Effects of Chronic Hypoxemia on Chemosensitivity in Patients With Univentricular Heart

AbstractObjectives. We sought to compare the arterial blood gas chemosensitivity in relation to exercise ventilatory response in patients with univentricular heart and cyanosis and in patients with univentricular heart and Fontan-type circulation without cyanosis.Background. Patients with univentricular heart demonstrate excessive ventilation during exercise. Chronic hypoxemia may alter chemoreceptor function, affecting ventilation.Methods. Cardiopulmonary exercise testing was performed in 10 patients with rest or stress-induced cyanosis (cyanotic group: mean age ± SE 30.5 ± 2.3 years; 5 men), 8 patients without cyanosis with Fontan-type circulation (Fontan group: mean age 29.4 ± 1.5 years; 4 men) and 10 healthy control subjects (normal group: mean age 30.7 ± 1.9 years; 5 men). Hypoxic and hypercapnic chemosensitivity were assessed by using transient inhalations of pure nitrogen and the rebreathing of 7% CO2in 93% O2, respectively.Results. Peak O2consumption was comparable in both patient groups (21.7 ± 2.5 [cyanotic group] vs. 21.0 ± 1.9 ml/kg per min [Fontan group]) but was lower than that in the normal group (34.7 ± 1.9 ml/kg per min). The ventilatory response to exercise, characterized by the regression slope relating minute ventilation to CO2output, was higher in the cyanotic group (43.4 ± 4.0) than in the Fontan group (31.4 ± 3.0, p = 0.02) and the normal group (23.1 ± 1.1). Hypoxic chemosensitivity was blunted in the cyanotic group compared with that in the Fontan and normal groups (0.148 vs. 0.448 [p = 0.02] vs. 0.311 liter/min per percent arterial O2saturation, respectively) and did not correlate with the ventilatory response to exercise (r = −0.36, p = 0.29). In contrast, hypercapnic chemosensitivity represented by the slope of the hypercapnic-ventilatory response line was similar in the cyanotic, Fontan and normal groups (1.71 vs. 1.76 vs. 1.70 liter/min per mm Hg, respectively), but the response line had shifted to the left in the cyanotic group (x intercept = 31.9 vs. 39.9 mm Hg [p = 0.026]), compared with 45.2 mm Hg in normal subjects. These findings suggest that in the cyanotic group, ventilation is greater for a given level of arterial CO2tension and thus may partly explain the increased exercise ventilatory response in this group.Conclusions. Hypoxic chemosensitivity is blunted in patients with univentricular heart and cyanosis and does not determine the exercise ventilatory response. CO2elimination appears more important. The blunting of hypoxic chemosensitivity is reversible once chronic hypoxemia is relieved, as evident in the Fontan group

Performance of prognostic risk scores in chronic heart failure patients enrolled in the European Society of Cardiology Heart Failure long-term registry

[Abstract] Objectives. This study compared the performance of major heart failure (HF) risk models in predicting mortality and examined their utilization using data from a contemporary multinational registry. Background. Several prognostic risk scores have been developed for ambulatory HF patients, but their precision is still inadequate and their use limited. Methods. This registry enrolled patients with HF seen in participating European centers between May 2011 and April 2013. The following scores designed to estimate 1- to 2-year all-cause mortality were calculated in each participant: CHARM (Candesartan in Heart Failure-Assessment of Reduction in Mortality), GISSI-HF (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico-Heart Failure), MAGGIC (Meta-analysis Global Group in Chronic Heart Failure), and SHFM (Seattle Heart Failure Model). Patients with hospitalized HF (n = 6,920) and ambulatory HF patients missing any variable needed to estimate each score (n = 3,267) were excluded, leaving a final sample of 6,161 patients. Results. At 1-year follow-up, 5,653 of 6,161 patients (91.8%) were alive. The observed-to-predicted survival ratios (CHARM: 1.10, GISSI-HF: 1.08, MAGGIC: 1.03, and SHFM: 0.98) suggested some overestimation of mortality by all scores except the SHFM. Overprediction occurred steadily across levels of risk using both the CHARM and the GISSI-HF, whereas the SHFM underpredicted mortality in all risk groups except the highest. The MAGGIC showed the best overall accuracy (area under the curve [AUC] = 0.743), similar to the GISSI-HF (AUC = 0.739; p = 0.419) but better than the CHARM (AUC = 0.729; p = 0.068) and particularly better than the SHFM (AUC = 0.714; p = 0.018). Less than 1% of patients received a prognostic estimate from their enrolling physician. Conclusions. Performance of prognostic risk scores is still limited and physicians are reluctant to use them in daily practice. The need for contemporary, more precise prognostic tools should be considered

