Ana Kadkhodayan

Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women.

Nitric oxide (NO) has been demonstrated to enhance the maximal shortening velocity and maximal power of rodent muscle. Dietary nitrate (NO3(-)) intake has been demonstrated to increase NO bioavailability in humans. We therefore hypothesized that acute dietary NO3(-) intake (in the form of a concentrated beetroot juice (BRJ) supplement) would improve muscle speed and power in humans. To test this hypothesis, healthy men and women (n = 12; age = 22-50 y) were studied using a randomized, double-blind, placebo-controlled crossover design. After an overnight fast, subjects ingested 140 mL of BRJ either containing or devoid of 11.2 mmol of NO3(-). After 2 h, knee extensor contractile function was assessed using a Biodex 4 isokinetic dynamometer. Breath NO levels were also measured periodically using a Niox Mino analyzer as a biomarker of whole-body NO production. No significant changes in breath NO were observed in the placebo trial, whereas breath NO rose by 61% (P < 0.001; effect size = 1.19) after dietary NO3(-) intake. This was accompanied by a 4% (P < 0.01; effect size = 0.74) increase in peak knee extensor power at the highest angular velocity tested (i.e., 6.28 rad/s). Calculated maximal knee extensor power was therefore greater (i.e., 7.90 ± 0.59 vs. 7.44 ± 0.53 W/kg; P < 0.05; effect size = 0.63) after dietary NO3(-) intake, as was the calculated maximal velocity (i.e., 14.5 ± 0.9 vs. 13.1 ± 0.8 rad/s; P < 0.05; effect size = 0.67). No differences in muscle function were observed during 50 consecutive knee extensions performed at 3.14 rad/s. We conclude that acute dietary NO3(-) intake increases whole-body NO production and muscle speed and power in healthy men and women.

Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure A Double-Blind, Placebo-Controlled, Randomized Trial

Background—Skeletal muscle strength, velocity, and power are markedly reduced in patients with heart failure, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially because of decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3−) would increase NO production and improve muscle function in patients with heart failure because of systolic dysfunction. Methods and Results—Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3− in 9 patients with heart failure. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol of NO3−. Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3− increased (P<0.05–0.001) breath NO by 35% to 50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the 2 highest movement velocities tested (ie, 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (ie, 4.74±0.41 versus 4.20±0.33 W/kg; P<0.05) after dietary NO3− intake. Calculated maximal velocity of knee extension was also higher after NO3− ingestion (ie, 12.48±0.95 versus 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred. Conclusions—In this pilot study, acute dietary NO3− intake was well tolerated and enhanced NO bioavailability and muscle power in patients with systolic heart failure. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356.

Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart FailureCLINICAL PERSPECTIVE

Background—Skeletal muscle strength, velocity, and power are markedly reduced in patients with heart failure, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially because of decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3−) would increase NO production and improve muscle function in patients with heart failure because of systolic dysfunction. Methods and Results—Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3− in 9 patients with heart failure. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol of NO3−. Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3− increased (P<0.05–0.001) breath NO by 35% to 50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the 2 highest movement velocities tested (ie, 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (ie, 4.74±0.41 versus 4.20±0.33 W/kg; P<0.05) after dietary NO3− intake. Calculated maximal velocity of knee extension was also higher after NO3− ingestion (ie, 12.48±0.95 versus 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred. Conclusions—In this pilot study, acute dietary NO3− intake was well tolerated and enhanced NO bioavailability and muscle power in patients with systolic heart failure. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356.

A ''PET'' area of interest: myocardial metabolism in human systolic heart failure

Myocardial substrate metabolism provides the energy needed for cardiac contraction and relaxation. The normal adult heart uses predominantly fatty acids (FAs) as its primary fuel source. However, the heart can switch and use glucose (and to a lesser extent, ketones, lactate, as well as endogenous triglycerides and glycogen), depending on the metabolic milieu and superimposed conditions. FAs are not a wholly better fuel than glucose, but they do provide more energy per mole than glucose. Conversely, glucose is the more oxygen-efficient fuel. Studies in animal models of heart failure (HF) fairly consistently demonstrate a shift away from myocardial fatty acid metabolism and toward glucose metabolism. Studies in humans are less consistent. Some show the same metabolic switch away from FA metabolism but not all. This may be due to differences in the etiology of HF, sex-related differences, or other mitigating factors. For example, obesity, insulin resistance, and diabetes are all related to an increased risk of HF and may complicate or contribute to its development. However, these conditions are associated with increased FA metabolism. This review will discuss aspects of human heart metabolism in systolic dysfunction as measured by the noninvasive, quantitative method—positron emission tomography. Continued research in this area is vital if we are to ameliorate HF by manipulating heart metabolism with the aim of increasing energy production and/or efficiency.

