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Alessandro Barbone

Publications and source records attributed to Alessandro Barbone.

11 recordsLinked to original sources
PubMed2005

Left ventricular assist device support normalizes left and right ventricular beta-adrenergic pathway properties.

OBJECTIVES: We hypothesized that some aspects of left ventricular assist device (LVAD) reverse remodeling could be independent of hemodynamic factors and would primarily depend upon normalization of neurohormonal milieu. BACKGROUND: The relative contributions of LVAD-induced hemodynamic unloading (provided to the left ventricle [LV]) and normalized neurohormonal milieu (provided to LV and right ventricle [RV]) to reverse remodeling are not understood. METHODS: Structural and functional characteristics were measured from hearts of 65 medically managed transplant patients (MED), 30 patients supported with an LVAD, and 5 nonfailing donor hearts not suitable for transplantation. RESULTS: Compared with MED patients, diastolic pulmonary pressures trended lower (p < 0.01) and cardiac output higher (p < 0.001) in LVAD patients; V(30) (ex vivo ventricular volume yielding 30 mm Hg, an index of ventricular size) in LVAD patients was decreased in the LV (p < 0.05) but did not change significantly in RV. The LVAD support improved force generation in response to beta-adrenergic stimulation in isolated LV (increase in developed force from 6.3 +/- 0.6 to 18.5 +/- 4.4 mN/m(2), p < 0.01) and RV (increase in developed force, from 10.9 +/- 2.0 to 20.5 +/- 3.1 mN/m(2), p < 0.05) trabeculae. The LVAD patients had higher myocardial beta-adrenergic receptor density in LV (p < 0.01) and RV (p < 0.01). Protein kinase A (PKA) hyperphosphorylation of the ryanodine receptor 2 (RyR2)/calcium release channel was significantly reduced by LVAD in both RV and LV (p < 0.01). CONCLUSIONS: Improved beta-adrenergic responsiveness, normalization of the RyR2 PKA phosphorylation, and increased beta-adrenergic receptor density in LV and RV after LVAD support suggest a primary role of neurohormonal environment in determining reverse remodeling of the beta-adrenergic pathway.

Adult↗
PubMed2004

Aspergillus left ventricular assist device endocarditis.

Left ventricular assist device (LVAD) support is an established therapy for patients with end-stage heart failure as a bridge to transplant; its usage as an alternative for those patients not eligible for transplant is not an established therapy yet. A 68-year-old male had a Thoratec-Heartmate LVAD implanted as destination therapy. After an uneventful (apart from early fever) recovery in the intensive care unit, the patient developed an intractable high temperature, and generalized sepsis and died 21 days following implant. The white cell blood count never exceeded the guard limits, and the patient succumbed with severe LVAD valve malfunction. At post-mortem examination friable material consisting of fungal hyphae was found on the inflow and outflow valves. According to published clinical trials, infection accounts for more than 40% of mortality in LVAD supported patients. Fungal LVAD endocarditis is a particularly deadly disease. Successful management requires a high level of suspicion and timely institution of antifungal therapy to control the infection. This has led some authors to recommend empiric antifungal therapy in LVAD recipients with culture-negative sepsis unresponsive to broad-spectrum antibiotics.

Aged↗
PubMed2003

Beta-blockers restore calcium release channel function and improve cardiac muscle performance in human heart failure.

BACKGROUND: Chronic beta-adrenergic receptor (beta-AR) blockade improves cardiac contractility and prolongs survival in patients with heart failure; however, the mechanisms underlying these favorable responses are poorly understood. Stress-induced activation of the sympathetic nervous system results in protein kinase A (PKA)-mediated phosphorylation of the calcium (Ca2+) release channel/cardiac ryanodine receptor (RyR2), required for cardiac excitation-contraction (EC) coupling, activating the RyR2 channel, and increasing cardiac contractility. The hyperadrenergic state of heart failure results in leaky RyR2 channels attributable to PKA hyperphosphorylation and depletion of the stabilizing FK506 binding protein, FKBP12.6. We tested the hypothesis that improved cardiac muscle function attributable to beta-AR blockade is associated with restoration of normal RyR2 channel function in patients with heart failure. METHODS AND RESULTS: We assessed the effects of beta-AR blockade on left ventricular volume using isolated perfused hearts and beta-agonist responsiveness using muscle strips from patients undergoing transplantation. Twenty-four human hearts were examined, 10 from patients with heart failure treated with beta-AR blockers (carvedilol, metoprolol, or atenolol), 9 from patients with heart failure without beta-AR blocker treatment, and 5 normal hearts. RyR2 PKA phosphorylation was determined by back-phosphorylation, FKBP12.6 in the RyR2 macromolecular complex was determined by coimmunoprecipitation, and channel function was assayed using planar lipid bilayers. beta-AR blockers reduced left ventricular volume (reverse remodeling) and restored beta-agonist response in cardiac muscle from patients with heart failure. Improved cardiac muscle function was associated with restoration of normal FKBP12.6 levels in the RyR2 macromolecular complex and RyR2 channel function. CONCLUSIONS: Improved cardiac muscle function during beta-AR blockade is associated with improved cardiac Ca2+ release channel function in patients with heart failure.