Clinical Correlates and Prognostic Significance of the Ventilatory Response to Exercise in Chronic Heart Failure

AbstractObjectives. This study sought to investigate the clinical characteristics of patients with chronic heart failure and an increased ventilatory response to exercise and to examine the prognostic usefulness of this response.Background. The ventilatory response to exercise is increased in many patients with chronic heart failure and may be characterized by the regression slope relating minute ventilation to carbon dioxide output (V̇e–V̇co2slope) during exercise.Methods. One hundred seventy-three consecutive patients (155 men; mean [±SD] age 59.8 ± 11.5 years; radionuclide left ventricular ejection fraction [LVEF] 28.4 ± 14.6%) underwent cardiopulmonary exercise testing (peak oxygen consumption 18.5 ± 7.3 ml/kg per min; V̇e–V̇co2slope 34.8 ± 10.6) over a 2-year period. Using 1.96 standard deviations above the mean V̇e–V̇co2slope of 68 healthy age-matched subjects (mean slope 26.3 ± 4.1), we defined a high ventilatory response to exercise as a slope >34.Results. Eighty-three patients (48%) had an increased V̇e–V̇co2slope (mean 43.1 ± 8.9). There was a difference in age (62.2 vs. 57.3 years, p = 0.005), New York Heart Association functional class (2.9 vs. 2.1, p < 0.001), LVEF (24.7 vs. 31.9%, p = 0.0016), peak oxygen consumption (14.9 vs. 21.7 ml/kg per min, p < 0.0001) and radiographic cardiothoracic ratio (0.58 vs. 0.55, p = 0.002) between these patients and those with a normal slope. In the univariate Cox proportional hazards model, the V̇e–V̇co2slope was an important prognostic factor (p < 0.0001). In the multivariate Cox analyses using several variables (age, peak oxygen consumption, V̇e–V̇co2slope and LVEF), the V̇e–V̇co2slope gave additional prognostic information (p = 0.018) beyond peak oxygen consumption (p = 0.022). Kaplan-Meier survival curves at 18 months demonstrated a survival rate of 95% in patients with a normal V̇e–V̇co2slope compared with 69% in those with a high slope (p < 0.0001).Conclusions. A high V̇e–V̇co2slope selects patients with more severe heart failure and is an independent prognostic marker. The V̇e–V̇co2slope may be used as a supplementary index in the assessment of patients with chronic heart failure.(J Am Coll Cardiol 1997;29:1585–90

The incidence of all-cause, cardiovascular and respiratory disease admission among 20,252 users of lisinopril vs. perindopril: a cohort study

Background: Major international guidelines do not offer explicit recommendations on any specific angiotensin-converting enzyme inhibitor (ACEI) agent over another within the same drug group. This study compared the effectiveness of lisinopril vs. perindopril in reducing the incidence of hospital admission due to all-cause, cardiovascular disease and respiratory disease. Methods: Adult patients who received new prescriptions of lisinopril or perindopril from 2001 to 2005 in all public hospitals and clinics in Hong Kong were included, and followed up for ≥2 years. The incidence of admissions due to all-cause, cardiovascular disease and respiratory disease were evaluated, respectively, by using Cox proportional hazard regression models. The regression models were constructed with propensity score matching to minimize indication biases. Results: A total of 20,252 eligible patients with an average age of 64.5 years (standard deviation 15.0) were included. The admission rate at 24 months within the date of index prescription due to any cause, cardiovascular disease and respiratory disease among lisinopril vs. perindopril users was 24.8% vs. 24.8%, 13.7% vs. 14.0% and 6.9% vs. 6.3%, respectively. Lisinopril users were significantly more likely to be admitted due to respiratory diseases (adjusted hazard ratios [AHR] = 1.25, 95% CI 1.08 to 1.43, p = 0.002 at 12 months; AHR = 1.17, 95% CI 1.04 to 1.31, p = 0.009 at 24 months) and all causes (AHR = 1.12, 95% CI 1.05 to 1.19, p &lt; 0.001 at 24 months) than perindopril users. Conclusions: These findings support intra-class differences in the effectiveness of ACEIs, which could be considered by clinical guidelines when the preferred first-line antihypertensive drugs are recommended

