Losartan improves heart rate variability and heart rate turbulence in heart failure due to ischemic cardiomyopathy

BackgroundHeart rate variability (HRV) and heart rate turbulence are known to be disturbed and associated with excess mortality in heart failure. The aim of this study was to investigate whether losartan, when added on top of β-blocker and angiotensin-converting enzyme inhibitor (ACEI) therapy, could improve these indices in patients with systolic heart failure.Methods and ResultsSeventy-seven patients (mean age 60.4 ± 8.0, 80.5% male) with ischemic cardiomyopathy (mean ejection fraction 34.5 ± 4.4%) and New York Heart Association Class II-III heart failure symptoms, already receiving a β-blocker and an ACEI, were randomly assigned to either open-label losartan (losartan group) or no additional drug (control group) in a 2:1 ratio and the patients were followed for 12 weeks. The HRV and heart rate turbulence indices were calculated from 24-hour Holter recordings both at the beginning and at the end of follow-up. The baseline clinical characteristics, HRV, and heart rate turbulence indices were similar in the 2 groups. At 12 weeks of follow-up, all HRV parameters except pNN50 increased (SDNN: 113.2 ± 34.2 versus 127.8 ± 24.1, P = .001; SDANN: 101.5 ± 31.7 versus 115.2 ± 22.0, P = .001; triangular index: 29.9 ± 11.1 versus 34.2 ± 7.9, P = .008; RMSSD: 29.1 ± 20.2 versus 34.3 ± 23.0, P = .009; NN50: 5015.3 ± 5554.9 versus 6446.7 ± 6101.1, P = .024; NN50: 5.65 ± 6.41 versus 7.24 ± 6.99, P = .089; SDNNi: 45.1 ± 13.3 versus 50.3 ± 14.5, P = .004), turbulence onset decreased (−0. 61 ± 1.70 versus −1.24 ± 1.31, P = .003) and turbulence slope increased (4.107 ± 3.881 versus 5.940 ± 4.281, P = .004) significantly in the losartan group as compared with controls.ConclusionsA 12-week-long losartan therapy significantly improved HRV and heart rate turbulence in patients with Class II-III heart failure and ischemic cardiomyopathy already on β-blockers and ACEI.     

Ultrafiltration is Associated With Fewer Rehospitalizations than Continuous Diuretic Infusion in Patients With Decompensated Heart Failure: Results From UNLOAD

BackgroundCompare outcomes of ultrafiltration (UF) versus standard intravenous (IV) diuretics by continuous infusion or bolus injection in volume overloaded heart failure (HF) patients. In the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated heart Failure (UNLOAD) study, UF produced greater fluid reduction and fewer HF rehospitalizations than IV diuretics in 200 hospitalized HF patients. Outcomes may be due to greater fluid removal, but UF removes more sodium/unit volume than diuretics.Methods and ResultsOutcomes of 100 patients randomized to UF were compared with those of patients randomized to standard IV diuretic therapy with continuous infusion (32) or bolus injections (68). Choice of diuretic therapy was by the treating physician. Forty-eight hour weight loss (kg): 5.0 ± 3.1 UF, 3.6 ± 3.5 continuous infusion, and 2.9 ± 3.5 bolus diuretics (P = .001 UF versus bolus diuretic; P > .05 for the other comparisons). Net fluid loss (L): 4.6 ± 2.6 UF, 3.9 ± 2.7 continuous infusion, and 3.1 ± 2.6 bolus diuretics (P < .001 UF versus bolus diuretic; P > .05 for the other comparisons). At 90 days, rehospitalizations plus unscheduled visits for HF/patient (rehospitalization equivalents) were fewer in UF group (0.65 ± 1.36) than in continuous infusion (2.29 ± 3.23; P = .016 versus UF) and bolus diuretics (1.31 ± 1.87; P = .050 versus UF) groups. No serum creatinine differences occurred between groups up to 90 days.ConclusionsDespite similar fluid loss with UF and continuous diuretic infusion, fewer HF rehospitalizations equivalents occurred only with UF. Removal of isotonic fluid by UF compared with hypotonic urine by diuretics more effectively reduces total body sodium in congested HF patients.     

