Abumoawad, Abdelrhman

Background: There is a paucity of data regarding the temporal trends and outcomes of transcatheter aortic valve replacement (TAVR) among patients with prior coronary artery bypass graft (CABG) surgery. Methods: We queried the Nationwide Readmissions Database (2016-2019) for hospitalized patients who underwent TAVR using ICD-10 codes. We evaluated the trends and outcomes of TAVR among patients with versus without a history of prior CABG. Multivariable regression analysis was used to adjust for patients’ and hospitals' characteristics when comparing the study groups. The primary outcome was in-hospital mortality. Results: The final analysis included 173,274 admissions who underwent TAVR of whom 31,271 (18.3%) had a history of prior CABG. During the study years, there was a decrease in the proportion of patients with prior CABG among those undergoing TAVR (22.0% in 2016 vs. 16.2%, Ptrend=0.01), while there was no change in their in-hospital mortality rate (1.08% in 2016 vs. 1.25% in 2019, Ptrend= 0.43). Patients with prior CABG were younger and less likely to be women compared with those without prior CABG. On multivariable adjustment, In-hospital mortality was lower among the group with versus without prior CABG (adjusted odds ratio [aOR] 0.77; 95% confidence interval [CI] 0.65-0.91, p<0.01). Adjusted analysis showed lower rate of 90-day readmission (OR 0.95; 95%CI 0.90-0.98, p=0.01), and similar rate of ischemic stroke (aOR 0.89; 95%CI 0.76-1.03, p=0.89), permanent pacemaker (PPM) implantation (aOR 0.99; 95%CI 0.93-1.05, p=0.99). Among those with prior CABG, female gender, and chronic kidney disease ≥3 were independently associated with higher in-hospital mortality, and obesity was associated with lower in-hospital mortality. Conclusion: In this analysis, there was a decrease in the proportion of patients with prior CABG among those undergoing TAVR. TAVR among those with prior CABG was not associated with increased short-term mortality or PPM implantation.

Abstract Introduction Patients with hypertrophic obstructive cardiomyopathy (HOCM) have a unique pathophysiological profile that increases their chances of having adverse events in the postoperative period following surgical procedures. Owing to the rarity of the disease, few studies are available for assessing readmission risk in HOCM patients undergoing noncardiac surgical procedures. Purpose Our study aimed to assess 30-day readmission rates and causes for readmissions among HOCM patients who had undergone noncardiac surgeries in hospitals across the United States (US). Methods We used appropriate International Classification of Diseases Code, 10th Revision Clinical Modification (ICD-10-CM) codes to identify patients who had been admitted for non-cardiac surgeries between January 2016 and December 2019 based on data from the National Readmissions Database (NRD). The NRD is a publicly available all-payer in-patient database sponsored by the Agency for Healthcare Research and Quality, containing discharge data from approximately 18 million discharges each year, accounting for 61.8% of the total US resident population. Patients were subdivided into two sub-groups based on the presence or absence of HOCM. 30-day readmission rates and causes of readmissions were compared between both groups. STATA version 17 (College Station,TX: StataCorp LLC) was used for statistical analyses. Results A total of 5,497,134 patients out of whom 2,089 had HOCM were identified and included for analysis. Patients with HOCM had statistically significant higher rates of readmissions for central nervous system related complications such as stroke or transient ischemic attack (TIA), cardiogenic shock, acute heart failure, unspecified iatrogenic cardiac complications, acute kidney injury, sepsis in addition to higher rates of post op respiratory failure, acute myocardial infarction and major adverse cardiovascular and cerebrovascular events (MACCE) during the index admission when compared to the other subgroup. Conclusion Our study, despite being retrospective in nature, is one of the largest to date assessing readmission risk in HOCM patients undergoing noncardiac surgeries. Similar to previous studies, HOCM patients have higher rates of readmissions and MACCE in the 30-day period following noncardiac surgical procedures. In light of these findings, shared medical decision making and appropriate counseling regarding complications in the postoperative period will be necessary for HOCM patients who undergo noncardiac surgical procedures. Funding Acknowledgement Type of funding sources: None.

AbstractCell stress may give rise to insuperable growth arrest, which is defined as cellular senescence. Stenotic kidney (STK) ischemia and injury induced by renal artery stenosis (RAS) may be associated with cellular senescence. Mesenchymal stem cells (MSCs) decrease some forms of STK injury, but their ability to reverse senescence in RAS remains unknown. We hypothesized that RAS evokes STK senescence, which would be ameliorated by MSCs. Mice were studied after 4 weeks of RAS, RAS treated with adipose tissue‐derived MSCs 2 weeks earlier, or sham. STK senescence‐associated β‐galactosidase (SA‐β‐Gal) activity was measured. Protein and gene expression was used to assess senescence and the senescence‐associated secretory phenotype (SASP), and staining for renal fibrosis, inflammation, and capillary density. In addition, senescence was assessed as p16+ and p21+ urinary exosomes in patients with renovascular hypertension (RVH) without or 3 months after autologous adipose tissue‐derived MSC delivery, and in healthy volunteers (HV). In RAS mice, STK SA‐β‐Gal activity increased, and senescence and SASP marker expression was markedly elevated. MSCs improved renal function, fibrosis, inflammation, and capillary density, and attenuated SA‐β‐Gal activity, but most senescence and SASP levels remained unchanged. Congruently, in human RVH, p21+ urinary exosomes were elevated compared to HV, and only slightly improved by MSC, whereas p16+ exosomes remained unchanged. Therefore, RAS triggers renal senescence in both mice and human subjects. MSCs decrease renal injury, but only partly mitigate renal senescence. These observations support exploration of targeted senolytic therapy in RAS.

