Candidacy and long-term outcomes of subcutaneous implantable cardioverter-defibrillators in current practice in patients with hypertrophic cardiomyopathy.

BACKGROUND: In patients with Hypertrophic Cardiomyopathy (HCM) S-ICD is usually the preferred option as pacing is generally not indicated. However, limited data are available on its current practice adoption and long-term follow-up. METHODS: Consecutive HCM patients with S-ICD implanted between 2013 and 2021 in 3 international centers were enrolled in this observational study. Baseline, procedural and follow-up data were regularly collected. Efficacy and safety were compared with a cohort of HCM patients implanted with a tv-ICD. RESULTS: Seventy patients (64% males) were implanted with S-ICD at 41 ± 15 years, whereas 168 patients with tv-ICD at 49 ± 16 years. For S-ICD patients, mean ESC SCD risk score was 4,5 ± 1.9%: 25 (40%) at low-risk, 17 (27%) at intermediate and 20 (33%) at high-risk. Patients were followed-up for 5.1 ± 2.3 years. Two patients (0.6 per 100-person-years, vs 0.4 per 100 person-years with tv-ICD, p = 0.45) received an appropriate shock on VF, 17 (24%) were diagnosed with de-novo AF. Inappropriate shocks occurred in 4 patients (1.2 per 100-person-years, vs 0.9 per 100 person-years with tv-ICD, p = 0.74), all before Smart-Pass algorithm implementation. Four patients experienced device-related adverse events (1.2 per 100-person-years, vs 1 per 100 person-years with tv-ICD, p = 0.35%). CONCLUSIONS: S-ICDs were often implanted in patients with an overall low-intermediate ESC SCD risk, reflecting both the inclusion of additional risk markers and a lower decision threshold. S-ICDs in HCM patients followed for over 5 years showed to be effective in conversion of VF and safe. Greater scrutiny may be required to avoid overtreatment in patients with milder risk profiles.

Different baseline sympathovagal balance and cardiac autonomic responsiveness in ischemic and non-ischemic congestive heart failure.

BACKGROUND: A profound autonomic unbalance is present in heart failure: its correlation with the etiology of the disease has never been investigated. AIMS: We characterized the sympatho-vagal balance and autonomic responsiveness of 42 patients (21 with ischemic heart failure, 21 with idiopathic dilated cardiomyopathy). Patients had comparable NYHA class, ejection fraction, exercise pVO(2), exercise ventilatory response, incidence of beta-blocking treatment. None showed periodic breathing or nocturnal arterial desaturation. METHODS: Heart rate variability was assessed in the time and frequency domain during: (1) 10 min of quiet supine resting and free breathing; (2) 10 min of regular breathing at a frequency of 20 acts/min (=parasympathetic stimulus); and (3) 10 min of active standing (=sympathetic stimulus). The ratio of the low- to high-frequency components of each autospectrum obtained in the frequency domain (LF/HF) was used as an index of sympathovagal balance. RESULTS: Patients with ischemic heart failure had a greater baseline sympathetic activation (higher LF/HF) than those with idiopathic dilated cardiomyopathy, maintaining some parasympathetic responsiveness as well (reduced LF/HF with regular breathing). CONCLUSIONS: There is a distinct autonomic control according to the etiology of heart failure, a finding that may help understanding its pathophysiology, and could be useful in the clinical management of patients.

Non-invasive measurement of stroke volume during exercise in heart failure patients.

