Initial experience of hypoxia-inducible factor prolyl hydroxylase inhibitors in patients with heart failure and renal anemia.

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors might improve renal anemia maintaining fewer cardiovascular complications. However, its safety and efficacy, as well as its impact on inflammatory biomarkers, in heart failure patients remain unknown. We initiated HIF-PH inhibitors in 13 patients with chronic heart failure and renal anemia (median age 77 years, median estimated glomerular filtration rate 24.9 mL/min/1.73m2) between September 2021 and February 2022. There were no drug-related complications, except for a patient who had a headache and hot flash, resulting in discontinuation of HIF-PH inhibitor at 3 months. Among 10 patients who continued HIF-PH inhibitors for over 3 months, hemoglobin levels increased significantly (median from 9.6 g/dL to 10.7 g/dL, p = 0.004) and hepcidin-25 levels tended to decrease (median from 11.5 ng/mL to 3.0 ng/mL, p = 0.294) at 3-month follow-up. In conclusion, HIF-PH inhibitors might be safe and effective for the treatment of renal anemia in patients with chronic heart failure.

Prognostic impact of remote dielectric sensing value following TAVR.

Remote dielectric sensing (ReDS) system non-invasively quantifies pulmonary congestion. Re-admission following trans-catheter aortic valve replacement (TAVR) remains an unsolved matter. Residual pulmonary congestion is a strong risk factor of worse clinical outcomes in patients with heart failure. ReDS system may have a prognostic impact in patients undergoing TAVR. Patients who received TAVR and ReDS measurements during index hospitalization between 2021 and 2022 were included. The prognostic impact of ReDS value on the composite endpoint of death or re-admission following index discharge was investigated. Totally, 42 patients (median 84 years, 14 men) were included. Median ReDS value at index discharge was 27% (24%, 30%) and 10 patients had ReDS values > 30%. During a median of 316 (282, 354) days following index discharge, a higher ReDS value at baseline was independently associated with the incidence of composite endpoint with an adjusted hazard ratio of 1.32 (95% confidence interval between 1.10 and 1.58) with a calculated cutoff of 30%, which significantly stratified the cumulative incidence of the composite endpoint (78% in the high ReDS group [N = 10] and 36% in the normal ReDS group [N = 32], p = 0.002). ReDS technology may be a promising tool to predict future clinical outcomes following TAVR by quantifying residual pulmonary congestion. The clinical implication of ReDS-guided aggressive intervention following TAVR remains the next concern.

Decoupling Between Pulmonary Artery Diastolic and Wedge Pressure Following Transcatheter Aortic Valve Replacement.

BACKGROUND: Coexistent pulmonary hypertension with severe aortic stenosis confers a greater risk of mortality for patients undergoing transcatheter aortic valve replacement (TAVR). In this patient population, the impact of significant decoupling between pulmonary artery diastolic and pulmonary capillary wedge, as it relates to clinical risk, remained uncertain.Methods and Results:Patients with severe aortic stenosis who underwent TAVR and completed pre-procedural and post-procedural invasive hemodynamic assessments with right heart catheterization were retrospectively assessed. The impact of post-TAVR decoupling, defined as a pressure difference ≥3 mmHg, on 2-year all-cause mortality or risk of heart failure admission was analyzed. Among 77 included patients (median age 86 years, 23 men), 16 had post-TAVR decoupling. The existence of post-TAVR decoupling was associated with a higher cumulative incidence of the primary endpoint (44% vs. 7%, P=0.001), with an adjusted hazard ratio of 5.87 (95% confidence interval 1.58-21.9, P=0.008). CONCLUSIONS: A greater risk of worse outcomes in those with post-TAVR decoupling was observed. A therapeutic strategy for post-TAVR decoupling and its clinical implication need to be created and investigated in the future.

Validation of Inter-Rater and Intra-Rater Reliability of Remote Dielectric Sensing Measurement.

