Impact of Chronic Kidney Disease on the Outcomes of Patients Undergoing Left Atrial Appendage Occlusion: Insights from a Large National Database

Introduction Studies exploring the effectiveness and safety of left atrial appendage occlusion (LAAO) in patients with chronic kidney disease (CKD) are limited. Methods We utilized the National Inpatient Sample (NIS) to identify hospitalizations for LAAO from 2016 to 2020 and further identified cases with concomitant CKD. The primary outcome was mortality, and secondary outcomes were cerebrovascular accidents, major bleeding, vasopressor requirements, percutaneous coronary intervention, cardiac arrest, acute respiratory failure, transfusion, length of stay (LOS), and total hospital charges. Multivariable logistic regression was performed to further adjust for covariates. Results A total of 89,309 LAAO procedures from 2016 to 2020 were identified, of which 21,559 (24.1%) reported concomitant CKD, with males comprising the majority (62.2%). An increasing trend in LAAO procedures was seen from 2.24 to 13.9 per 10,000 patients from 2016 to 2020. Despite patients with CKD having a higher rate of most comorbidities, there was no difference in mortality (non-CKD vs. CKD, 0.07% vs. 0.42%; aOR: 1.3, 95% CI: 0.4-4.4, p = 0.686) and complications for CKD and non-CKD patients, while CKD patients had longer LOS and higher total hospital charge. No significant sex differences in outcomes among CKD patients were observed except for a longer LOS in females. Conclusion Despite generally having more comorbidities, outcomes of patients with CKD following LAAO are similar to those without CKD, suggesting that LAAO can be offered as a safe option for the treatment of atrial fibrillation in eligible patients with CKD

The renin-angiotensin system as a primary cause of polyarteritis nodosa in rats

Polyarteritis nodosa is a necrotizing vasculitis of medium-sized arteries of unknown origin. Hypertension is present in 30% of patients with polyarteritis nodosa. In those cases, high renin levels are thought to be secondary to renal involvement. The present study was performed to identify causal factors of polyarteritis nodosa. In cyp1a1ren-2 transgenic rats, vasculitis of medium-sized arteries resembling classical polyarteritis nodosa can be induced. In this model, oral administration of indole-3-carbinol (I3C) activates the liver-specific cyp1a1 promoter, leading to prorenin expression in a dose-dependent manner. After the first 6 weeks of chronic induction with 0.125% I3C, the mean arterial pressure reached a plateau of about 170 mmHg. Ten out of 11 I3C-treated rats, which were chronically instrumented with a telemetric device to measure blood pressure, developed polyarteritis nodosa within 10 weeks of I3C treatment. I3C alone or instrumentation alone did not cause polyarteritis nodosa. The angiotensin-converting enzyme inhibitor captopril completely prevented the development of polyarteritis nodosa, indicating that local angiotensin II generation is a pathogenetic factor in this model. The renin-angiotensin system can play a primary role in the development of polyarteritis nodosa in rats

Transient Induction of ANG II-Dependent Malignant Hypertension Causes Sustained Elevation of Blood Pressure and Augmentation of the Pressor Response to ANG II in CYP1A1-REN2 Transgenic Rats

BACKGROUND: Transgenic rats with inducible expression of the mouse Ren2 renin gene [strain name: TGR(Cyp1a1Ren2)] allow induction of various degrees of ANG II-dependent hypertension. Dietary administration of the aryl hydrocarbon indole-3-carbinol (I3C) at a dose of 0.15% induces a slowly developing form of ANG II-dependent hypertension whereas dietary administration of a higher dose (0.3%) of I3C results in the development of ANG II-dependent malignant hypertension. Cessation of administration of 0.15% I3C results in the normalization of blood pressure, indicating the reversibility of hypertension induced by this dose of I3C. The present study was performed to determine if ANG II-dependent malignant hypertension is similarly reversible following cessation of dietary administration of 0.3% I3C. METHODS: Cyp1a1-Ren2 rats (n=6) were fed a normal diet containing 0.3% I3C for 11 days to induce malignant hypertension. RESULTS: Cyp1a1-Ren2 rats induced with I3C exhibited pronounced increases in systolic blood pressure (SBP) (132±3 to 229±11 mmHg, P<0.001) and marked decreases in body weight (303±4 to 222±2 g, P<0.001). When I3C administration was terminated, SBP decreased to 167±4 mmHg (P<0.01) and body weight increased to normal levels (309±2 g, P<0.01) within 12 days. However, SBP remained significantly elevated (172±1 mmHg, P<0.01) for up to 3 weeks following termination of dietary administration of 0.3% I3C. In addition, the magnitude of the blood pressure response to intravenous bolus administration of 50 ng of ANG II (50 μl in volume) 3 weeks following cessation of dietary I3C administration was substantially higher than that observed in normotensive control rats (134±1 mmHg, n=6) not previously induced with 0.3% I3C (53±2 vs. 38±3 mmHg, P<0.05). CONCLUSIONS: The present findings demonstrate that transient induction of ANG II-dependent malignant hypertension results in prolonged elevations of arterial blood pressure and marked augmentation of the magnitude of the pressor response to ANG II in Cyp1a1-Ren2 transgenic rats

