Sicherheit und Effektivität des interventionellen Vorhofohrverschlusses - Eine klinische, radiologische und laborchemische Studie -

In der vorliegenden Arbeit wurden zu verschiedenen Zeitpunkten vor und nach interventionellem Vorhofohrverschluss eine breite Auswahl von klinischen, radiologischen und laborchemischen Parametern erhoben, die potentiell Einfluss auf die direkte oder langfristige Effektivität und Sicherheit dieser Prozedur nehmen. Insgesamt wurden 58 Patienten vom Screening bis zum klinischen Follow-Up nach sechs Monaten intensiv betreut. Die häufigste Indikation für den interventionellen Vorhofohrverschluss waren Blutungsereignisse, die eine Beendigung der oralen Antikoagulation erforderlich machten. Verwendet wurden 30 Watchman-Devices und 28 Amplatzer Cardiac Plug / Amulet. Bei 98% der Patienten konnte das LAA erfolgreich verschlossen werden, ohne dass sich signifikante Unterschiede zwischen den beiden Devices zeigten. Im Rahmen von Intervention und postinterventionellem Aufenthalt traten sechs ungünstige Ereignisse auf (respiratorische Insuffizienz, Deviceembolie, Blutungen ≥ BARC 3a). Die postinterventionelle Antikoagulation wurde mit einer dualen Thrombozytenaggregationshemmung für sechs Monate durchgeführt und beim Vorliegen von zusätzlichen Blutungsrisiken individuell angepasst. Insgesamt müssen sowohl bei Indikationsstellung als auch postinterventionell vorliegende Blutungs- und Thrombembolierisiken gegeneinander abgewogen werden, um für jeden einzelnen Patienten ein individuell optimiertes Therapiekonzept zu erstellen. In dieser Analyse konnte der Einfluss der Vorhofohrmorphologie auf den interventionellen Vorhofohrverschluss untermauert werden. So wiesen die Implantationsparameter Unterschiede auf, die vor allem die Implantation bei vorliegender Chicken-Wing-Morphologie komplizierter darstellen, ohne jedoch signifikanten Einfluss auf die prozedurale Erfolgsquote zu nehmen. Insgesamt konnte im Vergleich mit Metaanalysen eine sehr positive Erfolgsquote bei vergleichbar geringen Komplikationsraten erreicht werden. Zum Follow-Up zeigte sich eine Reduktion des Blutungsrisikos und vollständige Schlaganfallprävention. Durch strukturierte Betrachtung per kardialer computertomografischer Angiografie (cCTA) konnte mit dem „LAA Occluder View for post-implantation Evaluation“ (LOVE) ein effektiver und reproduzierbarer Bildgebungsalgorithmus zur Darstellung aller wichtigen Aspekte nach interventionellem Vorhofohrverschluss erstmals entwickelt werden. Anhand von sechs beschrieben Schritten lässt sich sowohl das Watchman- als auch das ACP-Device verlässlich in drei Ebenen darstellen. Mithilfe des LOVE ist es möglich, schnell und untersucherunabhängig die Qualität des interventionellen Vorhofohrverschlusses zu beurteilen und kritische Fehler auszuschließen. Beschrieben wurde außerdem die einfache und strukturierte Analyse der klinisch relevanten Fragestellungen: Lage zu benachbarten Strukturen, Peri-Device-Leak, inkomplette Lobusabdeckung und Neoendothelialisierung. Mit dem LOVE stellt die Verwendung eines modernen CT-Gerätes zur Kontrolle des interventionellen Vorhofohrverschlusses eine wertvolle Alternative zur vorwiegend verwendeten transösophagealen Echokardiografie dar. Die cCTA bietet auf Kosten der Strahlenbelastung und höheren Kosten eine bessere und verlässlichere Darstellung aller entscheidenden Faktoren, in Kombination mit geringerer zeitlicher und physischer Belastung für den Patienten. Die Expression kardialer Biomarker zeigte einen signifikanten Anstieg von MR-proANP, während NT-proBNP und die Troponine unverändert blieben. Dieser Anstieg könnte durch die mechanische Stimulation des Vorhofohrendokards durch das Device während der Herzaktivität ausgelöst werden. ANP spielt eine wichtige Rolle im Wasser und Elektrolythaushalt, weswegen es bereits als Ziel für die medikamentöse Blutdruckeinstellung erwogen wurde. Ob dieser Anstieg jedoch positive oder nachteilige Wirkung mit sich bringt, konnte im Rahmen dieser Studie nicht beantwortet werden. Ein weiterer Faktor ist die progrediente Neoendothelialisierung des verschlossenen Vorhofohres entlang des Devices, sodass nach vollständigem Verschluss die Ausschüttung von MR-proANP zurückgehen könnte. Zusammenfassend konnten im Rahmen dieser Studie vielfältige neue Erkenntnisse zum interventionellen Vorhofohrverschluss gewonnen, sowie Hypothesen für weitere Untersuchungen aufgestellt werden. Die weiterführende Analyse beschriebener Ergebnisse kann in Zukunft zur weiteren Verbesserung und Ausweitung der Indikation dieser modernen Therapieoption in der interventionellen Kardiologie betragen