Remote dielectric sensing (ReDS) is a recently introduced non-invasive electromagnetic-based device used to quantify lung fluid levels. Nevertheless, its inter-rater and intra-rater reliability remain uncertain. In 10 healthy volunteers, ReDS values were measured three times successively by the officially trained expert examiner to validate intra-rater reliability. Similar measures were performed by a total of three examiners to validate inter-rater reliability. Intra-class correlation (ICC) was applied to validate each reliability. Ten healthy volunteers [median 34 (32, 40) years old, 10 men, body mass index 23.0 (21.2, 23.9) ] were included. Median ReDS value was 28% (25%, 31%). For the intra-rater reliability, ICC (1, 1) and ICC (1, 3) were 0.966 and 0.988, respectively (P < 0.001). For the inter-rater reliability, ICC (2, 1) and ICC (2, 3) were 0.683 and 0.866, respectively (P < 0.001). Given almost perfect intra-rater reliability, an examiner does not need to repeat ReDS measurement. Given substantial inter-rater reliability, ReDS measurements had better be measured by multiple examiners if possible.

A Rescue Use of ECPELLA for Sepsis-Induced Cardiogenic Shock Followed by Mitral Valve Replacement.

The use of veno-arterial extracorporeal membrane oxygenation (ECMO) in patients with sepsis-induced cardiogenic shock has been reported, but the clinical implication of the Impella percutaneous axial-flow left ventricular assist device for such patients remains unknown. We had a 37-year-old man with septic shock and severely reduced cardiac function. Veno-arterial ECMO and concomitant Impella CP support ameliorated his end-organ dysfunction and achieved cardiac recovery, whereas severe mitral valve regurgitation due to chordal rupture developed later. Mitral valve replacement concomitant with ECMO removal as well as an Impella upgrade successfully treated the patient. ECMO and Impella support might be an effective therapeutic strategy for the bridge to recovery in patients with sepsis-induced cardiogenic shock; however, paying attention to mitral chordal rupture is highly encouraged.

Trans-Apical Transcatheter Aortic Valve Replacement in a Dialysis Patient with Systolic Heart Failure.

Mortality and morbidity remain high following transcatheter aortic valve replacement (TAVR) in dialysis patients or those with low left ventricular ejection fraction. Therapeutic strategy for those with these comorbidities remains unestablished. We had a dialysis patient with peripheral artery disease and low left ventricular ejection fraction, who received successfully scheduled trans-apical TAVR following sufficient reverse remodeling by 3-month optimal medical therapy. Our strategy should be validated in a larger robust cohort.

The implication of optimal heart rate in patients with systolic dysfunction following TAVR.

Heart rate reduction therapy using ivabradine has demonstrated its prognostic implication in patients with heart failure with reduced ejection fraction. However, the target heart rate with optimal clinical outcomes, particularly for those with systolic dysfunction following a transcatheter aortic valve replacement (TAVR), remains unknown. Consecutive patients with left ventricular ejection fraction (LVEF) < 50% and sinus rhythm following TAVR received transthoracic echocardiography at index discharge. The ideal heart rate was calculated using a formula: 93 - 0.13 × (deceleration time [ms]). Those whose actual heart rates at discharge were within 10 bpm of the calculated ideal heart rate were assigned to the optimal heart rate group, and their prognosis was compared with those without. Twenty-four patients (83 [78, 85] years old, LVEF 41% [35%, 44%], 16 males) were included. The median difference between actual heart rate and ideal heart rate was 12 (0, 16) bpm and 11 patients were assigned to the optimal heart rate group. One year later, the optimal heart rate group achieved more improvement in LVEF (24% [15%, 28%] vs. 7% [7%, 12%], p = .003) and had lower heart failure readmission rates (0.059 vs. 0.116 events/year; p = .49). In conclusion, an optimal heart rate might be associated with cardiac reverse remodeling and prevention of heart failure recurrences in patients with systolic dysfunction following TAVR. The implication of deceleration time-guided heart rate optimization therapy for such cohorts remains the next concern.

Risk assessment in patients with left ventricular systolic dysfunction following transcatheter aortic valve replacement.

