitoring, each with an episode of torsade de pointes as part of the terminal dysrhythmia, are reported. In the first case, pause-dependent changes of the TU waves favour early after-depolarisations and triggered activity as the initiating mechanism of torsade. Quinidine therapy was probably an aggravating factor. Torsade was not initiated in a pause-dependent fashion in the second patient, who had ECG evidence of an episode of ischaemia as trigger for the terminal dysrhythmia. Both patients had impaired left ventricular function and underlying coronary artery disease.