Altered breathing syndrome in heart failure: newer insights and treatment options.

In patients with heart failure (HF), altered breathing patterns, including periodic breathing, Cheyne-Stokes breathing, and oscillatory ventilation, are seen in several situations. Since all forms of altered breathing cause similar detrimental effects on clinical outcomes, they may be considered collectively as an "altered breathing syndrome." Altered breathing syndrome should be recognized as a comorbid condition of HF and as a potential therapeutic target. In this review, we discuss mechanisms and therapeutic options of altered breathing while sleeping, while awake at rest, and during exercise.

Characteristics of patients with severe heart failure exhibiting exercise oscillatory ventilation.

This study aims to elucidate the characteristics of patients with severe nonischemic heart failure exhibiting exercise oscillatory ventilation (EOV) and the association of these characteristics with the subjective dyspnea. Forty-six patients with nonischemic heart failure who were classified into the New York Heart Association (NYHA) functional class III underwent cardiopulmonary exercise testing (CPX) and were divided into two groups according to the presence or absence of EOV. We evaluated the patients by using the Specific Activity Scale (SAS), biochemical examination, echocardiographic evaluation, results of CPX and symptoms during CPX (Borg scale), and reasons for exercise termination. EOV was observed in 20 of 46 patients. The following characteristics were observed in patients with EOV as compared with those without EOV with statistically significant differences: more patients complaining dyspnea as the reason for exercise termination, lower SAS score, higher N-terminal pro-brain natriuretic peptide level, larger left atrial dimension and volume, left ventricular end-diastolic volume, higher Borg scale score at rest and at the anerobic threshold, higher respiratory rate at rest and at peak exercise, and higher slope of the minute ventilation-to-CO2 output ratio, and lower end-tidal CO2 pressure at peak exercise. Among the subjects with NYHA III nonischemic heart failure, more patients with EOV had a stronger feeling of dyspnea during exercise as compared with those without EOV, and the subjective dyspnea was an exercise-limiting factor in many cases.

Controlled modulation of all the arms of the immunity including innate immunity by biological response modifier glucans, a simple yet potential nutritional supplement strategy to fight COVID-19.

Immune modulation, being one of the potential strategies to combat COVID-19 infection, emphasis has been laid on enhancing the innate immune response in a balanced manner. Beta (ß)-glucans have been suggested as nonspecific immunostimulatory adjuvants to beneficially boost protective antiviral immunity. Through this article, we wish to emphasize that ß-glucans not only enhance the innate immunity but also possess the capability to modulate all the arms of the immunity viz., innate, adaptive, TRIM at different sites including those postulated to be the entry site of the SARS-CoV2. Other than immune modulation capabilities, the beneficial metabolic- and coagulation-related effects of ß-glucans, a simple nutritional supplementation strategy, make them be considered for larger clinical studies to validate their prophylactic vaccine adjuvant and nutritional-based therapeutic supplement activities to effectively fight the COVID-19 pandemic. PRACTICAL APPLICATIONS: A 360° wholesome protection from viral infections is possible only when all the arms of the immune system function in a balanced and effective manner which is especially important in COVID-19. Nutritional supplementation using biological response modifier beta (ß)-glucans (BRMGs) is worth considering for large-scale clinical studies based on their track record of safety and their beneficial regulation of all the arms of the immune system.

ß­glucan vaccine adjuvant approach for cancer treatment through immune enhancement (B­VACCIEN) in specific immunocompromised populations (Review).

The incidence of cancer, which is the second leading cause of mortality globally, continues to increase, although continued efforts are being made to identify effective treatments with fewer side­effects. Previous studies have reported that chronic microinflammation, which occurs in diseases, including diabetes, along with weakened immune systems, may ultimately lead to cancer development. Chemotherapy, radiotherapy and surgery are the mainstream approaches to treatment; however, they all lead to immune system weakness, which in turn increases the metastatic spread. The aim of the present review was to provide evidence of a biological response modifier ß­glucan [ß­glucan vaccine adjuvant approach to treating cancer via immune enhancement (B­VACCIEN)] and its beneficial effects, including vaccine­adjuvant potential, balancing metabolic parameters (including blood glucose and lipid levels), increasing peripheral blood cell cytotoxicity against cancer and alleviating chemotherapy side effects in animal models. This suggests its value as a potential strategy to provide long­term prophylaxis in immunocompromised individuals or genetically prone to cancer.