BACKGROUND: Mortality following transcatheter aortic valve replacement (TAVR) in patients with post-procedural left ventricular systolic dysfunction remains high. We investigated clinical variables associating with worse clinical outcomes following TAVR in patients with systolic dysfunction. METHODS: We retrospectively investigated 2588 patients with severe aortic stenosis who received TAVR and were enrolled in the optimized transcatheter valvular intervention (OCEAN-TAVI) multicenter registry (UMIN000020423). The association between the clinical variables following TAVR and 2-year cardiovascular mortality was investigated among those with post-TAVR left ventricular ejection fraction less than 50%. RESULTS: A total of 298 patients (median 85 years old, 131 men) were included. The presence of moderate or greater tricuspid regurgitation following TAVR was independently associated with 2-year mortality (adjusted hazard ratio 3.41, 95% confidence interval 1.15-10.1), and significantly discriminated 2-year cardiovascular mortality (30% vs. 12%, p = 0.001). No patients with any improvement in tricuspid regurgitation had cardiovascular death. CONCLUSION: Following TAVR, the existence of significant tricuspid regurgitation was associated with cardiovascular mortality in patients with heart failure with reduced ejection fraction.

How to Estimate the Optimal Heart Rate in Patients with Heart Failure with Preserved Ejection Fraction.

Ideal heart rate (HR), particularly for those with heart failure with preserved ejection fraction (HFpEF), remains unknown. We hypothesized that cardiac output would be maximum when the overlap between E-wave and A-wave at the trans-mitral flow is "zero" in the Doppler echocardiography. We retrospectively investigated the association among the overlap length between two waves, actual HR, and other echocardiographic parameters to construct a formula for estimating theoretically ideal HR among those with HFpEF. In total, 48 HFpEF patients were included (70-year-olds, 18 males). Given the results of multivariate linear regression analyses, the overlap length was estimated as follows: -1,050 + 8.4 × (HR [bpm]) + 0.6 × (deceleration time [millisecond]) + 1.7 × (A-width [millisecond]), which had a strong agreement with the actually measured overlap length (r = 0.86, P < 0.001). Theoretically ideal HR was calculated by substituting zero into the estimated overlap length as follows: 125 - 0.07 × (deceleration time [millisecond]) - 0.20 × (A-width [millisecond]). In the validation cohort including another 143 HFpEF patients, the estimated overlap using the formula again had a strong agreement with the actually measured overlap (r = 0.72, P < 0.001). In this study, we proposed a novel formula for calculating theoretically ideal HR, consisting of deceleration time and A-width, in the HFpEF cohort. Clinical implication to optimize the HR targeting the theoretically ideal HR should be investigated in prospective studies.

Creatinine Score Can Predict Persistent Renal Dysfunction Following Trans-Catheter Aortic Valve Replacement.

Severe aortic stenosis (AS) is often accompanied by renal dysfunction, which portends a poor prognosis. Trans-catheter aortic valve replacement (TAVR) is an accepted therapy for patients with severe AS, whereas the prediction of persistent renal dysfunction following TAVR remains challenging. In this study, we aimed to evaluate the pre-procedural score to assess the reversibility of renal dysfunction following TAVR. A total of 2,588 patients with severe AS who received TAVR and were enrolled in the Optimized transCathEter vAlvular iNtervention (OCEAN-TAVI) multicenter registry (UMIN000020423) were retrospectively investigated and those with serum creatinine (Cre) data at baseline and one year following TAVR were included. The Cre score was calculated using the formula: 0.2 × (age [years]) + 3.6 × (baseline serum Cre [mg/dL]). This score was evaluated to assess the risk of persistent renal dysfunction defined as serum Cre level > 1.5 mg/dL at one year following TAVR. Of the 1705 patients (84.3 ± 5.0 years old) included, 246 (14%) had persistent renal dysfunction following TAVR. The Cre score predicted the incidence of persistent renal dysfunction with an adjusted incidence rate ratio of 1.48 (95% confidence interval 1.42-1.56) with a cutoff of 21.4 (43% versus 5%, P < 0.001). The Cre score also predicted 4-year survival following TAVR (70% versus 52%, P < 0.001) with an adjusted hazard ratio of 1.75 (95% confidence interval 1.29-2.37). In conclusion, the Cre score identified those with a high risk of one-year persistent renal dysfunction following TAVR. The implication of Cre score-guided therapeutic strategy is the next concern.