Difficulty taking medications, depression, and health status in heart failure patients

BackgroundLittle is known about medication nonadherence in heart failure populations. We evaluated the association between 1 aspect of medication nonadherence, patient-reported difficulty taking medications as directed, and health status among heart failure outpatients, and then examined whether this association was explained by depression.Methods and ResultsA total of 522 outpatients with left ventricular ejection fraction <0.40 completed clinical evaluation, Kansas City Cardiomyopathy Questionnaire (KCCQ), Medical Outcomes Study-Depression questionnaire, and categorized their difficulty taking medications (5-level Likert-scale question). Multivariable regression was used to evaluate the cross-sectional association between difficulty taking medications and health status, with incremental adjustment for medical history and depressive symptoms. Patients with difficulty taking medications (n = 64; 12.2%) had worse health status (8.2 ± 2.7 point lower mean KCCQ summary scores; P = .008) and more depressive symptoms (43.8% versus 27.1%; P = .006). Adjusting for demographic and clinical factors had little effect on the association between difficulty taking medications and health status (8.0 ± 3.2 point lower KCCQ scores; P = .01); however, the relationship was attenuated with adjustment for depressive symptoms (4.7 ± 2.9 point lower KCCQ scores; P = .11).ConclusionsAmong heart failure outpatients, difficulty taking medications is associated with worse health status. This association appears to be explained, in part, by coexistent depression. Future studies should evaluate interventions such as depression treatment to improve medication adherence and health status.     

Reduced Relative Lymphocyte Count in African-Americans With Decompensated Heart Failure

BackgroundA reduction in relative lymphocyte count (%L) has been reported in whites with heart failure that inversely correlated with jugular venous pressure thereby implicating systemic venous hypertension with splanchnic congestion.ObjectivesTo study whether a reduced %L (<20%) occurs in African-Americans (AA) with heart failure and to address pathophysiologic mechanisms having the potential to influence lymphocyte biology and survival, we monitored patients with or without systemic venous hypertension, hypoalbuminemia, hypovitaminosis D, and secondary hyperparathyroidism.MethodsIn 131 AA (90 men; 53 ± 12 years): 113 were hospitalized, 50 with decompensated biventricular failure (DecompHF), 24 with acute left heart failure, and 39 with heart disease, but no heart failure (HDNHF); and 18 were outpatients with compensated heart failure. At the time of admission or outpatient visit, we monitored: white blood cell count and %L; and serum albumin, 25(OH)D, and parathyroid hormone (PTH).ResultsWhite blood cell count did not differ among the groups, whereas %L was reduced only in those with DecompHF (15 ± 1%; P < 0.05) versus 25 ± 2% with left heart failure, 29 ± 1% in HDNHF, and 28 ± 3% in compensated heart failure. Serum albumin was reduced in DecompHF (2.8 ± 0.1; P < 0.05), but not in any of the other groups. Reduced 25(OH)D (<30 ng/mL), in keeping with hypovitaminosis D, was found in all AA, whereas elevated serum PTH (>65 pg/mL) was found only in those with DecompHF (123 ± 22 pg/mL).ConclusionsA relative lymphocytopenia, together with hypoalbuminemia and elevated PTH, were found only in hospitalized AA with DecompHF. These findings implicate splanchnic congestion and the enteric loss of lymphocytes and albumin with an associated secondary hyperparathyroidism.     

Enhanced inotropic state of the failing left ventricle by cardiac contractility modulation electrical signals is not associated with increased myocardial oxygen consumption

BackgroundPrevious studies in patients and in dogs with experimentally induced heart failure (HF) showed that electrical signals applied to the failing myocardium during the absolute refractory period improved left ventricular (LV) function. We examined the effects these same cardiac contractility modulating (CCM) electrical signals on myocardial oxygen consumption (MVO₂) in both patients and dogs with chronic HF.Methods and ResultsSix dogs with microembolizations-induced HF and 9 HF patients underwent CCM leads and generator (OPTIMIZER II) implantation. After baseline measurements, CCM signals were delivered continuously for 2 hours in dogs and for 30 minutes in patients. MVO₂ was measured before and after CCM therapy. In dogs, CCM therapy increased LV ejection fraction at 2 hours (26 ± 1 versus 31 ± 2 %, P = .001) without increasing MVO₂ (257 ± 41 versus 180 ± 34 μmol/min). In patients, CCM therapy increased LV peak +dP/dt by 10.1 ± 1.5 %. As with dogs, the increase in LV function after 30 minutes of CCM therapy was not associated with increased MVO₂ (13.6 ± 9.7 versus 12.5 ± 7.2 mL O₂/min).ConclusionsThe study results suggest that unlike cAMP-dependent positive inotropic drugs, the increase in LV function during CCM therapy is elicited without increasing MVO₂.     

