Plasma concentrations of coffee polyphenols and plasma biomarkers of diabetes risk in healthy Japanese women.

Coffee consumption has been reported to reduce the risk of type 2 diabetes in experimental and epidemiological studies. This anti-diabetic effect of coffee may be attributed to its high content in polyphenols especially caffeic acid and chlorogenic acid. However, the association between plasma coffee polyphenols and diabetic risks has never been investigated in the literature. In this study, fasting plasma samples were collected from 57 generally healthy females aged 38-73 (mean 52, s.d. 8) years recruited in Himeji, Japan. The concentrations of plasma coffee polyphenols were determined by liquid chromatography coupled with mass tandem spectrometer. Diabetes biomarkers in the plasma/serum samples were analysed by a commercial diagnostic laboratory. Statistical associations were assessed using Spearman's correlation coefficients. The results showed that plasma chlorogenic acid exhibited negative associations with fasting blood glucose, glycated hemoglobin and C-reactive protein, whereas plasma total coffee polyphenol and plasma caffeic acid were weakly associated with these biomarkers. Our preliminary data support previous findings that coffee polyphenols have anti-diabetic effects but further replications with large samples of both genders are recommended.

Restoration of sinus rhythm results in early and late improvements in the functional reserve of the heart following direct current cardioversion of persistent AF: FRESH-AF.

BACKGROUND: The improvement in cardiac physiological parameters after restoration of sinus rhythm in patients with persistent atrial fibrillation (AF) can be challenging to quantify. Overall cardiac function assessment is better assessed by peak cardiac power output (CPOpeak), rather than indirect measures of cardiac performance such as peak oxygen consumption (VO2peak). CPO was used to quantify improvement in cardiac function early and later following electrical cardioversion. METHODS AND RESULTS: 29 patients with persistent AF underwent maximal treadmill cardiopulmonary exercise (CPEx) testing within 14days (±3) 8weeks (±3) following electrical cardioversion (DCCv). This enabled measurement of VO2peak, cardiac output (COpeak) and calculation of CPOpeak. Quality of life (QoL) data (EQ5D) was also recorded. Three patients attended for 2 CPEx tests and 3 were lost to follow-up (total n=26). Fourteen were successfully cardioverted and 12 remained in AF. In patients successfully cardioverted exercise duration increased significantly between all tests. CPOpeak, VO2peak, CO peak and QoL were improved significantly between Tests 1 and 2 (p<0.02) and Tests 1 and 3 (p<0.05). QoL improved by 15%. CONCLUSIONS: Restoration of SR confers significant, early and sustained cardiac functional improvement following DCCv with a significant 14% increase in the calculated peak power output of the heart. Such increase in functional reserve suggests that pursuit of a rhythm control strategy in the treatment of AF may be warranted in terms of both improving quality of life and cardiac function with objective improvement of cardiac function.

Impacts of valve intervention on the Functional REServe of the Heart: The FRESH-valve pilot study.

PURPOSE: Severe valve lesions require corrective interventions to avoid progression to heart failure (HF) and premature demise. We tested the hypothesis that despite operative risks, corrective valvular interventions will lead to significant improvements in overall cardiac pump function, especially before the onset of cardiac decompensation. METHODS: We compared the cardiopulmonary exercise performance and non-invasive haemodynamics of 46 consecutive patients with severe valvular disease before and after valvular intervention with reference to 101 healthy male and 139 female controls without cardiovascular disease. Cardiac and physical functional reserves were measured with standard respiratory gas analyses and CO2 rebreathing to measure cardiac output non-invasively during peak treadmill exercise. Data are given as mean ± SD and statistical significance accepted at P<0.05. RESULTS: The entire patient cohort showed no significant improvement in peak O2 consumption (V˙O2max, P=0.74) or in peak cardiac power (CPOmax, P=0.34) after valvular intervention, but we found instead a dichotomous outcome depending on preoperative cardiac function: (i) the pre-operative cardiac decompensatory subgroup (LoW, n=26) showed increased CPOmax (2.63 ± 0.67 to 3.42 ± 0.98 W, P<0.0001) and V˙O2max (1.38 ± 0.55 to 1.56 ± 0.59 L·min(-1), P<0.01); and (ii) the pre-operative non-decompensatory subgroup (HiW) showed reduced CPOmax (4.58 ± 0.96 to 3.84 ± 0.92 W, P<0.001) and V˙O2max (2.29 ± 0.72 to 1.97 ± 0.75 L·min(-1), P<0.01). Changes in NYHA class were found to be discrepant with these objective measurements. CONCLUSION: This investigation found an unexpected finding that valvular interventions performed in routine clinical practice do not consistently improve cardiac function, especially in those without pre-operative cardiac decompensation. Assessing cardiac functional gains would open up new avenues for future trials of valvular interventions.

