Plasma renin activity as a marker for predicting the antihypertensive effect of switching to sacubitril/valsartan in treated hypertensive patients: Usefulness in daily clinical practice.

The authors investigated the antihypertensive effect of sacubitril/valsartan (Sac/Val) when switching from other drugs and assessed whether brain natriuretic peptide (BNP) or plasma renin activity (PRA) before drug switching was a predictor of blood pressure lowering after switching to Sac/Val. In 92 patients with treated hypertension, clinic blood pressure, plasma BNP, and PRA were examined before and after switching to Sac/Val. Clinic systolic and diastolic blood pressures significantly decreased after drug switching to Sac/Val (p < .0001, respectively). The level before drug switching of BNP had no correlation with the change in systolic blood pressure (Δ-SBP) before and after switching to Sac/Val, but that of PRA was significantly correlated with Δ-SBP (r = .3807, p = .0002). A multiple regression analysis revealed that PRA before drug switching was an independent determinant of Δ-SBP. Our findings suggest that low PRA may become a useful marker to predict the antihypertensive effect of switching to Sac/Val in treated hypertensive patients.

Impact of epicardial adipose tissue on diastolic dysfunction in patients with chronic coronary syndrome and preserved left ventricular ejection fraction.

Aims: This study aims to investigate the association between left ventricular diastolic dysfunction (LVDD) and epicardial adipose tissue (EAT) accumulation in patients with chronic coronary syndrome (CCS) and preserved left ventricular ejection fraction (LVEF). Methods and results: The study included 314 patients with preserved LVEF who underwent coronary computed tomographic angiography (CCTA) and thoracic tissue Doppler echocardiography (TTDE). The EAT volume was measured using CCTA. LVDD was categorized into three groups: absent LVDD, undetermined LVDD, and LVDD. Multivariate logistic regression analysis was performed to assess the association between the clinical parameters, TTDE and CCTA findings, and LVDD. Patients (mean age: 66 ± 13 years; 52% men) were divided into LVDD present (30 patients, 9.6%), LVDD absent (219 patients, 69.7%), and LVDD undetermined (65 patients, 20.7%) groups. CCTA showed that patients with LVDD had a significantly higher coronary artery calcium (CAC) score and % plaque volume (%PV) than those without LVDD, whereas the prevalence of obstructive coronary artery disease was comparable between the groups. The EAT volume index correlated with each LVDD diagnostic component, except for tricuspid regurgitation velocity. A multivariate model showed that age [odds ratio (OR), 1.13; P < 0.001] and EAT volume index (OR, 1.02; P = 0.038) were independently associated with LVDD, even after adjusting for left ventricular mass index (OR, 1.05; P = 0.005). There was no significant association between the CAC score and %PV or LVDD. Conclusion: This study demonstrated that EAT volume index and left ventricular mass index were robust predictors of LVDD; however, there was no independent association between coronary atherosclerotic disease burden and LVDD.

Durability of output-dependent QRS transition and left bundle branch capture in left bundle branch area pacing.

BACKGROUND: Although output-dependent QRS transition is a specific indicator that confirms left bundle branch (LBB) capture during left bundle branch area pacing (LBBAP), its durability remains unclear. OBJECTIVE: The purpose of this study was to evaluate the presence of output-dependent QRS transition and capture thresholds of the LBB and left ventricular septal myocardium immediately and up to 1 year after the LBBAP procedure. METHODS: We enrolled 129 patients with successful LBBAP who were available for 1-year follow-up postoperatively. Threshold testing was performed immediately after LBBAP on postoperative day 0 (POD-0) and after 3 days (POD-3), 6 months (POD-180), and 1 year (POD-360). RESULTS: Output-dependent QRS transition persisted in 64 patients (88%) on POD-360, from among the 73 patients with output-dependent QRS transition on POD-0. In contrast, 55 of 56 patients without QRS transition on POD-0 (98%) did not exhibit QRS transition thereafter. LBB thresholds were slightly elevated on POD-360, albeit without statistical significance, compared with those on POD-0 (1.22 ± 1.00 V vs 1.43 ± 1.29 V at 0.4 ms; P = .26). The LBB thresholds increased by ≥1.5 V in 7 patients (11%). However, in 93% of patients with an LBB threshold of ≤2.5 V on POD-0, LBB capture was maintained at 2.5 V on POD-360. Left ventricular septal thresholds were similar on POD-0 and POD-360 (0.81 ± 0.36 V vs 0.83 ± 0.24 V; P > .99) and did not increase by ≥1.5 V in any patient. CONCLUSION: Output-dependent QRS transitions were highly reproducible after implantation. Furthermore, LBB thresholds remained stable in most cases during the first postoperative year.