Adrenergic beta-Antagonists↗
PubMed2003

Cryoablation of the left posterior atrial wall: 95 patients and 3 years of mean follow-up.

OBJECTIVE: Endocardial ablation of the left atrial posterior wall has been used to treat atrial fibrillation. Aim of the study was to evaluate its efficacy looking for the ablation pattern allowing a fast execution with limited interference on atrial contractility. Moreover a statistical analysis to identify predictors of long-term sinus rhythm recovery has been provided. METHODS: From April 1998 to May 2002, 95 patients with permanent (mean duration 65 months) or persistent (33%) atrial fibrillation have undergone three different ablation patterns, only 1 patient being affected by lone atrial fibrillation. Mean antero-posterior left atrial diameter was 76.2 mm. The prospective study collected information regarding variables related to patients' demographics, disease's characteristics and type of surgical ablation employed. Dependent variables were presence of sinus rhythm either at discharge and at 6 months. A logistic regression analysis was used to estimate the association between the collected variables and sinus rhythm restoration. RESULTS: In-hospital and late mortality rate were 3.2 and 6.3% respectively. At discharge 67 patients (72.8%) were in sinus rhythm while at a mean follow-up of 3 years, 81.4% of 86 surviving patients are in sinus rhythm. Major adverse events rate including cardiac reoperation, pace-maker implantation and cerebrovascular accident were 8.5, 6.3 and 4.2%, respectively. Pre-operative atrial fibrillation duration, left atrial dimension and type of mitral disease did not show any correlation with long term success while the lesion pattern and the rhythm at discharge were significant predictive factors. Survival is significantly higher in patients who converted to sinus rhythm at discharge (P=0.014) with respect to those who remained in atrial fibrillation. CONCLUSIONS: Permanent and persistent atrial fibrillation associated to a major cardiac disease can be safely treated with a linear ablation of the left atrial posterior wall. Satisfactory results in terms of rhythm restoration may be achieved regardless of the duration of the arrhythmia and its effects on atrial diameter. Any effort should be prompted to discharge patients in sinus rhythm. Life expectancy is longer if sinus rhythm is restored.

Aged↗
PubMed2003

Surgical treatment of atrial fibrillation in the beating heart: a novel approach.

Up to 50% of patients undergoing mitral valve surgery have concomitant atrial fibrillation. An epicardial approach may offer the benefit of reducing the aortic cross-clamping time and avoiding an undue left atriotomy. During the last year we have been developing a simple technique to reproduce epicardially the same lesion pattern we had previously achieved endocardially. Two patients with chronic atrial fibrillation received atrial ablation using a microwave energy probe (Flex-10, AFx Inc., Fremont, CA, USA) immediately before undergoing a concomitant cardiac procedure. The procedure is relatively quick to perform and with appropriate care can be conducted with a low risk of perioperative adverse events.

Atrial Fibrillation↗
PubMed2002

LVAD support in patients with bioprosthetic valves.

The presence of mechanical or bioprosthetic valves has traditionally excluded patients from mechanical circulatory support. However, several centers have now developed algorithms for the surgical management of native or prosthetic valve disease in patients requiring left ventricular assist device insertion. We report adverse events associated with bioprosthetic valves in the mitral and tricuspid positions in 2 patients who received long-term mechanical support. We recommend anticoagulation for all patients with prosthetic valves in the mitral or tricuspid position to avoid thromboembolism, inflow conduit occlusion, or valvular incompetence.

Aortic Valve↗
PubMed2002

Disease-specific remodeling of cardiac mitochondria after a left ventricular assist device.

BACKGROUND: Failing hearts can exhibit elements of structural and molecular "reverse remodeling" after support with a left ventricular assist device (LVAD). The present study examined LVAD-induced remodeling of cardiac mitochondria. METHODS: Left ventricular tissue from 20 failing and 21 LVAD-supported hearts, catagorized as ischemic (ICM) or dilated (DCM) cardiomyopathy and four nonfailing hearts were studied. Myocyte mitochondrial ultrastructure was assessed by high-performance liquid chromatography determination of cardiolipin, a specific lipid component of the inner membrane, and its three major molecular species: L4, L3O, and L2O2. RESULTS: Both failing and LVAD-supported hearts exhibited a reduction in cardiolipin content that was independent of the type of cardiomyopathy. However, in failing/ICM hearts, there was a 25% increase in the L4/L3O ratio and a 70% increase in the L4/L2O2 ratio, indicating a change in cardiolipin composition. These alterations were normalized by LVAD support. In sharp contrast, molecular species ratios in DCM hearts were the same as those in nonfailing hearts regardless of whether LVAD support had been used or not. CONCLUSIONS: These data demonstrate LVAD-induced reverse remodeling of myocyte cardiolipin composition in ICM but not DCM hearts.

Adult↗
PubMed2002

Endogenous endothelium-derived nitric oxide inhibits myocardial caspase activity: implications for treatment of end-stage heart failure.