Hypercholesterolemia exacerbates ventricular remodeling in the rat model of myocardial infarction

BackgroundDetrimental left ventricular (LV) remodeling is exacerbated in hypercholesterolemic patients with myocardial infarction; however, this could result from either larger infarcts or more extensive remodeling itself in this population. Therefore, we sought to investigate whether high cholesterol feeding exacerbates LV remodeling and heart failure in rats with myocardial infarction independently from its influence on infarct size.Methods and ResultsMyocardial infarction was induced by permanent ligation of left coronary artery in rats fed normal and high-cholesterol diet and the animals were followed for 8 weeks. Hypercholesterolemic rats were matched with normocholesterolemic animals for infarct size 24 hours after infarction and exhibited more pronounced LV dilation at 8 weeks after infarction (LV systolic/diastolic diameter 8.1 ± 0.2/10.2 ± 0.3 versus 6.7 ± 0.2/8.9 ± 0.2, respectively, measured by echocardiography, P < .05 each). Pressure-volume curves obtained in isolated Langendorff-perfused hearts revealed higher diastolic LV volumes (1677 ± 102 versus 1385 ± 46 μL/kg body weight, P < .05) and hemodynamic examination demonstrated higher LV end-diastolic pressure (21.8 ± 0.7 versus 18.7 ± 1.0 mm Hg, P < .05) in hypercholesterolemic rats compared with normocholesterolemic animals.ConclusionIn a rat model of myocardial infarction, LV remodeling and heart failure are more pronounced in rats fed high-cholesterol diet in comparison to animals fed normal chow. This effect is independent from effect of hypercholesterolemia on infarct size.     

Impact of atrial fibrillation in heart failure with normal ejection fraction: a clinical and echocardiographic study

BackgroundThe clinical significance of atrial fibrillation (AF) in heart failure with normal ejection fraction (HFNEF) remains undetermined.Methods and ResultsWe compared the clinical and echocardiographic characteristics among 238 patients hospitalized for HF. Using the cutoff of left ventricular EF of 50%, there were 146 patients with HFNEF (AF = 42) and 92 with systolic HF (AF = 30). When compared among HFNEF, the New York Heart Association (NYHA) class (2.61 ± 0.51 versus 2.21 ± 0.46; P < .05), 6-minute walk distance (279.7 ± 66.0 versus 338.0 ± 86.1 m; P < .01), quality of life score (26.1 ± 14.3 versus 19.5 ± 10.3; P < .05), and previous HF hospitalization were significantly worse in the AF group. These variables were significantly better in HFNEF than systolic HF with sinus rhythm, but the differences were not detected among those with AF. Patients with HFNEF and AF were associated with more severe diastolic dysfunction when compared to sinus rhythm. With a median follow-up of 10.5 months, the proportion of HFNEF patients in AF with recurrent HF hospitalization or death was significantly higher than those in sinus rhythm (28.6% versus 10.6%; P < .01). Both AF and restrictive diastolic dysfunction were independent predictors of HF hospitalization or death in HFNEF.ConclusionPatients with HFNEF and AF were associated with more severe diastolic dysfunction and worse clinical outcomes than those in sinus rhythm.     