The APOA1 p.Leu202Arg variant potentially causes autosomal recessive cardiac amyloidosis.

ApoA-I amyloidosis is an extremely rare form of systemic amyloidosis that commonly involves the heart, kidneys, and liver. ApoA-I amyloidosis is caused by amyloidogenic variants of APOA1 that are inherited in an autosomal dominant manner. Here, we report a 69-year-old man with sporadic cardiac amyloidosis who was born to consanguineous parents and carried a homozygous variant of p.Leu202Arg in APOA1.

Effects of smoking cessation on endothelial function as assessed by flow-mediated total dilation.

BACKGROUND: In assessing the effects of smoking cessation on endothelial function, low-flow-mediated constriction (L-FMC) may provide complementary information to flow-mediated dilation (FMD). However, the value of flow-mediated total dilation (FMTD), an index that incorporates L-FMC into FMD, remains underreported. We aimed to evaluate the effect of smoking cessation on endothelial function, as assessed by FMD and FMTD, and clarify its associated clinical factors. METHODS: We enrolled 118 consecutive current smokers without previous coronary artery disease (72.9% were men; age: 59 ± 11 years) who underwent smoking cessation treatment. The clinical variables %FMD, %L-FMC, and %FMTD were examined before and 20 weeks after treatment initiation. A multivariate linear regression model was used to investigate the effects of smoking cessation on %FMD and %FMTD and the interaction between smoking cessation and baseline clinical variables. RESULTS: After 20 weeks, 85 smokers (69.4% were men; age: 59 ± 12 years) ceased smoking (abstainers), whereas 33 smokers (81.8% were men; age: 58 ± 11 years) did not (continued smokers). The estimated group differences (abstainers - continued smokers) in changes in the %FMD and %FMTD were 0.77% (95% confidence interval [CI], -0.22-1.77%; p = 0.129) and 1.17% (95% CI, 0.16-2.18%; p = 0.024), respectively. Smoking cessation-associated improvement in %FMTD was greater in women than in men (5.41% [95% CI, 3.15-7.67%] versus 0.24% [95% CI, -0.81-1.28%]; p-value for interaction, < 0.001). Additionally, a greater %FMTD improvement was observed in patients who smoked fewer cigarettes per day (p-value for interaction, 0.042) and those who had a smaller resting baseline lumen diameter (Dbase) (p-value for interaction, 0.023). CONCLUSIONS: Smoking cessation was associated with an improvement in %FMTD. Sex, cigarettes smoked per day, and Dbase significantly affected this improvement. The FMTD may help in risk stratification after smoking cessation.

Clinical Benefit of Sacubitril/Valsartan for Hypertensive Patients in Daily Practice and Predictors of Its Antihypertensive Effect.

Background: The blood pressure (BP)-lowering effect of sacubitril/valsartan (Sac/Val) is greater than that of angiotensin II receptor blockers (ARBs) but in in real-world clinical practice, Sac/Val is used in a variety of patterns other than switching from ARBs. In the present study we investigated the effects of Sac/Val on BP and biochemical parameters when switching from or adding it to various antihypertensive drugs and examined what factors could be predictors of the antihypertensive effect of Sac/Val. Methods and Results: In 108 hypertensive patients treated with antihypertensive agents (including 4 naïve cases), clinic BP and various biochemical parameters were assessed before and after switching to/adding Sac/Val (200 mg/day). Systolic and diastolic BPs significantly decreased after treatment with Sac/Val (P<0.0001, respectively). As for biochemical parameters, alanine aminotransferase, triglycerides, C-reactive protein, and uric acid significantly decreased after administration of Sac/Val, but renal function, B-type natriuretic peptide, and plasma renin activity (PRA) did not change before or after treatment with Sac/Val. Multiple regression analysis revealed that low PRA and high baseline systolic BP were independent determinants of systolic BP reduction after Sac/Val treatment. Conclusions: Sac/Val is beneficial for poorly controlled hypertension in daily clinical practice and low PRA may be a predictor of the antihypertensive effect of switching to/adding Sac/Val.