Background Hypertension may be associated with renal cellular injury. Cells in distress release extracellular vesicles ( EV s), and their numbers in urine may reflect renal injury. Cellular senescence, an irreversible growth arrest in response to a noxious milieu, is characterized by release of proinflammatory cytokines. We hypothesized that EV s released by senescent nephron cells can be identified in urine of patients with hypertension. Methods and Results We recruited patients with essential hypertension ( EH ) or renovascular hypertension and healthy volunteers (n=14 each). Renal oxygenation was assessed using magnetic resonance imaging and blood samples collected from both renal veins for cytokine‐level measurements. EV s isolated from urine samples were characterized by imaging flow cytometry based on specific markers, including p16 (senescence marker), calyxin (podocytes), urate transporter 1 (proximal tubules), uromodulin (ascending limb of Henle's loop), and prominin‐2 (distal tubules). Overall percentage of urinary p16+ EV s was elevated in EH and renovascular hypertension patients compared with healthy volunteers and correlated inversely with renal function and directly with renal vein cytokine levels. Urinary levels of p16 + /urate transporter 1 + were elevated in all hypertensive subjects compared with healthy volunteers, whereas p16 + /prominin‐2 + levels were elevated only in EH versus healthy volunteers and p16 + /uromodulin + in renovascular hypertension versus EH . Conclusions Levels of p16 + EV s are elevated in urine of hypertensive patients and may reflect increased proximal tubular cellular senescence. In EH , EV s originate also from distal tubules and in renovascular hypertension from Henle's loop. Hence, urinary EV s levels may be useful to identify intrarenal sites of cellular senescence.

AbstractAimsPatients with renovascular hypertension (RVH) exhibit elevated urinary mtDNA copy numbers, considered to constitute surrogate markers of renal mitochondrial injury. The modest success of percutaneous transluminal renal angioplasty (PTRA) in restoring renal function in RVH has been postulated to be partly attributable to acute reperfusion injury. We hypothesized that mitoprotection during revascularization would ameliorate PTRA–induced renal mitochondrial injury, reflected in elevated urinary mtDNA copy numbers and improve blood pressure and functional outcomes 3 months later.MethodsWe prospectively measured urinary copy number of the mtDNA genes COX3 and ND1 using qPCR in RVH patients before and 24 hrs after PTRA, performed during IV infusion of vehicle (n = 8) or the mitoprotective drug elamipretide (ELAM, 0.05 mg/kg/h, n = 6). Five healthy volunteers (HV) served as controls. Urinary mtDNA levels were also assessed in RVH and normal pigs (n = 7 each), in which renal mitochondrial structure and density were studied ex‐vivo.ResultsBaseline urinary mtDNA levels were elevated in all RVH patients vs HV and directly correlated with serum creatinine levels. An increase in urinary mtDNA 24 hours after PTRA was blunted in PTRA+ELAM vs PTRA+Placebo. Furthermore, 3‐months after PTRA, systolic blood pressure decreased and estimated glomerular filtration rate increased only in ELAM–treated subjects. In RVH pigs, mitochondrial damage was observed using electron microscopy in tubular cells and elevated urinary mtDNA levels correlated inversely with renal mitochondrial density.ConclusionsPTRA leads to an acute rise in urinary mtDNA, reflecting renal mitochondrial injury that in turn inhibits renal recovery. Mitoprotection might minimize PTRA–associated mitochondrial injury and improve renal outcomes after revascularization.

Hypertension, an important cause of chronic kidney disease, is characterized by peritubular capillary (PTC) loss. Circulating levels of endothelial microparticles (EMPs) reflect systemic endothelial injury. We hypothesized that systemic and urinary PTC-EMPs levels would reflect renal microvascular injury in hypertensive patients. We prospectively measured by flow cytometry renal vein, inferior vena cava, and urinary levels of EMPs in essential (n=14) and renovascular (RVH; n=24) hypertensive patients and compared them with peripheral blood and urinary levels in healthy volunteers (n=14). PTC-EMPs were identified as urinary exosomes positive for the PTC marker plasmalemmal-vesicle–associated protein. In 7 RVH patients, PTC and fibrosis were also quantified in renal biopsy, and in 18 RVH patients, PTC-EMPs were measured again 3 months after continued medical therapy with or without stenting (n=9 each). Renal vein and systemic PTC-EMPs levels were not different among the groups, whereas their urinary levels were elevated in both RVH and essential hypertension versus healthy volunteers (56.8%±12.7% and 62.8%±10.7% versus 34.0%±17.8%; both P ≤0.001). Urinary PTC-EMPs levels correlated directly with blood pressure and inversely with estimated glomerular filtration rate. Furthermore, in RVH, urinary PTC-EMPs levels correlated directly with stenotic kidney hypoxia, histological PTC count, and fibrosis and inversely with cortical perfusion. Three months after treatment, the change in urinary PTC-EMPs levels correlated inversely with a change in renal function ( r =−0.582; P =0.011). Therefore, urinary PTC-EMPs levels are increased in hypertensive patients and may reflect renal microcirculation injury, whereas systemic PTC-EMPs levels are unchanged. Urinary PTC-EMPs may be useful as novel biomarkers of intrarenal capillary loss.