Effectiveness of conduction system pacing for cardiac resynchronization therapy: A systematic review and network meta-analysis.

INTRODUCTION: Cardiac resynchronization therapy (CRT) with biventricular pacing (BiV-CRT) is ineffective in approximately one-third of patients. CRT with Conduction system pacing (CSP-CRT) may achieve greater synchronization. We aimed to assess the effectiveness of CRT with His pacing (His-CRT) or left bundle branch pacing (LBB-CRT) in lieu of biventricular CRT. METHODS AND RESULTS: The PubMed, Embase, Web of Science, Scopus, and the Cochrane Library were systematically searched until August 19, 2023, for original studies including patients with reduced left ventricular ejection fraction (LVEF) who received His- or LBB-CRT, that reported either CSP-CRT success, LVEF, QRS duration (QRSd), or New York Heart Association (NYHA) classification. Effect measures were compared with frequentist network meta-analysis. Thirty-seven publications, including 20 comparative studies, were included. Success rates were 73.5% (95% CI: 61.2-83.0) for His-CRT and 91.5% (95% CI: 88.0-94.1) for LBB-CRT. Compared to BiV-CRT, greater improvements were observed for LVEF (mean difference [MD] for His-CRT +3.4%; 95% CI [1.0; 5.7], and LBB-CRT: +4.4%; [2.5; 6.2]), LV end-systolic volume (His-CRT:17.2mL [29.7; 4.8]; LBB-CRT:15.3mL [28.3; 2.2]), QRSd (His-CRT: -17.1ms [-25.0; -9.2]; LBB-CRT: -17.4ms [-23.2; -11.6]), and NYHA (Standardized MD [SMD]: His-CRT:0.4 [0.8; 0.1]; LBB-CRT:0.4 [-0.7; -0.2]). Pacing thresholds at baseline and follow-up were significantly lower with LBB-CRT versus both His-CRT and BiV-CRT. CSP-CRT was associated with reduced mortality (R = 0.75 [0.61-0.91]) and hospitalizations risk (RR = 0.63 [0.42-0.96]). CONCLUSION: This study found that CSP-CRT is associated with greater improvements in QRSd, echocardiographic, and clinical response. LBB-CRT was associated with lower pacing thresholds. Future randomized trials are needed to determine CSP-CRT efficacy.

[Device-based remote monitoring : Current evidence]. / Devicebasiertes Telemonitoring : Aktuelle Studienlage.

Telemedicine is increasingly used in clinical cardiology. It offers early detection of arrhythmias, technical device follow-up and support of heart failure management. Regarding technical device follow-up, remote monitoring significantly reduces usage of the health care system. Furthermore, remote monitoring is associated with a significantly reduced time from device malfunction to physician's perception of the event. Using remote monitoring, inappropriate ICD (implantable cardioverter defibrillator) shocks can be significantly reduced compared to routine in-office follow-up. In retrospective studies and meta-analyses a prognostic benefit with respect to mortality has been shown. Device-based detection of atrial fibrillation and atrial high rate episodes is feasible. However, clinical relevance is currently studied in prospective randomized clinical trials. Heart failure management based on surrogate parameters has not been shown to significantly improve outcome. However, therapeutic management based on pulmonary artery pressure has been shown to significantly reduce morbidity and mortality. This review offers a comprehensive overview on the role of remote monitoring in heart failure management, technical device follow-up and detection of atrial fibrillation and atrial high rate episodes.

Electric smog: telemetry interference between ICD and LVAD.

Electromagnetic interferences between implantable cardioverter/defibrillators (ICD) and left ventricular assist devices (LVAD) impacting telemetry have been described in previous generations of ICD as well as LVAD, but have been predominantly overcome in current ICD generations. After introduction of a new fully magnetically levitated centrifugal continuous-flow circulatory pump, we report a case of tenacious telemetry interference between the HeartMate 3 LVAD and an ICD after battery exchange to an Iforia 5. Initialization of the initial telemetry handshake was only possible using several specific maneuvers simultaneously. In order to exclude device-device interference, we suggest to place the ICD above the LVAD before implantation and to test for possible telemetry interferences.

High evening salivary cortisol is an independent predictor of increased mortality risk in patients with systolic heart failure.

AIMS: Serum cortisol independently predicts mortality risk in patients with systolic heart failure. Salivary cortisol may provide advantages as it better reflects the biologically active free compound. Furthermore, sampling is non-invasive and may easily be performed in outpatients. We comparatively evaluated associations of morning (MSC) vs. evening salivary cortisol (ESC) and all-cause mortality risk. METHODS AND RESULTS: MSC (8 am) and ESC (9 pm) were determined in 229 patients with heart failure participating in the Interdisciplinary Network for Heart Failure program (66 ± 13 years; 21% female; 37% New York Heart Association (NYHA) class III/IV, median left ventricular ejection fraction 33%). The association of cortisol with mortality risk was determined by univariate and Cox multivariable regression analyses adjusting for age, sex, NYHA class, and N-terminal pro-hormone B-type natriuretic peptide. Compared to ESC, MSC was significantly higher and exhibited a higher variance: median 0.59 ng/ml (interquartile range 0.41-0.93) vs. 0.25 ng/ml (0.15-0.48), p<0.001. During 18 months of follow-up, 25 (11%) patients died. In univariate and multivariable models mortality risk was not increased in the highest MSC quartile: crude hazard ratio (HR) 1.81 (95% confidence interval 0.79-4.14, p=0.160), adjusted HR 1.26 (0.51-3.13, p=0.616). However, patients in the highest ESC quartile had a significantly increased mortality risk, suggesting that associations of high ESC and increased mortality were independent of disease severity: crude HR 3.33 (1.50-7.42, p=0.003), adjusted HR 2.49 (1.01-6.14, p=0.047). ESC alone proved the best predictor of mortality. CONCLUSION: High ESC but not MSC levels independently predict increased mortality risk in heart failure.