Impact of ventricular dyssynchrony on postexercise accommodation of systolic myocardial motion in hypertensive patients with heart failure and a normal ejection fraction: a tissue-Doppler echocardiography study

BackgroundWe hypothesized left ventricular (LV) dyssynchrony would affect postexercise accommodation of regional myocardial motion in patients with heart failure and a normal ejection fraction (HFNEF).Methods and ResultsTissue-Doppler echocardiography was studied in 100 hypertensive patients with LV ejection fraction >50%. Among them, 70 HFNEF patients were classified into the systolic dyssynchrony (Dys: >65 ms difference of electromechanical delay between septal and lateral segments) (43 patients) and nondyssynchrony (Ndys: 27 patients) groups, and the other 30 patients were as the control (Ctrl). The systolic myocardial velocities (Sm) of 6-basal LV segments at baseline and after exercise were analyzed. When compared with the Ctrl group, the baseline lower mean Sm of 6 LV segments in the Ndys group could increase to a similar postexercise level as that in the Ctrl group, whereas that in the Dys group remained lower after exercise (7.8 ± 1.3 versus Ndys: 8.6 ± 1.5 and Ctrl: 8.9 ± 1.2 cm/s, P < .05, respectively). This is mainly due to a much higher percentage increase of lateral Sm after exercise in the Ndys group (Ndys: 49 versus Dys: 29%, P < .05).ConclusionsDyssynchrony-related regional myocardial contractile abnormality after exercise in HFNEF patients suggested the detrimental impact of electromechanical uncoupling on HF symptoms.     

Levosimendan improves renal function in patients with advanced chronic heart failure awaiting cardiac transplantation

BackgroundLong-term impact of levosimendan on renal function remains undefined. Prospectively, we evaluated effects of levosimendan on renal function in patients with advanced chronic heart failure awaiting cardiac transplantation.Methods and ResultsOf 40 patients, 20 were randomized to receive levosimendan (10-minute bolus 12 μg/kg, followed by 0.1 μg/kg/min for 24 hours; LS Group), and 20 received no levosimendan (Controls). The groups did not differ in age, heart failure etiology, left ventricular ejection fraction, and plasma brain natriuretic peptide. Patients were followed for 3 months. At baseline, the groups did not differ in serum creatinine (1.92 ± 0.13 mg/dL in LS Group versus 1.91 ± 0.12 mg/dL in Controls, P = .81) and creatinine clearance (43.7 ± 2.9 mL/min versus 43.9 ± 2.8 mL/min, P = .84). At 3 months, we found a decrease in serum creatinine and an increase in creatinine clearance in LS Group, but not in Controls, leading to a significant intergroup difference in serum creatinine (1.60 ± 0.26 mg/dL in LS Group versus 1.90 ± 0.14 mg/dL in Controls, P = .005) and creatinine clearance (53.6 ± 8.6 mL/min versus 44.0 ± 3.3 mL/min, P = .005). An improvement in creatinine ≥0.5 mg/dL occurred in 50% patients from LS Group compared with 10% of Controls (P = .005).ConclusionsLevosimendan improves long-term renal function in advanced chronic heart failure patients awaiting cardiac transplantation.     

Hemodynamic effects of oral ephedrine given alone or combined with nitroprusside infusion in patients with severe left ventricular failure

Potent vasodilator or inotropic agents alone may be of limited value in some patients with severe congestive heart failure because of their exaggerated peripheral vascular effects. Nitroprusside and potent inotropic agents in combination are hemodynamically more effective than either alone. Although oral vasodilators can mimic nitroprusside, there is a need for potent oral inotropic agents. Ephedrine is an oral sympathomimetic inotropic drug. The hemodynamic effects of ephedrine alone (50 mg orally), nitroprusside alone and the two agents combined were studied in 11 patients with severe congestive heart failure. Heart rate increased from 89.9 ± 5.2 (standard error of the mean) to 98.2 ± 5.0 beats/min after ephedrine (P < 0.001) and to 96.4 ± 4.7 beats/min with ephedrine plus nitroprusside (P < 0.02); it was unchanged with nitroprusside alone. Mean systemic arterial pressure increased from 83.7 ± 2.1 to 89.2 ± 2.7 mm Hg after ephedrine (P < 0.02) and decreased to 73.4 ± 2.4 mm Hg with nitroprusside added (P < 0.01). Left ventricular filling pressure was unchanged after ephedrine but decreased from 30.9 ± 2.3 to 20.6 ± 2.1 mm Hg during nitroprusside infusion (P < 0.01). Control cardiac output averaged 3.94 ± 0.30 liters/min and increased by 1.25 ± 0.31 liters/min with nitroprusside, by 1.09 ± 0.30 liters/min after ephedrine and by 2.20 ± 0.34 liters/min with the two combined. Although the increases in cardiac output with each agent alone were significant and similar, the increase with the two combined was significantly greater than with either alone. The data suggest that ephedrine is an orally effective inotropic agent especially when combined with a vasodilator. Further evaluation of ephedrine in congestive heart failure is warranted.     

