Riccardo Sinatra - Academia.edu (original) (raw)
Papers by Riccardo Sinatra
European Journal of Cardio-Thoracic Surgery, 2019
PubMed, 1981
Hyperbaric oxygenation was used in two patients with extensive neurologic damage from cerebral ai... more Hyperbaric oxygenation was used in two patients with extensive neurologic damage from cerebral air embolism occurring during open-heart surgery. One patient made a full recovery. The use of hyperbaric oxygenation produces the most direct relief of the mechanical obstruction and provides the definitive treatment for cerebral air embolism. First consideration must be given to the prevention of this complication, but once an embolus has occurred, hyperbaric treatment should be instituted promptly and early. Therefore every team engaged in open-heart operations should be familiar with the diagnosis and the therapy of air embolism.
American Journal of Cardiology, Aug 1, 1992
PubMed, Sep 1, 2000
We report the diagnosis of mammary artery graft dysfunction by high-resolution transthoracic Dopp... more We report the diagnosis of mammary artery graft dysfunction by high-resolution transthoracic Doppler and venous adenosine infusion. The patient was treated by percutaneous balloon angioplasty, with optimal angiographic results. Coronary flow reserve in the distal left anterior descending artery was abnormal before angioplasty, and recovered soon after the procedure. The utility of this new non-invasive technique in the diagnosis of flow-limiting stenoses and follow-up of coronary angioplasty is described.
The Journal of Thoracic and Cardiovascular Surgery, Oct 1, 2001
Hemodynamic and clinical performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus aortic ... more Hemodynamic and clinical performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus aortic valves (St Jude Medical, Inc, St Paul, Minn) were compared with those of 21-mm and 23-mm St Jude Medical standard cuff aortic valves in the first such multicenter, prospective, randomized study. Hemodynamic Plus valves are mechanical, bileaflet prostheses suitable for the small aortic anulus. Patients with 21-mm and 23-mm anulus diameters were randomized to receive either a Hemodynamic Plus or a standard cuff valve. Postoperatively and at 6 months after the operation, patients underwent 2-dimensional Doppler echocardiography. Ejection fraction, cardiac output, peak gradient, mean gradient, effective orifice area, effective area index, and performance index were calculated. Postoperative and 6-month echocardiographic measurements and their variations across observation times were analyzed statistically. Of the 140 patients enrolled, 5 died at operation and 1 died of aortic dissection during the follow-up period. Eight patients were lost to follow-up. A total of 125 patients completed the study. In 1 patient a sewing cuff escaped intraoperatively. At 6 months the 21-mm and 23-mm Hemodynamic Plus valves showed significantly lower peak gradients and mean gradients than those of the 21-mm and 23-mm standard cuff valves. The 21-mm Hemodynamic Plus valves had gradients similar to those of the 23-mm Hemodynamic Plus valves. The effective orifice area did not differ significantly between the Hemodynamic Plus and standard cuff valves at either measurement. No valve mismatch was found in the 4 groups of patients. A more enhanced decrease of peak gradients and mean gradients and a more enhanced increase of effective orifice areas, effective area indices, and performance indices were found across observation times for patients with Hemodynamic Plus valves compared with those with standard cuff valves. Clinical hemodynamic performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus valves correspond closely with those of standard cuff valves, and gradients are substantially better than those of standard cuff valves of the same diameter. Therefore, use of this valve may minimize the need for aortic anulus enlargement. Early follow-up results with the Hemodynamic Plus valves were excellent, although more time is required to confirm this outcome.
Journal of Cardiovascular Electrophysiology, Dec 1, 1987
Unexpected Discharge from an Implanted Automatic Defibrillator. The occurrence of inappropriate d... more Unexpected Discharge from an Implanted Automatic Defibrillator. The occurrence of inappropriate discharge from an implanted cardioverter-defibrillator is reported. The device was triggered by an episode of induced nonsustained ventricular tachycardia, and the shock was delivered 10 sec after spontaneous termination of the arrhythmia. This observation demonstrates that unexpected discharges from an implanted cardiaverter/defibrillator can occur while the patient is asymptomatic. In order to avoid such an adverse effect, improvement of the detection system of the device is advisable.
