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It has long been assumed, since the early works of Mather, that the centromere plays a central role in chiasma position determination, so much so that in all sequential models chiasma determination was supposed to start or finish at this point. More specifically, it has been asssumed that the centromere acts as a barrier to the transmission of interference, so that a chiasma in the vicinity of a centromere would not affect the probability of chiasma formation across this point. Some statistical analyses seemed to ratify this supposition. However, a reassessment of the literature led us to the conclusion that the statistical analyses that were not flawed were consistent in showing that interference may act across the centromere. Using large sets of chiasma data from the grasshoppers Leptysma argentina and Chorthippus brunneus and applying statistical approaches that involved either the calculation of coincidence or correlating the distances between the centromere and the nearest chiasma in either arm, it is concluded: 1 that interference acts across the centromere; 2 that the action of interference is not changed by the presence of an intervening centromere. [ABSTRACT FROM AUTHOR]

There is renewed interest in the utility of the intra-aortic balloon pump (IABP) for short-term and durable support in patients with chronic systolic heart failure (HF) who present with acute decompensation and cardiogenic shock (CS). However, the clinical characteristics of IABP-responders and non-responders remain incompletely defined. We sought to identify predictors of early IABP response to guide optimal use of IABP therapy in this population. We retrospectively analyzed the records of chronic systolic HF patients who presented at our institution between 2011-2018 with acute decompensated HF with hemodynamic evidence of CS and underwent IABP placement. IABP-responder was defined as having an immediate increase in cardiac output (CO) and an immediate decrease in mean pulmonary artery pressure (MPAP) above the median values of the cohort. Logistic regression was used to identify predictors of hemodynamic response. During the study period, 218 chronic systolic HF patients underwent IABP insertion for acute decompensation with CS. The mean age was 59.4 ±13.4 years, 79.8% were men, and 38.5% had ischemic cardiomyopathy (ICM). The average hemodynamic response to IABP in the whole cohort was a CO increase of 0.57 ±0.85L/min and a MPAP reduction of 5.1 ±7.6mmHg; IABP-responders had a CO increase of 1.21 ±0.87L/min and a MPAP reduction of 12.1 ±5.9mmHg (figure). Univariable predictors of IABP-response were ICM, presence of severe mitral regurgitation, baseline heart rate, elevated MPAP, and elevated systemic vascular resistance (SVR). Following multivariable logistic regression, independent predictors of IABP-response were elevated baseline SVR (OR 2.05, 95% CI 1.01 - 4.17; p=0.047) and elevated MPAP (OR 2.47, 95% CI 1.23 - 5.00; p=0.01). MPAP reduction decreased the odds of death or need for escalation to another short-term circulatory support device while CO increase did not [OR 0.52 (0.28 - 0.97; p=0.04) vs. 0.83 (0.45 - 1.54; p=0.56)]. A subset of chronic systolic HF patients had a robust hemodynamic response to IABP insertion with CO augmentation and MPAP reduction. Elevated baseline SVR and MPAP are predictors of robust response following device insertion. These parameters may be used to identify patients who may respond favorably to IABP counterpulsation therapy. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: The association of obesity on outcomes in patients with cardiogenic shock requiring acute mechanical circulatory support has not been thoroughly investigated. Methods: We evaluated the National Readmission Database for adults with either acute myocardial infarction or heart failure complicated by cardiogenic shock requiring acute mechanical circulatory support between January 2016 and November 2017. Exposure was assessed using International Classification of Diseases , Tenth Revision codes for the degree of obesity with the reference being body mass index (BMI) of 20.0 to 29.9 group. Multiple logistic regression and Cox regression analysis were used to analyze in-hospital mortality and 30-day readmission, respectively. Results: The survey-weighted sample included a total of 35 555 hospitalizations with a mean age of 65.4±0.2 years and 29.8% females. Obesity was associated with higher in-hospital mortality (no obesity, 26.4% [BMI, 20.0–29.9] versus class I obesity, 25.0% [BMI, 30.0–34.9] versus class II obesity, 