A randomized, placebo-controlled, trial to assess the photosensitizing, phototoxic and carcinogenic potential of hydrochlorothiazide in healthy volunteers.

BACKGROUND AND AIMS: Pharmacovigilance reports, associating hydrochlorothiazide (HCT) with skin cancer, resulted in a significant decrease of HCT prescriptions for hypertension and heart failure. Whether HCT exhibits phototoxic properties thereby causing skin cancer remains unknown. This study aimed to examine the photosensitizing, phototoxic and carcinogenic potential of HCT in a randomized, placebo-controlled, double-blind trial in vivo and also in vitro . METHODS: The trial assigned 30 healthy, normotensive adult volunteers in a 2:1 ratio to either HCT 25 mg/day or placebo for 15 days. Photosensitivity of the skin with and without the effect of HCT treatment were assessed. Following whole-body ultraviolet A (UVA) and B (UVB, 311 nm) irradiation, phototoxic and carcinogenic reactions by measuring urinary excretion of pyrimidine dimers were evaluated. For the in-vitro studies, human keratinocytes (HaCaT) were incubated with HCT, irradiated with UVB, and analysed for markers of inflammation, apoptosis and carcinogenesis. RESULTS: Skin photosensitivity following exposure to UVA and UVB remained unchanged from baseline to 15-day follow-up in both groups (UVA change HCT 0.0 J/cm 2 vs. placebo 0.0 J/cm 2 ; P  = 0.99; UVB change HCT 0.0 J/cm 2 vs. placebo -0.2 J/cm 2 ; P  = 0.06). Pyrimidine dimers were not detected in either group. In vitro , combination of HCT and UVB irradiation did not induce the expression of oxidative stress marker proteins, inflammatory proteins, apoptotic proteins or activation of oncoproteins. CONCLUSION: HCT did not increase photosensitivity for UVA or UVB in healthy volunteers compared with placebo, and was not associated with phototoxic or carcinogenic reactions. In vitro , HCT was also not associated with phototoxicity or carcinogenesis (NCT04654312).

Fifty Years of Global Cardiovascular Research in Africa: A Scientometric Analysis, 1971 to 2021.

Background To analyze the quantity and impact of cardiovascular research done in Africa or coauthored by researchers based in Africa, their determinants, and the patterns of research collaboration. Methods and Results We retrieved data from Web of Science and additional sources. We analyzed temporal trends from 1971 to 2021 and geographical distribution, research impact using country-level h-index, international research cooperation, and associations of research quantity and quality using linear regression. The annual volume of cardiovascular research from Africa has increased from 4 publications in 1971 to 3867 in 2020 and currently represents ~3% of the global cardiovascular research output. Authors from South Africa (28.1%) and Egypt (24.1%) accounted for more than half of all publications from African countries, and they had the highest h-index (209 and 111, respectively). Important collaborators outside Africa included the United States, United Kingdom, France, Germany, and Australia. The country's publication count was associated with larger population size (P<0.001), whereas the country's h-index was associated with larger population size (P=0.001) and higher human development index (P=0.023). International collaboration was dominated by the United States, South Africa, United Kingdom, Egypt, and Canada. The level of collaboration between African countries was lower than their collaboration with non-African countries. Conclusions Cardiovascular research output from African authors remains low, despite marked progress over the past 5 decades. These findings highlight the urgent need to improve the quantity and quality of cardiovascular research in Africa through increased investments, training of human resources, improved infrastructures, and expansion of collaborative research networks, particularly within Africa.

Inhibition of TRIF-Dependent Inflammation Decelerates Afterload-Induced Myocardial Remodeling.

Pressure-overload-induced cardiac hypertrophy represents one cause of the development of heart failure. The aim of this study is to characterize the influence of the TIR-domain-containing adapter-inducing interferon-ß (TRIF) during afterload-induced myocardial remodeling. After trans-aortic constriction (TAC), cardiac pressure overload leads to an early increase in MyD88- (Myeloid differentiation primary response gene 88) and TRIF-dependent cytokines. The maximum cytokine expression appeared within the first week and decreased to its control level within five weeks. While cardiomyocyte hypertrophy was comparable, the myocardial accumulation of the inflammatory cells was lower in TRIF-/-mice. At d7, TRIF deficiency reduced transcription factors and TRIF-dependent cytokines. Through the modulation of the TGF-ß-signaling pathway and anti-fibrotic microRNAs, TRIF was involved in the development of interstitial fibrosis. The absence of TRIF was associated with a decreased expression of proapoptotic proteins. In echocardiography and working heart analyses, TRIF deficiency slowed left-ventricular wall thickening, myocardial hypertrophy, and reduces the ejection fraction. In summary, TRIF is an important adapter protein for the release of inflammatory cytokines and the accumulation of inflammatory cells in the early stage of maladaptive cardiac remodeling. TRIF is involved in the development of cardiac fibrosis by modulating inflammatory and fibrotic signal transduction pathways.