Improvement in Vascular Endothelial Function following Transcatheter Aortic Valve Implantation.

Background and objectives: Endothelial dysfunction is associated with exercise intolerance and adverse cardiovascular events. Transcatheter aortic valve implantation (TAVI) is applied to treat elderly patients with severe aortic stenosis, but less is known about the impact of TAVI on endothelial dysfunction, which can be assessed by measuring flow-mediated vasodilation (FMD). In this parameter, a low value indicates impaired endothelial function. Materials and Methods: Vascular endothelial function was evaluated by FMD of the brachial artery just before and one week after TAVI. Factors associated with the normalization of FMD and their prognostic impact were investigated. Results: Fifty-one patients who underwent TAVI procedure (median 86 years old, 12 men) were included. FMD improved significantly from baseline to one week following TAVI (from 5.3% [3.7%, 6.7%] to 6.3% [4.7%, 8.1%], p < 0.001). Among 33 patients with baseline low FMD (≤6.0%), FMD normalized up to >6.0% following TAVI in 15 patients. Baseline higher cardiac index was independently associated with normalization of FMD following TAVI (odds ratio 11.8, 95% confidence interval 1.12-124; p < 0.04). Conclusions: Endothelial dysfunction improved following TAVI in many patients with severe aortic stenosis. The implication of this finding is the next concern.

B-type Natriuretic Peptide Regulation in Patients with Severe Aortic Stenosis Following Transaortic Valvular Implantation.

Peri-procedural elevated B-type natriuretic peptide (BNP) is also associated with worse outcomes following transcatheter aortic valve implantation (TAVI). However, the mechanism of BNP regulation in patients with severe aortic stenosis (AS) remains unknown. Consecutive patients with severe AS who were referred for TAVI were enrolled in our prospective registry. BNP levels were correlated with other clinical variables. Ninety-six patients (84.7 ± 5.0 years old, 34% males) were investigated in this study. Plasma BNP averaged 353 ± 179 pg/mL. Log10 BNP had no significant correlation with severity of AS including aortic valve area and maximum flow velocity across the aortic valve (P > 0.05 for all), whereas a higher left ventricular end-diastolic dimension (LVDd) index was a significant factor associating with BNP >100 pg/mL with an odds ratio of 1.34 (95% confidence interval 1.06-1.52, P = 0.004) adjusted for several other echocardiographic parameters, with a cutoff of 30.8 mm/m2 (equivalent to LVDd 44 mm). In conclusion, among the patients with severe AS who undergo TAVI, even slight eccentric hypertrophy can cause a considerable increase in BNP level.

Regulation and Clinical Implication of Arginine Vasopressin in Patients with Severe Aortic Stenosis Referred to Trans-Catheter Aortic Valve Implantation.

Background and objectives: Plasma arginine vasopressin (P-AVP) is regulated by the non-osmotic pathway in patients with heart failure (HF) and reduced ejection fraction. However, the regulation of P-AVP in patients with severe aortic stenosis (AS) remains unknown. Materials and Methods: Consecutive patients with severe AS who received trans-catheter aortic valve implantation (TAVI) between Apr 2016 and Apr 2019 were enrolled in this prospective study. Clinical data including P-AVP were obtained just before TAVI, and the correlation between P-AVP and other variables was investigated. Results: In total, 159 patients with severe AS (85.3 ± 4.6 years, male 26%) were enrolled. P-AVP was 1.45 ± 1.13 ng/mL and cardiac index was relatively preserved (2.76 ± 0.54 L/min/m2). There was no significant correlation between cardiac index and P-AVP (p > 0.05), whereas plasma osmolality had a moderate positive correlation with P-AVP (r = 0.35, p < 0.01), predominantly due to blood urea nitrogen (r = 0.27, p < 0.01). Patients with diuretics had significantly higher P-AVP than those without diuretics (1.65 ± 1.43 vs. 1.22 ± 0.57 pg/mL, p < 0.01). Two-year survivals free from HF readmission were statistically comparable irrespective of the level of pre-procedural P-AVP (p = 0.44). Conclusion: In patients with severe high-gradient AS who received TAVI, the P-AVP level was dominantly regulated by plasma osmolality instead of arterial underfilling. The clinical implication of elevated P-AVP in the TAVI candidates is the next concern.