Extraction of apex beat waveform from acoustic pulse wave by sound sensing system using stochastic resonance.

With a sound sensing system using stochastic resonance (4SR), it became possible to obtain an acoustic pulse wave (APW)-a waveform created via a mixture of apex beat and heart sound. We examined 50 subjects who were healthy, with no underlying cardiovascular diseases. We could determine boundary frequency (BF) using APW and phonocardiogram signals. APW data was divided into two bands, one from 0.5 Hz to BF, and a second one from BF to 50 Hz. This permitted the extraction of cardiac apex beat (CAB) and cardiac acoustic sound (CAS), respectively. BF could be expressed by a quadratic function of heart rate, and made it possible to collect CAB and CAS in real time. According to heart rate variability analysis, the fluctuation was 1/f, which indicated an efficient cardiac movement when heart rate was 70 to 80/min. In the frequency band between 0.5 Hz and BF, CAB readings collected from the precordial region resembled apex cardiogram data. The waveforms were classified into five types. Therefore, the new 4SR sensing system can be used as a physical diagnostic tool to obtain biological pulse wave data non-invasively and repeatedly over a long period, and it shows promise for broader applications, including AI analysis.

Change in bilirubin level following acute myocardial infarction is an index for heme oxygenase activation.

OBJECTIVES: Heme oxygenase 1 (HO-1) is rapidly induced by stress, degrading pro-oxidant heme into carbon monoxide, bilirubin, and free iron (Fe). Induction of HO-1 is an important defense mechanism against tissue injury. Here, we tested the hypothesis that HO-1 is activated in the myocardium after acute myocardial infarction (AMI) in humans. METHODS: Changes in the HO-1 activity after AMI were analyzed by measuring serum levels of bilirubin and Fe. Blood samples were collected in patients with AMI (n = 41) serially after the interventional therapy and compared with non-AMI subjects (n = 18). HO-1 protein levels were measured in a sample of AMI patients (n = 12). RESULTS: In AMI patients, but not in non-AMI subjects, serum levels of bilirubin (1.57 fold, P < 0.001) and Fe (1.35 fold, P < 0.01) were transiently elevated, both levels peaking 18-21 hours after the start of sampling. The peak changes in the levels of bilirubin and Fe in AMI patients were significantly correlated with each other. Furthermore, the serum HO-1 protein level was elevated, and its change was significantly correlated with the change in bilirubin level (r = 0.82, P < 0.005). Those with a high bilirubin response (peak levels >0.5 mg/dL) had richer collateral flow into the ischemic myocardium. CONCLUSIONS: These results suggest that heme oxygenase (HO) was activated following AMI, and it was detectable in the serum. Our data provide the first evidence of HO-1 induction following stress in humans. The change in bilirubin level may be a novel index for high collateral flow formation following AMI.

Three Dimensional Motion Analysis of Hand Tremors During Endoscopic Ear Surgery.

BACKGROUND: Endoscopic surgery is developing in various clinical specialties. During ear endoscopic surgery, a surgeon has to hold an endoscope with one hand and operate the surgical instruments with another hand. Therefore, the stability of the surgeon's hand affects the field of surgical view and quality of the surgery considerably. There are few techniques which are used during surgery to stabilize the endoscope. However, no study has evaluated the efficacy of such techniques in detail. This study examined the three dimensional movement of an endoscope to compare and evaluate the effect of various stabilization techniques to reduce the hand tremor while using the endoscope. METHODS: A non-randomized controlled trial involving 15 medical students was conducted in Tottori University, Japan. Subjects held an endoscope with their non-dominant hand and manipulated it using three different stabilization techniques i.e. with resting the elbow on the table, resting the endoscope on the ear canal, both with the elbow on the table and endoscope on the ear canal. For the control, subjects were made to use the endoscope without any stabilization technique. The endoscopic movement was measured with and without using the stabilization techniques. RESULTS: The results obtained in this study indicated that manipulating the endoscope with resting the elbow on the table restrains both vertical (Y-axis) and optical axis (Z-axis) direction of tremor, and manipulating the endoscope by resting it on the ear canal restrains both vertical (Y-axis) and horizontal axis (X-axis) direction while the combined use of both the techniques reduces the endoscope movement in all the three X, Y and Z axes. CONCLUSION: In conclusion, concomitant use of both techniques appears to be clinically beneficial in endoscopic ear surgery.