Ischemic Stroke-A Scientometric Analysis.

Background: Stroke is the second leading cause of death world-wide. A comprehensive scientometric study regarding ischemic stroke research has not been performed yet. This study aims at investigating the global research output on ischemic stroke research. Methods: All 21,115 articles regarding ischemic stroke were retrieved from the Web-of-Science-Core-Collection and analyzed regarding regional differences, the authors' sex, subtopics of stroke, as well as international research collaborations. Results: A total of 132 different countries participated, with the USA contributing most publications with 4,614 (21.9%), followed by China with 3,872 (18.3%), and Germany with 1,120 (5.3%). Analyzing the scientific quality of different countries by H-index, the USA ranked first with an H-index of 202, followed by Germany (H-index 135) and the United Kingdom (UK;H-index 129). The most frequently used topic was "Clinical Neurology" with 9,028 publications. Among all first authors attributed to their sex, 32.3% of all first authors were female and 67.7% were male (4,335 vs. 9,097). The proportion of female last authors was comparatively lower at 22.4% (3,083 publications) compared with 77.6% male authors (10,658 publications). There was a broad network of international collaborations. Conclusions: Research in ischemic stroke has substantially increased over time. Scientists from the USA have the highest number of publications, followed by China and Germany. Measured by the H-index, the USA held the highest publication quality, followed by Germany and the UK. The scientific landscape was male-dominated with 67.7% of all first authors being male. Worldwide international collaborations play a major role in ischemic stroke research.

Heart-Focused Anxiety, General Anxiety, Depression and Health-Related Quality of Life in Patients with Atrial Fibrillation Undergoing Pulmonary Vein Isolation.

(1) Background: Atrial fibrillation (AF) is associated with anxiety, depression, and chronic stress, and vice versa. The purpose of this study was to evaluate potential effects of pulmonary vein isolation (PVI) on psychological factors. (2) Methods: Psychological assessment was performed before PVI as well as after six months. (3) Results: A total of 118 patients [age 64 ± 9 years, 69% male, left ventricular ejection fraction 57 ± 8%, 56% paroxysmal AF] undergoing PVI were included. After PVI, significant improvements were observed in the mean total heart-focused anxiety (HFA) score, as well as in the Cardiac Anxiety Questionnaire (CAQ) sub-scores: HFA attention, HFA fear, and HFA avoidance scores. Subgroup analyses showed an association of improvement with freedom of documented AF recurrence. Mean scores of general anxiety and depression evaluated by the Hospital Anxiety and Depression Scale (HADS) decreased significantly after PVI in all subgroups regardless of AF recurrence. Further, both physical and mental composite scores of the Short Form Health Survey (SF-12) increased significantly from baseline. (4) Conclusions: PVI results in a significant reduction in HFA. Improvements in general anxiety and depressive symptoms did not seem to be related only to rhythm control per se. Therefore, CAQ may represent a more specific evaluation tool as HADS in patients with AF.

Photoinduced skin reactions of cardiovascular drugs-a systematic review.