Cardiologia (Rome, Italy), 1991
From January 1981 to January 1991, 40 patients underwent operation for acute ascending aorta diss... more From January 1981 to January 1991, 40 patients underwent operation for acute ascending aorta dissection (AAD, 14 patients), chronic ascending aorta dissection (CAD, 9 patients) or aortic ectasia (AE, 17 patients), with simultaneous aortic valve replacement in 30 cases (75%). Average age was 54 years with a 3:1 M/F ratio. In 20 cases (50%) a composite graft bearing a mechanical bileaflet valve was inserted with coronary artery reattachment (Bentall operation). In 16 cases (40%) the ascending aorta was replaced by a woven dacron graft alone (7 cases) or associated with aortic valve substitution (7 cases) or resuspension (2 cases). In 1 case (2.5%) a sutureless ring graft replacement of ascending aorta was carried out and 3 patients (7.5%) underwent aortoplasty with aortic valve substitution. Postoperative mortality rate was 21% for AAD group, 11% for CAD group and 6% for AE group. Non-fatal postoperative complications developed in 36% of AAD patients and in 78% and 29% of CAD and AE p...
The Journal of Thoracic and Cardiovascular Surgery, Sep 1, 2013
To determine whether the SYNTAX score can predict the outcomes of patients with left ventricular ... more To determine whether the SYNTAX score can predict the outcomes of patients with left ventricular dysfunction undergoing coronary artery bypass grafting. We studied a consecutive series of 191 patients (mean age, 67 ± 10 years) with a left ventricular ejection fraction of 40% or less who were undergoing isolated coronary artery bypass grafting. All patients were stratified according to their SYNTAX score, indicating coronary artery disease complexity: low, 0 to 22; intermediate, 23 to 32; and high, 33 or more. The primary outcome was all-cause mortality. Secondary outcomes included the late occurrence of major adverse cardiac and cerebrovascular events, left ventricular function, and New York Heart Association functional class. The mean SYNTAX score was 32 ± 13, and the mean preoperative left ventricular ejection fraction was 35% ± 6%. At a median follow-up of 43 months, the primary outcome had occurred in 46 of 191 patients (24%). Kaplan-Meier analysis showed a survival of 81% ± 15% for low, 77% ± 7% for intermediate, and 53% ± 7% for high coronary artery disease complexity (χ(2), 29.4; P = .001). The rate of major adverse cardiac and cerebrovascular events was significantly greater in patients with a SYNTAX score of 33 or more (P = .002). Greater degrees of left ventricular ejection fraction improvement were found in patients with a SYNTAX score of 32 or less (+15% ± 10% vs +4% ± 11%; P = .17) and translated into a better New York Heart Association functional class among patients with a lower SYNTAX score (P = .01). Receiver operating characteristic curve analysis showed the SYNTAX score (area under the curve, 0.70; 95% confidence interval, 0.63-0.77) to have the best predictive power for late mortality with respect to the preoperative left ventricular ejection fraction (area under the curve, 0.59; difference, P = .04) and incomplete revascularization (area under the curve, 0.55; difference, P = .02). The results of the present study have shown a direct relationship between coronary artery disease complexity and late outcomes of patients with left ventricular dysfunction who are undergoing coronary artery bypass grafting. Additional studies are needed to confirm these findings.
International Journal of Cardiology, 2019
Background: The modified Bentall procedure is still the treatment of choice for patients requirin... more Background: The modified Bentall procedure is still the treatment of choice for patients requiring combined replacement of the ascending aorta and aortic valve. We compared the long-term outcome of patients >65 years of age undergoing Bentall procedure with biological vs mechanical valved conduits in a multi institutional study. Methods: A total of 282 patients, undergoing a Bentall operation (January 1994-May 2015), with a biological (Group1, 173 patients) or a mechanical (Group2, 109 patients) conduit were reviewed, the primary outcome being analysis of late survival and freedom from major adverse events. Results: Hospital mortality was 5% (9 patients) and 2% (2 patients) for Group 1 and Group 2 (p=0.2). Median follow-up was 77 months (range Q1-Q3: 49-111) for Group 1 vs 107 months (range Q1-Q3: 63-145) for Group 2 (p< 0.001). A not statistically significant advantage in late survival was found in patients receiving mechanical valved conduits (36% for Group1 vs 58% for Group2 at 12 years; p=0.09), although freedom from major adverse events was similar between the 2 groups (33% in Group 1 vs 50% in Group 2 at 12 years; p=0.3). Conclusions: In conclusion, mechanical-valved conduits employed for the modified Bentall procedure show a trend towards an improved late survival in patients ≥65 years of age and particularly in those between 65 and 75 years, despite a higher incidence of major adverse events. Our results indicate the need for specific guidelines to better define the ideal age limit for each type of valved conduit.
