Georgios Tzanis

Impairment of Autonomic Nervous System Activity in Patients With Pulmonary Arterial Hypertension: A Case Control Study

BACKGROUND Chronotropic response to exercise (CR) and heart rate recovery (HRR) immediately after exercise are indirect indices of sympathetic and parasympathetic activity, respectively. The aim of this study was to evaluate CR and HRR in patients with pulmonary arterial hypertension (PAH) in relation to disease severity. METHODS AND RESULTS Ten PAH patients (6 females/4 males, mean age: 48+/-12 years) and 10 control subjects matched for age, gender, and body mass index (6 females/4 males, mean age: 46+/-6 years) performed a ramp incremental symptom-limited cardiopulmonary exercise test on a cycle ergometer. Main measurements included heart rate at rest (HR), CR=[(peak HR-resting HR/220-age-resting HR)x100, %], HRR(1)=HR difference from peak exercise to 1minute after, ventilatory efficiency during exercise (VE/VCO(2) slope), peak oxygen uptake (VO(2)p), and the first-degree slope of VO(2) for the first minute of the recovery period (VO(2)/t-slope). PAH patients had a significantly decreased CR (58+/-31 vs 92+/-13, %, P < .001) and HRR(1) (10+/-5 vs 29+/-6, beats/min, P < .001) as well as VO(2)p (11.9+/-3.5 vs 26.9+/-6.6, mL.kg.min) and VO(2)/t-slope (0.2+/-0.1 vs. 0.9+/-0.2, mL.kg.min(2)) compared with controls. CR and HRR(1) correlated well with VO(2)p (r=0.7; P < .001 and r=0.85; P < .001, respectively) and VO(2)/t-slope (r=0.66; P < .001 and r=0.85; P < .001, respectively) and had a significant inverse correlation with VE/VCO(2) slope (r=-0.47; P < .01 and r=-0.77; P < .001, respectively). CONCLUSIONS PAH patients present a significant impairment of CR and HRR(1) in relation to disease severity, indicating profound autonomic nervous system abnormalities.

Skeletal muscle microcirculatory abnormalities are associated with exercise intolerance, ventilatory inefficiency, and impaired autonomic control in heart failure

BACKGROUND Several skeletal muscle abnormalities have been identified in patients with chronic heart failure (CHF), including endothelial dysfunction. We hypothesized that skeletal muscle microcirculation, assessed by near-infrared spectroscopy (NIRS), is impaired in CHF patients and is associated with disease severity. METHODS Eighty-three stable patients with mild-moderate CHF (72 males, mean age 54 ± 14 years, body mass index 26.7 ± 3.4 kg/m(2)) and 8 healthy subjects, matched for age, gender and body mass index, underwent NIRS with the vascular occlusion technique and cardiopulmonary exercise testing (CPET) evaluation on the same day. Tissue oxygen saturation (StO(2), %), defined as the percentage of hemoglobin saturation in the microvasculature compartments, was measured in the thenar muscle by NIRS before, during and after 3-minute occlusion of the brachial artery. Measurements included StO(2), oxygen consumption rate (OCR, %/min) and reperfusion rate (RR, %/min). All subjects underwent a symptom-limited CPET on a cycle ergometer. Measurements included VO(2) at peak exercise (VO(2)peak, ml/kg/min) and anaerobic threshold (VO(2)AT, ml/kg/min), VE/VCO(2) slope, chronotropic reserve (CR, %) and heart rate recovery (HRR(1), bpm). RESULTS CHF patients had significantly lower StO(2) (75 ± 8.2 vs 80.3 ± 6, p < 0.05), lower OCR (32.3 ± 10.4 vs 37.7 ± 5.5, p < 0.05) and lower RR (10 ± 2.8 vs 15.7 ± 6.3, p < 0.05) compared with healthy controls. CHF patients with RR ≥9.5 had a significantly greater VO(2)peak (p < 0.001), VO(2)AT (p < 0.01), CR (p = 0.01) and HRR(1) (p = 0.01), and lower VE/VCO(2) slope (p = 0.001), compared to those with RR <9.5. In a multivariate analysis, RR was identified as an independent predictor of VO(2)peak, VE/VCO(2) slope and HRR(1). CONCLUSIONS Peripheral muscle microcirculation, as assessed by NIRS, is significantly impaired in CHF patients and is associated with disease severity.

