The Insular Cortex, Alzheimer Disease Pathology, and Their Effects on Blood Pressure Variability.

Recent findings indicate that the human cardiovascular system is regulated by a cortical network comprised of the insular cortex (Ic), anterior cingulate gyrus, and amygdala which is necessary for the regulation of the central autonomic network system. Alzheimer disease (AD) affects the Ic at a preclinical stage. The pathology of AD at the Ic is suggested to predispose the cardiovascular system to detrimental changes such as increased blood pressure variability (BPV). In this review article, we focus on the physiology of the Ic in the relationship between the central autonomic network and BPV. We provide a summary of the published evidence regarding the relationship between Ic damage and exaggerated BPV in the context of AD pathology.

Early drop in systolic blood pressure, heart rate at admission, and their effects on worsening renal function in elderly patients with acute heart failure.

BACKGROUND: Regardless of patients' baseline renal function, worsening renal function (WRF) during hospitalization is associated with poor outcomes. In individuals with acute heart failure (AHF), one predictor of WRF is an early drop in systolic blood pressure (SBP). Few studies have investigated WRF in elderly AHF patients or the influence of these patients' heart rate (HR) at admission on the relationship between an early SBP drop SBP and the AHF. METHODS: We measured the SBP and HR of 245 elderly AHF inpatients (83 ± 6.0 years old, females 51%) at admission and another six times over the next 48 h. We defined 'WRF' as a serum creatinine increase ≥0.3 mg/dL by Day 5 post-admission. We calculated the 'early SBP drop' as the difference between the admission SBP value and the lowest value during the first 48 h of hospitalization. RESULTS: There were significant differences between the 36 patients with WRF and the 209 patients without WRF: early SBP drop (51 vs. 33 mmHg, p < 0.01) and HR at admission (79 vs. 90 bpm, p < 0.05), respectively. In the multiple logistic regression analysis adjusted for the confounders, higher early SBP drop (p < 0.04) and lower HR at admission (p < 0.01) were significantly associated with WRF. No significant association was shown for the interaction term of early SBP drop × HR at admission with WRF. CONCLUSIONS: In these elderly AHF patients, exaggerated early SBP drop and lower HR at admission were significant independent predictors of WRF, and these factors were additively associated with WRF.

International Expert Consensus Document on Takotsubo Syndrome (Part II): Diagnostic Workup, Outcome, and Management.

The clinical expert consensus statement on takotsubo syndrome (TTS) part II focuses on the diagnostic workup, outcome, and management. The recommendations are based on interpretation of the limited clinical trial data currently available and experience of international TTS experts. It summarizes the diagnostic approach, which may facilitate correct and timely diagnosis. Furthermore, the document covers areas where controversies still exist in risk stratification and management of TTS. Based on available data the document provides recommendations on optimal care of such patients for practising physicians.

International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology.

Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy.

Insular cortex lesion and autonomic instability in a herpes simplex virus encephalitis patient.

The cardiovascular system is regulated by a central autonomic network (CAN) consisting of the insular cortex, anterior cingulate gyrus, and amygdala. Because the insular cortex often tends to be damaged in patients with herpes simplex virus (HSV) encephalitis, the autonomic instability observed in these patients was suggested to be moderated by an insular cortex lesion. Here, we report the case of a 51-year-old Japanese male who was hospitalized following a collapse 5 days earlier; he was diagnosed as herpes encephalitis. Diffusion-weighted MRI revealed asymmetric right greater hyperintensity throughout his insular cortex and anterior cingulate gyrus. At 1 week after admission, transthoracic echo showed diffuse hypokinesis in the left ventricle (LV). Cardiac 123I-meta-iodobenzylguanidine uptake (123I-MIBG) scintigraphy revealed reduced uptake in the inferior and posterior wall. Electrocardiograhy at rest showed that the coefficient variation of RR intervals (CVR-R) was reduced, and the corrected QT (QTc) interval length was prolonged. In this HSV encephalitis patient, signs of a right insular cortex lesion and autonomic instability were observed: LV hypokinesis, regional reduced 123I-MIBG uptake, decreased CVR-R, and QTc interval prolongation. Our patient's autonomic instability may thus be derived from disrupted autonomic balance due to the right insular cortex lesion.

Blood Pressure Variability After Non-invasive Low-level Tragus Stimulation in Acute Heart Failure.

