Hemodynamic and Lesion Characteristics Associated with Discordance between the Instantaneous Wave-Free Ratio and Fractional Flow Reserve.

BACKGROUND: The instantaneous wave-free ratio (iFR) is an invasive coronary physiological index that is not inferior to fractional flow reserve- (FFR-) guided revascularization. The indexes of iFR and FFR are similar and closely correlated, but there are a few key differences. Previous studies suggested that patient characteristics and lesion severity could induce discordance between iFR and FFR. This study aimed to clarify the hemodynamics and lesion characteristics that influence discordance between iFR and FFR. METHODS: In this retrospective study, we enrolled 225 patients (304 lesions) who underwent clinically indicated invasive coronary angiography and both iFR and FFR examinations between 2012 and 2017. We included only patients who underwent right heart catheterization and had blood pressure and heart rates recorded immediately prior to iFR and FFR. RESULTS: Discordance (iFR ≤0.89 and FFR >0.8 or iFR >0.89 and FFR ≤0.8) was observed in 80 lesions (26.3%). The heart rate, rate-pressure product, and cardiac index tended to be higher in the iFR ≤0.89 group than in the iFR >0.89 group. These trends were not seen between the FFR ≤0.8 group and FFR >0.8 group. A multivariate analysis showed that independent predictors of iFR ≤0.89 and FFR >0.8 discordance were female sex and higher rate-pressure product. iFR >0.89 and FFR ≤0.8 discordance was rare in hemodialysis patients. CONCLUSION: Even if iFR is functionally significant in intermediate stenosis, additional FFR evaluations should be considered for women, especially those with a high rate-pressure product, to avoid unnecessary percutaneous coronary intervention. If iFR is not functionally significant with intermediate stenosis in hemodialysis patients, then further FFR evaluations are unnecessary.

Variations in the eicosapentaenoic acid-arachidonic acid ratio associated with age in acute myocardial infarction patients undergoing primary percutaneous coronary intervention.

Acute myocardial infarction (AMI) is a life-threatening disease, and its incidence has been increasing even in the young population. Although a low eicosapentaenoic acid (EPA)-arachidonic acid (AA) ratio is associated with an increased risk of coronary artery disease, the effect of age on EPA/AA ratios in AMI patients remains unclear. This study aimed to clarify the independent polyunsaturated fatty acid (PUFA)-related determinants of age in younger and older AMI patients. A total of 153 consecutive patients who underwent primary percutaneous coronary interventions (PCIs) for de novo AMIs were enrolled in this study. Patients' background data, including PUFA and lipid profiles during PCI, were evaluated retrospectively. The EPA/AA ratio correlated positively with age (r = 0.21; P = 0.011) and increased markedly from age 60 years. Patients aged < 60 years (n = 35) had a lower mean EPA/AA ratio (0.25 ± 0.16) than patients aged ≥ 60 years (n = 118) (0.38 ± 0.25) (P < 0.001). The AA level was more dependent on age than on EPA level (r = - 0.34, P < 0.001 vs. r = 0.12, P = 0.16). The multivariate analysis revealed that a 0.1 EPA/AA ratio increase (odds ratio 1.50; 95% confidence interval 1.09-2.06), body mass index, triglyceride level, and aspirin administration were independently associated with the age stratification of AMI patients. The EPA/AA ratio was higher in younger AMI patients who have undergone primary PCIs than in older patients. Younger population at risk for AMI should be managed with multiple interventions including PUFA profiling.

Pilot Cohort Study Assessing the Efficacy of Endovascular Revascularization in the Restoration of Peripheral Sensory Disturbance in Patients With Critical Limb Ischemia.