X-chromosome lineages and the settlement of the Americas.

Most genetic studies on the origins of Native Americans have examined data from mtDNA and Y-chromosome DNA. To complement these studies and to broaden our understanding of the origin of Native American populations, we present an analysis of 1,873 X-chromosomes representing Native American (n = 438) and other continental populations (n = 1,435). We genotyped 36 polymorphic sites, forming an informative haplotype within an 8-kb DNA segment spanning exon 44 of the dystrophin gene. The data reveal continuity from a common Eurasian ancestry between Europeans, Siberians, and Native Americans. However, the loss of two haplotypes frequent in Eurasia (18.8 and 7%) and the rise in frequency of a third haplotype rare elsewhere, indicate a major population bottleneck in the peopling of the Americas. Although genetic drift appears to have played a greater role in the genetic differentiation of Native Americans than in the latitudinally distributed Eurasians, we also observe a signal of a differentiated ancestry of southern and northern populations that cannot be simply explained by the serial southward dilution of genetic diversity. It is possible that the distribution of X-chromosome lineages reflects the genetic structure of the population of Beringia, itself issued from founder effects and a source of subsequent southern colonization(s).

Tracing genetic history of modern humans using X-chromosome lineages.

Genetic variability of the compound interrupted microsatellite DXS1238, in intron 44 of the dystrophin gene, provides evidence for a complex structure of the ancestral population that led to the emergence of modern humans. We sequenced DXS1238 in 600 X-chromosomes from all over the world. Forty four percent of African-specific chromosomes belong to the ancestral lineage that did not participate in the out-of-Africa expansion and subsequent colonization of other continents. Based on the coalescence analysis these lineages separated from those that contributed to the out-of-Africa expansion 366 +/- 136 thousands years ago (Kya). Independently, the analysis of the variance in the repeat length and of the decay of the ancestral alleles of the two DXS1238 repeats, GT and GA, dates this separation at more than 200 Kya. This suggests a complex demographic history and genetic structure of the African melting pot that led to the emergence of modern humans and their out-of-Africa migration. The subsequent subdivisions of human populations among different continents appear to be preceded by even more structured population history within Africa itself, which resulted from a restricted gene flow between lineages allowing for genetic differences to accumulate. If the transition to modern humans occurred during that time, it necessarily follows that genes associated with this transformation spread between subpopulations via gene flow. Otherwise, in spite of subsequent anatomical variation, Homo sapiens as a species could have emerged in Africa already between 300 and 200 Kya, i.e. before the mitochondrial DNA and well before the Y-chromosome most recent common ancestors.

Haplotypes in the dystrophin DNA segment point to a mosaic origin of modern human diversity.

Although Africa has played a central role in human evolutionary history, certain studies have suggested that not all contemporary human genetic diversity is of recent African origin. We investigated 35 simple polymorphic sites and one T(n) microsatellite in an 8-kb segment of the dystrophin gene. We found 86 haplotypes in 1,343 chromosomes from around the world. Although a classical out-of-Africa topology was observed in trees based on the variant frequencies, the tree of haplotype sequences reveals three lineages accounting for present-day diversity. The proportion of new recombinants and the diversity of the T(n) microsatellite were used to estimate the age of haplotype lineages and the time of colonization events. The lineage that underwent the great expansion originated in Africa prior to the Upper Paleolithic (27,000-56,000 years ago). A second group, of structurally distinct haplotypes that occupy a central position on the tree, has never left Africa. The third lineage is represented by the haplotype that lies closest to the root, is virtually absent in Africa, and appears older than the recent out-of-Africa expansion. We propose that this lineage could have left Africa before the expansion (as early as 160,000 years ago) and admixed, outside of Africa, with the expanding lineage. Contemporary human diversity, although dominated by the recently expanded African lineage, thus represents a mosaic of different contributions.

Y-chromosome evidence for differing ancient demographic histories in the Americas.

To scrutinize the male ancestry of extant Native American populations, we examined eight biallelic and six microsatellite polymorphisms from the nonrecombining portion of the Y chromosome, in 438 individuals from 24 Native American populations (1 Na Dené and 23 South Amerinds) and in 404 Mongolians. One of the biallelic markers typed is a recently identified mutation (M242) characterizing a novel founder Native American haplogroup. The distribution, relatedness, and diversity of Y lineages in Native Americans indicate a differentiated male ancestry for populations from North and South America, strongly supporting a diverse demographic history for populations from these areas. These data are consistent with the occurrence of two major male migrations from southern/central Siberia to the Americas (with the second migration being restricted to North America) and a shared ancestry in central Asia for some of the initial migrants to Europe and the Americas. The microsatellite diversity and distribution of a Y lineage specific to South America (Q-M19) indicates that certain Amerind populations have been isolated since the initial colonization of the region, suggesting an early onset for tribalization of Native Americans. Age estimates based on Y-chromosome microsatellite diversity place the initial settlement of the American continent at approximately 14,000 years ago, in relative agreement with the age of well-established archaeological evidence.