Enhanced Urinary Angiotensinogen Excretion in Cyp1a1-Ren2 Transgenic Rats With Inducible ANG II-Dependent Malignant Hypertension

BACKGROUND: Previous studies have demonstrated that the urinary excretion of angiotensinogen is significantly increased in ANG II-infused hypertensive rats, which is associated with an augmentation of intrarenal ANG II levels. These findings suggest that urinary angiotensinogen excretion rates provide an index of intrarenal ANG II levels in ANG II-dependent hypertensive states. However, little information is available regarding the urinary excretion of angiotensinogen in ANG II-dependent malignant hypertension. METHODS: The present study was performed to determine if urinary angiotensinogen excretion is increased in Cyp1a1-Ren2 transgenic rats [strain name: TGR(Cyp1aRen2)] with inducible ANG II-dependent malignant hypertension. Adult male Cyp1a1-Ren2 rats (n=6) were fed a normal diet containing 0.3% indole-3-carbinol (I3C) for 10 days to induce ANG II-dependent malignant hypertension. RESULTS: Rats induced with I3C exhibited pronounced increases in systolic blood pressure (SBP) (208±7 vs. 127±3 mmHg, P<0.001), marked proteinuria (29.4±3.6 vs. 5.9±0.3 mg/day, P<0.001), and augmented urinary angiotensinogen excretion (996±186 vs. 241±31 ng/day, P<0.01). Chronic administration of the AT(1) receptor antagonist, candesartan (25 mg/L in drinking water, n=6), prevented the I3C-induced increases in SBP (125±5, P<0.001), proteinuria (7.3±1.0 mg/day, p<0.001) and urinary angiotensinogen excretion (488±51 ng/day, P<0.01). CONCLUSIONS: These data demonstrate that the urinary excretion of angiotensinogen is markedly augmented in ANG II-dependent malignant hypertension. Such increased urinary angiotensinogen excretion may contribute to augmented intrarenal ANG II levels and, thereby, to the increased blood pressure in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension

Sex differences in trends and outcomes of acute myocardial infarction with mechanical complications in the United States

Mechanical complications (MC) are rare but significant sequelae of acute myocardial infarction (AMI). Current data on sex differences in AMI with MC is limited. We queried the National Inpatient Sample database to identify adult patients with the primary diagnosis of AMI and MC. The main outcome of interest was sex difference in-hospital mortality. Secondary outcomes were sex differences in the incidence of acute kidney injury (AKI), major bleeding, use of inotropes, permanent pacemaker implantation (PPMI), performance of percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), surgery (VSD repair and MV surgery), pericardiocentesis, use of mechanical circulatory support (MCS), ischemic stroke, and mechanical ventilation. Among AMI-MC cohort, in-hospital mortality was higher among females compared to males (41.24% vs 28.13%: aOR 1.39. 95% CI 1.079–1.798; p = 0.01). Among those who had VSD, females also had higher in-hospital mortality compared to males (56.7% vs 43.1%: aOR 1.74, 95% CI 1.12–2.69; p = 0.01). Females were less likely to receive CABG compared to males (12.03% vs 20%: aOR 0.49 95% CI 0.345–0.690; p  Despite the decreasing trend in AMI admission, females had higher risk of MC and associated mortality. Significant sex disparities still exist in AMI treatment.</p