Detection of dynamic lung hyperinflation using cardiopulmonary exercise testing and respiratory function in patients with stable cardiac disease: a multicenter, cross-sectional study.

BACKGROUND: Many patients with heart disease potentially have comorbid chronic obstructive pulmonary disease (COPD); however, there are not enough opportunities for screening, and the qualitative differentiation of shortness of breath (SOB) has not been well established. We investigated the detection rate of SOB based on a visual and qualitative dynamic lung hyperinflation (DLH) detection index during cardiopulmonary exercise testing (CPET) and assessed potential differences in respiratory function between groups. METHODS: We recruited 534 patients with heart disease or patients who underwent simultaneous CPET and spirometry (369 males, 67.0 ± 12.9 years) to scrutinize physical functions. The difference between inspiratory and expiratory tidal volume was calculated (TV E-I) from the breath-by-breath data. Patients were grouped into convex (decreased TV E-I) and non-convex (unchanged or increased TV E-I) groups based on their TV E-I values after the start of exercise. RESULTS: Among the recruited patients, 129 (24.2%) were categorized in the convex group. There was no difference in clinical characteristics between the two groups. The Borg scale scores at the end of the CPET showed no difference. VE/VCO2 slope, its Y-intercept, and minimum VE/VCO2 showed no significant difference between the groups. In the convex group, FEV1.0/FVC was significantly lower compared to that in the non-convex group (69.4 ± 13.1 vs. 75.0 ± 9.0%). Moreover, significant correlations were observed between FEV1.0/FVC and Y-intercept (r=-0.343), as well as between the difference between minimum VE/VCO2 and VE/VCO2 slope (r=-0.478). CONCLUSIONS: The convex group showed decreased respiratory function, suggesting a potential airway obstruction during exercise. A combined assessment of the TV E-I and Y-intercept of the VE/VCO2 slope or the difference between the minimum VE/VCO2 and VE/VCO2 slopes could potentially detect COPD or airway obstruction.

The concept of detection of dynamic lung hyperinflation using cardiopulmonary exercise testing.

Dynamic lung hyperinflation (DLH) caused by air trapping, which increases residual air volume, is a common cause of shortness of breath on exertion in chronic obstructive pulmonary disease (COPD). DLH is commonly evaluated by measuring the decrease in maximal inspiratory volume during exercise, or using the hyperventilation method. However, only few facilities perform these methods, and testing opportunities are limited. Therefore, we investigated the possibility of visually and qualitatively detecting DLH using data from a cardiopulmonary exercise test (CPET). Four men who underwent symptom-limiting CPET were included in this study, including a male patient in his 60s with confirmed COPD, a 50s male long-term smoker, and 2 healthy men in their 20s and 70s, respectively. We calculated the difference between the inspiratory tidal volume (TV I) and expiratory tidal volume (TV E) per breath (TV E-I) from the breath-by-breath data of each CPET and plotted it against the time axis. No decrease in TV E-I was observed in either of the healthy men. However, in the patient with COPD and long-term smoker, TV E-I began to decrease immediately after the initiation of exercise. These results indicate that DLH can be visually detected using CPET data. However, this study was a validation of a limited number of cases, and a comparison with existing evaluation methods and verification of disease specificity are required.

Higher Serum Soluble TREM2 as a Potential Indicative Biomarker for Cognitive Impairment in Inadequately Controlled Type 2 Diabetes Without Obesity: The DOR-KyotoJ-1.