BACKGROUND: Sensory disturbance (SD) is a common consequence of peripheral nerve damage associated with diabetes and severe ischemia. Progression of SD places patients at high risk for lower extremity ulcers and amputations. SD has been thought to be progressive and irreversible, and possibly caused by microvascular dysfunction. The aim of this study was to determine whether endovascular revascularization (EVR) induces quantifiable changes in SD in chronic critical limb ischemia (CLI) patients with neuropathy.Methods and Results:In all, 36 legs from 28 chronic CLI patients who underwent elective EVR were prospectively enrolled in this study (64% with diabetes and 54% on maintenance hemodialysis). The current perception threshold (CPT), an established diagnostic parameter for SD, was measured before and 3 months after EVR. Of the target lesions, 11%, 47%, and 81% were in the aortoiliac, femoropopliteal, and below-the-knee arteries, respectively, and 58% were totally occluded. Overall CPT in the target foot had improved significantly 3 months after EVR (from 53 to 30 µA; P=0.010); however, EVR did not change CPT in the non-target foot (from 44 to 33 µA; P=0.33). Patients with improved SD after EVR had a significantly higher 180-day survival rate (94% vs. 63%; P=0.040). CONCLUSIONS: EVR improved CPT in target limbs of patients with CLI, and may be a promising option to improve SD associated with peripheral ischemic sensory neuropathy.

Efficacy of 24-Hour Blood Pressure Monitoring in Evaluating Response to Percutaneous Transluminal Renal Angioplasty.

BACKGROUND: Percutaneous transluminal renal angioplasty (PTRA) improves patency in atherosclerotic renal artery stenosis (ARAS), but improvement in clinic blood pressure (BP) is seen in only 20-40% of patients who undergo PTRA. This study investigated the effects of PTRA on BP lowering, assessed on 24-h ambulatory BP monitoring (ABPM), and identified preoperative features predictive of satisfactory BP improvement after PTRA. METHODS AND RESULTS: Of 1,753 consecutive patients undergoing coronary angiography, 31 patients with angiographically significant ARAS and translesional pressure gradient (TLPG) >20 mmHg underwent PTRA. ABPM was performed before, at 1 month and at 1 year after PTRA; patients with average systolic ABPM-BP decrease >10 mmHg at 1 month from baseline were categorized as responders. There was no obvious relationship between clinic BP and ABPM-BP at baseline. ABPM-BP was significantly higher in responders at baseline (SBP: 148 vs. 126 mmHg, P<0.01) and was improved 1 month after PTRA. This difference persisted until 1 year after PTRA. Night-time BP improved more than daytime BP in responders. Patients with higher baseline ABPM-BP achieved a larger decrease in ABPM-BP, but the severity of stenosis reflected by TLPG; renal duplex findings; and neurohumoral parameters other than baseline renal function, did not differ between the groups. CONCLUSIONS: Clinic BP does not represent daily hemodynamic status, whereas high ABPM-BP is a potent predictor of satisfactory BP response to PTRA. (Circ J 2016; 80: 1922-1930).

Direct Link Between Cardiac Failure and Global Cerebral Atrophy in a Young Adult: A Case Report on Reduced Cerebral Artery Blood Flow.

BACKGROUND Heart failure is associated with structural brain abnormalities, including atrophy of multiple brain regions. Previous studies have reported brain atrophy in middle-aged patients with systolic heart failure. In this report, we present the case of a 21-year-old woman with idiopathic dilated cardiomyopathy, cardiac failure, and global cerebral atrophy due to reduced cerebral artery blood flow. We also discuss the impact of brain atrophy in this young adult patient with severe heart failure and no risk factors for atherosclerosis. CASE REPORT A 21-year-old woman with dyspnea and leg edema was admitted to our hospital. After several examinations, an endomyocardial biopsy led to a diagnosis of idiopathic dilated cardiomyopathy, and transthoracic ultrasound cardiography revealed that her left ventricular ejection fraction was 36%. One year after the first hospitalization, her heart failure was classified as New York Heart Association Class III. Magnetic resonance imaging showed severe global brain atrophy, and single-photon emission computed tomography combined with brain computed tomography showed reduced blood flow to the entire brain. She had no risk factors for atherosclerosis and no atherosclerotic changes to her brain or carotid arteries, but her neuropsychological and neurological findings indicated more pronounced brain and cognitive dysfunction. CONCLUSIONS This young adult patient with idiopathic dilated cardiomyopathy, cardiac failure, and global cerebral atrophy showed reduced cerebral artery blood flow and cognitive impairment. The findings of this report indicate that low cardiac output may directly cause brain atrophy in patients with systolic heart failure.