- LAA Occluder View for post-implantation Evaluation (LOVE) - standardized imaging proposal evaluating implanted left atrial appendage occlusion devices by cardiac computed tomography

Background: A standardized imaging proposal evaluating implanted left atrial appendage (LAA) occlusion devices by cardiac computed tomography angiography (cCTA) has never been investigated. Methods: cCTA datasets were acquired on a 3rd generation dual-source CT system and reconstructed with a slice thickness of 0.5 mm. An interdisciplinary evaluation was performed by two interventional cardiologists and one radiologist on a 3D multi-planar workstation. A standardized multi-planar reconstruction algorithm was developed in order to assess relevant clinical aspects of implanted LAA occlusion devices being outlined within a pictorial essay. Results: The following clinical aspects of implanted LAA occlusion devices were evaluated within the most appropriate cCTA multi-planar reconstruction: (1) topography to neighboring structures, (2) peri-device leaks, (3) coverage of LAA lobes, (4) indirect signs of neo-endothelialization. These are illustrated within concise CT imaging examples emphasizing the potential value of the proposed cCTA imaging algorithm: Starting from anatomical cCTA planes and stepwise angulation planes perpendicular to the base of the LAA devices generates an optimal LAA Occluder View for post-implantation Evaluation (LOVE). Aligned true axial, sagittal and coronal LOVE planes offer a standardized and detailed evaluation of LAA occlusion devices after percutaneous implantation. Conclusions: This pictorial essay presents a standardized imaging proposal by cCTA using multi-planar reconstructions that enables systematical follow-up and comparison of patients after LAA occlusion device implantation

Follow-up of iatrogenic aorto-coronary "Dunning" dissections by cardiac computed tomography imaging

Background: Iatrogenic aorto-coronary dissections following percutaneous coronary interventions (PCI) represent a rare but potentially life threatening complication. This restrospective and observational study aims to describe our in-house experience for timely diagnostics and therapy including cardiovascular imaging to follow-up securely high-risk patients with Dunning dissections. Methods: Dunning dissections (DD) occurred during clinical routine PCIs, which were indicated according to current ESC guidelines. Diagnostic assessment, treatment and follow-up were based on coronary angiography with PCI or conservative treatment and cardiac computed tomography (cCTA) imaging. Results: A total of eight patients with iatrogenic DD were included. Median age was 69 years (IQR 65.8–74.5). Patients revealed a coronary multi-vessel-disease in 75% with a median SYNTAX-II-score of 35.3 (IQR 30.2–41.2). The most common type of DD was type III (50%), followed by type I (38%) and type II (13%). In most patients (88%) the DD involved the right coronary arterial ostium. 63% were treated by PCI, the remaining patients were treated conservatively. 88% of patients received at least one cCTA within 2 days, 50% were additionally followed-up by cCTA within a median of 6 months (range: 4–8 months) without any residual. Conclusion: Independently of the type of DD (I-III) it was demonstrated that cCTA represents a valuable imaging modality for detection and follow-up of patients with DDs

Arterial access-site complications after use of a vascular closure device related to puncture height

Background: To analyze differences of access-site complications related to the height of femoral arterial puncture and the use of a vascular closure device (VCD) following percutaneous coronary intervention (PCI). Methods: A subgroup of the FERARI study being treated by femoral arterial access and valuable inguinal angiography before implantation of a VCD were included. Inguinal angiographies were systematically reviewed by two independent cardiologists to determine the correct height of femoral arterial puncture. Bleeding complications were documented within 30 days after PCI and were categorized according to BARC, TIMI, GUSTO and FERARI classifications. Results: Femoral access point imaging was available in 95 patients compared to 105 patients without. The common femoral artery (CFA) was the most accessed artery in 41%, followed by the femoral arterial bifurcation (39%) and lower access sites distally from the femoral arterial bifurcation (low puncture: 20%). No differences were observed regarding indication of PCI, procedural data and anticoagulation therapies in relation to the heights of femoral arterial access (p > 0.05). Despite using VCD, arterial puncture at the CFA resulted in numerically highest numbers of overall bleedings (62%) compared to femoral arterial bifurcation (41%) (p = 0.059). 58% of bleedings occurred after arterial puncture below the femoral bifurcation (low puncture). Though no significant differences of bleedings regarding classifications of BARC, GUSTO, TIMI and FERARI as well as other vascular endpoints were observed regarding puncture height. Conclusions: The present analysis demonstrates no significant differences of bleeding complications in relation to the height of femoral arterial puncture and subsequent use of a VCD