Pulmonary Arterial Hypertension in Neurofibromatosis Type 1: A Case with a Novel NF1 Gene Mutation.

Neurofibromatosis type 1 (NF1) is an autosomal dominant multi-organ disease. The clinical manifestations include not only skin lesions and malignant tumors but also lung complications, including pulmonary arterial hypertension (PAH). However, the association between gene mutations in NF1 and the occurrence of PAH has not yet been elucidated. We herein report a case of isolated PAH in a 67-year-old woman with NF1, presumably caused by a novel heterozygous mutation, c.4485_4486delinsAT (p.Lys1496Ter), in the NF1 gene.

Successful revascularization of coronary occlusion due to lotus root-like plaques by IVUS-based real-time three-dimensional wiring using the tip detection method in a patient with cardiac arrest.

A 32-year-old man, who was treated for T-cell lymphoma, presented in cardiac arrest. He had been treated for heart failure with reduced ejection fraction. Veno-arterial extracorporeal membrane oxygenation was initiated immediately. We diagnosed him as non-ST elevated myocardial infarction. Coronary angiography demonstrated the occlusion of the trifurcation in the proximal left anterior descending artery (LAD). We failed to advance the first guidewire into the distal LAD by angio-based conventional wiring. Intravascular ultrasonography (IVUS) of the proximal diagonal branch revealed two diaphragms separating the distal lumen without connection, which looks like lotus root-like appearance. We quickly penetrated the plaque using IVUS-based real-time 3D wiring using the tip detection method. The contrast injection via the microcatheter showed the distal diagonal branch (D2). After the balloon dilation in D2, IVUS image revealed a torn plaque between D2 and the distal LAD. Subsequently we advanced the guidewire to the distal LAD using IVUS-based real-time 3D wiring using the tip detection method through the tear of the plaque. Finally, we successfully performed the revascularization of LAD in a preferable procedure time. The patient recovered well and was discharged 39 days after cardiac arrest. This case highlights the efficacy of IVUS-based real-time 3D wiring using the tip detection method even in the emergent and challenging situation.

Predictive value of early-phase heart rate reduction for subsequent recovery of left ventricular systolic function in heart failure with reduced ejection fraction.

INTRODUCTION: Predictors of heart failure with recovered ejection fraction (HFrecEF) remain to be fully elucidated. This study investigated the impact of heart rate and its change on the recovery of left ventricular ejection fraction (LVEF) in heart failure with reduced ejection fraction (HFrEF). MATERIAL AND METHODS: From 398 outpatients who had a history of hospitalisation for heart failure, 138 subjects diagnosed as HFrEF (LVEF < 40%) on heart failure hospitalisation were enrolled and longitudinally surveyed. During follow-up periods more than one year, 64 and 46 patients were identified as HFrecEF (improved LVEF to ≥ 40% and its increase of ≥ 10 points) and persistent HFrEF, respectively. RESULTS: In the overall subjects, the reduction of heart rate through the observation periods was closely correlated with the improvement of LVEF (r = -0.508, p < 0.001). Heart rate on hospital admission for heart failure was markedly higher in patients with HFrecEF (112 ± 26 bpm) than in those with persistent HFrEF (90±18 bpm). Whereas heart rate at the first outpatient visit after discharge was already lower in the HFrecEF group (80 ± 13 vs. 85 ± 13 bpm in the persistent HFrEF group). A multivariate logistic regression analysis revealed that the decrease in heart rate from admission to the first visit after discharge was a significant determinant of HFrecEF (p < 0.001), independently of confounding factors such as ischemic heart disease and baseline LVEF and left ventricular dimension. CONCLUSIONS: Our findings suggest that heart rate reduction in the early phase after heart failure onset is a powerful independent predictor of the subsequent recovery of LVEF in HFrEF patients.

Neurological prognosis prediction upon arrival at the hospital after out-of-hospital cardiac arrest: R-EDByUS score.