28.7% [BMI, 35.0–39.9] versus class III obesity, 34.9% [BMI, ≥40]; P <0.001). On stratified analysis, compared with a nonobese phenotype, younger adults (age <60) with class II and class III obesity (odds ratio, 1.9 [95% CI, 1.1–3.5], P =0.02; odds ratio, 2.1 [95% CI, 1.2–3.7], P =0.01) and older adults (age ≥60) with class III obesity (odds ratio, 1.7 [95% CI, 1.2–2.4], P =0.005) had higher mortality. There was no association between the degree of obesity and 30-day readmission. Conclusions: Among adults with acute myocardial infarction or acute heart failure resulting in cardiogenic shock requiring acute mechanical circulatory support, younger adults with class II and class III obesity and older patients with class III obesity have a higher risk of in-hospital mortality compared with nonobese patients. [ABSTRACT FROM AUTHOR]

Accuracy of serum creatinine (sCr) in the estimation of renal function among heart transplant (HT) pts may be limited by changes in muscle mass. Cystatin C (CysC) is independent from muscle mass and provides an alternative measure of estimated glomerular filtration rate (eGFR). We hypothesized that: i) sCr would overestimate renal function due to muscle wasting; and ii) this would cause overdosing of valganciclovir (VGC) and, thereby, leukopenia. Herein, we aimed to: i) compare post-HT changes in CysC- and sCr-based eGFR; and ii) explore whether the use of CysC in lieu of sCr carries the potential to reduce the rate of VGC-induced leukopenia. Pts transplanted between 6/2016 and 4/2019 had serial measurements of CysC and sCr pre- and post-HT. eGFR was assessed using CKD-EPI-CysC (eGFR CysC) and MDRD (eGFR sCr). Linear mixed models were used to regress post-HT changes in eGFR CysC , eGFR sCr and sCr/CysC ratio (a validated marker of muscle mass). In a subgroup of patients receiving VGC, eGFR was assessed as a time-varying covariate at 1-, 3-, and 6-months post-HT. The primary endpoint was rate of VGC-induced leukopenia within 1-month of renal function assessment. Appropriateness of VGC dosing for renal impairment was assessed using, in addition to eGFR CysC and eGFR sCr, creatinine clearance (CrCl) as per manufacturer's recommendation. A total of 309 samples were collected in 83 pts. eGFR CysC was markedly lower than eGFR sCr early post-HT (Figure A). While eGFR sCr declined long-term, eGFR CysC showed an opposite trend with a gradual improvement. The decline in eGFR sCr mirrored the rise in sCr/CysC ratio, suggesting that increase in muscle mass may contribute to this decline. Among 57 pts who were on VGC at 1-, 3-, and 6-months post-HT, 117 samples were available. Based on sCr-based equations (eGFR sCr and CrCl), VGC was appropriately dosed in the majority of samples (72% and 64%, respectively). However, based on eGFR CysC , VGC was inappropriately dosed in 54 (46%) samples: 11 (9%) underdosed, 43 (37%) overdosed (Figure B). Among 31 episodes of VGC-induced leukopenia within 1-month of sampling, 15 (48%) occurred in samples with VGC overdosed by eGFR CysC. In adjusted models, higher CysC but not sCr was associated with increased risk for leukopenia (OR: CysC: 1.47, 95%CI 1.04-2.06; sCr: 1.19, 95%CI 0.79-1.79). eGFR CysC and eGFR sCr markedly differ early post-HT with critical implications in the dosing of VGC. The use of CysC in lieu of sCr may prevent VGC overdosing and reduce the rate of leukopenia in HT pts. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic imposed severe restrictions on traditional methods of patient care. During the pandemic, the heart failure program at New York-Presbyterian Hospital in New York, NY rapidly and comprehensively transitioned its care delivery model and administrative organization to conform to a new healthcare environment while still providing high-quality care to a large cohort of patients with heart failure, heart transplantation, and left ventricular assist device. In addition to the widespread adoption of telehealth, our program restructured outpatient care, initiating a shared clinic model and introducing a comprehensive remote monitoring program to manage patients with heart failure and heart transplant. All conferences, including administrative meetings, support groups, and educational seminars were converted to teleconferencing platforms. Following the peak of COVID-19, many of the new changes have been maintained, and the program structure will be permanently altered as a lasting effect of this pandemic. In this article, we review the details of our program's transition in the face of COVID-19 and highlight the programmatic changes that will endure. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Advanced heart failure therapies such as left ventricular assist device (LVAD) implantation require intricate follow-up and complex care. We sought to explore the burden of psychosocial risk factors among patients with LVAD and their impact on postimplant outcomes using the Interagency Registry for Mechanically Assisted Circulatory Support. Methods: Adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support requiring durable LVAD between 2008 and 2017 were included. Individuals were determined to have psychosocial risk if they had one of the following: (1) limited social support; (2) limited cognition; (3) substance abuse (alcohol and drug); (4) severe psychiatric disease (including major depression and other major psychiatric diagnosis); and (5) repeated noncompliance. Univariate and multivariate Cox proportional hazard regression models were used to analyze predictors of survival and complications. Results: A total of 15 403 continuous-flow LVAD recipients were included. A total of 3163 (20.5%) had one or more psychosocial risk factors. The most prevalent psychosocial risk factor was substance abuse in 1941 (12.6%) recipients. Patients with psychosocial risk factors were significantly younger at LVAD implant, less likely to be White, and less likely to be female compared with those without psychosocial risk, P <0.001 for all. Patients with psychosocial risk were significantly more likely to receive an LVAD as destination therapy, P <0.001. In adjusted models, patients with psychosocial risk were at increased hazards for device-related infection, gastrointestinal bleeding, pump thrombosis, and readmission and reduced hazards for cardiac transplantation (P <0.05 for all). There was no statistically significant difference in survival on pump support or stroke. Conclusions: Psychosocial risk is an important component of patient selection for advanced heart failure therapies. Addressing these specific components may help improve access to advanced therapies and post-LVAD outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the presence of Rickettsia in soft ticks (Acari: Argasidae) collected from insectivorous bats (Chiroptera) in Santa Fe province, Argentina. First, a subset of ticks were mounted in Hoyer's medium to be determined by morphological characters and then confirmed by sequencing the mitochondrial 16S rRNA gene. Also ticks were processed by PCR assays using primers CS-78 and CS-323, which amplify a fragment of the Rickettsia spp. gltA gene. Positive ticks were subjected to a second PCR round with primers Rr190.70p and Rr190.701n of the spotted fever group rickettsiae ompA gene. A phylogenetic analysis was performed with Maximum-likelihood method, and the best fitting substitution models were determined with the Akaike Information Criterion. Five bats of the species Eptesicus diminutus Osgood, 1915, Eptesicus furinalis (d'Orbigny and Gervais, 1847), Eptesicus spp. (Vespertilionidae), and Molossops temminckii Burmeister, 1854 (Molossidae) were parasitized with Ornithodoros hasei (Schulze, 1935) larvae. One E. diminutus ticks' tested positive to " Candidatus Rickettsia wissemanii", a spotted fever group rickettsiae. The association O. hasei –" Ca. R. wissemanii" detected in this study represents the first evidence of a Rickettsia in Ornithodoros ticks in Argentina and the third report of this association in America. Also, this finding constitutes the first record of " Ca. R. wissemanii" in Argentina. Finally, we found for the first time the insectivorous bats E. diminutus and E. furinalis parasitized with O. hasei larvae. These findings add two new hosts and a new location, the southernmost recorded to date, for O. hasei. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal bleeding (GIB) is a common complication of left ventricular assist device (LVAD) therapy accounting for frequent hospitalizations and high resource utilization.Methods: We previously developed an endoscopic algorithm emphasizing upfront evaluation of the small bowel and minimizing low-yield procedures in LVAD recipients with GIB. We compared the diagnostic and therapeutic yield of endoscopy, health-care costs, and re-bleeding rates between conventional GIB management and our algorithm using chi-square, Fisher's exact test, Wilcoxon-Mann-Whitney, and Kaplan-Meier analysis.Results: We identified 33 LVAD patients with GIB. Presentation was consistent with upper GIB in 20 (61%), lower GIB in 5 (15%), and occult GIB in 8 (24%) patients. Forty-one endoscopies localized a source in 23 (56%), resulting in 14 (34%) interventions. Algorithm implementation compared with