The objective of the present study was to determine the variability of the arterio-venous O(2) concentration difference [C(a-v)O(2)] at anaerobic threshold and at peak oxygen uptake (VO(2)) during a progressively increasing cycle ergometer exercise test, with the purpose of assessing the possible error in estimating stroke volume from measurements of VO(2) alone. We sampled mixed venous and systemic arterial blood every 1 min during a progressively increasing cycle ergometer exercise test and measured, in each blood sample, haemoglobin concentration and blood gas data. Ventilation, VO(2) and CO(2) uptake were also measured continuously. We studied 40 patients with normal haemoglobin concentrations and with stable heart failure due to ischaemic or idiopathic cardiomyopathy. Mean values (+/-S.D.) for C(a-v)O(2) were 7.8+/-2.6, 13.0+/-2.4 and 15. 0+/-2.7 ml/100 ml at rest, anaerobic threshold and peak VO(2) respectively. The patients with heart failure were divided into classes according to their peak VO(2). Classes A, B and C contained patients with peak VO(2) values of>20, 15-20 and 10-15 ml.min(-1). kg(-1) respectively. At anaerobic threshold, C(a-v)O(2) was 12.3+/-1. 3, 13.1+/-2.7 and 13.5+/-2.6 ml/100 ml for classes A, B and C respectively (class A significantly different from classes B and C; P<0.05). At peak exercise C(a-v)O(2) was 13.6+/-1.4, 15.6+/-2.5 and 15.4+/-3.2 ml/100 ml for classes A, B and C respectively (class A significantly different from classes B and C; P<0.05). Stroke volume was estimated for each subject using the mean values of the measured C(a-v)O(2) in each functional class and individual values of VO(2) and heart rate using the Fick formulation. The average difference between the stroke volume estimated from mean C(a-v)O(2) and that obtained using the patient's actual C(a-v)O(2) value was 9.2+/-9.7, 1.0+/-8.8 and -0.2+/-6.1 ml at anaerobic threshold, and -1.9+/-11.3, 0.9+/-10.0 and -2.3+/-8.5 ml at peak exercise, in classes A, B and C respectively. Among the various classes, the most precise estimation of stroke volume was observed for class C patients. We conclude that stroke volume during exercise can be estimated with the accuracy needed for most purposes from measurement of VO(2) at the anaerobic threshold and at peak exercise, and from population-estimated mean values for C(a-v)O(2) in heart failure patients.

Thrombin activation and late restenosis after percutaneous transluminal coronary angioplasty.

BACKGROUND: Mechanisms of restenosis after percutaneous transluminal coronary angioplasty (PTCA) have not been defined yet. Experimental studies have shown that thrombin, by stimulating platelet growth factor secretion and smooth muscle cell proliferation, can play a major role. METHODS AND RESULTS: In 34 patients with single-vessel coronary disease undergoing PTCA, thrombin activity was evaluated through serial fibrinopeptide A (FPA) plasma determinations. Samples were performed before PTCA, immediately after and 24 hours, 72 hours, and 6 months later. Patients were grouped according to the development (group 1, n = 13) or nondevelopment (group 2, n = 21 ) of restenosis at a 6-month angiographic control. No difference in the two groups was found concerning baseline FPA values. In patients in group 1, soon after PTCA higher FPA levels (27.3 +/- 13.7 ng/ml) than those in group 2 (9.2 +/- 5.6 ng/ml; p < 0.05 vs pre-PTCA, and p < 0.01 between the two groups) were observed. No differences in FPA levels were detected at the other steps between the two groups. CONCLUSION: Our data suggest that thrombin plays a role in the process of restenosis after PTCA; acute FPA response to the procedure seems to have a predictive value.

[Mechanisms facilitating oxygen delivery during exercise in patients with chronic heart failure]. / Meccanismi di facilitazione della cessione di ossigeno durante esercizio nel paziente con scompenso cardiaco cronico]

