Sex Differences in Heart Failure

Heart failure (HF) continues to be a major contributor of morbidity and mortality for men and women alike, yet how the predisposition for, course and management of HF differ between men and women remains underexplored. Sex differences in traditional risk factors as well as sex-specific risk factors influence the prevalence and manifestation of HF in unique ways. The pathophysiology of HF differs between men and women and may explain sex-specific differences in clinical presentation and diagnosis. This in turn, contributes to variation in response to both pharmacologic and device/surgical therapy. This review examines sex-specific differences in HF spanning prevalence, risk factors, pathophysiology, presentation, and therapies with a specific focus on highlighting gaps in knowledge with calls to action for future research efforts.     

Changes in Cardiopulmonary Exercise Testing Parameters Following Continuous Flow Left Ventricular Assist Device Implantation and Heart Transplantation

BackgroundReduced exercise tolerance from impaired cardiac output is an important criterion for left ventricular assist device (LVAD) implantation. However, little is known about how exercise capacity changes after LVAD and how changes compare with patients undergoing heart transplantation.Methods and ResultsWe compared changes in cardiopulmonary exercise testing performed pre- and postoperatively in patients who underwent HeartMate II LVAD implantation (n = 25) and heart transplantation (n = 74) at the Mayo Clinic in Rochester, Minnesota, between 2007 and 2012. Preoperatively, patients undergoing LVAD and transplant had markedly reduced exercise time (mean 5.1 minutes [45% predicted] and 5.0 minutes [44% predicted], respectively), low peak oxygen consumption (VO₂; mean 11.5 mL·kg·min [43% predicted] and 11.9 mL·kg·min [38% predicted]), and abnormal ventilatory gas exchange (ratio of minute ventilation to carbon dioxide production [VE/VCO₂] nadir 39.4 and 37.4). After LVAD and transplant, there were similar improvements in exercise time (mean Δ +1.2 vs. 1.7 minutes, respectively, P = .27) and VE/VCO₂ nadir (mean Δ −3.7 vs. −4.2, P = .74). However, peak VO₂ increased posttransplant but did not change post-LVAD (mean Δ +5.4 vs. +0.9 mL·kg·min, respectively, P < .001). Most patients (72%) had a peak VO₂ < 14 mL·kg·min post-LVAD.ConclusionsAlthough improvements in exercise capacity and gas exchange are seen after LVAD and heart transplant, peak VO₂ doesn't improve post-LVAD and remains markedly abnormal in most patients.     

心肺运动试验评估慢性左心衰竭患者的运动能力

目的:应用心肺运动试验(CPET)评估国人慢性左心衰竭患者的运动能力.方法:入选2010-08至2010-12期间入住本中心的慢性左心衰竭患者20例(心衰组),并选择27例心肺功能正常的匹配人群作为对照组,均进行CPET,同时收集两组人群的临床资料和常规检查结果.结果:运动过程中,心衰组较对照组峰值心率、峰值收缩压、无氧域、峰值氧摄取量、峰值氧摄取量占预计值的百分比(峰值VO2/Pred.)、峰值氧脉搏等指标均显著降低(P<0.001或<0.05),而二氧化碳通气当量(VE/VCO2)斜率显著升高(P<0.01),差异均有统计学意义.校正年龄、性别、体重指数后,偏相关分析结果提示氨基末端B型脑钠肽原(NT-proBNP)仍与VE/VCO2斜率相关性最高(r=0.685,P<0.001);左心室射血分数与峰值氧摄取量相关性最高(r=0.679,P<0.001);峰值心率与峰值VO2/Pred.相关性最高(r=0.791,P<0.001);峰值收缩压与峰值氧摄取量相关性最高(r=0.677,P<0.001);而且,用力肺活量、一秒量均与峰值氧摄取量相关性最高(分别为r=0.559,P<0.001和r=0.589,P<0.001).结论:CPET可以客观、定量地评价慢性左心衰竭患者的运动能力.     

Cardiopulmonary Exercise Testing Identifies Low Risk Patients With Heart Failure and Severely Impaired Exercise Capacity Considered for Heart Transplantation