This systemic review aims to provide a practical overview of the prevalence, clinical manifestation, and management of adverse photoinduced skin reactions caused by frequently used cardiovascular drugs and to assess their potential relevance for skin cancer development. Data search included PubMed, Web of Science, and the Cochrane Library. A systematic review of peer-reviewed studies reporting the photosensitizing and/or skin cancer-inducing properties of common cardiovascular drugs was performed and a guide to clinical management of photoinduced skin eruptions by cardiovascular drugs was provided. Study quality was assessed for major methodological biases. A total of 58 studies were identified (i.e. 23 case reports, 14 observational studies, 10 review articles, 10 experimental studies, and 1 meta-analysis). Most commonly, drug-associated adverse photoinduced cutaneous reactions were caused by phototoxic and photoallergic mechanisms. There is evidence suggesting that amiodarone and dronedarone, thiazide diuretics, thiazide-like diuretics, angiotensin receptor blockers, dihydropyridine-type calcium channel blockers, and certain angiotensin-converting enzyme inhibitors and statins may cause photoinduced adverse cutaneous reactions. Other drugs such as anticoagulants, antiplatelets, aldosterone antagonists, and fibrates have not been linked with photosensitizing reactions or adverse cutaneous reactions. Some drugs, i.e. thiazides and thiazide-like diuretics, were associated with an increased risk of non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma). Certain commonly used cardiovascular drugs have been associated with adverse photoinduced cutaneous reactions. If they occur, further diagnosis and treatment might be needed, depending on the severity and progress. Whether photosensitizing drugs increase the risk of skin cancer remains elusive and further randomized controlled trials are required.

Sex Differences in Cardiovascular Research: A Scientometric Analysis.

Background We sought to investigate sex-specific differences in authorship of cardiovascular research over the past decade. Methods and Results All 387 463 cardiovascular publications between 2010 and 2019 were retrieved from Web of Science. Articles increased from 19 960 to 29 604 articles per year (P>0.001). The number of articles written by female first authors increased by 76.3% (6434-11 343 articles) and by 35.0% for male first authors (13 526-18 261) (P<0.001). The first author was more likely to be a female author in articles with female last authors. The median impact factor (IF) for articles by female first authors was lower (2.46 [interquartile range, 7 1.11-4.03] versus 2.51 [interquartile range, 1.17-4.10]; P<0.001). Female authorship articles reached the highest IF in North America (average IF, 3.7), with the lowest in Africa (average IF, 1.8). Conclusions Publications in cardiovascular research have increased over the past decade, particularly by female authors. Female researchers are cited less often compared with their male peers. The IF remains lower for articles by female researchers.

Differences in management of telemedicine alerts on weekdays and public holidays: Results from the OptiLink heart failure trial.

BACKGROUND: In the OptiLink heart failure study, timely and appropriate reactions to telemedicine alerts improved clinical outcomes in heart failure patients. This analysis investigates the relation between the weekday of alert transmission and the subsequent patient contact. METHODS: In patients enrolled in the intervention arm of the OptiLink heart failure study (n = 505, age 66.1 ± 10.1, 77.2% male, left-ventricular ejection fraction 26.7% ± 6.1%), fluid index threshold crossing alerts were analysed according to the weekday of the transmission. Transmissions on Mondays-Thursdays were categorized as TD1, Fridays-Sundays as well as public holidays as TD2. RESULTS: Of 1365 transmitted alerts, 867 (63.5%) were categorized as TD1 and 498 (36.5%) as TD2. Same day telephone contacts were more frequent in TD1 (46.2%) than in TD2 (18.3%; p < 0.001). Accordingly, the median time to contact was significantly longer in TD2 compared with TD1 (2(1-3) vs 0(0-1) days; p < 0.001). Rates of no telephone contact were no different between the groups (12.1% vs 12.4%; p = 0.866). Although signs of worsening heart failure were prevalent in 32.4% in TD1 versus 32.1% in TD2 (p = 0.996), initiation of a pharmacological intervention occurred more likely in TD1 compared with TD2 (27.9% vs 22.9%; p = 0.041). No differences existed concerning hospitalization for heart failure within 30 days after alert transmission (3.9% vs 3.4%; p = 0.636). CONCLUSION: Alert transmissions during weekends and public holidays were less likely associated with timely patient contacts and initiation of pharmacological interventions than during the week. Telemedical centres providing 24/7 remote monitoring service and specific education programmes for physicians might help to optimize patient care.

Mapping of an atrial tachycardia after Epicor™ high-intensity focused ultrasound ablation: A case report.

BACKGROUND: Surgical techniques, such as the application of high-intensity focused ultrasound (HIFU), can be used for pulmonary vein isolation (PVI). CASE SUMMARY: We report a case of a 73-year old patient, in whom HIFU failed to achieve PVI but promoted the occurrence of a scar-related atrial tachycardia (AT). Voltage mapping of the left atrium revealed multiple gaps along the ablation line. Coherent mapping with visualization of velocity vectors allowed the correct interpretation and the targeted ablation of the AT. DISCUSSION: Cardiac surgery can promote scar-related AT. The coherent mapping function could simplify the mapping of scar-related AT in the future.