Objective: Type 2 diabetes is a risk factor for dementia. We investigated whether serum levels of soluble triggering receptor expressed on myeloid cell 2 (sTREM2), a soluble form of the cell surface receptor TREM2, were predictive of cognitive impairment in type 2 diabetes without obesity. Methods: A total of 166 Japanese patients with type 2 diabetes without obesity were followed-up for 2 years. We measured clinical parameters, assessed cognitive function using the mini-mental state examination (MMSE), quantified and divided serum sTREM2 levels into quartiles, and examined the longitudinal associations. Results: During the follow-up, HbA1c levels were elevated in 98 patients and decreased in 68 patients. In the HbA1c-elevated group, higher sTREM2 levels at baseline showed a significant association with a greater tendency for reduction in MMSE scores (P for trend = 0.015), whereas they were not significantly associated with other examined parameters. In the HbA1c-decreased group, there was no significant association between sTREM2 levels at baseline and changes in MMSE scores, but higher sTREM2 levels at baseline were significantly associated with a greater tendency for reduction in waist circumference (P for trend = 0.027), homeostasis model assessment of insulin resistance (P for trend = 0.039), and sTREM2 levels (P for trend = 0.023). Conclusions: Glycemic control is suggested to be important in preventing cognitive impairment in patients with type 2 diabetes without obesity. Higher serum sTREM2 levels would be a predictive marker for cognitive impairment in inadequately controlled type 2 diabetes without obesity.

Diagnostic performance of nutritional indicators in patients with heart failure.

AIMS: The aim of this study was to compare the diagnostic performance of the nutritional indicators, the mini nutritional assessment-short form (MNA-SF), the geriatric nutritional risk index (GNRI), and the controlling nutritional status (CONUT), in heart failure (HF) patients. METHODS AND RESULTS: Nutritional status was prospectively assessed by the aforementioned three nutritional indicators in 150 outpatients with HF who were then followed for 1 year. The prevalence of patients with the nutritional risk as assessed by the MNA-SF, GNRI, and CONUT scores was 50.0%, 13.3%, and 54.0%, respectively. There was slight agreement of nutritional risk assessment between the MNA-SF and GNRI scores (κ coefficient = 0.16), as well as the GNRI and CONUT scores (κ = 0.11), but poor agreement between the MNA-SF and CONUT scores (κ = -0.09). The CONUT score had the lowest area under the curve (AUC) for the identification of low body weight, low muscle mass, and low physical function among the three indicators (all P < 0.05). Compared with the MNA-SF score, both the GNRI and CONUT scores had lower AUCs for the identification of reduced dietary intake and weight loss (all P < 0.05). There was no significant difference in predicting all-cause mortality or HF rehospitalization among the three indicators. The prescription of statins reduced the diagnostic performance of the CONUT score, as the CONUT score includes cholesterol level assessment. CONCLUSIONS: Of the three indicators, the diagnostic ability of the MNA-SF score was the highest, and that of the CONUT score was the lowest, for the assessment of HF patient nutritional status. The CONUT score may misrepresent nutritional status, particularly in patients receiving statins.

Antibody responses induced by the BNT162b2 mRNA COVID-19 vaccine in healthcare workers in a single community hospital in Japan.

INTRODUCTION: The effectiveness of several vaccines against coronavirus disease (COVID-19) has been reported in the real-world setting. However, it is still unknown how long antibodies persist following vaccination and whether or not the persistence of antibodies has a protective effect against COVID-19. METHODS: Healthcare workers who had received two doses of the BNT162b2 mRNA COVID-19 vaccine were enrolled, and a single-center study was conducted at the National Hospital Organization Hakodate National Hospital. Serum samples from all participants were collected 13-21 weeks (median: 20 weeks) after the second dose of vaccination. The antibody titers were measured using an electrochemiluminescence immunoassay (Elecsys® Anti-SARS-CoV-2 S). Data on characteristics of the participants were gathered from patient records and interview sheets. RESULTS: A total of 401 participants, among whom 70.1% were women and the median age was 42 years, were evaluated in this study. None of the participants had a definite COVID-19 history, and all participants who received complete vaccination showed positive antibody titers. The antibody titer was observed to be higher in participants with younger age (p < 0.001) and those who were females (p = 0.028). Despite the higher risk of infection than that of the general public, no vaccinated staff developed breakthrough infections. CONCLUSIONS: This study demonstrates the significant contribution of the BNT162b2 vaccine in the acquisition of anti-SARS-CoV-2S antibodies; therefore, the general population should benefit from these two vaccine doses, which are expected to be protective for at least five months.