HIV-1 drug resistance in adults and adolescents on protease inhibitor-based antiretroviral therapy in KwaZulu-Natal Province, South Africa

Objectives: In low–middle-income countries, increasing levels of HIV drug resistance (HIVDR) on second-line protease inhibitor (PI)-based regimens are a cause for concern given the limited drug options for third-line antiretroviral therapy (ART). We conducted a retrospective analysis of routine HIV-1 genotyping laboratory data from KwaZulu-Natal, South Africa, to describe the frequency and patterns of HIVDR mutations and their consequent impact on standardised third-line regimens. Methods: This was a cross-sectional analysis of all HIV-1 genotypic resistance tests conducted by the National Health Laboratory Service in KwaZulu-Natal (January 2015 to December 2016) for adults and adolescents (age ≥10 years) on second-line PI-based ART with virological failure. We assigned a third-line regimen to each record based on a national treatment algorithm and calculated the genotypic susceptibility score (GSS) for that regimen. Results: Of 348 samples analysed, 287 (82.5%) had at least one drug resistance mutation (DRM) and 114 (32.8%) had at least one major PI DRM. Major PI resistance was associated with longer duration on second-line ART (aOR per 6-months = 1.11, 95% CI 1.04–1.19) and older age (aOR = 1.03, 95% CI 1.01–1.05). Of 112 patients requiring third-line ART, 12 (10.7%) had a GSS of <2 for the algorithm-assigned third-line regimen. Conclusion: One-third of people failing second-line ART had significant PI DRMs. A subgroup of these individuals had extensive HIVDR, where the predicted activity of third-line ART was suboptimal, highlighting the need for continuous evaluation of outcomes on third-line regimens and close monitoring for emergent HIV-1 integrase inhibitor resistance

'Reaching the hard to reach' - lessons learned from the VCS (voluntary and community Sector). A qualitative study.

Background The notion 'hard to reach' is a contested and ambiguous term that is commonly used within the spheres of social care and health, especially in discourse around health and social inequalities. There is a need to address health inequalities and to engage in services the marginalized and socially excluded sectors of society. Methods This paper describes a pilot study involving interviews with representatives from eight Voluntary and Community Sector (VCS) organisations . The purpose of the study was to explore the notion of 'hard to reach' and perceptions of the barriers and facilitators to accessing services for 'hard to reach' groups from a voluntary and community sector perspective. Results The 'hard to reach' may include drug users, people living with HIV, people from sexual minority communities, asylum seekers, refugees, people from black and ethnic minority communities, and homeless people although defining the notion of the 'hard to reach' is not straight forward. It may be that certain groups resist engaging in treatment services and are deemed hard to reach by a particular service or from a societal stance. There are a number of potential barriers for people who may try and access services, including people having bad experiences in the past; location and opening times of services and how services are funded and managed. A number of areas of commonality are found in terms of how access to services for 'hard to reach' individuals and groups could be improved including: respectful treatment of service users, establishing trust with service users, offering service flexibility, partnership working with other organisations and harnessing service user involvement. Conclusions: If health services are to engage with groups that are deemed 'hard to reach' and marginalised from mainstream health services, the experiences and practices for engagement from within the VCS may serve as useful lessons for service improvement for statutory health services

Impact of pretreatment low-abundance HIV-1 drug-resistant variants on virological failure among HIV-1/TB-co-infected individuals.

OBJECTIVES: To determine the impact of pretreatment low-abundance HIV-1 drug-resistant variants (LA-DRVs) on virological failure (VF) among HIV-1/TB-co-infected individuals treated with NNRTI first-line ART. METHODS: We conducted a case-control study of 170 adults with HIV-1/TB co-infection. Cases had at least one viral load (VL) ≥1000 RNA copies/mL after ≥6 months on NNRTI-based ART, and controls had sustained VLs <1000 copies/mL. We sequenced plasma viruses by Sanger and MiSeq next-generation sequencing (NGS). We assessed drug resistance mutations (DRMs) using the Stanford drug resistance database, and analysed NGS data for DRMs at ≥20%, 10%, 5% and 2% thresholds. We assessed the effect of pretreatment drug resistance (PDR) on VF. RESULTS: We analysed sequences from 45 cases and 125 controls. Overall prevalence of PDR detected at a ≥20% threshold was 4.7% (8/170) and was higher in cases than in controls (8.9% versus 3.2%), P = 0.210. Participants with PDR at ≥20% had almost 4-fold higher odds of VF (adjusted OR 3.7, 95% CI 0.8-18.3) compared with those without, P = 0.104. PDR prevalence increased to 18.2% (31/170) when LA-DRVs at ≥2% were included. Participants with pretreatment LA-DRVs only had 1.6-fold higher odds of VF (adjusted OR 1.6, 95% CI 0.6-4.3) compared with those without, P = 0.398. CONCLUSIONS: Pretreatment DRMs and LA-DRVs increased the odds of developing VF on NNRTI-based ART, although without statistical significance. NGS increased detection of DRMs but provided no additional benefit in identifying participants at risk of VF at lower thresholds. More studies assessing mutation thresholds predictive of VF are required to inform use of NGS in treatment decisions