Objectives. The 3-year survival rates of 500 patients with congestive heart failure (CHF) referred for heart transplantation were assessed to evaluate the clinical and exercise variables most useful for estimating prognostic risk.Background. Detailed prognostic risk stratification of patients with a peak exercise oxygen consumption (Vo₂) 14 ml/min per kg to identify lower risk patient subsets has been limited in earlier series by relatively small sample size.Methods. Cardiopulmonary exercise testing was performed in 500 patients with CHF referred for heart transplantation; 154 (31%) had a peak exercise Vo₂≤14 ml/min per kg. Univariate and multivariate analyses were performed to identify the 3-year prognostic risk.Results. The 55% 3-year survival rate of the 77 patients with a peak exercise Vo₂≤14 ml/min per kg unable to reach a peak exercise systolic blood pressure (SBP) of 120 mm Hg was significantly lower than the 83% survival rate in the 74 patients able to reach this exercise blood pressure (p = 0.004). Multivariate analysis revealed that peak exercise SBP (p = 0.0005) and percent predicted peak Vo₂≤50% (p = 0.04) were the two most important predictors for the combined end point of death or listing as Status 1.Conclusions. Peak exercise SBP and percent predicted peak exercise Vo₂are two inexpensive and easily measured noninvasive variables that can be used to further prognostically risk stratify ambulatory patients with CHF referred for heart transplantation with a peak exercise Vo₂≤14 ml/min per kg.     

Sex Differences in the Management of Advanced Heart Failure

Purpose of review

Heart failure (HF) is prevalent among women and remains a leading cause of morbidity and mortality in the United States. Currently, 3 million women live with HF and the prevalence is projected to continue to increase. The purpose of this review is to highlight sex differences in the use and response to evidence-based pharmacological, device, and advanced HF therapies, as well as explore emerging areas of research in sex differences in the treatment of HF.

Recent findings

Under-representation of women in clinical HF trials has limited our understanding of sex-related differences in the treatment and outcomes of HF.

Summary

Important sex differences exist in the use of evidence-based HF therapies and clinical response among women with HF. In general, women tend to obtain the same clinical benefit from evidence-based HF drug and device therapies, but the utilization rates of guideline-directed medical therapies remain poor compared to men. Future research efforts should focus on increasing the enrollment of women in HF trials to help gain helpful insight into sex-specific differences in treatment effects and subsequent clinical outcomes.

     

慢性心力衰竭患者Tei指数与心肺运动耐量的相关性研究

<正>日本学者Tei于1995年提出了一种无创综合评价心脏整体收缩和舒张功能的超声检查指标-Tei指数(亦称心肌工作指数),此参数不受心脏几何形态及心脏瓣膜返流等因素的影响[1]。本文分析了Tei指数与心肺运动耐量指标(6分钟步行距离及运动峰耗氧量等指数)的相关性,同时进一步探讨了Tei指数对慢性心力衰竭患者心肺运动耐量的预测价值。     

Cardiopulmonary and Noninvasive Hemodynamic Responses to Exercise Predict Outcomes in Heart Failure

BackgroundAn impaired cardiac output response to exercise is a hallmark of chronic heart failure (HF). We determined the extent to which noninvasive estimates of cardiac hemodynamics during exercise in combination with cardiopulmonary exercise test (CPX) responses improved the estimation of risk for adverse events in patients with HF.Methods and ResultsCPX and impedance cardiography were performed in 639 consecutive patients (mean age 48 ± 14 years), evaluated for HF. Clinical, hemodynamic, and CPX variables were acquired at baseline and subjects were followed for a mean of 460 ± 332 days. Patients were followed for the composite outcome of cardiac-related death, hospitalization for worsening HF, cardiac transplantation, and left ventricular assist device implantation. Cox proportional hazards analyses including clinical, noninvasive hemodynamic, and CPX variables were performed to determine their association with the composite endpoint. There were 113 events. Among CPX variables, peak oxygen uptake (VO₂) and the minute ventilation (VE)/carbon dioxide production (VCO₂) slope were significant predictors of risk for adverse events (age-adjusted hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.05–1.11 for both; P < .001). Among hemodynamic variables, peak cardiac index was the strongest predictor of risk (HR 1.08, 95% CI 1.0–1.16; P = .01). In a multivariate analysis including CPX and noninvasively determined hemodynamic variables, the most powerful predictive model included the combination of peak VO₂, peak cardiac index, and the VE/VCO₂ slope, with each contributing significantly and independently to predicting risk; an abnormal response for all 3 yielded an HR of 5.1 (P < .001).ConclusionsThese findings suggest that noninvasive indices of cardiac hemodynamics complement established CPX measures in quantifying risk in patients with HF.     

Cardiopulmonary Exercise Test in Chronic Heart Failure: Beyond Peak Oxygen Consumption

Patients with cardiovascular diseases commonly present with exercise intolerance, clinically manifest as shortness of breath and fatigue, and these symptoms have important prognostic implications. Cardiopulmonary exercise testing is a well-established method for evaluation of cardiopulmonary diseases. It provides an objective assessment of maximal aerobic capacity (peak VO₂), estimates prognosis, and allows the physician to discriminate among many subtle and often overlapping etiologies. This review focuses on the evaluation of important exercise parameters, in addition to the peak VO₂, during cardiopulmonary exercise testing.     