Higher blood pressure (BP) variability (BPV) was shown to be strong predictors of poor cardiovascular outcomes in heart failure (HF). It is currently unknown if low-level tragus stimulation (LLTS) would lead to improvement in BPV in acute HF (AHF). The 22 patients with AHF (median 80 yrs, males 60%) were randomly assigned to active or sham group using an ear clip attached to the tragus (active group) or the earlobe (sham group) for 1 h daily over 5 days. In the active group, standard deviation (SD), coefficient of variation (CV) and δ in SBP were significantly decreased after LLTS (all p < 0.05). All the changes in SD, CV and δ in SBP before and after stimulation were also significantly different between active and sham groups (all p < 0.05). This proof-of-concept study demonstrates the beneficial effects of LLTS on BPV in AHF.

Obstructive sleep apnea and non-dipper: epiphenomena or risks of Alzheimer's disease?: a review from the HOPE Asia Network.

Obstructive sleep apnea (OSA) and associated nocturnal blood pressure (BP) surges is associated with non-dipper. On the other hand, the relationship between neurodegenerative diseases and non-dipper hypertension has been reported. To date, few studies have evaluated the relationships of nocturnal BP dipping patterns and OSA in relation to neurodegenerative diseases, particularly Alzheimer's disease (AD). This review examines the etiology of the association between OSA and the non-dipper pattern of hypertension and how both are involved in the development of AD. To set the stage for this review, we first focus on the pathophysiology of AD, which is interrelated with sleep apnea and non-dipper through dysregulation of central autonomic network.

Should we emergently revascularize occluded coronaries for cardiac arrest?: rapid-response extracorporeal membrane oxygenation and intra-arrest percutaneous coronary intervention.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) and percutaneous coronary intervention (PCI) may be useful in cardiopulmonary resuscitation. However, little is known about the combination of ECMO and intra-arrest PCI. This study investigated the efficacy of rapid-response ECMO and intra-arrest PCI in patients with cardiac arrest complicated by acute coronary syndrome who were unresponsive to conventional cardiopulmonary resuscitation. METHODS AND RESULTS: This multicenter cohort study was conducted with the use of the database of ECMO in Hiroshima City, Japan. Between January 2004 and May 2011, rapid-response ECMO was performed in 86 patients with acute coronary syndrome who were unresponsive to conventional CPR. The median age of the study patients was 63 years, and 81% were male. Emergency coronary angiography was performed in 81 patients (94%), and intra-arrest PCI was performed in 61 patients (71%). The rates of return of spontaneous heartbeat, 30-day survival, and favorable neurological outcomes were 88%, 29%, and 24%, respectively. All of the patients who received intra-arrest PCI achieved return of spontaneous heartbeat. In patients who survived up to day 30, the rate of out-of-hospital cardiac arrest was lower (58% versus 28%; P=0.01), the intra-arrest PCI was higher (88% versus 70%; P=0.04), and the time interval from collapse to the initiation of ECMO was shorter (40 [25-51] versus 54 minutes [34-74 minutes]; P=0.002). CONCLUSIONS: Rapid-response ECMO plus intra-arrest PCI is feasible and associated with improved outcomes in patients who are unresponsive to conventional cardiopulmonary resuscitation. On the basis of these findings, randomized studies of intra-arrest PCI are needed.

Percutaneous coronary intervention for postcardiac arrest syndrome.

PURPOSE OF REVIEW: Sudden cardiac arrest is a major cause of unexpected death, as well as a major clinical issue. Primary percutaneous coronary intervention (PCI) can drastically improve outcomes among patients with ST-elevation myocardial infarction without cardiac arrest. Recent studies reported that using emergency PCI to resuscitate patients has the potential to improve their outcomes. The purpose of this review is to elucidate the effects of PCI among resuscitated patients. RECENT FINDINGS: To the best of current understanding, no randomized clinical trial has assessed PCI for postcardiac arrest syndrome. Several observational studies suggested a positive effect of PCI for resuscitated out-of-hospital cardiac arrest (OHCA) patients, and a number of observational studies reported a limited beneficial effect. Several studies reported that a combination of therapeutic hypothermia and PCI may be feasible and effective. However, the presence of bias and unmeasured confounders in these studies may have affected the outcomes. SUMMARY: PCI for postcardiac arrest syndrome may improve outcomes of OHCA patients; however, randomized trials of PCI for postcardiac arrest syndrome are necessary to confirm this issue. Alternative cardiopulmonary resuscitation using venoarterial extracorporeal membrane oxygenation and PCI may have the potential to improve the outcomes of refractory cardiac arrest patients.

Denervation or stimulation? Role of sympatho-vagal imbalance in HFpEF with hypertension.