The aim of the study was to estimate the relative importance of the Bohr effect and redistribution of blood from the non-exercising tissues on the arterial-venous oxygen content differences across the exercising extremities and the central circulation in patients with chronic heart failure; the relationship among femoral vein, systemic and pulmonary artery oxygen partial pressure and hemoglobin saturation was determined. It has been reported that the maximal reduction in femoral vein pO2 precedes peak oxygen consumption and lactic acidosis threshold in patients with chronic heart failure and normal subjects during exercise. The increase in oxygen consumption at work rates above lactic acidosis threshold, therefore, must be accounted for by increase in blood flow in the exercising muscles and right-ward shift on the oxyhemoglobin dissociation curve. Since the total cardiac output increase is blunted in patients with chronic heart failure, diversion of blood flow from non-exercising to exercising tissues may account for some of the increase in muscle blood flow. Ten patients with chronic heart failure performed a progressively increasing leg cycle ergometer exercise test up to maximal effort while measuring ventilation and gas concentration for computation of oxygen uptake and carbon dioxide production, breath-by-breath. Blood samples were obtained, simultaneously, from systemic and pulmonary arteries and femoral vein at rest and every minute during exercise to peak oxygen consumption. At comparable levels of exercise, femoral vein pO2, hemoglobin saturation and oxygen content were lower than in the pulmonary artery. PCO2 and lactate concentration increased steeply in femoral vein and pulmonary artery blood above lactic acidosis threshold (due to lactic acid build-up and buffering), but more steeply in femoral vein blood. These increases allowed femoral vein oxyhemoglobin to dissociate without a further decrease in femoral vein pO2 (Bohr effect). The lowest femoral vein pO2 (16.6 +/- 3.9 mmHg) was measured at 66 +/- 22% of peak VO2 and before the lowest oxyhemoglobin saturation was reached. Artero-venous oxygen content difference was higher in the femoral vein than in the pulmonary artery; this difference became progressively smaller as oxygen consumption increased. "Ideal" oxygen consumption for a given cardiac output (oxygen consumption expected if all body tissues had maximized oxygen extraction) was always higher than the measured oxygen consumption; however the difference between the two was lost at peak exercise. This difference positively correlated with peak oxygen consumption and cardiac output increments at submaximal but not at maximal exercise. In conclusion, femoral vein pO2 reached its lowest value at a level of exercise at or below the lactic acidosis threshold. Further extraction of oxygen above the lactic acidosis threshold was accounted for by a right shift of the oxyhemoglobin dissociation curve. The positive correlation between increments of cardiac output vs "ideal" and measured oxygen consumption suggests a redistribution of blood flow from non-exercising to exercising regions of the body. Furthermore the positive correlation between exercise capacity and the difference between "ideal" and measured oxygen consumption suggests that patients with the poorer function have the greater capability to optimize blood flow redistribution during exercise.

Oxygen transport to muscle during exercise in chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy.

In chronic heart failure, oxygen delivery during exercise is impaired mainly because of failure of cardiac output to increase normally. Compensatory mechanisms are hemoglobin concentration increase, right-ward shift in the oxyhemoglobin dissociation curve, and blood flow redistribution from the nonexercising organs to the exercising muscles.

Contribution of PO2, P50, and Hb to changes in arteriovenous O2 content during exercise in heart failure.

Arteriovenous O2 content (a-vCO2) differences increase during exercise in normal subjects through several mechanisms including PO2, O2 pressure at which hemoglobin (Hb) is half saturated with O2 (P50), and Hb concentration changes. The present study was undertaken to evaluate how much these biochemical changes are relevant to a-vCO2 difference through exercise in patients with heart failure. Twenty-seven patients with congestive heart failure [10 patients in functional class A (peak exercise O2 uptake >20 ml x kg-1 x min-1), 9 in class B (20-15 ml x kg-1 x min-1), and 8 in class C (15-10 ml x kg-1 x min-1)] underwent a cardiopulmonary exercise test with once-per-minute simultaneous blood sampling from the pulmonary and systemic arteries for determination of Hb, PO2, PCO2, pH, O2 content (CO2), Hb saturation and lactic acid (pulmonary artery only), and calculation of P50. Analysis of data was done at six exercise stages: the first at rest, the last at peak exercise, and the second to the fifth at one-, two-, three-, and four-fifths of O2 consumption increase. a-vCO2 difference at peak exercise was 14.3 +/- 2.1, 16.9 +/- 2.4, and 14.7 +/- 2.1 (SD) ml/dl in class A, B, and C patients, respectively. The contribution of Hb, P50, and PO2 changes to the increments of a-vCO2 difference during exercise was 21, 17, and 63%, respectively; the only interclass difference observed was for P50, which plays a greater role in a-vCO2 difference in class A. Hb changes act mainly at the arterial site, whereas P50 and PO2 act at the venous site. Hb increase was constant through the test, venous P50 increase was greater above anaerobic threshold, and venous PO2 reduction was most remarkable at the onset of exercise; in class C patients, no venous PO2 change was recorded in the second half of exercise. Thus a-vCO2 difference increase during exercise is notable in patients with heart failure but unrelated to the severity of the syndrome. Hb, P50, and, to the greatest degree, PO2 changes participate in the increment of a-vCO2 difference. In class C patients, the lack of PO2 reduction in the second half of exercise suggests the achievement of a "whole body critical venous PO2."

Late activation of the fibrinolytic system in myocardial infarction treated with thrombolytic therapy. Influence of the coronary anatomical substrate.