Is low VO2max/kg in obese heart failure patients indicative of cardiac dysfunction?

PURPOSE: Low peak O2 consumption (VO2max/kg) has been widely used as an indirect indicator of poor cardiac fitness, and often guides management of patients with severe heart failure (HF). We hypothesized that it should be as good an indicator of cardiac dysfunction in obese and non-obese HF patients. METHODS: We compared the cardiopulmonary exercise performance and non-invasive hemodynamics of 152 obese (BMI>34 kg.m(-2)) and 173 non-obese (BMI≤32) male HF patients in NYHA classes II and III, with reference to 101 healthy male controls. Their physical and cardiac functional reserves were measured during treadmill exercise testing with standard respiratory gas analyses and CO2 rebreathing to measure cardiac output non-invasively during peak exercise. Data are given as mean ± SD. RESULTS: Obese HF patients with BMI 40.9 ± 7.5 kg·m(-2) (age 56.1 ± 14.0 years, NYHA 2.5 ± 0.5) exercised to acceptable cardiopulmonary limits (peak RER=1.07 ± 0.12), and achieved a mean VO2max/kg of 18.6 ± 5.2 ml·kg(-1)·min(-1), significantly lower than in non-obese HF counterparts (19.9 ± 5.6 ml·kg(-1)·min(-1), P=0.02, age 55.8 ± 10.6 years, BMI 26.6 ± 3.1, NYHA 2.4 ± 0.5, peak RER=1.07 ± 0.09), with both lower than controls (38.5 ± 9.7 ml·kg(-1)·min(-1), P<10(-6)). In contrast, the uncorrected VO2max was higher in obese (2.31 ± 0.69 ml·min(-1)) than non-obese HF patients (1.61 ± 0.49 ml·min(-1), P<10(-6)). When cardiac dysfunction was evaluated directly, peak cardiac power was significantly greater in obese than non-obese HF patients (4.11 ± 1.21 W vs 2.73 ± 0.82 W, P<10(-6)), with both lower than controls (5.42 ± 1.04 W, P<10(-6)). CONCLUSION: These results demonstrate that VO2max/kg is not a generally reliable indicator of cardiac fitness in all patients. Instead, we found that despite having lower VO2max/kg, obese HF patients had stronger hearts capable of generating greater cardiac power than non-obese HF patients of equivalent clinical HF status.

B-type natriuretic peptide in lymphedema.