BACKGROUND: Apoptosis contributes to ventricular remodeling in heart failure (HF). Nitric oxide (NO) inhibits caspase 3, a key effector apoptotic enzyme. We hypothesized that reduced endogenous NO in HF disinhibits cardiac caspase 3 to promote apoptosis. METHODS: Caspase 3 activity was measured colorimetrically in myocardial cell lysates from endothelial NO synthase (eNOS)-deficient mice (eNOS -/-; n = 18), cardiomyopathic (CMP) hamsters (n = 8), and explanted failing human hearts (n = 10). We stimulated myocardial caspase 3 activity by adding upstream caspase 8 or 9. Cell lysates were incubated with 10(-4) mol/liter NO donor, S-nitroso-N-acetyl penicillamine; NOS inhibitor, nitro-L-arginine-methyl ester (L-NAME); or angiotensin-converting enzyme (ACE) inhibitor, enalaprilat. Hamsters underwent echocardiography so we could study the progression of ventricular dysfunction. RESULTS: Stimulated caspase 3 activity was lower in myocardium of eNOS +/+ compared with eNOS -/- mouse hearts (5.1 +/- 0.5 vs 7.6 +/- 1.0 pmol/10 microg/min, p < 0.05). L-NAME increased enzyme activity only in eNOS +/+ mice, indicating that endogenous NO inhibits caspase 3. Stimulated caspase 3 activity was lower in control hamsters, 3.3 +/- 0.3 pmol/10 microg/min, compared with CMP hamsters, 9.6 +/- 0.7 and 6.9 +/- 0.4 pmol/10 microg/min at 4 and 9 months, respectively. This was associated with progressive ventricular dysfunction, thinning, and dilatation. L-NAME increased enzyme activity in normal but not in CMP hamsters. In failing human myocardium, L-NAME failed to alter caspase activity, indicating reduced NO availability. Enalaprilat inhibited caspase 3, which was reversed by L-NAME. S-nitroso-N-acetyl penicillamine reversed caspase 3 activation in all groups. CONCLUSIONS: Nitric oxide reversibly inhibits myocardial caspase 3 independent of the apoptotic signaling pathway. Reduced NO in HF increases myocardial caspase 3 activity. Agents that promote NO synthesis, including ACE inhibitors, may prevent caspase activation in HF.

Animals↗
PubMed2002

Assessment of synchrony relationships between the native left ventricle and the HeartMate left ventricular assist device.

BACKGROUND: It has been suggested that the cardiac cycle becomes synchronized with the LVAD. Synchronization between the left ventricle and the LVAD may be important for ventricular unloading and coronary flow. In this study, we assessed the synchrony between the cardiac and LVAD cycles. METHODS: We studied 24 patients with HeartMate LVAD support. Native heart rate from an electrocardiogram and LVAD rate were measured at rest and peak exercise. Three patients underwent simultaneous invasive pressure measurement from the left ventricle and the aorta, and 3 patients underwent simultaneous recording of electrocardiogram and LVAD electrical signal. RESULTS: Resting heart rate was significantly higher than LVAD rate (96 +/- 17 vs 66 +/- 15 beats [b]/min, p < 0.0001), with no correlation between the 2 (r = 0.25). Peak heart rate was significantly higher than LVAD rate (142 +/- 16 vs 102 +/- 14 b/min, p < 0.0001), with no correlation observed (r = 0.31). Electrical signal recording confirmed the absence of cardiac-LVAD synchrony. Pressure measurements revealed a cyclical intraventricular pressure variation, determined by the relationship between the cardiac and LVAD cycles. Intraventricular pressure was lowest when left ventricular systole occurred during pump filling and highest when left ventricular systole occurred during pump ejection. CONCLUSIONS: The cardiac and LVAD cycles are not in synchrony at rest or at peak exercise. However, a cyclical variation in left ventricular pressure exists, dependent upon the phasic relationship of the cardiac-LVAD cycles, which significantly effects ventricular loading. Better understanding of this relationship may be important in developing assist devices for optimal left ventricular unloading and improvement of myocardial recovery.

Adult↗
PubMed2002

A video-assisted thoracoscopic technique to encircle the four pulmonary veins: a new surgical intervention for atrial fibrillation ablation.

BACKGROUND: Atrial fibrillation (AF) is the most common of the so-called benign arrhythmias. It affects not only life expectancy but also quality of life. Until recently, surgeons have most often encountered AF in association with ischemic or valvular disease but rarely as lone atrial fibrillation (LAF). For the subset of LAF patients, a minimally invasive procedure is recommended. METHODS: Using an animal model, we have developed a video-assisted thoracoscopic approach to atrial ablation whereby the ablation is performed encircling the four pulmonary veins as through a median sternotomy. RESULTS: Fifteen animals were used, and in 5 a complete encircling of the pulmonary veins was accomplished using the thoracoscopic approach. DISCUSSION: Video-assisted thoracoscopy is a feasible and safe approach for epicardial pulmonary vein ablation. This technique offers the option of surgery to a class of patients who are resistant to medical therapy but for whom the presence of LAF contraindicates the open chest approach.

Animals↗