Imaging of Inflammation in Unexplained Cardiomyopathy

Myocarditis is a recognized but underdiagnosed cause of cardiomyopathy due to its wide clinical spectrum and nonspecific presentation. Accurate diagnosis is important because 25% of patients with acute myocarditis develop cardiomyopathy, and of those, approximately 5% per year require heart transplantation or die. Current guidelines for the recognition and treatment of the inflammatory cardiomyopathies are limited. The gold standard for diagnosis, endomyocardial biopsy, has low sensitivity, and thus, multimodality imaging of inflammation plays a crucial role in defining the cardiac abnormalities and in assisting with diagnosis and management. The literature on inflammatory cardiomyopathies is limited to small studies of selected populations due to the diverse etiologies and inherent difficulties in definitive diagnosis. This review focuses on the current and projected use of various imaging modalities, including echocardiography, cardiac magnetic resonance, and nuclear imaging to better define inflammatory cardiomyopathies and aid in their management; it specifically focuses on cardiac sarcoidosis, and giant cell, eosinophilic, and lymphocytic myocarditis.

Dietary Nitrate Increases VO2peak and Performance but Does Not Alter Ventilation or Efficiency in Patients With Heart Failure With Reduced Ejection Fraction

BACKGROUND Patients with heart failure with reduced ejection fraction (HFrEF) exhibit lower efficiency, dyspnea, and diminished peak oxygen uptake (VO2peak) during exercise. Dietary nitrate (NO3-), a source of nitric oxide (NO), has improved these measures in some studies of other populations. We determined the effects of acute NO3- ingestion on exercise responses in 8 patients with HFrEF using a randomized, double-blind, placebo-controlled, crossover design. METHODS AND RESULTS Plasma NO3-, nitrite (NO2-), and breath NO were measured at multiple time points and respiratory gas exchange was determined during exercise after ingestion of beetroot juice containing or devoid of 11.2 mmol of NO3-. NO3- intake increased (P < .05-0.001) plasma NO3- and NO2- and breath NO by 1469 ± 245%, 105 ± 34%, and 60 ± 18%, respectively. Efficiency and ventilation during exercise were unchanged. However, NO3- ingestion increased (P < .05) VO2peak by 8 ± 2% (ie, from 21.4 ± 2.1 to 23.0 ± 2.3 mL.min-1.kg-1). Time to fatigue improved (P < .05) by 7 ± 3 % (ie, from 582 ± 84 to 612 ± 81 seconds). CONCLUSIONS Acute dietary NO3- intake increases VO2peak and performance in patients with HFrEF. These data, in conjunction with our recent data demonstrating that dietary NO3- also improves muscle contractile function, suggest that dietary NO3- supplementation may be a valuable means of enhancing exercise capacity in this population.

Dietary nitrate-induced increases in human muscle power: High versus low responders

Maximal neuromuscular power is an important determinant of athletic performance and also quality of life, independence, and perhaps even mortality in patient populations. We have shown that dietary nitrate (NO3−), a source of nitric oxide (NO), improves muscle power in some, but not all, subjects. The present investigation was designed to identify factors contributing to this interindividual variability. Healthy men (n = 13) and women (n = 7) 22–79 year of age and weighing 52.1–114.9 kg were studied using a randomized, double‐blind, placebo‐controlled, crossover design. Subjects were tested 2 h after ingesting beetroot juice (BRJ) either containing or devoid of 12.3 ± 0.8 mmol of NO3−. Plasma NO3− and nitrite (NO2−) were measured as indicators of NO bioavailability and maximal knee extensor speed (Vmax), power (Pmax), and fatigability were determined via isokinetic dynamometry. On average, dietary NO3− increased (P < 0.05) Pmax by 4.4 ± 8.1%. Individual changes, however, ranged from −9.6 to +26.8%. This interindividual variability was not significantly correlated with age, body mass (inverse of NO3− dose per kg), body mass index (surrogate for body composition) or placebo trial Vmax or fatigue index (in vivo indicators of muscle fiber type distribution). In contrast, the relative increase in Pmax was significantly correlated (r = 0.60; P < 0.01) with the relative increase in plasma NO2− concentration. In multivariable analysis female sex also tended (P = 0.08) to be associated with a greater increase in Pmax. We conclude that the magnitude of the dietary NO3−‐induced increase in muscle power is dependent upon the magnitude of the resulting increase in plasma NO2− and possibly female sex.