European Journal of Internal Medicine, 2011
European Heart Journal, 2018
co-expression networks and classify cell types. RNA in situ hybridization analysis was conducted ... more co-expression networks and classify cell types. RNA in situ hybridization analysis was conducted to validate the spatial expression profiles of novel cell type-specific gene. Furthermore, we performed genetic ablation to dissect the molecular and functional properties of the cell type-specific gene. Results: Computational analysis of single-cell transcriptomes clearly separated non-CMs into 4 cell groups and revealed their distinct gene programs. By transcriptional network analysis, we identified high-temperature requirement factor A3 (HtrA3) as a novel cardiac fibroblast-specific gene. RNA in situ hybridization analysis revealed a marked increase of HtrA3-expressing cardiac fibroblasts in response to pressure overload. HtrA3 knockout mice show that HtrA3 in cardiac fibroblast is essential for preventing TGFβ signaling activation, interstitial fibrosis, and cardiac dysfunction after pressure overload. Biochemical assay confirmed that HtrA3 represses the activity of TGFβ signaling by promoting cleavage of TGFβ. We also demonstrated that HTRA3 expression in heart is up-regulated in patients with heart failure, and is down-regulated after mechanical unloading. Conclusion: Single-cell RNA-seq analysis of non-CMs from healthy and failing hearts revealed the transcriptional stress response and distinct gene programs specific for cell types. We further identified HtrA3 in cardiac fibroblasts as a critical regulator of cardiac homeostasis, providing a potential therapeutic target for heart failure.
AORTA, 2014
Alkaptonuria is an autosomal recessive trait resulting in an error of aromatic amino acids metabo... more Alkaptonuria is an autosomal recessive trait resulting in an error of aromatic amino acids metabolism. Heyde's syndrome is a condition clustering together aortic valve stenosis and gastrointestinal bleeding from colonic angiodysplasia. At present, there is no report describing the association of the latter two syndromes in the same patient. Here we present the case of a patient with severe aortic stenosis, alkaptonuria, and Heyde's syndrome. The patient underwent aortic valve replacement by means of a valvular bioprosthesis and the histological examination of the aortic cusps revealed calcific degeneration. This was associated with stromal degeneration characterized by extra-cellular deposition of granular, brownish-pigmented material along with macrophages and multiple foci of calfication showing the same brownish pigmentation. This configuration represents the typical pattern of homogentisic acid accumulation known as ochronosis. The postoperative course was uneventful and the echocardiographic follow-up at 6 months postoperatively showed good-functioning of the aortic valve bioprosthesis.
Journal of Cardiovascular Medicine, 2010
Preoperative renal function is an important risk factor in cardiac surgery for long-term and shor... more Preoperative renal function is an important risk factor in cardiac surgery for long-term and short-term outcomes. Renal function is best assessed by measuring or calculating the glomerular filtration rate (GFR). Several algorithms using the endogenous marker serum creatinine have been developed to estimate renal function. These include the Cockcroft and Gault and the modification of diet in renal disease (MDRD) formulae. The aim of this study was to compare the predictive power of the two formulae towards short-term outcomes after cardiac surgery, such as the length of intensive care unit (ICU) stay, the length of mechanical ventilation time, and the length of in-hospital stay. One hundred and fifty patients undergoing cardiac surgery and not affected by renal failure were followed up until hospital discharge. We collected data before, during and after surgery. Before surgery data consisted of date of birth, sex, height, weight, plasma creatinine level; during surgery data consisted of type of intervention (including number of bypasses, if any), cardiopulmonary bypass time and aortic cross-clamp time; after surgery data consisted of length of ICU stay, mechanical ventilation time, length of in-hospital stay after intensive-care discharge (ward stay), incidence of acute renal failure (expressed as the need for dialysis) and mortality. The dataset was analyzed using Cox regression. The average mechanical ventilation time, ICU stay and ward stay were 11 h, 49 h and 10 days, respectively. After having adjusted for chronic obstructive pulmonary disease, diabetes and postsurgical dialysis, the GFR calculated with the Cockcroft and Gault formula appeared to be a predictor of ICU stay and mechanical ventilation time with very strong evidence (P = 0.002 and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001, respectively) and a predictor of ward stay with some evidence (P = 0.062). After an identical case-mix adjustment, the GFR calculated with the MDRD formula appeared to be a predictor of ICU stay with strong evidence (P = 0.007), a predictor of mechanical ventilation time with some evidence (P = 0.075) and it has shown no evidence of predicting ward stay (P = 0.197). There is an indication that the Cockcroft and Gault formula could be more powerful than the MDRD formula for the preoperative prediction of early postoperative clinical outcomes in cardiac surgery, in patients not affected by renal failure. Further research is needed to confirm this result.