Effects of combined candesartan and ACE inhibitors on BNP, markers of inflammation and oxidative stress, and glucose regulation in patients with symptomatic heart failure

BackgroundWe assessed the effects of candesartan in addition to angiotensin-converting enzyme (ACE) inhibitors on N-terminal pro-type natriuretic peptide (Nt-proBNP), systemic markers of inflammation and oxidative stress as well as on glucose regulation in patients with heart failure (HF).Methods and ResultsEighty patients with HF ages 62.5 ± 8.4 years presenting mostly with New York Heart Association class II symptoms (class II = 57.5%, III = 41.3%), and mean left ventricular ejection fraction 27.1 ± 7.3% were recruited. The patients were randomized to receive candesartan titrated to 32 mg 1 per day versus placebo in double-blind fashion for 6 months. Nt-proBNP, markers of inflammation and oxidative stress, glucose, insulin, and fasting insulin resistance index were analyzed. Candesartan decreased Nt-proBNP (median value = 12.4% versus −20.4%; [candesartan] P = .05), and high-sensitivity C-reactive protein (hsCRP) (+5.32% versus −20.3% [candesartan]; P = 0.046), without significantly influencing serum interleukin-6, interleukin-18, adhesion molecules, or markers of oxidative stress. Blood glucose decreased in patients treated with candesartan with a significantly greater effect in patients with higher blood glucose levels (P < .01 for interaction).ConclusionsThe addition of candesartan to ACE inhibitor and β-blocker decreases Nt-proBNP and hsCRP, but does not change the other markers of inflammation or oxidative stress in patients with heart failure. Dual angiotensin-II suppression also decreased blood glucose with a greater impact in patients with higher blood glucose level.     

Chronotropic incompetence in adolescents and adults with congenital heart disease after cardiac surgery

BackgroundChronotropic incompetence (CI) is one of the major problems in adults with congestive heart. Little is known about CI in adults with congenital heart disease (ACHD) after cardiac surgery. The purpose of our study was to investigate the presence and risk factors of CI in ACHD patients.Methods and ResultsClinical and echocardiographic data, NT-pro brain natriuretic peptide (N-BNP), and peak oxygen uptake (VO_2peak) during spiroergometry were obtained in 345 consecutive ACHD patients. CI was defined as the failure to achieve ≥80% of the predicted maximal heart rate. A total of 117 (34%) of study patients fulfilled the CI criterion. These patients were in a higher New York Heart Association class (1.7 ± 0.06 versus 1.4 ± 0.03, P < .0001; mean ± SEM), had significantly higher N-BNP levels (230 ± 31 versus 121 ± 10 pg/mL, P < .0001) and a more pronounced impairment of VO_2peak (23.8 ± 0.6 versus 28.4 ± 0.5 mL·kg·min, P < .0001) than those without CI. Elevated odds ratios for CI were found in patients with a single ventricle (4.03), Mustard operation for transposition of the great arteries (3.11), and aortic coarctation (2.14).ConclusionsOur results indicate that CI in ACHD patients is a frequent problem and is related to the severity of the heart failure as measured by symptom assessment (New York Heart Association class), plasma N-BNP level and peak oxygen uptake.     

Caffeine prolongs exercise duration in heart failure

BackgroundCaffeine increases submaximal exercise performance in healthy young subjects; its effects on exercise tolerance in heart failure (HF) have not been characterized.Methods and ResultsTo determine whether caffeine increases exercise tolerance in HF, caffeine (4 mg/kg intravenously, equivalent to 2 cups of coffee) or vehicle were infused into 10 treated HF patients (left ventricular ejection fraction 25 ± 2 %), and 10 age-matched normal subjects (N) on 2 separate days in a double-blind, randomized, crossover design. We measured heart rate, blood pressure, and ventilation at rest and during graded cycling (15 W/minute) to peak effort. Peak oxygen consumption was unaffected in either group. Mean exercise time was unchanged in N (1013 ± 87 versus 988 ± 107 seconds; P = .86) but was significantly increased by caffeine in HF (from 511 ± 28 to 560 ± 37 seconds; P = .004) despite an increase in peak minute ventilation (P < .05). Resting and peak blood pressures were higher after caffeine (P < .05) in HF, not N.ConclusionCaffeine allows HF patients to exercise longer at peak effort.     