Inducibility of atrial fibrillation after catheter ablation predicts recurrences of atrial fibrillation: a meta-analysis.

BACKGROUND: Pulmonary vein isolation (PVI) is a component of standard care for patients with symptomatic atrial fibrillation (AF). Procedural inducibility of AF following PVI has been suggested as predictor of AF recurrence but is discussed controversially. This meta-analysis aimed at evaluating the relevance of electrophysiological inducibility of AF following PVI for future AF recurrences. METHODS: A literature search of MEDLINE and Web of Science was performed until April 2020. Prospective trials of PVI in patients with AF and post-procedural atrial stimulation to test for inducibility of AF as well as adequate follow-up for AF recurrence (defined as AF >10 s to >10 min at follow-up) were included. Odds ratios (ORs) were analyzed using random-effects models. RESULTS: A total of 11 trials with 1544 patients (follow-up 7-39 months, age 56 ± 6 years, predominantly male 74 ± 6%) were included. Inducibility of AF post-PVI was predictive for AF recurrence during follow-up (OR 2.08; 95% CI 1.25 to 3.46). Prediction for AF recurrence at follow-up was better for patients with paroxysmal AF (OR 4.06; 95% CI 1.39 to 11.91), stimulation in the CS (OR 2.82, 95% CI 1.17 to 6.79). A trend towards higher ORs was seen without the use of isoproterenol (OR 2.43; 95% CI 1.17 to 5.07), as well as few stimulations during induction and a short definition of AF in meta-regression analyses. CONCLUSIONS: Electrophysiological inducibility of AF following PVI was predictive for future recurrence of AF, in particular in patients with paroxysmal AF, stimulation in only CS and no use of isoproterenol.

Cardiovascular Outcomes According to Polypharmacy and Drug Adherence in Patients with Atrial Fibrillation on Long-Term Anticoagulation (from the RE-LY Trial).

Prevalence of atrial fibrillation (AF) increases with age, along with comorbidities and, thus, polypharmacy. Non-adherence is associated with polypharmacy. This study aimed to identify patients at risk for cardiovascular events according to their pharmacological treatment intensity and adherence. Patients (n = 18,113) with a mean age of 71.5 ± 8.7 years, at high cardiovascular risk were followed between December 2005 until December 2007 for a median time of 2 years. The association between polypharmacy and adherence and their impact on cardiovascular and bleeding events were explored. Adherence was defined as a study drug intake of ≥80%. Patients with more co-medications had a higher body mass index, higher prevalence of hypertension, coronary heart disease, heart failure, and diabetes mellitus (all p < 0.0001) compared to ≤4 or 5-8 co-medications, but no differences in history of stroke (p = 0.68) or transient ischemic attack (p = 0.065). Across all treatments, the adjusted hazard ratios (HRs) increased in patients with more co-medications (≥9 vs ≤4) for all-cause death (HR 1.30; 1.06-1.59), major bleeding (HR 1.65; 1.33-2.05), and all bleeding events (HR 1.44; 1.31-1.59). Yearly event rates were higher in non-adherent than adherent patients for stroke and systemic embolism (SSE) (3.14 vs 1.00), all-cause death (7.76 vs 2.66), major bleeding (6.21 vs 2.65), and all bleeding (28.71 vs 19.05; all p < 0.0001). After an event the patients were more likely to become non-adherent (adherence after SSE 30.3%, after major bleeding 33.4%, after all bleeding 66.7%; all p < 0.0001). The treatment effects were consistent to the overall group in the different polypharmacy groups. In conclusion, polypharmacy and non-adherence are risk indicators for increased adverse cardiovascular and bleeding events. Dabigatran is safe to use across the full spectrum of AF patients, independent of the number of co-medications and adherence. Patients with co-medications and comorbidities require special attention and encouragement to adhere to oral anticoagulation.

Research Output and International Cooperation Among Countries During the COVID-19 Pandemic: Scientometric Analysis.