Mechanisms That Modulate Peripheral Oxygen Delivery during Exercise in Heart Failure.

Oxygen uptake ([Formula: see text]o2) measured at the mouth, which is equal to the cardiac output (CO) times the arterial-venous oxygen content difference [C(a-v)O2], increases more than 10- to 20-fold in normal subjects during exercise. To achieve this substantial increase in oxygen uptake [[Formula: see text]o2 = CO × C(a-v)O2] both CO and the arterial-venous difference must simultaneously increase. Although this occurs in normal subjects, patients with heart failure cannot achieve significant increases in cardiac output and must rely primarily on changes in the arterial-venous difference to increase [Formula: see text]o2 during exercise. Inadequate oxygen delivery to the tissue during exercise in heart failure results in tissue anaerobiosis, lactic acid accumulation, and reduction in exercise tolerance. H+ is an important regulatory and feedback mechanism to facilitate additional oxygen delivery to the tissue (Bohr effect) and further aerobic production of ATP when tissue anaerobic metabolism increases the production of lactate (anaerobic threshold). This H+ production in the muscle capillary promotes the continued unloading of oxygen (oxyhemoglobin desaturation) while maintaining the muscle capillary Po2 (Fick principle) at a sufficient level to facilitate aerobic metabolism and overcome the diffusion barriers from capillary to mitochondria ("critical capillary Po2," 15-20 mm Hg). This mechanism is especially important during exercise in heart failure where cardiac output increase is severely constrained. Several compensatory mechanisms facilitate peripheral oxygen delivery during exercise in both normal persons and patients with heart failure.

Comparison of the cardioprotective effect of prodromal angina pectoris and collateral circulation in patients with a first anterior wall acute myocardial infarction.

To compare the cardioprotective effect of prodromal angina pectoris and collateral circulation, 245 patients with first anterior acute myocardial infarction who underwent coronary angioplasty within 12 hours of symptoms were studied. Prodromal angina pectoris and collateral circulation were independently associated with higher predischarge left ventricular ejection fraction (LVEF), and a combination of prodromal angina pectoris and collateral circulation afforded cumulative improvement in LVEF in patients without diabetes mellitus. In patients with diabetes mellitus, collateral circulation, but not prodromal angina pectoris, was associated with higher predischarge LVEF.

Impact of prodromal angina pectoris and white blood cell count on outcome of patients with acute myocardial infarction.

BACKGROUND: Elevation of white blood cell (WBC) count at admission is associated with adverse outcome after acute myocardial infarction (AMI). Prodromal angina, by the mechanism of ischemic preconditioning, improves left ventricular (LV) function and survival after reperfusion therapy in patients with AMI. Recent experimental studies have reported that preconditioning has anti-inflammatory effect. METHODS: This study consisted of 598 patients with first anterior wall AMI who underwent coronary angiography within 12 h after symptom onset. WBC count was measured at the time of hospital admission. Prodromal angina was defined as angina occurring within 24 h before the onset of AMI. Serial measurements of LV ejection fraction (EF) were obtained before reperfusion therapy and before discharge in 421 patients (71%). RESULTS: High WBC count (>10.2 x 103/mm3, n=297) was associated with higher 30-day mortality (8% vs. 4%, p=0.02) and lower predischarge LVEF (51+/-15% vs. 57+/-14%, p<0.001), although there was no significant difference in acute LVEF (47+/-10% vs. 49+/-11%, p=0.07). High WBC count was an independent predictor of 30-day mortality (p=0.009) and predischarge LVEF (p=0.002). Prodromal angina was associated with lower 30-day mortality (3% vs. 7%, p=0.02) and preserved predischarge LVEF (57+/-15% vs. 53+/-14%, p=0.006). Patients with prodromal angina had lower WBC count (10.0+/-3.3 x 10(3)/mm3 vs. 11.0+/-3.9 x 10(3)/mm3, p=0.001) and prodromal angina was an independent predictor of WBC count (p<0.001). CONCLUSIONS: Elevation of WBC count and lack of prodromal angina were associated with impaired LV function and mortality after reperfusion in patients with AMI. Prodromal angina might have contributed to favorable outcome after AMI through its anti-inflammatory effect.