Clinical Advantages of Using Low Tube Voltage in Third-Generation 192-Slice Dual-Source Computed Tomographic Angiography Before Transcatheter Aortic Valve Implantation.

Low-voltage computed tomographic angiography (CTA) is a highly effective technique to reduce contrast media volume. We sought to examine the suitability of low tube voltage CTA with a reduced contrast media volume protocol using third-generation 192-slice dual-source CT in patients undergoing transcatheter aortic valve implantation (TAVI). CTA was performed to aid TAVI planning for 40 consecutive patients with severe aortic stenosis. For the first 10 patients (120/100 kV group), we used a conventional tube voltage combined CTA protocol (an ECG-gated helical scan; 120 kV, non-gated helical scan; 100 kV). For the subsequent 30 patients (70-kV group), we adopted a low tube voltage CTA protocol. We evaluated vascular attenuation, image noise, contrast-to-noise ratio (CNR), and renal function. The mean contrast media (CM) volume was 77.7 ± 17.7 mL in the 120/100-kV group and 30.9 ± 6.3 mL in the 70-kV group (P < 0.001). In the images of the aortic valve complex, the mean attenuation was not significant difference for both groups. In the images of the aorto-femoral arteries, mean attenuation was > 250 Hounsfield Units and CNR was > 10 in all vascular segments for both groups. There was no significant difference in the change of renal function in the 70-kV group, but renal function in the 120/100-kV group decreased within 1-3 months after CTA. Low tube voltage CTA using third-generation dual-source CT is suitable to assess procedural planning for TAVI. This approach maintains image quality and reduces the required CM volume.

Transcatheter Aortic Valve Implantation Improves Cardiac Sympathetic Nerve Activity on 123I-Metaiodobenzylguanidine Myocardial Scintigraphy in Severe Aortic Valve Stenosis.

BACKGROUND: There is a consensus that overactivation of the cardiac sympathetic nervous system (CSN) proportionately increases the severity of heart failure and is accompanied by worse prognosis. Because it is unknown whether patients with aortic valve stenosis (AS) have similar CSN activation, we investigated the effect of transcatheter aortic valve implantation (TAVI).Methods and Results:We enrolled 31 consecutive patients with AS treated by TAVI. 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed at baseline and at 2 weeks after TAVI. At baseline, the early heart-mediastinum ratio (H/M) was within normal limits (3.0±0.5), but the delayed H/M was low (2.6±0.6) and the washout rate (WR) was high (34±13%). WR negatively correlated with aortic valve area (r=-0.389, P<0.01) and cardiac output (r=-0.595, P<0.01) and positively correlated with norepinephrine (r=0.519, P<0.01) and log NT-proBNP level (r=0.613, P<0.01). After TAVI, there were significant decreases in the norepinephrine level (366±179 ng/mL vs. 276±125 ng/mL, P<0.01) and WR (34±13 vs. 26±11%, P<0.01). CONCLUSIONS: The WR of MIBG was a useful marker of CSN activity and severity of AS. Immediate improvement of CSN activity after TAVI implied that AS hemodynamics per se enhanced CSN.

Nicorandil Attenuates Ischemia-Reperfusion Injury Via Inhibition of Norepinephrine Release From Cardiac Sympathetic Nerve Terminals.