Recovery of Heart Rate Variability and Ventricular Repolarization Indices Following Exercise

Background: There is a heightened risk of sudden cardiac death related to exercise and the postexercise recovery period, but the precise mechanism is unknown. We have demonstrated that sympathoexcitation persists for ≥45 minutes after exercise in normals and subjects with coronary artery disease (CAD). The purpose of this study is to determine whether this persistent sympathoexcitation is associated with persistent heart rate variability (HRV) and ventricular repolarization changes in the postexercise recovery period. Methods and Results: Twenty control subjects (age 50.7 ± 1.4 years), 68 subjects (age 58.2 ± 1.5 years) with CAD and preserved left ventricular ejection fraction (LVEF), and 18 subjects (age 57.6 ± 2.4 years) with CAD and depressed LVEF underwent a 16‐minute submaximal bicycle exercise protocol with continuous ECG monitoring. QT and RR intervals were measured in recovery to calculate the time dependent corrected QT intervals (QTc), the QT–RR relationship, and HRV. QTc was dependent on the choice of rate correction formula. There were no differences in QT–RR slopes among the three groups in early recovery. HRV recovered quickly in controls, more slowly in those with CAD‐preserved LVEF, and to a lesser extent in those with CAD‐depressed LVEF. Conclusion: Despite persistent sympathoexcitation for the 45‐minute recovery period, ventricular repolarization changes do not persist for that long and HRV changes differ by group. Additional understanding of the dynamic changes in cardiac parameters after exercise is needed to explore the mechanism of increased sudden cardiac death risk at this time.     

Cardiopulmonary Response to Exercise at High Altitude in Adolescents with Congenital Heart Disease

Objective: To extend our knowledge on tolerance of acute high-altitude exposure and hemodynamic response to exercise in adolescents with congenital heart disease (AscCHD) without meaningful clinical or functional restriction. Methods: A symptom limited cardiopulmonary exercise stress test and a non-invasive cardiac output measurement during steady state exercise were performed at 540 m and at 3454 m a.s.l. Symptoms of acute mountain sickness were noted. Results: We recruited 21 healthy controls and 16 AscCHD (59% male, mean age 14.7 ± 1.1 years). Three subjects (2 controls, 1 AscCHD) presented light symptoms of acute mountain sickness (dizziness and headache). During the symptom limited exercise test at lowland, control subjects showed a significantly higher power to weight index (3.5 ± 0.6 W/kg vs. 3.0 ± 0.7 W/kg, p < 0.001), heart rate (188.8 ± 10.4 1/min vs. 179.4 ± 13.1 1/min, p < 0.050) and ventilation (92.8 ± 22.9 l/min vs. 75.4 ± 18.6 l/min, <0.050). At altitude, power to weight index only remained significantly higher in the control group (2.8 ± 0.6 W/kg vs. 2.6 ± 0.6 W/kg, p < 0.001). Pulmonary blood flow (PBF) at lowland showed no difference between the control and the AscCHD group, neither at rest (5.4 ± 0.8 l/min vs. 5.1 ± 0.9 l/min, p = 0.308), nor during the steady state test (10.6 ± 2.4 l/min vs. 10.5 ± 2.0 l/min, p = 0.825). At high altitude, PBF increased by 110% and 112%, respectively (12.8 ± 2.32 l/min vs. 12.5 ± 3.0 l/min; intergroup difference: p = 0.986). Conclusions: High altitude exposure was well tolerated in an unselected group of AscCHD. No significant difference in the cardio-pulmonary adaptation to a control group was noted during a steady state exercise. Symptoms of minor acute mountain sickness did occur, which should however not be misinterpreted as signs of hemodynamic maladaptation.     

Improved Cardiac Performance during Exercise Following Hydralazine Treatment in Chronic Heart Failure

Abstract Nine male patients with stable chronic heart failure of different etiology and optimally treated with digoxine and diuretics were given hydralazine. 50 mg b.i.d., during three months. Hemodynamic parameters were evaluated during upright submaximal exercise. An increase in cardiac index due to an increased stroke volume was noted following the first dose of hydralazine. After three months' treatment, cardiac index was further increased. The arteriovenous oxygen difference was initially unchanged, but significantly decreased following long-term treatment. These findings may indicate different effects of hydralazine acutely and after long-term treatment. It is suggested that the initial increase in blood flow is directed mainly to regions other than the exercising muscles, while more blood is directed to the muscles after long-term treatment. A possible mechanism to explain this postulated difference is discussed.