Recurrent takotsubo syndrome with worsening of left ventricular outflow obstruction during haemodialysis: a case report.

BACKGROUND: The recurrence rate of takotsubo syndrome (TS) has been reported as 1.8% per patient-year while left ventricular outflow tract (LVOT) obstruction is comorbid in 10-25% of all instances of TS. The clinical course of recurrent TS with associated LVOT while on haemodialysis has rarely been reported. CASE SUMMARY: This case report involves a 60-year-old female patient receiving regular haemodialysis who was admitted for chest pain during ballroom dancing. Four years prior, she had suffered TS, and fully recovered after the hospitalization. An emergent coronary angiogram done during the second hospitalization showed no significant stenosis, and left ventriculography demonstrated mid-apical akinesia and basal hyperkinesia. Based on these findings, we diagnosed the recurrence of TS. Later in the admission, chest pain reappeared with the start of haemodialysis. A transthoracic echocardiogram demonstrated mean pressure gradient (PG) of LVOT was 58 mmHg, with systolic anterior motion of the mitral valve and basal-wall hyperkinesia. The main aetiology for her symptoms was considered as an exacerbation of LVOT obstruction due to removing intravascular volume by haemodialysis. After starting landiolol at 3 µg/kg/min, PG of LVOT and symptoms gradually improved with uptitration of landiolol. Finally, her chest pain resolved when mean PG of LVOT was down to 38 mmHg using 10 µg/kg/min of landiolol. DISCUSSION: To our knowledge, this is the first report of a recurrent TS case comorbid with LVOT obstruction while on regular haemodialysis. Landiolol, the ultrashort-acting beta-blocker, may be a promising therapeutic option for rapid recovery of increased PG due to LVOT obstruction.

The Baseline Nutritional Status Predicts Long-Term Mortality in Patients Undergoing Endovascular Therapy.

INTRODUCTION: Peripheral artery disease (PAD) occurs at an advanced stage of atherosclerosis and its comorbidities are associated with poor prognoses. Malnutrition is related to the severity of atherosclerosis in patients with cardiovascular disease and it predicts mortality. The Controlling Nutritional Status (CONUT) score is calculated from serum albumin concentration, peripheral lymphocyte count and total cholesterol concentration, and it robustly represents the nutritional status of hospitalized patients. This study aimed to determine the prognostic value of the CONUT score in patients with peripheral artery disease (PAD) who were undergoing endovascular therapy (EVT). METHODS AND RESULTS: This study included 628 PAD patients who underwent EVT between 2013 and 2017 and were assigned to low (CONUT score 0: n = 81), mild (CONUT score 1-2: n = 250), moderate (CONUT score 3-4: n = 169), and high (CONUT score ≥ 5: n = 128) risk groups. The study's primary endpoint was any death. Patients in the groups with higher CONUT scores were more likely to have chronic kidney disease (p < 0.001), impaired left ventricular ejection fractions (p < 0.001), and critical limb ischemia (p < 0.001) on admission. During follow-up, 95 patients (15%) died. Kaplan-Meier analyses revealed that the patients with higher CONUT scores had lower survival rates (p < 0.001; log-rank trend test). Multivariate Cox regression analyses showed that following adjustments for the confounding factors, a higher CONUT score was significantly associated with any death (hazard ratio, 1.15; 95% confidence interval, 1.03-1.30). CONCLUSION: The simple index CONUT score at the time of EVT may predict long-term mortality in PAD patients.

Persistent high blood urea nitrogen level is associated with increased risk of cardiovascular events in patients with acute heart failure.

