Risk factors for erectile dysfunction (ED) (hypertension, diabetes, smoking, lipid abnormality) are also risk factors for coronary artery disease. However, most cardiologists do not routinely ask ...about ED and patients often are reluctant or embarrassed to discuss it. We determined how common ED was in a group of patients with chronic stable coronary artery disease.
We administered the validated Sexual Health Inventory for Men (SHIM) 5-item questionnaire, based on the International Index of Erectile Function questionnaire, to 76 men with chronic stable coronary artery disease during routine outpatient cardiology visits. Most of these men had not previously discussed ED with their cardiologist.
The mean patient age was 64 years (range 40 to 82). The questionnaire took about 5 minutes to complete. Of the patients 47% were on beta blockers, 92% statins, 28% diuretics. SHIM score was 21 or less in 53 men (70%), which is indicative of ED. Of the patients 75% had some difficulty achieving erections (question 2) and 67% had some difficulty maintaining an erection after penetration (question 3). The questionnaire reflected successful sildenafil treatment in 4 patients (SHIM scores 23 to 25). If these 4 men are included as having had ED then 57 of 76 (75%) had ED or recent history of ED.
ED is extremely common in men with chronic coronary artery disease (affecting approximately 75%) yet most cardiologists do not ask about it. The SHIM is a useful, quick and inexpensive tool for discussion and diagnosis of ED in this population. Although it is well established that cardiovascular risk factors are associated with erectile dysfunction, once it is present there is mixed information on whether treating the risk factors will treat the ED. Problems appear to be that lifestyle modification in midlife may simply be too late to effect a change, and some antihypertensive and lipid lowering drugs may actually exacerbate ED. Oral therapy for ED, namely the PDE5 inhibitors, is effective and safe in most cardiac and hypertensive patients. Organic nitrates such as nitroglycerin remain a contraindication to the concomitant use of these drugs. Guidelines for treatment of ED in the cardiac patient issued by the American College of Cardiology/American Heart Association and Princeton Guidelines may be useful in the approach to the cardiac patient with ED.
We present a case of a thrombosed prosthetic aortic valve that failed to respond to high dose intravenous heparin therapy. Thrombolytic therapy was contraindicated because of recent surgery. The ...valve was effectively treated by mechanical thrombolysis following the deployment of bilateral ACCUNET Embolic Protection Systems.
In the current research, we developed and printed by fused-filament fabrication polylactide-polyethylene-oxide blended membranes. The influence of relative content of polymers on the ease of ...extrusion and printing processes was studied. Ionic liquid N-butyl-N-methylpyrrolidinium bis(trifluoromethane-sulfonyl)imide (Pyr
14
TFSI) with dissolved LiTFSI salt was infused into the membranes to produce free-standing films of quasi-solid polymer electrolytes. The printed membranes were characterized by ESEM, DSC, XPS, NMR and EIS methods. Neat-printed PLA (polylactide) membrane exhibited poor wetting and low uptake of ionic liquid. However, the XPS tests of 3D-printed PLA-PEO membrane infused with LiTFSI solvated ionic liquid show evidence of the interaction between lithium cations with both, PEO (polyethylene oxide) and PLA. The measurements of diffusion coefficients by PGSE-NMR suggest that the Li
+
ions are coordinated by the PEO segments in the polymer blend. Increase of the PEO content at the expense of PLA polymer, leads to more than one order of magnitude improvement of bulk conductivity, approaching 0.2 mS cm
−1
at 60
°
C
.
The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic ...cardiomyopathy.
A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate.
Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.
LBA1004 Background: Sacituzumab govitecan (SG) is a TROP2 antibody drug conjugate (ADC) with a topoisomerase I inhibitor payload (SN-38) approved for previously treated triple negative and hormone ...receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (MBC). Double-strand DNA breaks induced by SN-38 activate cGAS-STING, stimulating type I IFN production and T cell recruitment. SN-38 can upregulate MHC class-I and PD-L1 expression, enhance cytotoxic T cell effector functions and deplete regulatory T cells. To evaluate if SG synergizes with pembrolizumab (PD-1 inhibitor) we conducted a randomized, open-label phase 2 study comparing SG with or without pembrolizumab in HR+/HER2- MBC (NCT04448886). Methods: Eligible patients (pts) had unresectable locally advanced or metastatic HR+ (ER≥1% and/or PR≥1%), HER2- breast cancer treated with ≥1 prior endocrine therapy and 0-1 chemotherapy (CT) for MBC. Pts with brain metastases were eligible if locoregional therapy was completed and steroids discontinued ≥7 days before study therapy. Pts who received prior topoisomerase I inhibitor ADC, irinotecan or PD-1/L1 inhibitors were excluded. Pts were randomized 1:1 to Arm A SG 10 mg/kg IV (D1, D8) + pembrolizumab 200 mg IV (D1), 21-day cycle or Arm B (SG alone). The primary endpoint was progression-free survival (PFS); secondary endpoints included PFS in PD-L1+ pts (22C3 CPS ≥1), overall survival (OS), objective response rate (ORR) and toxicity (NCI CTCAE v5.0). Baseline and on-treatment biopsies were performed for correlative analyses. For this preliminary analysis, data were locked 1/12/24. Results: Between 03/2021-01/2024, 110 pts enrolled; 104 pts (52 Arm A; 52 Arm B) started study therapy and were included in the analysis. Median age was 57 yrs (range: 27-81); 102 pts (98.1%) were female. 80 pts (76.9%) received prior CDK4/6 inhibitor for MBC; 58 (55.8%) had no prior CT, 46 (44.2%) had 1 prior line of CT for MBC. At a median follow-up of 9.2 months (mo), median PFS was 8.4 mo in Arm A vs 6.2 mo in Arm B (HR 0.76, 95% CI 0.47-1.23, log-rank p=0.26); ORR 21.2% and 17.3%, respectively. OS data are immature with only 26 events to date; OS was 16.9 mo vs 17.1 mo (HR 0.65, 95% CI 0.30-1.41, log-rank p=0.28), respectively. The most frequent treatment-related toxicities (≥G2) in Arm A were neutropenia (67.3%), fatigue (36.5%), alopecia (36.5%), anemia (32.7%), leukopenia (26.9%), diarrhea (21.2%) and nausea (21.2%); in Arm B, neutropenia (59.6%), alopecia (38.5%), diarrhea (34.6%), nausea (32.7%), fatigue (32.7%) and anemia (21.2%). Conclusions: Addition of pembrolizumab to SG showed a non-significant trend toward improved PFS in unselected HR+/HER2- MBC at this preliminary time point. Final PFS and updated OS with further follow-up will be presented at the meeting. Exploratory outcome analyses by TROP2 and PD-L1 expression will be reported. Clinical trial information: NCT04448886 .