Vonoprazan-associated long QT syndrome.

To our knowledge, this is the first report describing a case of vonoprazan-associated QT prolongation newly occurring after initiation of the drug and improving after its discontinuation in a patient concurrently receiving polypharmacy including a drug metabolized by CYP3A4.

Impact of Chronic Kidney Disease on the Associations of Cardiovascular Biomarkers With Adverse Outcomes in Patients With Suspected or Known Coronary Artery Disease: The EXCEED-J Study.

Background The impact of chronic kidney disease (CKD) on the prognostic utility of cardiovascular biomarkers in high-risk patients remains unclear. Methods and Results We performed a multicenter, prospective cohort study of 3255 patients with suspected or known coronary artery disease (CAD) to investigate whether CKD modifies the prognostic utility of cardiovascular biomarkers. Serum levels of cardiovascular and renal biomarkers, including soluble fms-like tyrosine kinase-1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin-I (hs-cTnI), cystatin C, and placental growth factor, were measured in 1301 CKD and 1954 patients without CKD. The urine albumin to creatinine ratio (UACR) was measured in patients with CKD. The primary outcome was 3-point MACE (3P-MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The secondary outcomes were all-cause death, cardiovascular death, and 5P-MACE defined as a composite of 3P-MACE, heart failure hospitalization, and coronary/peripheral artery revascularization. After adjustment for clinical confounders, sFlt-1, NT-proBNP, and hs-cTnI, but not other biomarkers, were significantly associated with 3P-MACE, all-cause death, and cardiovascular death in the entire cohort and in patients without CKD. These associations were still significant in CKD only for NT-proBNP and hs-cTnI. NT-proBNP and hs-cTnI were also significantly associated with 5P-MACE in CKD. The UACR was not significantly associated with any outcomes in CKD. NT-proBNP and hs-cTnI added incremental prognostic information for all outcomes to the model with potential clinical confounders in CKD. Conclusions NT-proBNP and hs-cTnI were the most powerful prognostic biomarkers in patients with suspected or known CAD and concomitant CKD.

Impact of citrus fruit intake on the mental health of patients with chronic heart failure.

BACKGROUND: The full impact of the intake of citrus fruits on the risk of depression in individuals with chronic heart failure (HF) is unknown. Here, we examined the associations between the estimated habitual intakes of citrus fruits and depressive symptoms in patients with chronic HF. METHODS: We enrolled 150 stable outpatients with chronic HF who had a history of worsening HF. To assess the patients' daily dietary patterns, we used a brief self-administered diet-history questionnaire to calculate the daily consumption of foods and nutrients. To assess the patients' mental state, we used a nine-item Patient Health Questionnaire (PHQ-9). RESULTS: Twelve patients (8%) were identified as having moderate-to-severe depression (PHQ-9 score ≥10). The patients with PHQ-9 ≥10 had lower daily intakes of citrus fruits compared to those with no or mild depressive symptoms (PHQ-9 <10). The daily intakes of various antioxidants, including vitamin C, ß-carotene, and ß-cryptoxanthin, all of which are abundant in citrus fruits, were reduced in the patients with PHQ-9 ≥10, accompanied by higher serum levels of 8-isoprostane (an oxidative stress marker). A multivariate logistic regression analysis using forward selection showed that a lowered daily intake of citrus fruits was an independent predictor of the comorbidity of moderate-to-severe depression in patients with chronic HF, after adjustment for age, gender, and the hemoglobin value. CONCLUSIONS: A lower daily consumption of citrus fruits was associated with higher prevalence of depression in patients with chronic HF. Our findings support the hypothesis that a daily consumption of citrus fruits has a beneficial effect on the prevention and treatment of depression in chronic HF patients.

Soluble vascular endothelial growth factor receptor 2 and prognosis in patients with chronic heart failure.