Advanced cancer is also a heart failure syndrome: a hypothesis

We present the hypothesis that advanced stage cancer is also a heart failure syndrome. It can develop independently of or in addition to cardiotoxic effects of anti-cancer therapies. This includes an increased risk of ventricular arrhythmias. We suggest the pathophysiologic link for these developments includes generalized muscle wasting (i.e. sarcopenia) due to tissue homeostasis changes leading to cardiac wasting associated cardiomyopathy. Cardiac wasting with thinning of the ventricular wall increases ventricular wall stress, even in the absence of ventricular dilatation. In addition, arrhythmias may be facilitated by cellular wasting processes affecting structure and function of electrical cells and conduction pathways. We submit that in some patients with advanced cancer (but not terminal cancer), heart failure therapy or defibrillators may be relevant treatment options. The key points in selecting patients for such therapies may be the predicted life expectancy, quality of life at intervention time, symptomatic burden, and consequences for further anti-cancer therapies. The cause of death in advanced cancer is difficult to ascertain and consensus on event definitions in cancer is not established yet. Clinical investigations on this are called for. Broader ethical considerations must be taken into account when aiming to target cardiovascular problems in cancer patients. We suggest that focused attention to evaluating cardiac wasting and arrhythmias in cancer will herald a further evolution in the rapidly expanding field of cardio-oncology

Percutaneous Mitral Valve Annuloplasty in Patients With Secondary Mitral Regurgitation and Severe Left Ventricular Enlargement.

This study sought to determine the effect of percutaneous mitral valve annuloplasty with the Carillon device versus guideline-directed medical therapy (GDMT) alone in patients with secondary mitral regurgitation (MR) and severe left ventricular (LV) enlargement.The clinical impact of the Carillon device in patients with severe LV dilation is not well established.This is a pooled analysis involving 3 prospective trials (TITAN [Transcatheter Implantation of Carillon Mitral Annuloplasty Device], TITAN II, and REDUCE FMR [CARILLON Mitral Contour System for Reducing Functional Mitral Regurgitation] trials) in which patients with functional MR and severe LV enlargement (LV end-diastolic diameter65 mm) were treated with GDMT and the Carillon device versus GDMT alone. Key outcomes of this analysis were changes over 1 year of follow-up in mitral valve and LV echocardiographic parameters, functional outcome, quality of life, mortality, and heart failure hospitalization (HFH).A total of 95 patients (67 in the Carillon group, 28 in the GDMT group) with severe LV enlargement were included. In the Carillon group, all mitral valve and LV morphology parameters were significantly improved at 1 year. Regurgitant volume decreased by 12 ml (p 0.001), MR grade decreased by 0.6 U (p 0.001), LV end-diastolic volume decreased by 25 cmIn patients with functional MR and severe LV enlargement, the Carillon device improved mitral valve function, LV morphology, and functional outcome compared with patients receiving GDMT only. Preoperative LV dimension should not be a limiting factor when evaluating patient eligibility or anticipated response to therapy with the Carillon device

Circulating heart failure biomarkers beyond natriuretic peptides:review from the Biomarker Study Group of the Heart Failure Association (HFA), European Society of Cardiology (ESC)

New biomarkers are being evaluated for their ability to advance the management of patients with heart failure. Despite a large pool of interesting candidate biomarkers, besides natriuretic peptides virtually none have succeeded in being applied into the clinical setting. In this review, we examine the most promising emerging candidates for clinical assessment and management of patients with heart failure. We discuss high-sensitivity cardiac troponins (Tn), procalcitonin, novel kidney markers, soluble suppression of tumorigenicity 2 (sST2), galectin-3, growth differentiation factor-15 (GDF-15), cluster of differentiation 146 (CD146), neprilysin, adrenomedullin (ADM), and also discuss proteomics and genetic-based risk scores. We focused on guidance and assistance with daily clinical care decision-making. For each biomarker, analytical considerations are discussed, as well as performance regarding diagnosis and prognosis. Furthermore, we discuss potential implementation in clinical algorithms and in ongoing clinical trials.</p