Mapping male circumcision for HIV prevention efforts in sub-Saharan Africa

Background HIV remains the largest cause of disease burden among men and women of reproductive age in sub-Saharan Africa. Voluntary medical male circumcision (VMMC) reduces the risk of female-to-male transmission of HIV by 50–60%. The World Health Organization (WHO) and Joint United Nations Programme on HIV/AIDS (UNAIDS) identified 14 priority countries for VMMC campaigns and set a coverage goal of 80% for men ages 15–49. From 2008 to 2017, over 18 million VMMCs were reported in priority countries. Nonetheless, relatively little is known about local variation in male circumcision (MC) prevalence. Methods We analyzed geo-located MC prevalence data from 109 household surveys using a Bayesian geostatistical modeling framework to estimate adult MC prevalence and the number of circumcised and uncircumcised men aged 15–49 in 38 countries in sub-Saharan Africa at a 5 × 5-km resolution and among first administrative level (typically provinces or states) and second administrative level (typically districts or counties) units. Results We found striking within-country and between-country variation in MC prevalence; most (12 of 14) priority countries had more than a twofold difference between their first administrative level units with the highest and lowest estimated prevalence in 2017. Although estimated national MC prevalence increased in all priority countries with the onset of VMMC campaigns, seven priority countries contained both subnational areas where estimated MC prevalence increased and areas where estimated MC prevalence decreased after the initiation of VMMC campaigns. In 2017, only three priority countries (Ethiopia, Kenya, and Tanzania) were likely to have reached the MC coverage target of 80% at the national level, and no priority country was likely to have reached this goal in all subnational areas. Conclusions Despite MC prevalence increases in all priority countries since the onset of VMMC campaigns in 2008, MC prevalence remains below the 80% coverage target in most subnational areas and is highly variable. These mapped results provide an actionable tool for understanding local needs and informing VMMC interventions for maximum impact in the continued effort towards ending the HIV epidemic in sub-Saharan Africa

Regional differences in psychiatric disorders in Chile

BACKGROUND: Psychiatric epidemiological surveys in developing countries are rare and are frequently conducted in regions that are not necessarily representative of the entire country. In addition, in large countries with dispersed populations national rates may have low value for estimating the need for mental health services and programs. METHODS: The Chile Psychiatric Prevalence Study using the Composite International Diagnostic Interview was conducted in four distinct regions of the country on a stratified random sample of 2,978 people. Lifetime and 12-month prevalence and service utilization rates were estimated. RESULTS: Significant differences in the rates of major depressive disorder, substance abuse disorders, non-affective psychosis, and service utilization were found across the regions. The differential prevalence rates could not be accounted by socio-demographic differences between sites. CONCLUSIONS: Regional differences across countries may exist that have both implications for prevalence rates and service utilization. Planning mental health services for population centers that span wide geographical areas based on studies conducted in a single region may be misleading, and may result in areas with high need being underserved

Association of polymorphisms in HCN4 with mood disorders and obsessive compulsive disorder

Hyperpolarization activated cyclic nucleotide-gated (HCN) potassium channels are implicated in the control of neuronal excitability and are expressed widely in the brain. HCN4 is expressed in brain regions relevant to mood and anxiety disorders including specific thalamic nuclei, the basolateral amygdala, and the midbrain dopamine system. We therefore examined the association of HCN4 with a group of mood and anxiety disorders. We genotyped nine tag SNPs in the HCN4 gene using Sequenom iPLEX Gold technology in 285 Caucasian patients with DSM-IV mood disorders and/or obsessive compulsive disorder and 384 Caucasian controls. HCN4 polymorphisms were analyzed using single marker and haplotype-based association methods. Three SNPs showed nominal association in our population (rs12905211, rs3859014, rs498005). SNP rs12905211 maintained significance after Bonferroni correction, with allele T and haplotype CTC overrepresented in cases. These findings suggest HCN4 as a genetic susceptibility factor for mood and anxiety disorders; however, these results will require replication using a larger sample