A large amount of norepinephrine (NE) released from cardiac sympathetic nerve terminals might accelerate myocardial ischemic injury. Nicorandil (NICO), KATP channel opener, could attenuate cardiac NE release from the sympathetic nerve terminals during ischemia. The present study aimed to investigate the effects of NICO-induced attenuation of cardiac NE release on myocardial ischemia-reperfusion (I/R) injury in rats, by comparison with the effect of cardiac sympathetic denervation on I/R injury.Cardiac interstitial NE (iNE) concentrations were determined using a microdialysis method. Rats were divided into 3 groups; control, NICO, and denervation groups. Cardiac sympathetic denervation was performed by painting 10% phenol on the left ventricular epicardium 7 days before producing ischemia. The left coronary artery was ligated for 30 minutes and then re-perfused for 120 minutes. NICO (50 µg/kg/minute) was infused intravenously starting 20 minutes before the coronary occlusion to the end of the ligation.The infarct size of the left ventricle was smaller in rats treated with NICO than in control rats (20.2 ± 3.0 versus 50.6 ± 14.7%, P < 0.01). Sympathetic denervation also reduced infarct size (28.5 ± 10.4 %, P < 0.01), which was not significantly different from that in the NICO group. At the end of 30-minute ischemia, iNE increased markedly in control rats (0.1 ± 0.1 to 20.6 ± 5.3 × 103 pg/mL), whereas the increase was completely inhibited in denervated rats. NICO markedly attenuated the increase (4.9 ± 3.0 × 103 pg/mL, P < 0.01) during ischemia.NICO-induced attenuation of neural NE release during ischemia might, at least in part, contribute to myocardial protection against I/R injury.

Waon therapy attenuates cardiac hypertrophy and promotes myocardial capillary growth in hypertensive rats: a comparative study with fluvastatin.

Cardiac hypertrophy and fibrosis in heart failure with preserved ejection fraction are associated with a pro-inflammatory state and reduced NO bioavailability. Effects on myocardial structural and molecular alterations were compared between Waon therapy (WT; repeated dry sauna therapy) and statin in hypertensive rats. Seven-week-old Dahl salt-sensitive rats were assigned to 4 groups: low-salt (LS) diet, high-salt (HS) diet, HS diet with oral fluvastatin (FL; 10 mg/kg/day for 4 weeks) starting from the age of 9 weeks, and HS diet with WT treatment in a far-infrared dry sauna (39 °C for 15 min followed by 34 °C for 20 min once daily for 4 weeks). HS rats developed left ventricular (LV) hypertrophy with preserved LV systolic function. WT reduced LV wall thickness and myocyte cross-sectional area along with decreased levels of myocardial ANP and BNP mRNA expression compared with HS rats. Reduction in LV fibrosis and increase in capillary density in WT animals were accompanied by reductions in myocardial levels of TGF-ß1, MMP2, p22(phox) and gp91(phox) mRNA expression, and increases in myocardial levels of VEGF and HSP90 mRNA and phosphorylated eNOS protein. These effects were comparable between WT and FL animals. WT improves structural and molecular alterations in salt-induced hypertensive rats similarly to fluvastatin.

Waon therapy improves quality of life as well as cardiac function and exercise capacity in patients with chronic heart failure.

Waon therapy (WT), which in Japanese means soothing warmth, is a repeated sauna therapy that improves cardiac and vascular endothelial function in patients with chronic heart failure (CHF). We investigated whether WT could improve the quality of life (QOL) of CHF patients in addition to improving cardiac function and exercise capacity.A total of 49 CHF patients (69 ± 14 years old) were treated with a 60°C far infrared-ray dry sauna bath for 15 minutes and then kept in a bed covered with blankets for 30 minutes once a day for 3 weeks. At baseline and 3 weeks after starting WT, cardiac function, 6-minute walk distance (6MWD), flow mediated dilation (FMD) of the brachial artery, and SF36-QOL scores were determined.WT significantly improved left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), 6MWD, and FMD (3.6 ± 2.3 to 5.1 ± 2.8%, P < 0.01). Moreover, WT significantly improved not only the physical (PC) but also mental component (MC) of the QOL scores. WT-induced improvement of PC was negatively correlated with changes in BNP (r = -0.327, P < 0.05), but MC improvement was not related directly to changes in BNP, LVEF, or 6MWD. WT-induced changes in MC were not parallel to PC improvement.WT improved QOL as well as cardiac function and exercise capacity in patients with CHF. Mental QOL improved independently of WT-induced improvement of cardiac function and exercise capacity.