Procoagulant activity, thrombin and fibrinolytic system activation have been demonstrated in the first 24-48 h after acute myocardial infarction treated with thrombolytic therapy. Little is known about what happens in the subsequent days, during which the incidence of ischaemic recurrence is high. In 21 patients treated with streptokinase and in 20 patients treated with urokinase we evaluated, with multiple plasma determinations, D-dimer and fibrinogen plasma levels in the first week after myocardial infarction. From the 2nd hour after the beginning of thrombolysis to the 4th day, all patients received intravenous heparin in doses sufficient to raise the partial thromboplastin time to twice its normal level; subcutaneous calcium heparin (12,000 U/day) was subsequently substituted for the intravenous route. Coronary angiography was performed 7 days after infarction. From the basal values 2.22 +/- 1.44 nmol.1(-1) in the streptokinase group and 3.28 +/- 3.05 nmol.1(-1) in the urokinase group, D-dimer rose consistently in the 1st hour after thrombolysis 269.4 +/- 206.7 nmol.1(-1) and 44.5 +/- 35.5 nmol.1(-1) in the streptokinase and urokinase groups, respectively; P < 0.001. After the peak value, which in both groups was reached after 5 h, D-dimer slowly decreased during the study period. It reverted to normal values only in 10/21 patients in the streptokinase group; in the urokinase group normalization was attained in 14/20 patients between the 3rd and 6th days. After withdrawal of i.v. heparin in patients of both groups with TIMI 0 or 1 grade of coronary patency, D-dimer rose to levels four to seven times greater than normal; in patients of both groups with TIMI 2 or 3 grade coronary flow, D-dimer showed a monophasic pattern of progressive normalization (P < 0.05 and P < 0.01 at the 6th and 7th days, respectively, for differences between TIMI 0-1 and TIMI 2-3 groups). After myocardial infarction, thrombolysis is followed by active and persistent fibrin degradation more marked and lasting after streptokinase than after urokinase. When occurring sooner, it is a consequence of plasmin activation induced by thrombolytic agents; later it seems to be related to intracoronary substrate, as suggested by the relationship of plasma elevation of D-dimer with the presence of occluded or suboccluded infarction-related vessels.

Evaluation of the dead space/tidal volume ratio in patients with chronic congestive heart failure.

Dead space/tidal volume ratio (VD/VT) evaluation is currently performed in patients with respiratory and cardiac disorders, and includes measurement of arterial CO2 partial pressure (PaCO2). PaCO2 is generally derived from either PETCO2 (end-expiratory CO2 pressure) or PJCO2 (calculated as PJCO2 = 5.5 + 0.9 PETCO2 - 2.1 VT). The applicability of these methods may be questionable in chronic heart failure due to its frequent association with lung dysfunction. In 63 patients with congestive heart failure, the authors compared PaCO2 versus PETCO2 and PJCO2 and VD/VT measured with PaCO2 versus VD/VT estimated with PETCO2 (estimation 1) or PJCO2 (estimation 2). Comparisons were made at rest, at submaximal exercise, and at peak exercise. Considering all 326 measurements, there was a strong correlation, but not an identity, between PaCO2 and PETCO2 (PaCO2 = 7.25 + 0.80 PETCO2, r = .84, P < .0001) and between PaCO2 and PJCO2 (PaCO2 = 6.18 + 0.84 PJCO2, r = .85, P < .0001). Results were comparable concerning PaCO2 versus PJCO2. Measured VD/VTs also strongly correlated with estimated VD/VTs (VD/VT measured = -0.03 + 1.11 VD/VT [estimation 1], r = .90, P < .0001, and VD/VT measured = 0.03 + 0.92 VD/VT [estimation 2], r = .90, P < .0001). However, only at rest and, solely for estimation 1, at submaximal exercise were the slopes and y intercepts of measured versus estimated VD/VT not different from 1 and 0, respectively; in this regard, lung dysfunction was more influential than the severity of cardiac failure. Although PaCO2 strongly correlates with PETCO2 and PJCO2, these measurements may not be reliable for a noninvasive calculation of VD/VT in chronic congestive heart failure.

Lung-heart interaction as a substrate for the improvement in exercise capacity after body fluid volume depletion in moderate congestive heart failure.