The “2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy” provides recommendations to guide clinicians in the management of patients with hypertrophic ...cardiomyopathy.
A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate.
Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the “2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy” have been updated with new evidence to guide clinicians.
The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic ...cardiomyopathy.
A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate.
Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.
Abstract only Introduction: Patients with congenital heart disease (CHD) may require cardiac transplantation for either primary management or failed surgical palliation. This study describes 1-year ...mortality of patients with CHD listed for transplant, trends in 1-year mortality over three decades, and use of mechanical support in this population. Methods: The United Network for Organ Sharing database was queried to identify patients aged 0-30 years with CHD listed for transplant from 1990 to 2019. VAD status at listing and 1-year mortality after listing were examined using the Cochran-Armitage trend test. Results: Overall, 9327 patients with CHD aged 0-30 years were listed for transplant between 1990 and 2019 with a total 1-year mortality rate of 26% (n=2466). For non-survivors to 1-year after listing, 66% (n=1619) died before transplant and 34% (n=847) after transplant. Patients <1 year of age were the most frequent age group listed for transplant (n=3678, 39%) and experienced the highest 1-year mortality after listing (n=1264, 34%). The 1-year overall mortality decreased over the study period (1990-1999: 33% vs 2000-2009: 30% vs 2010-2019: 19%, p<0.0001), including in infants <1 year of age (1990-1999: 41% vs 2000-2009: 37% vs 2010-2019: 26%, p<0.0001). Overall, few patients were supported with VAD at listing (3.1%). However, VAD use increased (1990-1999: 1.0% vs 2000-2009: 2.8% vs 2010-2019: 5.0%, p< 0.0001) and the 1-year mortality for patients with VAD at listing decreased over time (1990-1999: 57% vs 2000-2009: 35% vs 2010-2019: 20%, p<0.0001). Conclusions: Survival after listing for heart transplant is improving, however mortality amongst infants remains high. While there has been >50% improvement in survival in patients of all ages with CHD supported with a VAD at listing, VADs are used rarely in patients with CHD. Further study is needed to understand which patients may benefit from mechanical circulatory support, especially among infants.
Recently, a large family of G‐protein‐coupled receptors called Mas‐related genes (Mrgs), which is selectively expressed in small‐diameter sensory neurons of dorsal root ganglia, was described. A ...subgroup of human Mrg receptors (MrgX1–X4) is not found in rodents and this has hampered efforts to define the physiological roles of these receptors.
MrgX receptors were cloned from rhesus monkey and functionally characterized alongside their human orthologs. Most of the human and rhesus MrgX receptors displayed high constitutive activity in a cellular proliferation assay. Proliferative responses mediated by human or rhesus MrgX1, or rhesus MrgX2 were partially blocked by pertussis toxin (PTX). Proliferative responses mediated by rhesus MrgX3 and both human and rhesus MrgX4 were PTX insensitive. These results indicate that human and rhesus MrgX1 and MrgX2 receptors activate both Gq‐ and Gi‐regulated pathways, while MrgX3 and MrgX4 receptors primarily stimulate Gq‐regulated pathways.
Peptides known to activate human MrgX1 and MrgX2 receptors activated the corresponding rhesus receptors in cellular proliferation assays, Ca2+‐mobilization assays, and GTP‐γS‐binding assays. Cortistatin‐14 was selective for human and rhesus MrgX2 receptors over human and rhesus MrgX1 receptors. BAM22 and related peptides strongly activated human MrgX1 receptors, but weakly activated rhesus MrgX1, human MrgX2, and rhesus MrgX2 receptors.
These data suggest that the rhesus monkey may be a suitable animal model for exploring the physiological roles of the MrgX receptors.
British Journal of Pharmacology (2006) 147, 73–82. doi:10.1038/sj.bjp.0706448