Decreased myocardial free fatty acid uptake in patients with idiopathic dilated cardiomyopathy: evidence of relationship with insulin resistance and left ventricular dysfunction

BackgroundResults on myocardial substrate metabolism in the failing heart have been contradictory. Insulin resistance, a common comorbidity in heart failure patients, and medical therapy may modify myocardial metabolism in complex fashions. Therefore, we characterized myocardial oxidative and free fatty acid (FFA) metabolism in patients with idiopathic dilated cardiomyopathy (IDCM) and investigated the contributions of insulin resistance and β-blocker therapy.Methods and ResultsNineteen patients with IDCM (age 58 ± 8 years, ejection fraction 33 ± 8.8%) and 15 healthy controls underwent examination of myocardial blood perfusion, oxidative and FFA metabolism using positron emission tomography and [¹⁵O]H₂O, [¹¹C]acetate and [¹¹C]palmitate, respectively. Echocardiography was used to assess myocardial function, work, and efficiency of forward work. Insulin resistance was calculated using the homeostasis model assessment index (HOMA index) and the degree of β-blockade was estimated with a β-adrenoceptor occupancy test. IDCM patients were characterized by decreased cardiac efficiency (35 ± 2 versus 57 ± 12 mm Hg·L·g⁻¹, P < .0001) and reduced myocardial FFA uptake (5.5 ± 2.0 versus 6.4 ± 1.2 μmol·100 g⁻¹·min⁻¹, P < .05), but the FFA β-oxidation rate constant was not changed. In the patients, myocardial FFA uptake was inversely associated with left ventricular (LV) ejection fraction (r = −0.63, P < .01), indicating that further depression of LV function induces an opposite switch to greater FFA uptake. The FFA β-oxidation rate constant correlated positively with the HOMA index (r = 0.53, P < .05). In patients on β-1 selective β-blockers, β-1 adrenoceptor occupancy correlated inversely with LV work, oxidative metabolism, and FFA uptake; similar relationships were not found in patients on nonselective β-blocker.ConclusionsMyocardial FFA metabolism is reduced in patients with IDCM. However, when LV function is further depressed and insulin resistance manifested, myocardial FFA uptake and oxidation are, in turn, upregulated. These findings may partly explain the discrepancies between previous studies about cardiac metabolism in heart failure.     

Prolonged Electrical Muscle Stimulation Exercise Improves Strength,Peak VO2, and Exercise Capacity in Patients With Stable Chronic Heart Failure

BackgroundExercise training can help patients with chronic heart failure but may be limited in its applicability due to age and other comorbidities. This investigation evaluated training responses to prolonged electrical muscle stimulation (EMS) in patients with stable chronic heart failure.Methods and ResultsIn a crossover designed study, 10 patients (age 66 ± 6.5 years, 9 male) were randomized to 8 weeks of training or habitual activity before crossing over to the other limb after a washout period of 2 weeks. Training consisted of electrical muscle stimulation of the major leg muscles for a minimum of 1 hour, 5 days a week. Peak oxygen consumption, 6-minute walking distance test, body mass index, and quadriceps muscle strength were the end points. At baseline the mean values for peak oxygen consumption (VO₂), 6-minute walking distance, quadriceps strength, and body mass index were 19.5 ± 3.5 mL·kg·min, 415.1 ± 56.6m, 377.9 ± 110.4N, and 27.9 ± 3.1kg/m², respectively. After training, peak VO₂ increased to 21.2 ± 5.1 mL·kg·min (P < .05), walking distance increased to 454.9 ± 54.5M (P < .005), quadriceps strength increased to 404.9 ± 108.6N (P < .005), whereas we did not observe a significant effect on body mass index (P > .05).ConclusionsEMS can be used in sedentary adults with stable chronic heart failure to improve physical fitness and functional capacity. It may provide a viable alternative for patients unable to undertake more conventional forms of exercise.     

