Antonio D'Aloia

Bradykinin Antagonism Inhibits the Antigrowth Effect of Converting Enzyme Inhibition in the Dog Myocardium After Discrete Transmural Myocardial Necrosis

BACKGROUND Converting enzyme inhibitor (CEI) therapy, but not angiotensin II subtype I receptor blockade, has been shown to attenuate left ventricular remodeling in the dog after transmyocardial direct current (DC) shock. The purpose of this study was to address the importance of preservation of bradykinin to the antiremodeling effect of CEI treatment in this model. METHODS AND RESULTS Twenty-four hours after DC shock, adult mongrel dogs were assigned to one of three groups: a control group; a group treated with ramipril 10 mg BID; and a group treated with ramipril 10 mg BID along with a continuous subcutaneous infusion of HOE 140, a bradykinin antagonist. To assess change in left and right ventricular structure, a magnetic resonance imaging (MRI) study was performed 4 weeks after DC shock and compared with a baseline MRI study performed before DC shock. The increase in left ventricular mass (mean +/- SEM) in the control group was similar to that observed in the CEI-HOE 140 group (+0.73 +/- 0.19 versus +0.75 +/- 0.18 g/kg, P = NS), but both were greater than the change in mass in the ramipril group (-0.48 +/- 0.13 g/kg, P = .004 and P = .0005, respectively). No significant change occurred in left ventricular volume or right ventricular structure in any group. Mean arterial pressure was reduced by ramipril compared with the control group (-8 +/- 2 versus +7 +/- 2 mm Hg, P = .03), and this effect was not blunted by the addition of HOE 140 (-7 +/- 3 mm Hg). CONCLUSIONS Prevention by ramipril of the early increase in left ventricular mass in the DC shock model appears to be related to the preservation of bradykinin.

Haemodynamic effects of intravenous growth hormone in congestive heart failure

and were in sinus rhythm. Patients with other systemic diseases, or severe renal and hepatic failure, were not included. Patients gave written informed consent and the study protocol was approved by our ethics committee. Patients entered the study after 7 days in hospital. The 24 h after right-heart catheterisation were the control period. Over the next 24 h patients had a continuous intravenous infusion of 0·1 IU/kg over 24 h of recombinant human GH (Humatrope, Eli Lilly, Italy). In 11 patients, serial blood samples for GH assay (IRMA kit; Allegro, Nichols, USA) were taken during infusion. Blood samples for insulin-like growth factor 1 (IGF-1) (RIA kit after acid-ethanol extraction; Nichols, USA) assay were taken at the beginning and at the end of the GH infusion. Treatment for heart failure was unchanged throughout the study. Meals were served at 0700 h, 1200 h, and 1800 h. Pulmonary artery (PAP) pressure was measured with a 7·5 F Swan-Ganz catheter (Sorenson Research, USA) introduced through the right jugular vein; cardiac output was measured in triplicate by thermodilution; a brachial artery was cannulated with a 20 gauge catheter (Arrow, USA) to record arterial blood pressure. Measurements were made 30 min after right heart catheterisation, at the end of the control period, and every 4 h during GH infusion. Cardiac index (CI) was calculated from these measurements. Mean GH concentration increased five-fold during infusion (from 2·5 [SD 1·4] to 13·6 [8·3] μg/L) (figure). IGF-1 increased by about 50% compared with the perfusion concentration (from 168·7 [61·6] to 248·3 [86·6] μg/L). Patients had mean baseline CI 2·1 (0·8) L/min per m and mean PAP 40·3 (10·2) mm Hg. Four patients had a CI of 2·5 L/min per m or more and 11 had mean PAP of more than 20 mm Hg. Reproducibility of the haemodynamic measurements was excellent since all data at the beginning of the study were superimposable to those observed at the start of GH infusion. After 24 h of GH infusion, mean CI increased (3·3 [1·2] vs 2·1 [0·6] Lmin m , p<0·01). Ten patients had a CI of 2·5 Lmin m 2 or more at the end of GH infusion; one patient had a worsening CI (from 3 to 2·8 Lmin m ). In ten of the 11 responding patients, the CI continued to increase for the whole period of the infusion (figure). After 24 h of GH infusion, there was about a 25% drop in mean PAP (figure). Three patients had mean PAP of less than 20 mm Hg after GH infusion. The patient who did not have an improved CI had an increase in pulmonary pressures after GH. Eight patients reached the lowest mean PAP between 4 and 8 h from the beginning of the infusion. No cardiovascular or other ill effects were seen during GH infusion. Long-term treatment with high dose GH has been shown

A rationale for the use of β-blockers as standard treatment for heart failure☆

Abstract Background Cardiac sympathetic activation is one of the major and earlier changes observed in patients with heart failure. Its relation to the severity of the disease and its independent prognostic value show that it may directly contribute to the progression of heart failure. β-Blockers are the most effective tool to counteract the untoward effects of sympathetic activation on the cardiovascular system. Methods and Results We reviewed the results of the placebo-controlled, double-blind studies about the effects of β-blockers in patients with heart failure. These studies have involved almost 10,000 patients to date and have consistently shown that the long-term administration of β-blockers is associated with a highly significant improvement in both left ventricular function and prognosis of the patients with heart failure. The evidence supporting the use of ν-blockers now equals or even surpasses that of angiotensin-converting enzyme inhibitors; therefore β-blockers should be considered part of standard therapy. Issues that remain unclarified include the mechanisms through which β-blockers may improve cardiac function and their tolerability and efficacy in specific groups of patients (such as those with asymptomatic left ventricular dysfunction, severe heart failure, the elderly, or those with left ventricular diastolic dysfunction). It is not currently clear whether the pharmacologic differences between indvidual β-blockers are clinically relevant. If they are, the potential for even greater benefit with certain agents exists. It is hoped that these issues will be clarified by the results of ongoing multicenter trials.