AIMS: Endothelial cell vascular endothelial growth factor receptor 2 (VEGFR-2) plays a pivotal role in angiogenesis, which induces physiological cardiomyocyte hypertrophy via paracrine signalling between endothelial cells and cardiomyocytes. We investigated whether a decrease in circulating soluble VEGFR-2 (sVEGFR-2) levels is associated with poor prognosis in patients with chronic heart failure (HF). METHODS AND RESULTS: We performed a multicentre prospective cohort study of 1024 consecutive patients with HF, who were admitted to hospitals due to acute decompensated HF and were stabilized after initial management. Serum levels of sVEGFR-2 were measured at discharge. Patients were followed up over 2 years. The outcomes were cardiovascular death, all-cause death, major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death and HF hospitalization, and HF hospitalization. The mean age of the patients was 75.5 (standard deviation, 12.6) years, and 57% were male. Patients with lower sVEGFR-2 levels were older and more likely to be female, and had greater proportions of atrial fibrillation and anaemia, and lower proportions of diabetes, dyslipidaemia, and HF with reduced ejection fraction (<40%). During the follow-up, 113 cardiovascular deaths, 211 all-cause deaths, 350 MACE, and 309 HF hospitalizations occurred. After adjustment for potential clinical confounders and established biomarkers [N-terminal B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein], a low sVEGFR-2 level below the 25th percentile was significantly associated with cardiovascular death [hazard ratio (HR), 1.79; 95% confidence interval (CI), 1.16-2.74] and all-cause death (HR, 1.43; 95% CI, 1.04-1.94), but not with MACE (HR, 1.11; 95% CI, 0.86-1.43) or HF hospitalization (HR, 1.03; 95% CI, 0.78-1.35). The stratified analyses revealed that a low sVEGFR-2 level below the 25th percentile was significantly associated with cardiovascular death (HR, 1.76; 95% CI, 1.07-2.85) and all-cause death (HR, 1.49; 95% CI, 1.03-2.15) in the high-NT-proBNP group (above the median), but not in the low-NT-proBNP group. Notably, the patients with high-NT-proBNP and low-sVEGFR-2 (below the 25th percentile) had a 2.96-fold higher risk (95% CI, 1.56-5.85) for cardiovascular death and a 2.40-fold higher risk (95% CI, 1.52-3.83) for all-cause death compared with those with low-NT-proBNP and high-sVEGFR-2. CONCLUSIONS: A low sVEGFR-2 value was independently associated with cardiovascular death and all-cause death in patients with chronic HF. These associations were pronounced in those with high NT-proBNP levels.

Impact of Smoking Status on Growth Differentiation Factor 15 and Mortality in Patients With Suspected or Known Coronary Artery Disease: The ANOX Study.

Background Whether circulating growth differentiation factor 15 (GDF-15) levels differ according to smoking status and whether smoking modifies the relationship between GDF-15 and mortality in patients with coronary artery disease are unclear. Methods and Results Using data from a multicenter, prospective cohort of 2418 patients with suspected or known coronary artery disease, we assessed the association between smoking status and GDF-15 and the impact of smoking status on the association between GDF-15 and all-cause death. GDF-15 was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study (Development of Novel Biomarkers Related to Angiogenesis or Oxidative Stress to Predict Cardiovascular Events). Patients were followed up during 3 years. The age of the patients ranged from 19 to 94 years; 67.2% were men. Never smokers exhibited significantly lower levels of GDF-15 compared with former smokers and current smokers. Stepwise multiple linear regression analysis revealed that the log-transformed GDF-15 level was independently associated with both current smoking and former smoking. In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders. This association was still significant in never smokers, former smokers, and current smokers. However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in current smokers or in former smokers. Conclusions Not only current, but also former smoking was independently associated with higher levels of GDF-15. The prognostic value of GDF-15 on mortality was most pronounced in never smokers among patients with suspected or known coronary artery disease.