Fluvastatin-induced reduction of oxidative stress ameliorates diabetic cardiomyopathy in association with improving coronary microvasculature.

Diabetic cardiomyopathy is associated with increased oxidative stress and vascular endothelial dysfunction, which lead to coronary microangiopathy. We tested whether statin-induced redox imbalance improvements could ameliorate diabetic cardiomyopathy and improve coronary microvasculature in streptozotocin-induced diabetes mellitus (DM). Fluvastatin (10 mg/kg/day) or vehicle was orally administered for 12 weeks to rats with or without DM. Myocardial oxidative stress was assessed by NADPH (nicotinamide adenine dinucleotide phosphate) oxidase subunit p22(phox) and gp91(phox) mRNA expression, and myocardial 8-iso-prostaglandin F(2α) (PGF(2α)) levels. Myocardial vascular densities were assessed using anti-CD31 and anti-α-smooth muscle actin (SMA) antibodies. Fluvastatin did not affect blood pressure or plasma cholesterol, but attenuated increased left ventricular (LV) minimum pressure and ameliorated LV systolic dysfunction in DM rats in comparison with vehicle (LV dP/dt, 8.9 ± 1.8 vs 5.4 ± 1.0 × 10(3) mmHg/s, P < 0.05). Myocardial oxidative stress increased in DM, but fluvastatin significantly reduced p22(phox) and gp91(phox) mRNA expression and myocardial PGF(2α) levels. Fluvastatin enhanced myocardial endothelial nitric oxide synthase (eNOS) protein levels and increased eNOS, vascular endothelial growth factor, and hypoxia-inducible factor-1α mRNA expression. CD31-positive cell densities were lower in DM rats than in non-DM rats (28.4 ± 13.2 vs 48.6 ± 4.3/field, P < 0.05) and fluvastatin restored the number (57.8 ± 18.3/field), although there were no significant differences in SMA-positive cell densities between groups. Fluvastatin did not affect cardiac function, oxidative stress, or vessel densities in non-DM rats. These results suggest that beneficial effects of fluvastatin on diabetic cardiomyopathy might result, at least in part, from improving coronary microvasculature through reduction in myocardial oxidative stress and upregulation of angiogenic factor.

Prognostic impact of insomnia in patients receiving trans-catheter aortic valve replacement.

BACKGROUND: The presence of insomnia exhibits a profound association with diverse cardiovascular pathologies. However, its prognostic implications in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis remain ambiguous. METHODS: This retrospective study enrolled patients who underwent TAVR for severe aortic stenosis at a prominent academic center from 2015 to 2022. The impact of insomnia, operationally defined as the prescription of soporific agents, on the two-year composite primary outcome comprising all-cause mortality and hospital readmissions was scrutinized. RESULTS: A cohort of 345 patients (median age 85 years, 99 males) was encompassed in the analysis. All subjects underwent successful TAVR and subsequent discharge. The presence of insomnia (N = 91) emerged as an independent predictor of the two-year composite endpoint, with an adjusted hazard ratio of 1.66 (95 % confidence interval 1.08-2.57, p = 0.022), significantly delineating the two-year cumulative incidence of the primary endpoint (40 % versus 30 %, p = 0.035). CONCLUSION: Approximately one-fourth of TAVR candidates manifested symptoms of insomnia, a condition autonomously correlated with heightened mortality and morbidity following the TAVR procedure. The optimal strategy for addressing insomnia in TAVR candidates constitutes a paramount consideration for future interventions.