Peripheral Muscle Microcirculatory Alterations in Patients With Pulmonary Arterial Hypertension: A Pilot Study

BACKGROUND: Pulmonary microcirculation abnormalities are the main determinants of pulmonary arterial hypertension (PAH) pathophysiology. We hypothesized that PAH patients have peripheral tissue microcirculation alterations that might benefit from hyperoxic breathing. We evaluated peripheral muscle microcirculation with near-infrared spectroscopy, before and after hyperoxic breathing. METHODS: Eight PAH subjects, 8 healthy subjects (controls) matched for age, sex, and body mass index, and 16 subjects with chronic heart failure and matched for functional capacity with the PAH subjects underwent near-infrared spectroscopy. Tissue O2 saturation, defined as the hemoglobin saturation (%) in the microvasculature compartments, was measured on the thenar muscle. Then the 3-min brachial artery occlusion technique was applied before, during, and after 15 min of breathing 100% O2. We calculated the oxygen consumption rate (%/min), the reactive hyperemia time, and the time needed for tissue O2 saturation to reach its baseline value after the release of the occlusion. RESULTS: Compared to the controls, the PAH subjects had a significantly lower resting tissue O2 saturation (65.8 ± 14.9% vs 82.1 ± 4.0%, P = .005), a trend toward a lower oxygen consumption rate (35.3 ± 9.1%/min vs 43.4 ± 19.7%/min, P = .60), and a significantly higher reactive hyperemia time (3.0 ± 0.6 min vs 2.0 ± 0.3 min, P < .001). The PAH subjects also had lower tissue O2 saturation (P = .08), lower peripheral arterial oxygen saturation (P = .01), and higher reactive hyperemia time (P = .02) than the chronic heart failure subjects. After hyperoxic breathing, the PAH subjects had increased tissue O2 saturation (65.8 ± 14.9% to 71.4 ± 14.5%, P = .01), decreased oxygen consumption rate (35.3 ± 9.1%/min to 25.1 ± 6.6%/min, P = .01), and further increased reactive hyperemia time (3.0 ± 0.6 min to 4.2 ± 0.7 min, P = .007). CONCLUSIONS: The PAH subjects had substantial impairments of peripheral muscle microcirculation, decreased tissue O2 saturation (possibly due to hypoxemia), slower reactive hyperemia time, (possibly due to endothelium dysfunction), and peripheral systemic vasoconstriction. Acute hyperoxic breathing improved resting tissue O2 saturation (an expression of higher oxygen delivery) and decreased the oxygen consumption rate and reactive hyperemia time during reperfusion, possibly due to increased oxidative stress and evoked vasoconstriction.

Exercise Intolerance in Chronic Heart Failure: The Role of Cortisol and the Catabolic State

Chronic heart failure (CHF) is a complex clinical syndrome leading to exercise intolerance due to muscular fatigue and dyspnea. Hemodynamics fail to explain the reduced exercise capacity, while a significant skeletal muscular pathology seems to constitute the main underlying mechanism for exercise intolerance in CHF patients. There have been proposed several metabolic, neurohormonal and immune system abnormalities leading to an anabolic/catabolic imbalance that plays a central role in the pathogenesis of the wasting process of skeletal muscle myopathy. The impairment of the anabolic axes is associated with the severity of symptoms and the poor outcome in CHF, whereas increased cortisol levels are predictive of exercise intolerance, ventilatory inefficiency and chronotropic incompetence, suggesting a significant contributing mechanism to the limited functional status. Exercise training and device therapy could have beneficial effects in preventing and treating muscle wasting in CHF. However, specific anabolic treatment needs more investigation to prove possible beneficial effects.

Attenuated Microcirculatory Response to Maximal Exercise in Patients With Chronic Heart Failure.