our conventional cohort was associated with a 68% increase in endoscopic diagnostic yield (P< .01), a 113% increase in therapeutic yield (P= .01), a 27% reduction in the number of procedures per patient (P < .01), a 33% decrease in length of stay (P < .01), and an 18% reduction in estimated costs (P < .01). The same median number of red blood cell transfusions were used in the 2 cohorts, with no increase in re-bleeding events in the algorithm cohort (33.3%) compared with our conventional cohort (43.7%).Conclusions: Our endoscopic management algorithm for GIB in LVAD patients proved effective in reducing low-yield procedures, improving the diagnostic and therapeutic yield of endoscopy, and decreasing health-care resource utilization and costs, while not increasing the risk of a re-bleeding event. [ABSTRACT FROM AUTHOR]

Outcomes have improved in patients bridged to heart transplant on contemporary continuous-flow ventricular assist devices over the past decade. We evaluated mechanical circulatory support as a means to bridge patients to cardiac retransplantation. We retrospectively reviewed 464 patients who underwent cardiac retransplant from the United Network for Organ Sharing database between January 2006 and November 2016. Pre- and post-transplant data were compared between patients bridged to retransplant with mechanical circulatory support (n = 81) and those without mechanical circulatory support (n = 383). The mean ages for the patients in the mechanical circulatory support and nonmechanical circulatory support cohorts were 41.2 ± 16 years and 42.1 ± 15.7 years, respectively (P =.64). Patients bridged with mechanical circulatory support were placed on extracorporeal membrane oxygenation (n = 29, 35.8%), a total artificial heart (n = 13, 16.0%), or a temporary or durable ventricular assist device (n = 39, 48.1%). Twelve patients (14.8%) were placed on a second device before retransplant. Thirty-nine percent of the mechanical circulatory support group were indicated for listing because of primary graft dysfunction or acute rejection versus 6% of the nonmechanical circulatory support group (P <.01). Likewise, 30% of patients in the mechanical circulatory support group were listed for cardiac allograft vasculopathy compared with 59% of the nonmechanical circulatory support group (P <.01). Thirty-day mortality was significantly higher in the mechanical circulatory support group (17.8% vs 4.8%, P <.01). However, patients who were bridged with a ventricular assist device or total artificial heart had comparable midterm outcomes to the nonmechanical circulatory support group. Patients who require mechanical circulatory support bridge to retransplantation belong to a high-risk cohort. Comparable midterm outcomes to the nonmechanical circulatory support cohort were demonstrated when patients' conditions allow for bridge with a ventricular assist device or total artificial heart. Bridging to retransplantation with extracorporeal membrane oxygenation remains a relative contraindication. [ABSTRACT FROM AUTHOR]

Background The use of percutaneous mechanical circulatory support (MCS) in the treatment of cardiogenic shock has increased. However, limitations in flow capability, ventricular unloading effect, durability, and mobility remain. We reviewed our single-center experience with continuous-flow external ventricular assist devices (VADs) to determine the role of temporary VADs for cardiogenic shock in the contemporary MCS era. Methods We retrospectively reviewed 252 patients who underwent continuous-flow external VAD insertion between January 2007 and December 2016. To investigate the change in indications, device configurations, and outcomes, we divided the cohort into 2 groups—2007 to 2011 (Era 1; n = 127) and 2012 to 2016 (Era 2; n = 125)—and compared early and late outcomes. Results Indications and device configurations changed significantly over time. The use of preoperative percutaneous MCS (53% vs 23%; P < .01) and use of minimally invasive VAD configurations (23% vs 6.7%; P < .01) were greater in Era 2 compared with Era 1. The rate of bridge to the next destinations, including myocardial recovery, transplantation, and durable VAD, was similar in the 2 groups. In-hospital mortality was significantly better in Era 2 (50% vs 37%; P = .04). Overall survival at 1 year was 57% in Era 2 versus 43% in Era 1 ( P = .04). Conclusions Better outcomes in the recent era could be associated with the changes in practice patterns using continuous-flow external VAD in patients with refractory cardiogenic shock. [ABSTRACT FROM AUTHOR]