AIM: To develop a new scoring model for patients with cardiogenic out-of-hospital cardiac arrest (OHCA) to facilitate neurological prognosis prediction upon hospital arrival by using prehospital resuscitation features alone. METHODS: Between 2005 and 2019, we enrolled 942,891 adult patients with OHCA of presumed cardiac aetiology from the All-Japan Utstein Registry. Scoring models applied prehospital resuscitation features a priori from the variables the American College of Cardiology algorithm including age, duration to return of spontaneous circulation (ROSC) or hospital arrival, no bystander cardiopulmonary resuscitation (CPR), unwitnessed arrest, and nonshockable rhythm (R-EDByUS score) to predict unfavorable neurological outcomes defined as Cerebral Performance Category 3, 4, or 5 at 1 month. We created nomograms as a "Regression-based model," and created a "Simplified model" in which points were assigned by category for predicting unfavorable neurological outcomes for both the prehospital ROSC cohort (67,064 patients) and the ongoing CPR cohort (875,827 patients). For internal validation, bootstrap optimism-corrected estimates of predictive performance were calculated. RESULTS: A total of 46,971 (70.0%) and 870,991 (99.4%) patients in the prehospital ROSC and ongoing CPR cohorts, respectively, had unfavorable neurological outcomes. In the prehospital ROSC cohort, the C-statistics of the Regression-based and Simplified models were 0.851 and 0.842, and the bootstrap-validated C-statistics were 0.852 and 0.841, respectively. In the ongoing CPR cohort, the C-statistics of the Regression-based and Simplified models were 0.872 and 0.865, and the bootstrap-validated C-statistics were 0.852 and 0.841, respectively. CONCLUSIONS: The R-EDByUS score accurately predicted the neurological prognosis of cardiogenic OHCA upon hospital arrival.

Evaluation of novel indices of walking performance taking oxygen desaturation into account during six-minute walk test in cardiovascular disease patients.

In pulmonary disease patients since oxygen desaturation during 6-min walk test (6MWT) affects walk distance (6MWD), some novel indices such as desaturation/distance ratio [DDR, oxygen desaturation area (DAO2)/6MWD] and distance-saturation product [DSP, 6MWD × minimum peripheral oxygen saturation (SpO2)] are evaluated. However, there has been no study examining these indices that consider exercise-induced desaturation (EID) in patients with cardiovascular disease. In 94 cardiovascular disease patients without pulmonary complications, 6MWT and echocardiography were performed at the entry of cardiac rehabilitation. SpO2 was measured during 6MWT using a continuously monitorable pulse oximeter, and DSP and DDR were calculated using minimum SpO2 and DAO2 [sum of (100-SpO2) per second during 6MWT], respectively. EID was defined as SpO2 decrease of ≥ 4% or minimum SpO2 of < 90% during 6MWT. DSP was slightly lower and DDR was markedly higher in patients with EID than in those without. When examining correlations of DSP and DDR with their components, DSP was correlated with 6MWD much closely than minimum SpO2, while DDR was correlated as closely with DAO2 as 6MWD. Furthermore, DAO2, but not minimum SpO2, had a direct correlation with 6MWD. As for associations with cardiac function, DSP was correlated with several cardiac parameters, but DDR was not correlated with any of these parameters. Our findings suggest that oxygen desaturation during 6MWT affects walking distance in cardiovascular disease patients even without pulmonary complications and that DDR is more appropriate than DSP as an index of walking performance that takes EID into consideration, independently of cardiac function.

A case of repeated rate-dependent pacing threshold elevation after leadless pacemaker implantation.

The pacing threshold is important for leadless pacemakers, as the pacing output has a significant impact on battery longevity. Acute pacing rate-dependent threshold increases have also been reported with leadless pacemakers. In the present case, we experienced a case in which the threshold, which had been raised in the acute phase, once showed a tendency to improve, but then worsened again. And, as in previous reports, thresholds improved completely in the chronic phase. Repeated retrieval and reimplantation of leadless pacemakers increases the likelihood of fatal complications, so being aware of such phenomenon may prevent unnecessary procedure and complications.

LCZ696, an Angiotensin Receptor-Neprilysin Inhibitor, Ameliorates Endothelial Dysfunction in Diabetic C57BL/6 Mice.