Takotsubo-like transient biventricular dysfunction with pressure gradients.

A 78-year-old woman was admitted to our hospital due to chest oppressive sensation. Admission electrocardiography revealed ST-segment elevation in I, II, III, aV(F) and V(2-6) leads. Left ventriculography showed apical akinesis and basal hyperkinesis with a pressure gradient of 60 mmHg between the left ventricular apex and the base. Right ventriculography also showed similar abnormal wall motion with a pressure gradient of 28 mmHg. Follow-up cardiac catheterization after 16 days showed normal wall motion with no pressure gradients. However, dobutamine stress (10 microg/kg/min) caused a pressure gradient of 60 mmHg between the left ventricular apex and the aorta.

CO2 pulse and acid-base status during increasing work rate exercise in health and disease.

The CO2 pulse (VCO2/heart rate), analogous to the O2 pulse (VO2/heart rate), was calculated during cardiopulmonary exercise testing and evaluated in normal and diseased states. Our aim was to define its application in its release in excess of that from VCO2/heart rate in the presence of impaired cardiovascular and lung function. In the current study, forty-five patients were divided into six physiological states: normal, exercise-induced myocardial ischemia, chronic heart failure, pulmonary vasculopathy, chronic obstructive pulmonary disease, and interstitial lung disease. We subtracted the O2 pulse from the CO2 pulse to determine the exhaled CO2 that could be attributed to CO2 pulse of buffering of lactic acid. The difference between the CO2 pulse and O2 pulse (VCO2/heart rate-VO2/heart rate) includes CO2 generated from HCO3(-) buffering of lactic acid. The accumulated CO2 per body mass was found to be significantly correlated with the corresponding [HCO3(-)] decrease (R(2)=0.72; P<0.0001). In summary, the increase in CO2 pulse over the O2 pulse accounted for the anaerobically-generated excess-CO2 in each of the physiological states and correlated with the decreases in the arterial Bicarbonate concentration.

Acute myocardial infarction associated with myocardial bridging in a young adult.

A 28-year-old man was admitted because of chest pain. Emergency coronary angiography showed a massive thrombus in the proximal segment and another occlusive thrombus in the distal segment of the left anterior descending artery. He was treated with thrombolytic therapy. Repeat coronary angiography showed disappearance of the thrombi in the proximal and distal segments and obvious myocardial bridging in the mid segment. Intravascular ultrasound revealed an atherosclerotic plaque in the segment immediately proximal to the myocardial bridging, but did not reveal any plaque within or distal to the site. He was discharged 12 days later.

Aspiration thrombectomy for acute myocardial infarction resulting from the sequential occlusions of two major coronary arteries in a short time.

A 49-year-old man was admitted to our hospital due to chest oppressive sensation. Coronary angiography showed total occlusion in the proximal right coronary artery even after intracoronary nitroglycerin, but no stenosis in the left coronary artery. He was treated with aspiration thrombectomy and stent deployment. After 23 hours, he suddenly had severe chest pain, and ECG showed marked ST elevation in leads I, aVL and V2-6. Surprisingly, coronary angiography showed total occlusion in the proximal left anterior descending artery even after intracoronary nitroglycerin where there had been no stenosis on first angiogram just 23 hours earlier. He was treated with aspiration thrombectomy.

Cooperation between Heart Failure Center of Hiroshima University Hospital and a regional medical facility: Option for an end-of-life heart failure patient receiving palliative care.