We investigated exercise capacity after fluid depletion in patients with moderate congestive heart failure (CHF). Twenty-one patients underwent ultrafiltration (mean volume +/- SEM: 1,770 +/- 135 ml). Echocardiography, tests of pulmonary function, and a cardiopulmonary exercise test with hemodynamic and esophageal pressure monitoring were performed before ultrafiltration and 3 months later. Tests without invasive measurements were repeated 4 and 30 days after ultrafiltration. Twenty-one control patients followed the same protocol but did not have ultrafiltration. Patients who underwent ultrafiltration and increased their oxygen consumption at peak exercise (peak VO2) by > 10% at the 3-month evaluation (group A1, n = 9) were separated from those who did not (group A2, n = 8); 3 patients did not complete the follow-up. Four days after the procedure, peak VO2 had risen from 17.3 +/- 0.8 to 19.3 +/- 0.9 ml/min/kg in group A1, and from 11.9 +/- 0.7 to 14.1 +/- 0.7 ml/min/kg in group A2 (p < 0.01). Plasma norepinephrine and pulmonary function were consistent with a greater severity of the syndrome in group A2. At 3 months in group A1, the relations of filling pressure to cardiac index of the right and left ventricles were shifted upward; the esophageal pressure swing (differences between end-expiratory and end-inspiratory pressure) for a given tidal volume was lower; the peak exercise dynamic lung compliance had increased from 0.10 +/- 0.05 to 0.14 +/- 0.03 L/mm Hg (p < 0.01). None of these changes were detected in group A2 and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrafiltration in moderate heart failure. Exercise oxygen uptake as a predictor of the clinical benefits.

OBJECTIVE: Ultrafiltration (UF) can improve the exercise performance of patients with moderate congestive heart failure (CHF). Our aim was to define the starting levels of performance below which UF is beneficial. PATIENTS AND METHOD: We studied 26 patients in 2 to 3 NYHA class, whose clinical condition was stable, left ventricle ejection fraction (echocardiography) was < 35% and peak exercise oxygen uptake (VO2) was > or = 14 mL/min/kg. They underwent a single extracorporeal UF (about 600 mL of ultrafiltrate per hour). Before that, we evaluated pulmonary function (PFT), functional capacity (cardiopulmonary exercise test [CPX]), cardiac index, left ventricle ejection fraction, ventricular filling pressures, and plasma norepinephrine at rest. The PFTs and CPXs were repeated 3 months after UF. RESULTS: Sixteen patients had a rise of peak exercise VO2 > 1 mL/min/kg at the 3-month evaluation (group A, ultrafiltrate = 2,040 +/- 241 mL) and 10 did not (group B, ultrafiltrate = 1,870 +/- 169 mL). Forced expiratory volume (1 s), maximal voluntary ventilation, and vital capacity were lower in group A than in group B and improved after UF only in group A. Before UF, VO2 at peak exercise and at anaerobic threshold (15.5 +/- 0.4 mL/min/kg and 11.0 +/- 0.5, respectively) was also lower in group A than in group B (21.2 +/- 0.7 mL/min/kg and 14.8 +/- 0.9, p < 0.01). Patients whose pre-UF peak exercise VO2 was > 18.5 mL/min/kg (group B) had no increase in this variable. No significant group differences were detected regarding norepinephrine, left ventricular ejection fraction, and hemodyanmic parameters at rest. CONCLUSION: In patients with moderate CHF undergoing UF, exercise capacity improvement is inversely related to the pre-UF level of physical performance and pulmonary function; VO2 at peak exercise seems useful for identification of patients not benefiting from the procedure.

[Measurement of dead space/tidal volume ratio during exercise in patients with heart failure]. / Calcolo del rapporto spazio morto/volume corrente nello scompenso cardiaco durante esercizio.

