Tomohiko Kisaka

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.

Head-to-head comparison of the cardio-ankle vascular index between patients with acute coronary syndrome and stable angina pectoris.

We aimed to evaluate whether there was a difference in the arterial stiffness assessed by the cardio-ankle vascular index (CAVI) between patients with acute coronary syndrome (ACS) and those with stable angina pectoris (SAP). A total of 199 consecutive patients, 79 with ACS and 120 with SAP, who underwent emergency or elective coronary revascularization were enrolled. The CAVI was measured within 2 days after the procedures, and was compared between the ACS and SAP patients. As parameters related to arteriosclerosis, carotid intima–media thickness (IMT) and number of stenotic coronary vessels were also evaluated. Although IMT was significantly greater in SAP patients (2.1±1.1 vs. 2.4±0.9; P=0.022), CAVI was significantly higher in ACS patients (10.0±1.7 vs. 9.3±1.3; P=0.0012). After an adjustment for the clinical parameters with a significant difference between the two patient groups, CAVI remained significantly higher in ACS patients than in SAP patients (odds ratio 1.92, 95% confidence interval 1.30–3.02; P=0.0023). A multiple linear regression analysis revealed that age (β=0.44; P<0.0001) and ACS (β=0.3; P<0.0001) were the independent determinants of CAVI. A significant decrease in CAVI was observed at 6 months of follow-up as compared with the acute phase in 18 patients with ACS (10.9±1.6 vs. 10.0±1.5; P=0.019). In conclusion, CAVI was significantly and independently higher in patients with ACS than in those with SAP, which might result from a transient increase in the CAVI caused by acute myocardial ischemia.

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.

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.

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 Pericarditis Unmasks ST-Segment Elevation in Asymptomatic Brugada Syndrome

A 26‐year‐old man was admitted to our hospital because of acute pericarditis. The current patient had a saddle‐back type ST‐segment elevation shortly after the onset of acute pericarditis. Interestingly, it converted into a coved type ST‐segment elevation, subsequently regressed gradually as acute inflammation improved. After 3 months, right ventricular rapid pacing induced ventricular fibrillation, and intravenous sodium channel blocker induced a coved type ST‐segment elevation. The current case implies that a Brugada‐type ST‐segment elevation, which is thought to be false in acute pericarditis, may be true in some patients with asymptomatic Brugada syndrome.

Commentaries on Viewpoint: Why do some patients stop breathing after taking narcotics? Ventilatory chemosensitivity as a predictor of opioid-induced respiratory depression.

TO THE EDITOR: Patients who are to undergo opioid-induced ventilatory chemoreceptor depression respond variably to narcotics. This is illustrated in Potter and Moon’s (2) Fig. 1 in which great variability is shown of the hypercapnic ventilatory response (HCVR) test. In patients not undergoing pharmacological alterations (3, 4), there is great uniformity in hydrogen ion (H ) regulation. This might be explained by chemical stimulus being H and not carbon dioxide (CO2). Having tested their patients under partial anesthesia, increasing CO2, Potter and Moon (2) have a mix of stimuli but only an insensitive CO2 stimulus. Above the anaerobic threshold, H only drives ventilation. Patients may seriously underventilate and it does serious harm to patients when putting them under anesthesia. The reason for the variability is that the HCVR and the hypoxic ventilatory response (HVR) test of chemosensitivity may be insensitive and atypical when tested in nonphysiological ranges. This would be especially problematic if the patient has a background of heart or lung disease (4). Normal patients are extremely sensitive to H ventilatory regulation. However, they are insensitive to CO2 regulation over the entire range of chemical receptor control (3, 4). When arterial CO2 competes with hypoxemia or as the stimulus provided by CO2 gas, the CO2 loses its power and arterial [H ] wins. We conclude that the arterial [H ] is the chemical controller rather than CO2. See Fig. 4 in Ref. 3. This concept was in agreement with findings from other groups (1).

Very late stent thrombosis after drug-eluting stent implantation in a patient with antiphospholipid syndrome

A 74-year-old woman was admitted to our hospital with chest pain and shortness of breath. Coronary arteriograms revealed occlusion of a drug-eluting stent, which had been implanted 33 months earlier, in the middle right coronary artery. During percutaneous coronary intervention, distal embolization developed and a thrombus was detected with an aspiration catheter. Serological examinations performed 1 year before and during the present hospitalization revealed positive lupus anticoagulant activity. Thrombophilic tendencies, such as antiphospholipid syndrome, are noteworthy as one of the causative factors in very late stent thrombosis.

Documentation of acute increase in ventricular capture threshold after direct current cardioversion with AutoCapture threshold record.

This report describes acute and persistent increase in ventricular capture threshold after direct current cardioversion by using AutoCapture™ threshold record. Careful follow‐up is required to be sure that the system continues to function according to its design specifications.