Objective The role of short-term mechanical circulatory support has increased in patients with refractory cardiogenic shock. However, limited data exist on the outcomes of a bridge to a durable left ventricular assist device strategy using short-term mechanical circulatory support. Methods We retrospectively reviewed 382 patients who underwent continuous-flow left ventricular assist device insertion between 2004 and 2014. Of these, 45 (12%) were bridged with short-term mechanical circulatory support devices for refractory cardiogenic shock. We analyzed early and midterm outcomes in this bridged cohort. Multivariate Cox proportional hazards modeling was performed to evaluate the predictor of overall death in the entire cohort. Results The mean age of the bridged cohort was 53 ± 10 years, and 87% were male. The types of initial support included percutaneous devices in 24 patients (53%) and external continuous-flow ventricular assist device in 21 patients (47%). The median duration of short-term mechanical circulatory support was 14.0 (interquartile range, 7.5-29.5) days. The short-term mechanical circulatory support significantly improved end-organ function and hemodynamics. After conversion to durable left ventricular assist device insertion, in-hospital mortality was 18%. The incidence of right ventricular assist device use was high at 27%. The overall survival was 70% and 62% at 1 and 2 years, respectively. Cox multivariate hazard analysis in the entire cohort demonstrated that the use of a postoperative right ventricular assist device was a significant predictor of overall death (hazard ratio, 4.04; P < .001; 95% confidence interval, 1.97-7.94), but the use of a short-term mechanical circulatory support was not ( P = .937). Conclusions Short-term mechanical circulatory support can optimize patients in refractory cardiogenic shock and serve as a bridge to implantation of a durable left ventricular assist device. However, the early mortality rate after durable left ventricular assist device implantation is high because of unrecognized right ventricular failure. [ABSTRACT FROM AUTHOR]

Objectives Severe right ventricular failure often is considered a contraindication for left ventricular assist device (LVAD) therapy and necessitates use of biventricular assist devices (BiVADs). Available options for BiVADs are limited, and comparative outcomes are largely unknown. Methods Heart transplant candidates who were registered on the United Network for Organ Sharing waitlist and underwent long-term contemporary LVAD (n = 3195) or BiVAD (n = 408) implantation, from January 2010 through June 2014, were retrospectively analyzed. We evaluated clinical characteristics and outcomes of patients requiring a BiVAD, as well as regional differences in utilization of this technology. Results Patients requiring a BiVAD were younger (48.9 vs 53.3 years), had a higher proportion of nonischemic disease (69.1% vs 58.2%), a higher bilirubin level (0.9 vs 0.7 mg/dL), and a lower 6-month survival rate (68.1% vs 92.7%) after device implantation (all P < .05). Postimplantation and posttransplantation survival was comparable for commonly used BiVAD configurations, including total artificial heart, continuous flow BiVAD, a continuous-flow LVAD coupled with a right-sided device, and pulsatile flow. Significant variation was found in regional utilization of these devices, regardless of differences in transplantation waitlist times. A large body surface area was an independent predictor of mortality on a BiVAD (hazard ratio = 2.12, P = .017). Conclusions Outcomes of patients requiring a BiVAD remain poor in the contemporary device era, regardless of the configuration used. Among other clinical factors, body surface area should be incorporated into decision making for device selection in these patients. [ABSTRACT FROM AUTHOR]

Objective Patients evaluated for a continuous-flow left ventricular assist device frequently present with severe right ventricular dysfunction with tricuspid regurgitation. Long-term outcomes of concurrent tricuspid valve procedures in continuous-flow left ventricular assist device implantation are unclear. Methods From May 2004 to December 2013, 336 patients received continuous-flow left ventricular assist devices. Among these, 8 patients with prior tricuspid valve procedures were excluded. At continuous-flow left ventricular assist device implantation, 76 patients underwent tricuspid valve procedures (group A), including 68 repairs and 8 replacements. The remaining 252 patients did not receive concurrent tricuspid valve procedures (group B). Results Preoperatively, group A had higher central venous