Dead space (VD)/tidal volume (VT) ratio is an indirect index of ventilation/perfusion matching. Therefore, it is currently evaluated in patients with congestive heart failure to detect the organ system limiting the exercise tolerance. The VD/VT calculation requires measurement of arterial CO2 partial pressure (PaCO2). For practical reasons, the software of most metabolic carts substitutes the PaCO2 with the end-expiratory CO2 (PETCO2) or the PJCO2 (calculated as PJCO2 = 5.5 +/- 0.9 PETCO2-2.1 VT). Nonetheless, the applicability of these methods in congestive heart failure is unknown. We compared in 63 patients with congestive heart failure 326 measurements of PaCO2 versus PETCO2 and PJCO2 and VD/VT measured with PaCO2 versus VD/VT estimated with PETCO2 (estimation 1) or PJCO2 (estimation 2). Comparisons were made at rest (Phase 1), during submaximal exercise (Phase 2), and at peak exercise (Phase 3). We found a strong correlation, but not an identity, between PaCo2 and PETCO2 (PaCO2 = 7.25 +/- 0.80 PETCO2, r = 0.84; p < 0.0001); similarly for PaCO2 and PETCO2. Several observations were out of 95% confidence interval, and some measurements exceeded mean +/- 2 SD when the differences between PaCo2 and PETCO2 or PJCO2 were plotted against the averages from the two (Bland and Altman method). Measured VD/VTs also strongly correlated with the estimated ones (VD/VT measured = -0.03 +/- 1.11 VD/VT estimated 1 r = 0.90; p < 0.0001 e VD/VT measured = 0.03 +/- 0.92 VD/VT estimated 2 r = 0.90; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Inhibition of the neurohumoral axis after intravascular fluid depletion in congestive heart failure with water retention: mechanisms of the perpetuation of the syndrome]. / Inibizione dell'asse neuroumorale dopo deplezione di fluido intravascolare nello scompenso cardiaco congestizio con ritenzione idrica: meccanismi di perpetuazione della sindrome.

Hypovolemia stimulates the sympathoadrenal and renin systems and water retention. In congestive heart failure (CHF) reduced cardiac output and blood pressure have been suggested to be perceived as a volume deficit, which, if persistent, would perpetuate humoral activation and fluid retention. In the aim of probing this hypothesis, we monitored in patients with CHF the neurohumoral response to reduction of the body fluid obtained by ultrafiltration. In 22 patients with advanced CHF and fluid retention, ultrafiltration was performed with a diafilter, which was part of an external venous circuit, whose flow was regulated to produce 500 ml/hour of ultrafiltrate (average total amount 3,122 +/- 1,199 ml) until right atrial pressure was reduced to 50% of baseline. Hemodynamics, plasma renin activity, norepinephrine and aldosterone were measured before and in the 48 hours after ultrafiltration. Soon after the procedure, associated with a 20% reduction of plasma volume and a moderate decrease of cardiac output and blood pressure (consistent with a diminished degree of filling of the arterial compartment), there was an obvious fall of norepinephrine, plasma renin activity and aldosterone. In the next 48 hours we recorded an increasing neurohumoral axis depression, in spite of recovery of plasma volume, cardiac output and blood pressure and a striking enhancement in urinary output. Changes in norepinephrine, plasma renin activity or aldosterone were not related to the combination of changes in plasma volume, cardiac output and blood pressure (variations in the state of arterial filling) and significantly correlated with the increase in urinary output and sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

[Body fluid withdrawal with isolated ultrafiltration effects persistent improvement of functional capacity in patients with chronic congestive heart failure. Furosemide does not produce the same result]. / La rimozione di liquido corporeo con ultrafiltrazione isolata produce persistente miglioramento della capacità funzionale del soggetto con insufficienza cardiaca congestizia cronica. La furosemide non dà lo stesso risultato.

In moderate congestive heart failure pulmonary overhydration may be detected at chest X-ray even if therapy is optimized to keep the urinary output normal and to prevent weight gain and dependent edema formation. Removal of overhydration of the lung may help to define its significance. This study was aimed at investigating whether a subclinical accumulation of fluid in the lung interstitium in moderate congestive heart failure interferes with the patient's functional capacity, and whether furosemide is able to promote reabsorption of the excessive fluid. Patients whose digoxin, oral furosemide and ACE-inhibitor therapeutic regimen was kept constant, were randomly allocated to ultrafiltration (8 cases) or iv bolus (mean dose = 248 mg) of supplemental furosemide (8 cases). The amount of body fluid removed with each method approximated 1.600 ml. Functional performance was assessed with cardiopulmonary exercise tests. Soon after fluid withdrawal with either procedure the filling pressures of the two ventricles and body weight were reduced and plasma renin activity, norepinephrine and aldosterone were augmented. After furosemide hormones remained elevated in the subsequent 4 days, and, during this period, patients had positive water metabolism, recovery of the elevated ventricular filling pressures, recurrence of lung congestion without any improvement in functional capacity. In ultrafiltrated patients, renin, norepinephrine and aldosterone fell below control values within the first 48 hours and water metabolism was equilibrated at a new set point (less fluid intake and diuresis without weight gain). Functional capacity in these patients was improved through favorable circulatory and ventilatory adjustments consequent on reabsorption of lung water. This may also have restored the ability of the lung to clear norepinephrine, thus restraining its facilitation of renin release. Improvement persisted at 3 months after the procedure. In congestive heart failure the set point of fluid balance is altered despite oral furosemide; supplemental iv furosemide does not shift the set point, at least in the presence of ACE-inhibition; excessive, although silent, lung water limits the functional capacity of the patient.