A 64-year-old woman with recurrent mitral valve stenosis was hospitalized 30 years after open commissurotomy. Severe right cerebral embolism occurred at age 58, with left hemiparesis. She was debilitated with cardiac cachexia. Based on symptomatic valvular disease findings, surgery was considered, but deemed too high risk due to the combined insufficiencies. She refused this surgical operation and requested conservative therapy. Optimized medication and cardiac rehabilitation improved her general condition allowing transfer to another hospital. We explained the short life expectancy both to her and to her family. They decided to transfer to a hospice at a chronic care hospital and she was given best supportive care. Eventually, her urine output decreased and respiration deteriorated. She and her family refused resuscitation in the event of cardiopulmonary arrest, requesting only suffering reduction. Thus, continuous intravenous infusion of morphine was started. The optimized doses for pain alleviation were determined in consultation with palliative care specialists and maximized her consciousness level for the last four days. "Heart-failure hospice" is potentially a place to die for end-of-life patients, attended by their families and healthcare providers. They need prognostic information and options for end-stage. Our experience confirms results about palliative care from previous studies conducted overseas demonstrating the effectiveness of opioids relieving end-stage symptoms. .

Association of elevated plasma aldosterone-to-renin ratio with future cardiovascular events in patients with essential hypertension.

BACKGROUND: We investigated the relationship between the renin/aldosterone profiles of patients with essential hypertension and their prognosis using a long-term follow-up study design. METHODS: The cohort consisted of 125 Japanese patients with essential hypertension whose plasma-renin activity (PRA) (ng/ml per h), plasma-aldosterone concentration (PAC) (ng/dl), and ratio of PAC to PRA [aldosterone-renin ratio (ARR)] were determined under hospitalization from 1984 to 1993. The patients were divided into two groups according to their ARRs relative to the 50th percentile of the ARR value (ARR = 5.5); the low-ARR group (ARR <5.5, n = 66) and high-ARR group (ARR > 5.5, n = 59). Their clinical outcomes were monitored during follow-up by the attending physicians. RESULTS: Ninety-six patients with essential hypertension (77% of the original cohort) were eligible for the analyses. The mean follow-up time was 18.6 ± 5.2 years. The cardiovascular morbidity was significantly higher in the high-ARR group than in the low-ARR group 3.2 vs. 2.4 per 100 patient-years, respectively (P = 0.014 by Kaplan-Meier analysis). Among the cardiovascular events, the incidence of stroke was 2.7-fold higher in the high-ARR group than in the low-ARR group. High ARR was an independent risk marker for cardiovascular events by Cox proportional hazards model analysis. CONCLUSION: : High ARR was an independent risk marker for cardiovascular events in patients with essential hypertension.

Platelet function measured using a whole blood aggregometer can predict bleeding events.

AIM: We hypothesized that excessive suppression of platelet function due to antiplatelet therapy can increase the incidence of bleeding complications. The aim of the present study was to find whether we could predict bleeding events by measuring platelet function. METHODS: We enrolled 743 subjects whose platelet function was measured using a whole blood aggregometer based on a screen filtration pressure method. Of these subjects, 551 (74.2%) were treated with some type of antiplatelet agent. The endpoints were bleeding or ischemic events requiring hospitalization or extension of hospital stay. We prospectively compared the platelet function of subjects with and without bleeding or ischemic events. RESULTS: During 556 ± 207 days of follow-up, 52 (7.0%) bleeding events and 20 (2.7%) ischemic events were observed. Kaplan-Meier analysis using the log-rank test revealed that an aggregation rate of < 20% induced by 8 µ M adenosine diphosphate (ADP) was significantly associated with a greater number of bleeding events (11.9% vs. 5.2%; p = 0.0007). Cox proportional hazards model showed that age > 75 years (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.03-3.10; p = 0.039), estimated glomerular filtration rate < 60 ml/min/1.73 m(2) (HR, 1.82; 95% CI, 1.06-3.18; p = 0.031) and aggregation rate < 20% induced by 8 µ M ADP (HR, 2.18; 95% CI, 1.24-3.80; p = 0.0071) were independent predictors of bleeding events. CONCLUSIONS: Low platelet function demonstrated using a whole blood aggregometer was an independent predictor of bleeding complications.