pressure/pulmonary capillary wedge pressure ( P = .032), total bilirubin ( P = .009), and percentage of moderate or greater tricuspid regurgitation (98.7% vs 18.8%; P < .001). In group A, cardiopulmonary bypass time (136 ± 52.0 minutes vs 83.9 ± 38.8 minutes; P < .001), intraoperative platelet use (13.6 ± 6.70 units vs 11.7 ± 5.92 units; P = .042), and bleeding requiring reoperation (27.5% vs 16.7%; P = .046) were significantly increased. In-hospital mortality was similar (10.5% vs 6.4%; P = .22). On-device 2-year survival was 73.9% in group A and 74.2% in group B ( P = .24). At 2 years, mean cumulative readmissions for right heart failure was 0.21 in group A and 0.27 in group B ( P = .95). A generalized linear mixed-effects model showed that tricuspid valve procedures are protective for developing future significant tricuspid regurgitation (odds ratio, 0.38; 95% confidence interval, 0.19-0.76; P = .006). Conclusions Concomitant tricuspid valve procedures at continuous-flow left ventricular assist device implantation can be performed safely and are protective against worsening tricuspid regurgitation during the first 2 years of support. [ABSTRACT FROM AUTHOR]

Objectives Aortic insufficiency (AI) after continuous-flow left ventricular assist device implantation can affect patient outcomes. Central aortic valve closure (CAVC) is a strategy commonly practiced; however, its efficacy has not been extensively investigated. Methods From March 2004 to May 2014, a total of 340 patients received a continuous-flow left ventricular assist device (89; 26.2%) as destination therapy (DT). Outcomes were compared between patients with CAVC (n = 57 [16.8%]; group A) versus without repair (n = 283 [83.2%]; group B). Results Patients in group A were older, were more likely to be having DT, had a greater cardiopulmonary bypass and aortic crossclamp time, and more often received intraoperative transfusions than did patients in group B. Twenty-three (40.4%) patients in group A had significant pre-existing AI, defined as >mild AI, whereas none did in group B. Kaplan-Meier analysis revealed that freedom from significant AI was 66.7% and 59.9% at 2 years ( P = .77) in groups A and B, respectively. In the DT cohort, freedom from significant AI was 78.1% and 41.8% at 2 years ( P = .077). A generalized mixed-effects model demonstrated a 57% and 69% decrease in the odds of significant AI progression among repaired patients in the entire and DT cohort, respectively, after adjusting for time effect and degree of baseline pre-existing AI. Conclusions Despite pre-existing AI, the prevalence of significant AI in patients with CAVC was comparable to the AI in those without pre-existing AI/CAVC. The efficacy of this technique was more evident in DT patients. Thus, CAVC may be an effective and durable strategy, especially in patients who require lengthy device support. [ABSTRACT FROM AUTHOR]

Objectives Pulmonary hypertension is often considered a contraindication to orthotopic heart transplantation. Left ventricular assist device support may improve pulmonary hypertension by unloading the left ventricle, making patients eligible for transplantation. We sought to investigate the effect of continuous-flow left ventricular assist device support on pulmonary hypertension and compare post-transplantation outcomes in patients with preexisting pulmonary hypertension. Methods Between March 2004 and December 2013, 256 potential orthotopic heart transplantation candidates underwent continuous-flow left ventricular assist device implantation at Columbia University. Preimplantation right heart catheterization data were available for 227 patients. Patients were divided into 2 groups on the basis of preimplantation pulmonary vascular resistance: low (<5 Wood units) (n = 182) and high (≥5 Wood units) (n = 45). Postimplantation and post-transplantation outcomes were compared between the groups. Results Pulmonary vascular resistance in the high resistance group decreased significantly during left ventricular assist device support ( P < .001). Post-transplantation in-hospital mortality was significantly higher in patients with high vascular resistance ( P < .05). However, 3-year survival after transplantation was similar between groups (85.0% and 79.0% for low and high vascular resistance, respectively; P = .45). Conclusions Continuous-flow left ventricular assist device therapy reduced pulmonary vascular resistance. Subsequent orthotopic heart transplantation in patients with significantly elevated pulmonary vascular resistance resulted in higher in-hospital mortality but similar 3-year survival. [ABSTRACT FROM AUTHOR]