A Paradox between LV Mass Regression and Hemodynamic Improvement after Surgical and Transcatheter Aortic Valve Replacement

ABSTRACT Background: Surgical aortic valve replacement (SAVR) results in higher AV gradients than transcatheter AVR (TAVR), yet calculated left ventricular (LV) mass regresses faster and greater after SAVR vs. TAVR. We examined why LV mass regression is greater after SAVR. Methods: Serial echocardiographic studies of high-risk patients with severe aortic stenosis (AS) randomized to SAVR vs. TAVR with the CoreValve bioprosthesis were analyzed by an echocardiographic core laboratory blinded to treatment and outcomes. Measurements followed established guidelines and LV mass was calculated using the formula of Devereux and colleagues. Results: Echo data were available in 389 TAVR and 353 SAVR patients, whose baseline LVEDD, PWT, SWT, LV mass, and stroke volume (SV) as well as AS severity were similar. At discharge after SAVR, LV mass reduction was significant (227.45 ± 65.02 to 215.08 ± 59.02 g [p = 0.002]) due to decreased LVEDD (5.01 ± 0.64 to 4.81 ± 0.65 cm [p < 0.001]) associated with reduced SV (72.6 ± 27.0 mL to 58.9 ± 21.1 mL (p = 0.015]). PWT and SWT were unchanged. However, after TAVR, all these variables remained similar. At 1 year, LV mass, SV and LVEDD remained smaller following SAVR vs. TAVR. There was a trend toward higher 30-day mortality in patients with greater LV mass reduction in SAVR (4.7% vs. 0.8 %; p = 0.058) which was not observed after TAVR. Conclusion: The greater reduction in LV mass calculated after SAVR vs. TAVR is due to a smaller postoperative LVEDD and is associated with significantly reduced SV. There was a tendency for increased 30-day mortality associated with greater reduction in calculated LV mass after SAVR.

Anomalous papillary muscle insertion in hypertrophic cardiomyopathy

Half of the patients with hypertrophic cardiomyopathy (HCM) have left ventricular outflow (LVOT) obstruction as a result of systolic anterior motion of the mitral valve. A 51-year-old man with HCM presented with exertional dyspnoea and syncope refractory to medical therapy found to have an LVOT gradient of 27 mmHg at …

Reply to “Moving Beyond Linear Formulas for Left Ventricular Mass in Aortic Valve Replacement”

We thank Moneghetti and colleagues for acknowledging positively our investigative result related to a potential pitfall of the linear echocardiography method for calculating left ventricular (LV) mass. The Devereux LV mass formula is the most widely used echocardiographic method to estimate LV mass and it has been a reliable predictor of cardiovascular outcomes in various populations. The formula was originally derived from the cube function of the LV end-diastolic dimension, posterior wall thickness, and interventricular septal thickness. The LV mass estimated from this formula was validated against the anatomically measured LV mass in 34 patients. The main point of our paper was to provide an explanation for the paradoxical finding of a greater and faster LV mass reduction in patients with severe aortic stenosis after surgical aortic valve replacement (SAVR) compared to after transcatheter AVR (TAVR) despite better hemodynamics with transcatheter aortic prostheses. In evaluating the echocardiographic parameters used to calculate LV mass in the CoreValve highrisk trial, we found that LV end-diastolic dimension became significantly smaller soon after SAVR, but not after TAVR, while both posterior and ventricular septal wall thickness decreased in both groups over time and to a similar extent. The smaller LV end-diastolic dimension after SAVR was responsible for the paradoxical faster and greater regression of the calculated LV mass. The reduced LV dimension after SAVR appeared to be related to reduced stroke volume after SAVR which did not occur after TAVR. There are several other echocardiographic methods to calculate LV mass. The Area-length method has also been well-validated against LV mass calculated by cardiac magnetic resonance imaging (MRI). The Area-length method uses LV cavity long-axis dimension and short-axis area. However, the Area-length method would also be falsely reduced if stroke volume decreases immediately after SAVR. There are several alternative means to compare LV mass regression after SAVR and TAVR. As suggested by Moneghetti and colleagues, 3D echocardiography or other imaging techniques such as cardiac computed tomography (CT) or cardiac MRI should provide more accurate LV mass calculations without being affected by acute changes in LV dimensions. We are currently conducting a prospective study to compare LV mass after SAVR and TAVR using cardiac CT, and hope to share our data soon.