Beta-thromboglobulin plasma levels in the first week after myocardial infarction: influence of thrombolytic therapy.

In vitro and in vivo studies have shown both an inhibition and an activation of platelets after thrombolysis in acute myocardial infarction. Plasma beta-thromboglobulin, a marker of platelet activity, was evaluated daily during the first week after myocardial infarction in 24 patients who received intravenous streptokinase (group 1) and 26 who did not (group 2). On admission, levels of beta-thromboglobulin, as compared to those in healthy subjects (35 +/- 9 IU/ml), were similarly augmented in group 1 (105 +/- 27 IU/ml) and in group 2 (115 +/- 30 IU/ml); 3 hours later, values averaged 191 +/- 58 IU/ml in group 1 (p < 0.001 vs baseline) and 95 +/- 28 IU/ml in group 2 (not significant vs baseline; p < 0.001 between the two groups). From the second to the seventh day, beta-thromboglobulin augmented in those patients in both groups with postinfarction angina. From day 5 to day 7, patients of group 1 without angina had lower beta-thromboglobulin levels than patients of group 2 who had no symptoms. The lowest levels of platelet activity were observed in group 1 reperfused patients. These data indicate that in myocardial infarction an early platelet activation takes place that is enhanced by thrombolytic treatment; recurrence of angina is associated with persistent activation; in the absence of recurrent angina, thrombolysis can limit late platelet activation.

[The factors that regulate water-salt metabolism in congestive heart failure]. / Studio dei fattori che regolano il metabolismo idrosalino nello scompenso cardiaco congestizio.

We investigated the mechanisms involved in the regulation of salt and water metabolism in patients with congestive heart failure (CHF). Extracorporeal ultrafiltration was utilized as a nonpharmacologic method for withdrawal of body fluids. In 32 consecutive patients with CHF (NYHA class II to IV) and different degrees of water retention, 24-hour diuresis and natriuresis were inversely best correlated with the combination of circulating renin, aldosterone, norepinephrine, and renal perfusion pressure (RPP). Fluid removal (600 to 5,000 ml) at a rate of 500 ml/h, until right atrial pressure decreased to 50% of baseline, caused variable humoral, circulatory, and diuretic effects that were mainly related to the extent of fluid retention. In fact, in 10 patients (Group 1) with overhydration refractory to drug therapy and with urinary output less than 1,000 ml/24 h (mean 370 ml), soon after the procedure, plasma renin (-39%), aldosterone (-50%), and norepinephrine (-47%) were reduced and RPP was increased (+ 16%), and in the subsequent 24 hours, diuresis was increased by 493%; in 9 patients (Group 2) whose baseline urinary output exceeded 1,000 ml/24 h (mean 1,785 ml), renin increased by 40%, norepinephrine, aldosterone and RPP each decreased by 12%, and diuresis remained unchanged; in 13 patients (Group 3) with a daily urinary excretion as in Group 2 and without overhydration, RPP decreased (-7%), renin (+ 196%), aldosterone (+ 170%), and norepinephrine (+ 52%) increased, and diuresis decreased by 45%. There was an overall correlation (p < 0.0001) between the combination of changes in these circulatory and hormonal variables and changes in diuresis and natriuresis with ultrafiltration.(ABSTRACT TRUNCATED AT 250 WORDS)

Control of pulmonary vasomotility in congestive heart failure.