Epidemiology and cardiovascular risk factors of aortic stenosis

The abnormalities of aortic valve morphology and function represent the most common cardiac-valve lesion particularly in elderly. The etiology of aortic stenosis is degenerative-calcific in the majority of patients. Many risk factors seems to be linked to the calcification and the stenosis of the aortic valve but they must be confirmed. In this review the etiology and the possible physiopathology of the aortic valve stenosis is discussed.

Contribution of left atrial pressure and dimension to signal-averaged P-wave duration in patients with chronic congestive heart failure.

In a group of patients with chronic heart failure, a longer P-wave duration on signal-averaged electrocardiogram was found in those patients with higher pulmonary capillary wedge pressure, whereas the left atrium end-systolic diameter was not significantly different. Furthermore, an acute reduction in pulmonary capillary wedge pressure induced by sodium nitroprusside infusion was associated with a reduction in P-wave duration.

Effect of Spironolactone on Left Ventricular Ejection Fraction and Volumes in Patients With Class I or II Heart Failure

The beneficial effects of spironolactone in chronic heart failure (HF) have been demonstrated in patients with New York Heart Association (NYHA) class III to IV HF. This study examined the effect of spironolactone on left ventricular (LV) function and functional capacity of patients with mild to moderate HF (NYHA class I to II). One hundred sixty-eight patients with NYHA class I to II HF and LV ejection fraction ≤40% were randomized to spironolactone or placebo and assessed by echocardiography, gated single-photon emission computed tomography, technetium-99m sestamibi single-photon emission computed tomographic radionuclide ventriculography, and cardiopulmonary exercise testing at baseline and after 6 months of treatment. In the spironolactone group LV ejection fraction increased from 35.2 ± 0.7% to 39.1 ± 3.5% (p <0.001), with a decrease in LV end-diastolic and end-systolic volumes and myocardial mass and an improvement in LV diastolic filling pattern. Cardiopulmonary exercise testing parameters did not change. In conclusion, administration of spironolactone to patients with NYHA class I to II HF has beneficial effects on LV remodeling and diastolic function.

Direct transcatheter aortic valve implantation with self-expandable bioprosthesis: Feasibility and safety ☆

BACKGROUND Balloon valvuloplasty has been considered a mandatory step of the transcatheter aortic valve implantation (TAVI), although it is not without risk. The aim of this work was to evaluate the feasibility and safety of TAVI performed without pre-dilation (direct TAVI) of the stenosed aortic valve. MATERIAL AND METHODS Between June 2012 and June 2013, 55 consecutive TAVI performed without pre-dilation at our institution using the self-expandable CoreValve prosthesis (Medtronic, Minneapolis, MN) were analyzed and compared with 45 pre-dilated TAVI performed the previous year. Inclusion criteria were a symptomatic and severe aortic stenosis. Exclusion criteria were defined as presence of pure aortic regurgitation, degenerated surgical bioprosthesis or bicuspid aortic valve and prior procedure of balloon aortic valvuloplasty performed as a bridge to TAVI. RESULTS High-burden calcification in the device landing zone, assessed by CT scan, was found in most of the patients. The valve size implanted was similar in both groups. Device success was higher in direct TAVI (85%vs.64%,p=0.014), mostly driven by a significant lower incidence of paravalvular leak (PVL≥2;9%vs.33%,p=0.02). Safety combined end point at 30 days was similar in both groups. CONCLUSION Compared to TAVI with pre-dilation, direct TAVI is feasible regardless of the presence of bulky calcified aortic valve and the valve size implanted. Device success was higher in direct TAVI, mostly driven by a lower incidence of paravalvular leak. Safety at 30 days was similar in two groups.

How often we need to measure brain natriuretic peptide (BNP) blood levels in patients admitted to the hospital for acute severe heart failure? Role of serial measurements to improve short-term prognostic stratification.