Lymphedema often responds to compression therapy which can also cause undesirable cardiac overload if heart failure coexists. We hypothesized that the biomarker B-type natriuretic peptide (BNP) can be used to screen lymphedema patients for undetected cardiac dysfunction. We studied unselected consecutive patients with lymphedema to determine their BNP status and compared these data with those obtained from healthy subjects without known cardiovascular diseases. Out of a total of 305 subjects with lymphedema screened, 102 (33%) consented to take part in this study. The majority (87%) were female with a mean age of 60.5 +/- 13.2 (SD) years, and 47% had just lower limb swelling. The groups were equally divided between cancer and non-cancer related causes. There were 45 females and 4 males under 60 years old, and 44 female and 9 male patients over 60 years old. Median (IQR) BNP (ng/L) were as follows: <60 years females = 17.9 (15.2) (median [RR: 3 - 64] and males = 12.4 (14.7) [RR: 0.2 - 44], >60 years females = 35.8 (57.9) [RR: 2 -247)] and males = 47.2 (44.1) [RR: 2 - 238]. For this population, the BNP concentration 100 ng/L was adopted as the value to exclude heart failure. Using this definition, 7 lymphedema subjects had BNP concentrations of 120 (19.8) ng/L, and all were found to have cardiac abnormalities on echocardiography. This study demonstrated that 93% of unselected subjects with lymphedema had BNP concentrations that exclude a diagnosis of heart failure. Those subjects with elevated BNP were found on subsequent echocardiography to have cardiac abnormalities. The use of a BNP assay is of potential value in screening patients who are more likely to have cardiac failure. Indicative factors include bilateral leg swelling, over the age of 50 years, breathlessness, where there is no known cause for the swelling. A BNP assay using a BNP concentration threshold of 100 ng/L (29 pmol/L) will identify those patients who require more detailed investigations.

Two-dimensional strain imaging: a new echocardiographic advance with research and clinical applications.

Over the past two decades the quest for quantitative evaluation of left ventricular function and regional wall motion has escalated, allowing several aspects of myocardial contractile patterns to be quantified, both during stress echocardiography and in the assessment of dyssynchrony. Most of the literature to date has used Tissue Doppler Imaging (TDI) techniques to assess essentially long-axis function due to the angle dependency of Doppler based techniques. This brief review introduces the early development, validation and potential clinical applications of a new technique of quantifying two-dimensional (radial and circumferential) strains and strain rates through tracking myocardial "speckles". In-vivo and in-vitro validation of this 2D-strain imaging technique has been undertaken and reached a point where it is considered ready for more widespread investigations into clinical utility. One important advantage over TDI techniques is that it is not limited by dependency on the angle of insonation. Several recent studies looking at ventricular function in specific groups of patients have reported practical ability to distinguish the abnormally from the normally contracting regions of ventricular walls. It provides new and complementary quantitative information about ventricular dyssynchrony and regional wall motion abnormalities. More research studies are needed to determine the sensitivity and specificity of the measurements obtained using this technique and define its strengths and limitations. In particular, whether the measured values correlate well with clinical outcomes will need to be established in longitudinal interventional studies. The clinical utilities of this technique over the coming years are likely to expand rapidly.

CRT improves the exercise capacity and functional reserve of the failing heart through enhancing the cardiac flow- and pressure-generating capacity.

BACKGROUND: While information on how cardiac resynchronisation therapy (CRT) affects cardiac performance at rest is readily available, the mechanisms whereby CRT alters cardiac function during maximal exercise are unclear. AIMS: We examined the medium-term effects of CRT on cardiac and physical functional reserve of patients with severe heart failure (CHF) and prolonged QRS duration. METHODS: Seventeen consecutive patients with severe CHF (NYHA III-IV) and widened QRS underwent maximal cardiopulmonary exercise testing with non-invasive central haemodynamic measurements before and 6-8 weeks after CRT pacemaker implantation. RESULTS: After CRT there were significant increases in exercise cardiac output by 19.3% (P=0.0048) from 9.5+/-3.4 l min(-1), peak mean arterial blood pressure by 14.1% (P=0.0001) from 91.3+/-13.6 mm Hg, and peak cardiac power output by 37.2% (P=0.0008) from 1.92+/-0.74 W. There were no significant changes in these variables at rest. Exercise duration (+42.3%, P=0.0002), NYHA functional class (P=0.0001) and SF-36 symptom score (P=0.0006) were also significantly improved. Powerful surrogate indicators of prognosis were also significantly improved with CRT: peak O(2) consumption (+20.9%, P=0.0007), VE/VCO(2) slope (-20.0%, P=0.005) and circulatory power (+42.0%, P=0.0012). CONCLUSION: In this cohort of patients, post-implant CRT significantly improved the flow-, pressure- and power-generating capacity of the failing hearts. This may be causally related to the improvements observed in exercise capacity, functional class and symptom scores.

Complementary roles of simple variables, NYHA and N-BNP, in indicating aerobic capacity and severity of heart failure.