Distinct Characteristics of VEGF-D and VEGF-C to Predict Mortality in Patients With Suspected or Known Coronary Artery Disease.

Background VEGF-D (vascular endothelial growth factor D) and VEGF-C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF-C level is inversely and independently associated with all-cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF-D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF-D was measured. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3-year follow-up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N-terminal pro-B-type natriuretic peptide, cardiac troponin-I, and high-sensitivity C-reactive protein), and VEGF-C, the VEGF-D level was significantly associated with all-cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF-D, either alone or in combination with VEGF-C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all-cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF-D value seems to independently predict all-cause mortality.

Cardiovascular reactions for whole-body thermal therapy with a hot pack and Waon therapy.

Background: Waon therapy (WT) is the predominant thermal therapy for chronic heart failure in Japan, involving use of a far-infrared dry sauna. As sauna therapy requires certain equipment not readily available in hospitals, we tested the use of whole-body hot pack thermal therapy (HPTT). We compared the magnitude of skin vasodilation post-HPTT with that post-WT.Methods: We recruited 19 healthy men (age [mean ± S.D.]: 26.8 ± 4.6 years) and employed a simple randomized crossover design. The HPTT required subjects to remain in a supine position on a bed for at least 10 min. Hot packs were then applied on the back, lower abdomen, and popliteal regions for 15 min (warming phase). Participants continued bed rest for 30 min (heat-retention phase) after removal of the hot pack. WT was performed as previously described. Blood pressure (BP), heart rate (HR), tympanic temperature (TT), and peak and average flow velocity of the right radial artery (PFV and AFV, respectively) and right brachial artery (BA) diameter were measured during HPTT and WT.Results: HR, TT, PFV, and AFV persistently and significantly increased during warming and heat-retention phases of HPTT. In WT, HR and TT significantly increased during warming but decreased and plateaued during heat-retention. BP did not change significantly after either therapy; however, BA was dilated equally in both (HPTT: 3.70 ± 0.57 ⇒ 4.05 ± 0.59 mm, p = .001; WT: 3.63 ± 0.63 ⇒ 3.93 ± 0.61 mm, p < .001).Conclusion: HPTT may be equivalent to WT with respect to vasodilation response of the skin.

Demonstration of Improved Renal Congestion After Heart Failure Treatment on Renal Perfusion Imaging With Contrast-Enhanced Ultrasonography.

Background: Renal congestion is a critical pathophysiological component of congestive heart failure (CHF). Methods and Results: To quantify renal congestion, contrast-enhanced ultrasonography (CEUS) was performed at baseline and after treatment in 11 CHF patients and 9 normal subjects. Based on the time-contrast intensity curve, time to peak intensity (TTP), which reflects the perfusion rate of renal parenchyma, and relative contrast intensity (RCI), an index reflecting renal blood volume, were measured. In CHF patients, TTP at baseline was significantly prolonged compared with that in controls (cortex, 10.8±3.5 vs. 4.6±1.2 s, P<0.0001; medulla, 10.6±3.0 vs. 5.1±1.6 s, P<0.0001), and RCI was lower than that in controls (cortex, -16.5±5.2 vs. -8.8±1.5 dB, P<0.0001; medulla, -22.8±5.2 vs. -14.8±2.4 dB, P<0.0001). After CHF treatment, RCI was significantly increased (cortex, -16.5±5.2 to -11.8±4.5 dB, P=0.035; medulla, -22.8±5.2 to -18.7±3.7 dB, P=0.045). TTP in the cortex decreased after treatment (10.8±3.5 to 7.6±3.1 s, P=0.032), but it was unchanged in the medulla (10.6±3.0 to 8.3±3.2 s, P=0.098). Conclusions: Renal congestion can be observed using CEUS in CHF patients.

VEGF-C and Mortality in Patients With Suspected or Known Coronary Artery Disease.