AIMS: LCZ696 (sacubitril/valsartan) exerts cardioprotective effects. Recent studies have suggested that it improves the endothelial function; however, the underlying mechanisms have not been thoroughly investigated. We investigated whether LCZ696 ameliorates diabetes-induced endothelial dysfunction. METHODS: Diabetes was induced using streptozotocin in 8-week-old male C57BL/6 mice. Diabetic mice were randomly assigned to receive LCZ696 (100 mg/kg/day), valsartan (50 mg/kg/day), or a vehicle for three weeks. The endothelium-dependent and endothelium-independent vascular responses of the aortic segments were determined based on the response to acetylcholine and sodium nitroprusside, respectively. Human umbilical vein endothelial cells (HUVEC) and aortic segments obtained from C57BL/6 mice were used to perform in vitro and ex vivo experiments, respectively. RESULTS: LCZ696 and valsartan reduced the blood pressure in diabetic mice (P＜0.05). The administration of LCZ696 (P＜0.001) and valsartan (P＜0.01) ameliorated endothelium-dependent vascular relaxation, but not endothelium-independent vascular relaxation, under diabetic conditions. LCZ696, but not valsartan, increased eNOSSer1177 (P=0.06) and Akt (P＜0.05) phosphorylation in the aorta. In HUVEC, methylglyoxal (MGO), a major precursor of advanced glycation end products, decreased eNOSSer1177 phosphorylation (P＜0.05) and increased eNOSThr495 phosphorylation (P＜0.001). However, atrial natriuretic peptide (ANP) reversed these effects. ANP also ameliorated the MGO-induced impairment of endothelium-dependent vascular relaxation in the aortic segments (P＜0.05), although L-NAME completely blocked this effect (P＜0.001). CONCLUSION: LCZ696 ameliorated diabetes-induced endothelial dysfunction by increasing the bioavailability of ANP. Our findings suggest that LCZ696 has a vascular protective effect in a diabetic model and highlight that it may be more effective than valsartan.

Impact of diabetes mellitus and triglyceride glucose index on mortality and cardiovascular outcomes in patients with chronic coronary syndrome undergoing coronary computed tomography angiography.

Background: There is limited knowledge regarding whether an elevated triglyceride glucose (TyG) index can serve as a prognostic marker for mortality and cardiovascular outcomes, independent of diabetes mellitus (DM) and plaque burden, in patients with chronic coronary syndrome (CCS). Methods: Patients with CCS (n = 684) were categorized into subgroups based on the presence of DM, and patients without DM were further divided into two groups based on presence or absence of an elevation of TyG index >8.8. Coronary plaque burden was evaluated using coronary computed tomography angiography. Major cardiovascular adverse event (MACE) was defined as a composite event of nonfatal myocardial infarction, unstable angina or unplanned coronary revascularization, stroke, non-cardiovascular mortality and cardiovascular mortality. Results: Patients without DM exhibited significantly greater plaque and epicardial adipose tissue volumes than those with DM. Multivariable Cox proportional hazards models demonstrated that DM and an elevated TyG index >8.8 were independently associated with the risk of MACE after adjusting for age, sex, and plaque volume. Patients with DM (hazard ratio, 3.74; 95% confidence interval, 1.97-7.08; p < 0.001) and patients without DM with an elevated TyG index (hazard ratio, 1.99; 95% confidence interval, 1.01-3.91; p = 0.045) had an increased risk of MACE. Conclusion: This study indicates that DM and an elevated TyG index are predictors of MACE, independent of plaque volume, in patients with CCS.

Leadless Pacemaker Implantation in Severe Kyphosis: Challenging Implantation for Tortuous IVC and Narrow RA.

Leadless pacemaker implantation is recognized as safe and effective for treating bradycardia. However, there are limited descriptions of its use in patients with complex anatomical considerations. Here, we present a case detailing the successful implantation of a leadless pacemaker with a tortuous inferior vena cava and a narrow right atrium.

Severe Left Main Coronary Artery Stenosis and Aortic Regurgitation in a Patient Presenting with Takayasu Arteritis.

We herein report the case of a 46-year-old woman with Takayasu arteritis (TA), severe stenosis in the left main coronary artery (LMCA), and severe aortic regurgitation. Prednisolone and tacrolimus were initiated as TA treatments. Two months after initiating medical therapy, the aortic regurgitation severity improved to a moderate grade, although there was no obvious improvement in LMCA stenosis. Thus, after confirming the resolution of inflammation, we performed coronary artery bypass grafting alone without any aortic valve intervention. In TA patients with severe LMCA stenosis, surgical management of the coronary artery should therefore be considered only after successfully administering anti-inflammatory therapy.