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.

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.

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.

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.

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.

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.

Catheter-based ultrasound renal denervation in patients with resistant hypertension: the randomized, controlled REQUIRE trial.

Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (-6.6 mmHg) and sham control (-6.5 mmHg) groups (difference: -0.1, 95% confidence interval -5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: -1.8 mmHg [p = 0.488] and -2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. CLINICAL TRIAL REGISTRATION: NCT02918305 ( http://www.clinicaltrials.gov ).

A mid-ventricular variant of Takotsubo syndrome: was it triggered by insular cortex damage?

Takotsubo syndrome (TTS) is a transient cardiomyopathy that is often associated with cerebrovascular diseases. Earlier studies have supported the concept that the cardiovascular system is regulated by a central autonomic network (CAN) consisting of the insular cortex (IC), anterior cingulate gyrus and amygdala. We report the case of a 79-year-old female diagnosed with a mid-ventricular variant of TTS concomitant with right IC ischaemic stroke. After 12 h of hospitalization, she experienced a sudden collapse. Rapid cardiopulmonary resuscitation resulted in a return of spontaneous circulation. Subsequent left ventriculography revealed akinesis in the mid-portion of the left ventricle with vigorous contraction of the basal and apex segment. Two weeks after admission, cardiac ultrasound showed improved left ventricular contraction. Right IC ischaemia in this patient might have been associated with a dysregulation of the CAN and subsequent increased sympathetic nervous system activity that triggered TTS.

Long sleep duration and cardiovascular disease: Associations with arterial stiffness and blood pressure variability.

Although short and long sleep duration are both risk factors of cardiovascular disease (CVD), the recent meta-analyses have been shown that long sleep duration was closely associated with CVD mortality. While the specific mechanism underlying the association between long sleep duration and CVD remains unclear, long sleep duration was shown to be associated with arterial stiffness and blood pressure variability (BPV) in many Asian populations. This review article will focus on the pathophysiology of long sleep duration, arterial stiffness, BPV and their effects on CVD. To set the stage for this review, we first summarize the current insights for the relationship between long sleep duration and CVD in relation to arterial stiffness and BPV.