Background The lymphatic system has been suggested to play an important role in cholesterol metabolism and cardiovascular disease. However, the relationships of vascular endothelial growth factor-C ( VEGF -C), a central player in lymphangiogenesis, with mortality and cardiovascular events in patients with suspected or known coronary artery disease are unknown. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The primary predictor was serum levels of VEGF -C. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. During the 3-year follow-up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for established risk factors, VEGF -C levels were significantly and inversely associated with all-cause death (hazard ratio for 1- SD increase, 0.69; 95% confidence interval, 0.60-0.80) and cardiovascular death (hazard ratio, 0.67; 95% confidence interval, 0.53-0.87), but not with major adverse cardiovascular events (hazard ratio, 0.85; 95% confidence interval, 0.72-1.01). Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF -C levels further improved the prediction of all-cause death, but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within 1717 patients with suspected coronary artery disease. Conclusions In patients with suspected or known coronary artery disease, a low VEGF -C value may independently predict all-cause mortality.

Assessment of renal perfusion impairment in a rat model of acute renal congestion using contrast-enhanced ultrasonography.

Renal congestion is caused by elevated central venous pressure (CVP), and decreases glomerular filtration in patients with congestive heart failure. Since real-time contrast-enhanced ultrasonography (CEUS) using microbubble-based contrast agents can visualize the perfused microvascular bed, we sought to evaluate the impairment of renal perfusion during acute renal congestion with CEUS. In Wister rats, CEUS of kidney was performed with the direct monitoring of CVP and intra-renal pressure (IRP). When CVP was elevated to 10 and 15 mmHg after the bolus injection of normal saline via the femoral vein, peak intensity (PI, dB) and time to PI (TTP) in the renal cortex and medulla were compared with control rats. There was a strong correlation between IRP and CVP (r = 0.95, p < 0.0001). In the congestion model, more time was required for enhancement of the parenchyma, especially in the medulla compared to control; TTP of the medulla and cortex at 15 mmHg CVP (CVP15) was significantly prolonged compared with controls (medulla, 4351 ± 98 vs. 1415 ± 267 ms, p = 0.003; cortex, 3219 ± 106 vs. 1335 ± 264 ms, p = 0.005). In addition, medullary PI at CVP15 decreased, but not significantly, compared to those of controls and at 10 mmHg CVP (20.1 ± 0.9, 22.8 ± 1.6, 21.6 ± 0.2 dB). In contrast, cortical PIs at CVP15 were significantly lower than that of control (24.6 ± 1.0 vs. 31.4 ± 1.0 dB, p = 0.007). CEUS revealed that impaired renal parenchymal flow in an acute congestion model is accompanied with increased renal interstitial pressure.

Left ventricular noncompaction with intractable heart failure responsive to empagliflozin.

Despite several reports on the mechanism of the effect of empagliflozin, which has the potential for improved prognosis in heart failure, it is still not fully understood. We experienced a case of left ventricular noncompaction that caused fluid retention in a patient who showed resistance to existing diuretics. By using empagliflozin, we successfully treated this case of acute heart failure and observed stabilized symptoms with no renal dysfunction and deterioration of patient condition. Although the potential for improved prognosis with this drug in a high-risk group for cardiovascular events has been reported, based on EMPA-REG OUTCOME trial results, there are few reports on its effect of treatment and mechanism in treating acute heart failure. The effect of this drug in treating heart failure from the acute phase to the chronic phase can be expected. .

Quantification and physiological significance of the rightward shift of the V-slope during incremental cardiopulmonary exercise testing.