Heart Failure–Specific Relationship Between Muscle Sympathetic Nerve Activity and Aortic Wave Reflection

BackgroundReflected arterial waves contribute to left ventricular (LV) afterload. Heart failure patients with reduced ejection fraction (HFrEF) are afterload sensitive and sympathetically activated. We tested the hypothesis that HFrEF patients exhibit a positive relationship between sympathetic vasoconstrictor discharge and aortic wave reflection.MethodsSixteen treated patients with HFrEF (61 ± 9 years of age, left ventricular ejection fraction 30 ± 7%, 3 women) and 16 similar-aged healthy control subjects (57 ± 7 years of age, 4 women) underwent noninvasive measurements of radial pulse waveforms (applanation tonometry) to calculate central blood pressures and aortic wave reflection characteristics: augmentation pressure (AP), augmentation index (AI_x), and AI_x corrected to a heart rate of 75 beats/min (AI_x@75). Muscle sympathetic nerve activity (MSNA) burst frequency was recorded from the fibular nerve (microneurography).ResultsHFrEF patients had higher AI_x (26 ± 9 vs 17 ± 15%; P < .05) and MSNA burst frequency (48 ± 7 vs 39 ± 11 bursts/min; P < .05) and lower central diastolic pressure than control subjects (64 ± 8 vs 70 ± 9 mm Hg; P = 0.05). There were no between-group differences in heart rate, other measures of blood pressure (brachial and central; P > .05), AP (11 ± 5 vs 7 ± 8 mm Hg; P = 0.11), or AI_x@75 (19 ± 9 vs 13 ± 11%,-P = 0.14). MSNA correlated positively with AP (r = 0.50; P < .05), AI_x (r = 0.51; P < .05), and AI_x@75 (r = 0.54; P < .05) in HFrEF patients but not in control subjects (r = 0.002–0.18; P > 0.49).ConclusionsIn patients with HFrEF, but not similarly aged healthy subjects, indices of aortic wave reflection correlate positively with MSNA. By increasing LV afterload, such neurovascular coupling could impair LV performance and worsen heart failure symptoms. Therapies that attenuate neurogenic vasoconstriction may benefit HFrEF patients by diminishing arterial wave reflection.     

Aldosterone antagonism improves endothelial-dependent vasorelaxation in heart failure via upregulation of endothelial nitric oxide synthase production

BackgroundAltering the renin-angiotensin aldosterone system improve mortality in heart failure (HF) in part through an improvement in nitric oxide (NO)-mediated endothelial function. This study examined if spironolactone affects endothelial nitric oxide synthase (eNOS) and NO-mediated vasorelaxation in HF.Methods and ResultsRats with HF after coronary artery ligation were treated with spironolactone for 4 weeks. Rats with HF had a decrease (P < .05) in left ventricular (LV) systolic pressure (130 ± 7 versus 118 ± 6 mm Hg) and LV pressure with respect to time (9122 ± 876 versus 4500 ± 1971 mm Hg/second) with an increase in LV end-diastolic pressure (4 ± 2 versus 23 ± 8 mm Hg). Spironolactone did not affect hemodynamics but it improved (P < .05) endothelial-dependent vasorelaxation at more than 10⁻⁸ M acetylcholine that was abolished with N^G-monomethyl-L-arginine. The eNOS levels were decreased (P < .05) in the LV and the aorta; spironolactone restored LV and aortic eNOs levels to normal.ConclusionSpironolactone prevents the decrease in eNOS in the LV and aorta and improves NO-dependent vasorelaxation, suggesting that one potential mechanism of spironolactone is an improvement in vasoreactivity mediated though an increase in NO.     

Right ventricular dysfunction is a strong predictor of developing atrial fibrillation in acutely decompensated heart failure patients, ACAP-HF data analysis