AIMS: The extent of exercise intolerance in patients with chronic heart failure (CHF) is dependent on and representative of the severity of heart failure. However, few primary care physicians have direct access to facilities for formal exercise testing. We have therefore explored whether information readily obtainable in the community can reliably predict the functional capacity of patients. METHODS AND RESULTS: Ninety-six subjects with a wide range of cardiac function (10 healthy controls and 86 CHF patients with NYHA classes I-IV, LVEF 36.9+/-15.2%) were recruited into the study and had resting plasma N-BNP and cardiopulmonary exercise testing to measure peak oxygen consumption (VO2). Significantly higher N-BNP levels were found in the CHF group (299.3 [704.8] fmol/ml, median [IQR]) compared with the healthy control group (7.2 [51.2] fmol/ml), p<0.0001. There were significant correlations between peak VO2 and N-BNP levels (R=0.64, P<0.001), peak VO2 and NYHA class (R=0.76, P=0.001), but no significant correlation was seen between peak VO2 and LVEF (R=0.0788, P=0.33). Multivariate analysis identified plasma N-BNP (P<0.0001) and NYHA class (P<0.0001) as significant independent predictors of peak VO2. Logistic modelling with NYHA class and log N-BNP to predict peak VO2<20 ml/kg/min showed that the area under the curve of receiver-operating-characteristic (ROC) curve was 0.906 (95% CI 0.844-0.968). A nomogram based on the data has been constructed to allow clinicians to estimate the likelihood of peak VO2 to be <20 ml/kg/min for given values of plasma N-BNP and NYHA class. CONCLUSIONS: By combining information from a simple objective blood test (N-BNP) and a simple scoring of functional status (NYHA), a clinician can deduce the aerobic exercise capacity and indirectly the extent of cardiac dysfunction of patients with CHF.

The influence of body size on measurements of overall cardiac function.

The purpose of this study was to determine the best scaling method to account for the effects of body size on measurements of overall cardiac function and subsequently the interpretation of data based on cardiac power output (CPO). CPO was measured at rest (CPO(rest)) and at maximal exercise (CPO(max)) on 88 and 103 healthy but untrained men and women, respectively, over the age range of 20-70 yr. Cardiac reserve (CR) was calculated as CPO(max) - CPO(rest). CPO(rest), CPO(max), and CR were all significantly related to body mass (BM), body surface area (BSA), and lean body mass (LBM). The linear regression model failed to completely normalize these measurements. In contrast, the allometric model produced size-independent values of CPO. Furthermore, all the assumptions associated with the allometric model were achieved. For CPO(rest), mean body size exponents were BM(0.33), BSA(0.60), and LBM(0.47). For CPO(max), the exponents were BM(0.41), BSA(0.81), and LBM(0.71). For CR, mean body size exponents were BM(0.44), BSA(0.87), and LBM(0.79). LBM was identified (from the root-mean-squares errors of the separate regression models) as the best physiological variable (based on its high metabolic activity) to be scaled in the allometric model. Scaling of CPO to LBM(b) (where b is the scaling exponent) dramatically reduced the between-gender differences with only a 7% difference in CPO(rest) and CPO(max) values. In addition, the gender difference in CR was completely removed. To avoid erroneous interpretations and conclusions being made when comparing data between men and women of different ages, the allometric scaling of CPO to LBM(b) would seem crucial.

From CONSENSUS to CHARM--how do ACEI and ARB produce clinical benefits in CHF?