Heart failure (HF) in the elderly is an increasingly large and complex problem in modern society. Notably, the cause of HF with preserved ejection fraction (HFpEF) is multifactorial and its pathophysiology is not fully understood. Among these, hypertension has emerged as a pivotal factor in the pathophysiology and therapeutic targets of HFpEF. Neuronal elements distributed throughout the cardiac autonomic nervous system, from the level of the central autonomic network including the insular cortex to the intrinsic cardiac nervous system, regulate the human cardiovascular system. Specifically, increased sympathetic nervous system activity due to sympatho-vagal imbalance is suggested to be associated the relationship between hypertension and HFpEF. While several new pharmacological therapies, such as sodium-glucose cotransporter 2 inhibitors, have been shown to be effective in HFpEF, neuromodulatory therapies of renal denervation and vagus nerve stimulation (VNS) have received recent attention. The current review explores the pathophysiology of the brain-heart axis that underlies the relationship between hypertension and HFpEF and the rationale for therapeutic neuromodulation of HFpEF by non-invasive transcutaneous VNS.

Afterload reduction after non-invasive vagus nerve stimulation in acute heart failure.

Introduction: While central blood pressure (BP) has been recognized as a major indicator of left ventricular (LV) afterload, the reduction of central pressure decreases LV afterload and may prevent heart failure (HF) decompensation. Non-invasive transcutaneous vagus nerve stimulation (tVNS) was shown to improve cardiac function in HF patients. In this study, the relationship between active tVNS and reduction of central BP was investigated in patients with acute HF (AHF). Methods: The 22 patients hospitalized for AHF after initial stabilization (median 80 yrs, males 60%) were randomly assigned to active or sham group. For 1 h daily over 5 days, low-level transcutaneous electrical stimulation (LLTS) (20 Hz, 1 mA) was performed after attaching an ear clip to the tragus (active group) or the earlobe (sham control group). Before and after stimulation, central aortic systolic pressure (CASP), brachial systolic BP (SBP), diastolic BP (DBP) as well as heart rate (HR) were noninvasively measured. Results: No significant differences in baseline characteristics were observed between the active and sham groups. In the active group, CASP, SBP, DBP, and HR each decreased significantly after stimulation (all p < 0.05), whereas in the sham group, CASP, SBP, DBP, and HR each increased significantly after stimulation (all p < 0.05). All the changes in CASP, SBP, DBP and HR before and after stimulation were also significantly different between active and sham groups (all p < 0.01). There were no device-related side effects. Conclusion: In this study, the left tragus tVNS resulted in an acute afterload reduction in the elderly AHF patients. Non-invasive LLTS may be useful and safe for reducing afterload in AHF. Clinical trial registration: ClinicalTrials.gov, identifier UMIN000044121.

Sex Hormone-Specific Neuroanatomy of Takotsubo Syndrome: Is the Insular Cortex a Moderator?

Takotsubo syndrome (TTS), a transient form of dysfunction in the heart's left ventricle, occurs predominantly in postmenopausal women who have emotional stress. Earlier studies support the concept that the human circulatory system is modulated by a cortical network (consisting of the anterior cingulate gyrus, amygdala, and insular cortex (Ic)) that plays a pivotal role in the central autonomic nervous system in relation to emotional stressors. The Ic plays a crucial role in the sympathovagal balance, and decreased levels of female sex hormones have been speculated to change functional cerebral asymmetry, with a possible link to autonomic instability. In this review, we focus on the Ic as an important moderator of the human brain-heart axis in association with sex hormones. We also summarize the current knowledge regarding the sex-specific neuroanatomy in TTS.

A variant of Takotsubo syndrome concomitant with left atrial myxoma.

We treated an 80-year-old Japanese woman who had Takotsubo syndrome (TTS) concomitant with a left atrial (LA) tumor. Left ventriculography revealed a variant of TTS. In cardiac surgery, the LA mass was successfully resected without embolism, with the pathological diagnosis of myxoma.

Case report: SGLT2i, transcutaneous vagus nerve stimulation, and their effects on intrarenal venous flow pattern in HFpEF.

Renal congestion in heart failure (HF) is a predictor of the prognosis of cardiovascular disease. The effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and vagus nerve stimulation (VNS) on renal congestion has not been reported in HF. A 77-year-old man with HF with preserved ejection fraction (HFpEF) was referred to our hospital because of poor response to loop diuretics. Echocardiography showed severe tricuspid regurgitation with dilation of the right atrium. Three months after adding SGLT2i, body weight was lost without worsening of renal function. Left and right doppler-derived intrarenal venous flow (IRVF) has been changed from a monophasic to a discontinuous pattern with a systolic interruption. One month later, he discontinued SGLT2i administration at his own discretion. In order to stabilizing autonomic balance, transcutaneous VNS (tVNS) was performed via left ear tragus. One hour after transcutaneous tVNS, ipsilateral IRVF has been dramatically improved from a fusional biphasic to a discontinuous pattern with a systolic interruption. SGLT2i and tVNS may be associated with renal decongestion in HFpEF.