BackgroundHeart failure and atrial fibrillation (AFib) are the twin epidemics of modern cardiovascular disease. The incidence of new-onset AFib in acute decompensated heart failure (ADHF) patients is difficult to predict and the short- and long-term outcomes of AFib in a cohort of patients admitted with ADHF are unknown.Methods and ResultsA total of 904 patients admitted with ADHF were studied. Incidence of AFib on admission was recorded and a multivariate analysis was performed using echocardiographic parameters to specify the predictors of AFib incidence in this cohort. In 904 ADHF patients (57% male, mean age 69 ± 14 years), 81% had history of hypertension, 40% were diabetics, and 51% were smokers. A total of 63% of the patients had known heart failure (HF) with mean ejection fraction of 34% ± 21%, and 33% of the patients had ischemic cardiomyopathy as the etiology of HF. Echocardiographic parameters were: left atrial (LA) diameter 4.5 ± 0.8 cm, left ventricular end-systolic 4.1 ± 1.3 cm, left ventricular end-diastolic 5.3 ± 1.1 cm. Right ventricular dysfunction (RVD) was present in 34% of the patients. A total of 191 (21%) patients subsequently developed AFib with two thirds of the cases occurring in patients with RVD. Using a univariate analysis, older age (OR 1.02; P < .0001), history of HF (OR 2.93; P < .0001), LA dilation (OR 1.58; P < .0001), the presence of left ventricular hypertrophy (OR 3.01, P < .0001), and RVD (OR 4.93; P < .00001) were the strongest predictors for AFib. Controlling for LA size and left ventricular hypertrophy using a forward stepwise regression, RVD remained the strongest predictor (OR 4.45; P < .0001). Patients with RVD had more events (cardiac readmission and mortality) than those with normal RV (56% versus 38%; P < .00001), notably; all-cause mortality was 4.7%/year in the abnormal RV group versus 2.9%/year in the normal RV group; P < .05. RV function analyses by echocardiography further risk stratified these patients based on their rhythm categorizing those patients with abnormal RV and AFib as the ones with the worse prognosis.ConclusionRV dysfunction is a strong predictor for developing AFib in acutely decompensated systolic failure patients. Patients with AFib and RVD have the worse outcome specially when is combined with LV dysfunction, therefore; evaluation of RV function may substantiate the difference in HF prognosis.     

Large volume ultrafiltration for acute decompensated heart failure using standard peripheral intravenous catheters

BackgroundUltrafiltration for decompensated heart failure has recently generated significant clinical interest with the development of a portable machine that does not require an intensive care or dialysis unit. This case series was designed to demonstrate the feasibility and effectiveness of performing large volume ultrafiltration via peripherally inserted standard intravenous (IV) catheters in patients with acute decompensated heart failure.Methods and ResultsNine hospitalized patients with decompensated heart failure underwent peripheral ultrafiltration (PUF) therapy with peripheral IV catheters. The mean length of time of PUF therapy was 33.3 ± 20.0 hours with a mean volume removed of 7.0 ± 4.9 L. All patients experienced a statistically significant mean weight loss of 6.2 ± 5.0 kg, P = .01. There was no statistically significant change in renal function.ConclusionWe report the first successful implementation of ultrafiltration via standard peripheral IV catheters to remove a large volume of fluid over an extended period of time reliably in a small group of patients. The ability to use PUF therapy via peripheral IV catheters will potentially allow this therapy to be implemented more easily in a variety of care settings to treat patients with resistant heart failure.     

Endothelial Dysfunction is a Marker of Systemic Response to the Cardiac Resynchronization Therapy in Heart Failure

BackgroundCardiac resynchronization therapy (CRT) induces a significant improvement in patients with heart failure (HF), who are often characterized by the presence of endothelial dysfunction (ED) with impaired flow-mediated vasodilation (FMD). We aimed to study the ED in patients with HF candidates to CRT with defibrillator (CRT-D).Methods and ResultsWe studied 57 consecutive patients affected by HF and undergoing CRT-D. At the baseline we recorded a high prevalence of ED (64.9%) with impaired FMD (4.1 ± 3.8%). After 12 months of CRT, we reported a marked increase of the mean FMD (8.8 ± 4.8% vs 4.1 ± 3.8%; P < .05) along with significant improvement of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), New York Heart Association (NYHA) functional class, and 6-minute walk test (6MWT); 42 patients (73.7%) were classified as responders according to standard criteria. FMD was related to LVEF (r = 0.169; P < .05), LVESV (r = ?0.169; P < .05), NYHA functional class (r = ?0.27; P < .051), and 6MWT (r = 0.360; P < .01).ConclusionsED is not an independent predictor of CRT response, but it is able to intercept the systemic effects of CRT and is an affordable marker of response to CRT, especially in patients unable to perform the 6MWT.