Although enhanced sympathetic tone is a well-known component of the autonomic imbalance of heart failure, its influence on pulmonary vasomotility is undefined. We investigated the pulmonary circulation in 12 patients with congestive heart failure in NYHA functional class III and in a control group of 10 normal subjects. Sympathetic influence on pulmonary vessels was studied through adrenergic activation by the arithmetic test and the cold pressor test. A rubber balloon was distended in the inferior vena cava to reduce transpulmonary flow and its influence on vascular tone. In normal individuals the arithmetic test caused pulmonary vasodilation, probably because of the mechanical effect of a largely enhanced flow: in fact, caval obstruction unmasked a neurogenic vasoconstrictor response to the arithmetic test by simply reducing the amount of cardiac output increase. In patients with heart failure, cardiac output and pulmonary arteriolar resistance remained steady during the arithmetic test, no matter what the condition of the venous return was. The cold pressor test was always a vasoconstrictor stimulus, but only in normal subjects was vasoconstriction potentiated by reducing, with caval obstruction, transpulmonary flow and its vasodilatory influence. From these data an attenuation of the sympathetic influence on pulmonary vessels in congestive heart failure seems to be likely. This might be explained as the result of modifications of pulmonary vessels rather than of reduced sympathetic excitability since circulating catecholamine levels varied to similar extents in the two groups during the tests. In congestive heart failure interstitial edema and vascular wall imbibition might increase pulmonary vessel tone and decrease vascular receptor availability. Lower reactivity to sympathetic stimuli, particularly to the vasoconstrictor ones, would ensue.

[Interrelation of plasma volume, fluid metabolism and neurohormonal activation after ultrafiltration in congestive heart failure]. / Interrelazione tra volume plasmatico, metabolismo idrico ed attivazione neurormonale dopo ultrafiltrazione nello scompenso cardiaco congestizio.

Ultrafiltration improves the clinical condition of patients with congestive heart failure (CHF) through a reduction of excessive body water. We investigated the relationships among intra and extravascular fluids, hemodynamics and neurohumoral pattern following plasma water subtraction. In 55 patients with CHF (35 in NYHA class IV, Group A, and 20 in NYHA class II-III, Group B), removal of 3242 +/- 201 ml and 1741 +/- 119 ml of plasma water acutely reduced plasma volume (calculated from hematocrit changes) by -20.7% and -12.9% in Group A and in Group B, respectively. Plasma volume returned to baseline values within 48 hours. Body weight and ventricular filling pressures also lowered and remained so for 2 days. After ultrafiltration urinary output increased and norepinephrine, renin activity and aldosterone plasma levels decreased in Group A, while a fall of diuresis and a rapid rise of plasma levels of the 3 hormones were observed in Group B. Two days after ultrafiltration the persistence of reduced body weight with recovery of plasma volume indicates a shift of fluid from the extravascular to the intravascular compartment. The different behaviour of hemodynamics, urinary output and neurohumoral pattern changes observed in the 2 groups after ultrafiltration, suggest that in severe heart failure (Group A) the physiological responses to intravascular volume depletion are unsettled while are preserved in less severe stages of the disease (Group B).

[Changes in pulmonary vascular reactivity to adrenergic stimuli in congestive heart failure]. / Modificazioni della reattività vascolare polmonare agli stimoli adrenergici nello scompenso cardiaco congestizio.

Heart failure is associated with increased activity of sympathetic nervous system. As to the latter's effector organs, attention has been mainly drawn by heart and systemic circulation. In this study we investigated whether and how the neurogenic vasomotility of the lesser circulation is modified. Therefore, we compared 12 patients with heart failure in III NYHA functional class, with 10 subjects, undergoing hemodynamic study for diagnostic reasons and found to be normal. The neurogenic reactivity of pulmonary vessels was assayed by means of 2 sympathetic stimuli: arithmetic test (AT) and cold pressor test (CPT), performed both with and without obstruction to right heart venous return. This was obtained by expanding a balloon in inferior vena cava, in order to rid the neurogenic component of pulmonary vasomotility of the interference of the normally prevailing mechanical component (consisting in adaptations to flow variations). AT caused pulmonary vasodilation in normal subjects, as a passive consequence of the increase of cardiac output and, therefore, of pulmonary flow. Caval obstruction, by simply restraining this increase, induced a clearly neurogenic vasoconstrictor response. On the contrary, in failing patients, a slight vasodilation, independently from the condition of venous return, was observed. This took place in spite of the constant absence of any variations of cardiac output, which both indicates the reduction of myocardial function and helps to show the diminished nervous influence on pulmonary circulation. On the other hand, CPT had a vasoconstrictor effect in both groups, though potentiated by the reduction of transpulmonary flow in normal subjects only.(ABSTRACT TRUNCATED AT 250 WORDS)