AIMS: The association between kinetics of blood urea nitrogen (BUN) levels in hospital and cardiovascular outcomes in patients with acutely decompensated congestive heart failure (HF) is unclear. We aimed to estimate the impact of changes in BUN level during hospitalization on clinical prognosis in patients with acute HF. METHODS AND RESULTS: A total of 353 consecutive patients that were urgently hospitalized due to acutely decompensated HF and discharged alive were divided into four subgroups depending on their BUN level at admission and discharge, using a cut-off level of 21.0 mg/dL. Among 206 patients with high baseline BUN level, 46 (22%) and 160 (78%) had normal and persistent high BUN levels at discharge, respectively. In contrast, of the 147 patients with normal baseline BUN level, 55 (37%) and 92 (63%) had high and normal BUN levels at discharge, respectively. During the observational period after discharge, Kaplan-Meier analysis showed the highest rate of combined outcome of cardiovascular death and HF readmission in patients with persistent high BUN (log-rank test: P < 0.001). After adjustment for comorbidities, the hazard ratio for a combined outcome was significantly lower in patients with normalized BUN level compared with those with persistent high BUN (hazard ratio 0.48, 95% confidence interval 0.23-0.99, P = 0.049). CONCLUSIONS: Persistent high BUN levels in hospital are associated with an increased risk of cardiovascular death and HF readmission. Normalization of BUN levels during hospitalization may be associated with long-term clinical outcomes.

Intimal disruption affects drug-eluting cobalt-chromium stent expansion: A randomized trial comparing scoring and conventional balloon predilation.

BACKGROUND: Stent expansion remains one of the most important predictors of restenosis and subacute thrombosis, even with the use of drug-eluting stents. This study was designed to clarify the impact of lesion preparation on final stent expansion. METHODS: Sixty-six consecutive patients were included in this trial, and ultimately 52 enrolled non-calcified de novo lesions were randomly assigned to undergo single predilation with either a semi-compliant scoring balloon or a semi-compliant conventional balloon. Lesions were treated with a single 2.5- to 3.0-mm cobalt-chromium everolimus-eluting stent under optical coherence tomography (OCT) guidance without post-stenting dilation. Stent expansion was defined as the ratio of OCT-measured minimum stent area to the predicted stent area. RESULTS: Stent expansion was significantly higher after predilation by a scoring balloon (68.0% vs. 62.1%, p=0.017) with similar stent lumen eccentricity (0.84 vs. 0.80, p=0.18). Intimal disruption was induced significantly more frequently (68.0% vs. 38.4%, p=0.035) and was more extensive in the scoring group (122° vs. 65°, p=0.038). Lesions with intimal disruption after predilation achieved significantly higher stent expansion than that without it (67.7% vs. 61.6%, p=0.023). One case in the conventional group required target lesion revascularization; however, any other adverse clinical events including death, myocardial infarction, and stent thrombosis were not observed up to 9months after PCI in both groups. CONCLUSIONS: In this randomized study, pretreatment with a scoring balloon enhanced stent expansion partly through induction of intimal disruption. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000014176.

Randomized pilot trial comparing tolvaptan with furosemide on renal and neurohumoral effects in acute heart failure.

AIMS: Loop diuretics are first-line medications for congestive heart failure (CHF); however, they are associated with serious adverse effects, including decreased renal function, and sympathetic nervous and renin-angiotensin system activation. We tested whether tolvaptan, a vasopressin V2-receptor antagonist, could reduce unfavourable furosemide-induced effects during CHF treatment. METHODS AND RESULTS: Sixty patients emergently hospitalized owing to CHF-induced dyspnea were randomly assigned to receive either 40 mg intravenous furosemide daily or 7.5 mg oral tolvaptan for 5 days after admission. Both groups also received intravenous carperitide and canrenoate potassium. As results, baseline patient characteristics were similar between the furosemide (n = 30) and the tolvaptan (n = 30) groups, with no significant difference in 5 day urine volume or fluid balance. Brain natriuretic peptide and body weight improvements were similar between groups. However, serum creatinine (Cr) level did not increase, and the incidence of worsening renal function was significantly lower in the tolvaptan group. Consequently, the Cr increase to gain 1000 mL urine was 2.5-fold lower in the tolvaptan group. Furthermore, the blood urea nitrogen (BUN)/Cr ratio significantly decreased in the tolvaptan group, suggesting that renal perfusion was preserved, and urea reuptake and passive water reabsorption were suppressed following tolvaptan treatment. Although catecholamine improvements after treatment were not significantly different, plasma renin activity was enhanced in the furosemide group. CONCLUSIONS: As compared with furosemide, tolvaptan in patients with acute heart failure is associated with comparable decongestion, better preservation of renal function and less activation of renin-angiotensin system. (UMIN 000014134).