BACKGROUND Brain natriuretic peptide (BNP) is increasingly used in the management of patients with heart failure (HF). It is still unclear how to use serial BNP measurement in HF. AIM To evaluate the usefulness of three consecutive measurements of BNP in patients (pts) hospitalized for acute HF. METHODS Clinical evaluation, BNP levels and echocardiography were assessed in 150 pts (67% males, age: 69+/-12 years; left ventricular ejection fraction: 34+/-14%) admitted for severe HF (NYHA class III-IV: 146/150). BNP measurements were obtained: at admission (basal, T0), at discharge (T1) and at first ambulatory control (T2), after optimization of medical therapy in those with discharge BNP level >250 pg/mL. End-points were death and hospital readmission during 6-month follow-up. RESULTS According to BNP levels 3 groups of patients were identified: Group 1 (62 pts, 41%), in whom discharge (T1) BNP was high and persisted elevated at T2 despite aggressive medical therapy; at 6-month follow-up 72% died or were hospitalized for HF. Group 2 (36 pts, 24%), in whom discharge (T1) BNP was high but decreased after medical therapy (T2); death and HF-readmission were observed in 8 pts (26%). Group 3 (52 pts, 35%), in whom discharge (T1) BNP levels were <250 pg/mL and persisted below this value at T2; death and HF-hospital readmission were observed in 6 pts (12%). Event rate differences among groups were statistically significant (p<0.001). At Cox-analysis discharge BNP cutoff of 250 pg/mL was the only parameter predictive of a worse outcome. CONCLUSION These data suggest that 3 BNP measurements, at admission, at discharge and few weeks later can allow to identify HF pts whom, despite a further potentiation of medical therapy, will present a worsening or even will die during short-term follow-up.

Refractory Spasm of Coronary Arteries and Grafted Conduits After Isolated Coronary Artery Bypass Surgery

BACKGROUND Refractory vascular spasm (RVS) concomitantly involving the entire coronary artery system and grafted conduits after coronary artery bypass grafting (CABG) surgery is a rare, but dreadful event. No consensus exists in terms of appropriate management. METHODS Between 1986 and 2009, 5,762 patients underwent isolated CABG at our institution, and 7 patients experienced RVS involving the coronary arteries and implanted conduits. Mean age was 65.6 years and 3 were female. All patients received from 3 to 5 distal anastomoses, including use of the left internal mammary artery. During the same time period, 18 patients experienced perioperative vasospasm of a single coronary artery or of a grafted conduit. RESULTS All diffuse RVS events occurred between 3 and 8 hours after surgery. All patients had diffuse ischemic-like electrocardiographic changes, and 5 patients rapidly developed cardiogenic shock in the intensive care unit. Angiography was quickly performed in all patients and showed diffuse RVS involving either the native coronary arteries or the anastomosed arterial and venous conduits. The first 5 patients of this series died in the catheterization lab due to rapidly evolving refractory cardiogenic shock and unresponsive cardiac arrest, despite intraaortic counterpulsation and aggressive pharmacologic interventions (selective vasodilators and systemic inotropes). In the last 2 patients, extracorporeal membrane oxygenation was quickly instituted (1 in the catheterization lab, 1 in the operating room) and RVS could be successfully managed with complete resolution of ongoing vasospasm. In the single vascular spasm, there was only 1 death for refractory cardiac arrest, whereas all the other patients were successfully treated with direct infusion of vasodilators. CONCLUSIONS Diffuse RVS after CABG is a rare but lethal condition. Our experience, although limited, indicates that in such cases an aggressive treatment, that is, prompt extracorporeal membrane oxygenation institution and controlled cardiocirculatory assistance, represents the preferred solution to face such a dramatic event and may save patient lives.

Relative contribution of resting haemodynamic profile and lung function to exercise tolerance in male patients with chronic heart failure

OBJECTIVE To clarify the relative contribution of resting haemodynamic profile and pulmonary function to exercise capacity in patients with heart failure. SETTING Cardiology department and cardiac rehabilitation unit in a tertiary centre. DESIGN 161 male patients (mean (SD) age 59 (9) years) with heart failure (New York Heart Association class II–IV, left ventricular ejection fraction 23 (7)%) underwent spirometry, alveolar capillary diffusing capacity (DLCO), and mouth inspiratory and expiratory pressures (MIP, MEP, respectively, in 100 patients). Right heart catheterisation and a symptom limited cardiopulmonary exercise test were performed in 137 patients within 3–4 days. RESULTS Mean peak exercise oxygen consumption (V˙o 2) was 13 (3.9) ml/kg/min. Among resting haemodynamic variables only cardiac index showed a significant correlation with peakV˙o 2. There were no differences in haemodynamic variables between patients with peakV˙o 2 ⩽ or > 14 ml/kg/min. There was a moderate correlation (p < 0.05) between several pulmonary function variables and peak V˙o 2. Forced vital capacity (3.5 (0.9) v 3.2 (0.8) l, p < 0.05) and DLCO (21.6 (6.9) v 17.7 (5.5) ml/mm Hg/min, p < 0.05) were higher in patients with peakV˙o 2 > 14 ml/kg/min than in those with peak V˙o 2 ⩽ 14 ml/kg/min. Using a stepwise regression analysis, the respiratory and haemodynamic variables which correlated significantly with peakV˙o 2 were DLCO, MEP, and cardiac index, with an overall R value of 0.63. CONCLUSIONS The data confirm previous studies showing a poor correlation between resting indices of cardiac function and exercise capacity in heart failure. However, several pulmonary function variables were related to peak exerciseV˙o 2. In particular, lung diffusing capacity and respiratory muscle function seem to affect exercise tolerance during heart failure.