BACKGROUND: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has instigated immediate and massive worldwide research efforts. Rapid publication of research data may be desirable but also carries the risk of quality loss. OBJECTIVE: This analysis aimed to correlate the severity of the COVID-19 outbreak with its related scientific output per country. METHODS: All articles related to the COVID-19 pandemic were retrieved from Web of Science and analyzed using the web application SciPE (science performance evaluation), allowing for large data scientometric analyses of the global geographical distribution of scientific output. RESULTS: A total of 7185 publications, including 2592 articles, 2091 editorial materials, 2528 early access papers, 1479 letters, 633 reviews, and other contributions were extracted. The top 3 countries involved in COVID-19 research were the United States, China, and Italy. The confirmed COVID-19 cases or deaths per region correlated with scientific research output. The United States was most active in terms of collaborative efforts, sharing a significant amount of manuscript authorships with the United Kingdom, China, and Italy. The United States was China's most frequent collaborative partner, followed by the United Kingdom. CONCLUSIONS: The COVID-19 research landscape is rapidly developing and is driven by countries with a generally strong prepandemic research output but is also significantly affected by countries with a high prevalence of COVID-19 cases. Our findings indicate that the United States is leading international collaborative efforts.

Research in Atrial Fibrillation: A Scientometric Analysis Using the Novel Web Application SciPE.

OBJECTIVES: This study sought to determine the quantity and quality of publications in AF research using large-scale scientometric data analyses. BACKGROUND: Research in atrial fibrillation (AF) has increased over time. The increasing number of research papers makes it harder to identify relevant research work. METHODS: All 21,603 publications from 1945 to 2018 were retrieved from Web of Science and analyzed regarding geographical distribution of scientific output and international research cooperation. RESULTS: The total number of AF publications has significantly increased since the millennium change, from 3,063 (14.2%) in 1945 to 1999 to 18,540 (85.8%) publications in 2000 to 2018. AF research grew 10-fold compared with overall medical research since 1990 (ratio of AF publications to all publications: 0.02% (n = 99 of 410,701) in 1990 vs. 0.2% (n = 1,967 of 1,172,649) in 2018; p < 0.05). Quantitatively, the United States contributed 25.9% of AF research, followed by Japan (8.0%), Germany (7.8%), China (7.3%), and the United Kingdom (5.9%). In the all-time modified h-index, the United States ranked first (13.3% of all nations), followed by Canada (8.5%) and the United Kingdom (6.3%). In relation to population, Denmark was the best-rated nation, with the lowest number of inhabitants per publication (11,457), followed by Sweden (18,426) and the Netherlands (25,749), and per modified h-index (90,746), followed by Sweden (170,602) and the Netherlands (218,203). Measuring publications per research institute, Denmark again ranked first, with 19.2 publications per institute, followed by Italy (14.9) and Sweden (13.8). An intensive cooperation between nations was apparent. CONCLUSIONS: This study showed an increase in publication activity in AF research. The United States was the leading country in quantity of research efforts. Related to population and research institutes, Denmark ranked first.

Los registros de denervación renal, ¿completan la evidencia? / Registries in renal denervation-completing the picture?

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Catheter-based renal denervation as adjunct to pulmonary vein isolation for treatment of atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVE: Renal denervation (RDN) can reduce sympathetic activity and blood pressure (BP) in hypertensive patients, which both have an impact on atrial fibrillation. We performed a systematic meta-analysis on the effects of renal denervation (RDN) in addition to pulmonary vein isolation (PVI) in patients with atrial fibrillation. METHODS: All published randomized controlled trials investigating the effects of RDN as adjunctive treatment to PVI for rhythm control of atrial fibrillation were included. Primary endpoint was recurrence of atrial fibrillation after 12 months on average. RESULTS: A total of six randomized controlled studies including 689 patients with hypertension and symptomatic atrial fibrillation were included. In five studies, patients had uncontrolled BP despite prescription of an average of three antihypertensive agents. PVI was performed with irrigated radio-frequency catheters in 387 patients, and in 302 with cryoballoon. Cardiac ablation catheters were used for RDN in 78% of all cases. In the remaining 22%, RDN was performed using a designated, nonirrigated radio-frequency catheter system. After 12 months, the mean odds ratio for recurrence of atrial fibrillation for PVI with RDN compared with PVI alone was 0.43 (95% confidence interval 0.32-0.59). After RDN, BP was reduced significantly whereas no changes were reported in the PVI-only groups. No relevant complications associated to RDN were documented. CONCLUSION: This meta-analysis supports the concept of RDN as an adjunctive treatment for atrial fibrillation. Further studies with standardized PVI and RDN procedures are needed.