Two decades of research from CONSENSUS to CHARM using modulators of the renin-angiotensin-aldosterone system (RAAS) in chronic heart failure (CHF) patients have shown convincing clinical benefits, but the majority of clinicians prescribing these drugs are still unclear about what mechanisms are responsible for the observed benefits. Of the candidate mechanisms hitherto proposed, there emerges a theme that best fits the spectrum of known factors from pathophysiology of heart failure to how the drugs enhance longevity of patients. This concept can be summarised as follows: after the onset of heart failure, neurohormones are activated resulting in raised levels of angiotensin, aldosterone and catecholamines, which are all known cardiotoxic agents. Cumulatively over time, they are responsible for accelerated cardiomyocyte attrition, manifesting as a faster reduction of cardiac pumping reserve, leading to worsening heart failure, more neurohormonal activation, thus propagating a vicious cycle spiralling towards an earlier fatality. The vicious cycle can be interrupted by dampening the excessive neurohormonal activities, thereby minimising cardiomyocyte losses and preserving cardiac functional reserve for longer. This culminates in maintenance of a reasonable quality of life and enhanced longevity. Such a mechanistic understanding would enable clinicians to have a better perspective on how to apply data from various clinical trials involving these drugs into clinical practice, to optimise and tailor therapy to the individual patient so that each patient can gain maximal benefits.

The benefits of valsartan in the treatment of heart failure: results from Val-HeFT.

Angiotensin II receptor blockers (ARBs) are the most recent class of anti-hypertensive drug to enter clinical use for chronic heart failure (CHF). In the landmark Valsartan Heart Failure Trial (Val-HeFT), valsartan reduced the risk of the combined endpoint of all-cause mortality and morbidity by 13.2% over a 2-year follow-up. Although it significantly improved a pre-specified primary endpoint, it did not improve the endpoint of all-cause mortality. Valsartan administered to patients not receiving angiotensin-converting enzyme inhibitors (ACEI) at baseline reduced the endpoint of all-cause mortality by 33% and the combined endpoint of mortality and morbidity by 44%, compared with placebo. Based on these findings, valsartan became the first ARB to be approved by the US Food and Drug Administration for the treatment of New York Heart Association class II-IV HF in patients who are intolerant of ACEIs. This review provides a summary of the key Val-HeFT results and their implications in the treatment of CHF patients.

Does balloon mitral valvuloplasty improve cardiac function? A mechanistic investigation into impact on exercise capacity.

Procedural technical success of balloon mitral valvuloplasty (BMV) is indicated by an increase in valve area and a reduction in transvalvar gradient, but there are conflicting results regarding whether these indicators correlate with subsequent improvements in exercise capacity. We conducted a study to explore the effects of valvuloplasty on cardiac function to gain insight into the mechanisms responsible for the impact on exercise ability. Sixteen patients with mitral stenosis participated in the study and the five who did not proceed to valvuloplasty served as the control group. All patients performed maximal cardiopulmonary exercise tests before and 6 weeks after valvuloplasty (without valvuloplasty in controls). Central haemodynamics including cardiac output were measured non-invasively at rest and peak exercise. At baseline, the cardiopulmonary exercise test results were similar in the two groups. Following valvuloplasty, cardiac output did not alter at rest, but increased significantly at peak exercise (8.7+/-1.7 to 10.5+/-2.1 l min(-1), P<0.01), as did peak cardiac power output (1.88+/-0.55 to 2.28+/-0.74, P<0.05) and cardiac reserve (1.07+/-0.33 to 1.45+/-0.55 watts, P<0.05). Aerobic exercise capacity improved (13.9+/-4.2 to 16.4+/-4.3 ml kg(-1) min(-1), P<0.01) as did exercise duration (354+/-270 to 500+/-266 s, P<0.01). There were no significant changes in the controls. There was a significant correlation between the changes in peak VO(2) and changes in cardiac reserve (r=0.62, P<0.01) but not with changes in resting haemodynamics. These changes did not correlate with changes in peri-procedural mitral valve haemodynamics, despite increases in mitral valve area from 1.05+/-0.16 to 1.74+/-0.4 cm(2) (P<0.0001), accompanied by falls in the transvalvar gradient and pulmonary artery pressure (12.4+/-4.7 to 4.5+/-3 mmHg, and 26.8+/-8.4 to 17.4+/-5.2 mmHg, respectively, all P<0.0001). In conclusion, we found that successful mitral valvuloplasty in our patient cohort led to improved cardiac and physical functional capacity but not resting haemodynamics. Neither indicators of technical success nor resting haemodynamics were very reliable in predicting functional improvement.