BACKGROUND: Ventilatory anaerobic threshold (VAT) is frequently used as a measure of exercise tolerance, with the V-slope method being the standard; however, this needs to be visually determined. Over the years, we have observed that the V-slope itself often appears to shift rightward before the appearance of the VAT (RtShift: rightward shift of V-slope). This phenomenon has long been known to occur during the first 1-2 min of steady-state exercise and disappears thereafter; it is attributed to CO2 storage, presumably in active muscle. However, during incremental exercise, we have observed that the RtShift persists; furthermore, it seems to be related to the level of VAT. Therefore, we attempted to objectively quantify the RtShift, and to confirm its relationship to an index of exercise tolerance (VAT). METHODS: This study was based on a retrospective analysis of data from 100 cardiopulmonary ramp exercise tests (submaximal) performed by patients with cardiac disease. VAT was determined with the visual V-slope method. The horizontal distances between the diagonal R = 1 line and each data point on the V-slope plot to the right of R = 1 were measured; the average of these measurements was used as an objectively determined estimate of RtShift. RESULTS: The predominant portion of RtShift occurred earlier than VAT. The mean RtShift was 33.9 ± 25.0 mL⋅min-1 VO2, whereas the mean VAT was 635 ± 220 mL⋅min-1. RtShift positively correlated with VAT (r = 718, p < 0.001), confirming previous visual observations. It also significantly correlated with ΔVO2/Δwork rate, a marker of oxygen uptake efficiency (r = 0.531, p < 0.001). CONCLUSIONS: We identified that among patients with cardiac disease, V-slope is shifted rightward to varying degrees. The objectively quantified rightward shift of V-slope is significantly correlated with an index of exercise tolerance (VAT). Furthermore, it appears to occur at even lower work rates. This may offer a new objective means of estimating exercise tolerance; however, its exact biological basis still needs to be elucidated.

Vasodilatory effect of nitroglycerin in Japanese subjects with different aldehyde dehydrogenase 2 (ALDH2) genotypes.

The functional genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) influences the enzymatic activities of its wild type (Glu504 encoded by ALDH2*1) and mutant type (Lys504 encoded by ALDH2*2) proteins. The enzymatic activities of mutant-type ALDH2 are limited compared with those of the wild type. ALDH2 has been suggested as a critical factor for nitroglycerin-mediated vasodilation by some human studies and in vitro studies. Currently, there is no research on direct observations of the vasodilatory effect of nitroglycerin sublingual tablets, which is the generally used dosage form. In the present study, the contribution of ALDH2 to the vasodilatory effect of nitroglycerin sublingual tablets was investigated among three genotype groups (ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2) in Japanese. The results by direct assessments of in vivo nitroglycerin-mediated dilation showed no apparent difference in vasodilation among all genotypes of ALDH2. Furthermore, to analyze the effect of other factors (age and flow-mediated dilation), multiple regression analysis and Pearson's correlation coefficient analysis were carried out. These analyses also indicated that the genotypes of ALDH2 were not related to the degree of vasodilation. These results suggest the existence of other predominant pathway(s) for nitroglycerin biotransformation, at least with regard to clinical nitroglycerin (e.g., a sublingual tablet) in Japanese subjects.

Associations between increased renal resistive index and cardiovascular events.

BACKGROUND AND PURPOSE: Chronic kidney disease is a risk factor for cardiovascular disease (CVD). Renal resistive index (RI) measured by Doppler ultrasonography is associated with renal impairment. We investigated the relationship between RI and cardiac function, and evaluated the utility of RI for predicting cardiac events in patients with CVD. METHODS AND RESULTS: Renal Doppler ultrasonography and echocardiography were performed in a total of 452 patients with CVD. Correlations of RI with serum creatinine and estimated glomerular filtration rate (eGFR) were significant but not strong (r = 0.37, p < 0.001; r = -0.42, p < 0.001, respectively). RI correlated positively with age, left atrial volume index, left ventricular mass index, and early transmitral velocity to mitral annular early diastolic velocity (e') ratio (E/e'), and showed significant negative correlations with e' and diastolic blood pressure. Between two subgroups-112 patients hospitalized with cardiovascular events (Group A) and 200 age- and eGFR-matched controls (Group B)-RI was significantly higher in Group A than in Group B, although age and eGFR were similar. CONCLUSIONS: RI reflects the impairment of intrarenal hemodynamics that cannot be adequately elucidated by eGFR alone. Assessment of renal RI may be useful in conjunction with prognostic estimates for patients with CVD.