PURPOSE: Exercise training programs improve microcirculatory alternations in patients with chronic heart failure (CHF). However less is known about the acute effect of maximum exercise on the skeletal muscle microcirculation. We aimed to assess the effect of acute exercise on peripheral microcirculation of patients with CHF, as assessed by near-infrared spectroscopy with vascular occlusion technique. METHODS: Tissue oxygenation was evaluated in 8 stable patients with CHF (7 males; mean age, 60 ± 9 years; body mass index, 26.3 ± 3.8 kg/m2) and 8 healthy subjects (matched for age, sex, and body mass index) before and after cardiopulmonary exercise testing. Tissue oxygen saturation (StO2), StO2peak, oxygen consumption rate, and endothelial function (reperfusion rate), before and after maximum exercise, were assessed. RESULTS: Patients with CHF had lower StO2 and reperfusion rate compared with healthy subjects (71.4% ± 9.8% vs 81.0% ± 5.4% and 9 ± 1 %/min vs 13.9 ± 5.8%/min, respectively; P < .05) at rest. Oxygen consumption rate increased after exercise in patients with CHF and healthy subjects (from −31.7 ± 8.2 to −43.7 ± 12.7 and from −35.7 ± 6.7 to −42.4 ± 6.4, respectively; P < .05). StO2 decreased significantly after maximal exercise in patients with CHF (from 71.4 ± 9.8 to 65.2 ± 12.7; P < .05), whereas it returned to the preexercise values in healthy subjects (from 81.0 ± 5.4 to 80.3 ± 7.0). There was a significant between-group difference (P < .05). CONCLUSIONS: Patients with CHF present microcirculatory alternations. Acute exercise exerts an effect on microcirculation in peripheral, nonexercising muscles, with altered response in patients with CHF compared with healthy subjects.

REVERSAL OF RESPIRATORY MUSCLES DYSFUNCTION AND EXERCISE CAPACITY IMPROVEMENT AFTER CONTINUOUS-FLOW LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION

Methods: Eight consecutive CHF patients (6Males/2Females, mean age: 45±15 years) were enrolled in the study after LVAD (HeartMate II) implantation as destination therapy (N=4, Males, Ischemic CHF) and as a bridge to transplantation / recovery (N=4, Non-ischemic CHF). All patients received optimal “reverse” remodelling medical treatment including clenbuterol in the non-ischemic CHF group. Patients were evaluated with the use of a cardiopulmonary exercise testing and respiratory function tests at 1, 3 and 6 months.

Coronary artery disease in renal transplant recipients: an angiographic study

BACKGROUND Cardiovascular disease is the leading cause of mortality in renal transplant recipients (RT). Coronary artery disease (CAD) in such patients is poorly studied. METHODS During 2012-2017, 50 patients with a renal graft (functioning for a minimum of 6 months) were subjected to coronary angiography in our institution. They were matched (for age, gender, diabetes, and indication for angiography) with 50 patients with end-stage renal disease (ESRD) undergoing chronic dialysis and 50 patients with normal renal function who were subjected to coronary angiography during the same period. The extent and severity of CAD were assessed by using the SYNTAX score. RESULTS RT had a significantly longer duration of ESRD than patients on dialysis (17.5±7.1 vs. 8.5±8.7 years, p<0.01). Mean SYNTAX score was 13.3±12.0 in RT, 20.6±17.5 in patients on dialysis, and 9.4±9.2 in control patients (p<0.01). At least one significantly calcified lesion was present in 75.7% of RT recipients, 92.1% of patients on dialysis, and 15.8% of control patients (p<0.01). Percutaneous coronary intervention (PCI) was successful in 93.8% of the attempted cases in RT, 75% of patients on chronic dialysis, and 100% of control patients (p=0.04). In the RT group, SYNTAX score significantly correlated with smoking (p=0.02) and the total vintage of ESRD (p=0.04). CONCLUSIONS In this angiographic study, CAD was less severe in RT than in patients on long-term dialysis despite a longer duration of ESRD. Coronary artery calcification was highly prevalent after renal transplantation. PCI in RT had a high rate of angiographic success.

Muscle microcirculation alterations and relation to dipping status in newly diagnosed untreated patients with arterial hypertension - A pilot study

The importance of abnormalities observed in the microcirculation of patients with arterial hypertension (AH) is being increasingly recognized. The authors aimed to evaluate skeletal muscle microcirculation in untreated, newly diagnosed hypertensive patients with NIRS, a noninvasive method that evaluates microcirculation.

Letter by Tzanis et al Regarding Article, “Stress Testing in Asymptomatic Aortic Stenosis”

We read with great interest the state-of-the-art review by Redfors et al1 regarding the emerging role of stress testing in the field of asymptomatic aortic stenosis (AS) management. With this letter, we would like to highlight the role of cardiopulmonary exercise test (CPET) in the evaluation of symptoms and disease prognosis of asymptomatic AS. Insights from cardiopulmonary exercise tests could possibly answer how symptomatic asymptomatic AS could be. Five decades ago, Ross and Braunwald2 described the importance of symptom estimation in AS, stating, “Once symptoms develop, the average course is short.” Since then, little has changed in the management of severe AS. We know …