The Journal of Thoracic and Cardiovascular Surgery, 2009
International Journal of Cardiology, 2003
International Journal of Cardiology, 1997
We aimed at investigating contractile changes after hypoxia-reoxygenation and dobutamine challeng... more We aimed at investigating contractile changes after hypoxia-reoxygenation and dobutamine challenge in superfused human atrial pectinate muscle to see whether high versus low stimulation rate during hypoxia might account for outcome differences compatible with the definition of an in vitro model of myocardial stunning and whether pretreatment with the dihydropyridine Ca2+ entry blocker felodipine might afford protection. Human right atrial trabeculae obtained from adult patients were superfused in an organ bath with oxygenated (O2 content 16 ml/l) and modified (NaHCO3 25.7 mmol/l) Tyrode&amp;#39;s solution at 37 degrees C. Dobutamine (1 nmol/l to 10 micromol/l) was superfused in 10 oxygenated preparations to select the optimal drug concentration to be used in another 22 which were randomized. Group (A) consisted of time-related controls (Tyrodes&amp;#39;s solution for 225 min at cycle length (CL) 1600 ms and no dobutamine). There were two test groups, respectively: (B) low (1600 ms CL) and (C) high (400 ms CL) stimulation rate. After 60 min of stabilization, in groups B and C, hypoxic superfusion (O2 content 5 ml/l) lasted 60 min, then reoxygenation (60 min) and dobutamine challenge (1 micromol/l, 15 min) were performed. Analysis of variance for repeated measures with the Greenhouse-Geisser correction, and a repeated measures model with structured covariance (preparation mass, length, width and time-varying time to peak tension) matrices were used whereby grouping (G), time (T) and G x T interaction were weighted. Force-frequency relationship and post-pausal potentiation were studied after each phase. Electrophysiology, histomorphometry and electron microscopy were carried out (n=6). Felodipine (0.1 micromol/l, n=5) pretreatment (15 min before hypoxia) was given in parallel experiments. Time-related controls showed approximately 10% per hour decrease of developed tension and the Paradise test provided approximately 80% of control values. In test groups (as compared to baseline values) contractility was decreased approximately 65% after hypoxia-reoxygenation and it increased approximately 25% after dobutamine (G, 0.0065&amp;lt;P&amp;lt;0.0155; T, P=0.00005; G x T, P=0.00005). High stimulation rate during hypoxia worsened hypoxia-reoxygenation contractile changes, whereas reversibility after dobutamine was less. In both B and C groups during hypoxia, contractility decreased quite rapidly, although by 10 min or so a plateau (approximately 50%) was reached in group B, whereas in group C contractility decreased to &amp;lt;20%. None of the covariates contributed significantly to predict the dependent variables investigated. Force-frequency relationship and post-pausal potentiation were repeatable, paralleled overall changes due to hypoxia, reoxygenation and dobutamine challenge and were useful to discriminate Ca2+-related diastolic processes thus helping index myocardial contractile reserve. Force-frequency relationship was negative at high stimulation rates, concomitant to an abrupt change of shape and duration of action potential with little time for Ca2+-related Ca2+ release and ensuing systolic processes. Felodipine pretreatment enabled an unblunted response to dobutamine. Histomorphometry showed an unexpected &amp;#39;fibrotic core&amp;#39;. At electron microscopy, subendocardial and deep part of the same pectinate muscles showed identical degrees of degenerative lesions. Superfused samples showed, unexpectedly, less anoxic lesions than preparations fixed within 15 min from surgical explant, although lesions were higher than in samples fixed immediately after explant. This might be a relevant model, whereby pharmacological or physical interventions are tested. Native human atrial trabeculae might be used without dissection and/or preservatives. If high stimulation rate during hypoxia is used the power of hypothesis testing is maximized. Future studies with this material will be easier and comparatively smaller series might be investigated. Felo
European Journal of Cardio-Thoracic Surgery, 2013
OBJECTIVE: A number of factors limit the effectiveness of current aortic arch studies in assessin... more OBJECTIVE: A number of factors limit the effectiveness of current aortic arch studies in assessing optimal neuroprotection strategies, including insufficient patient numbers, heterogenous definitions of clinical variables, multiple technical strategies, inadequate reporting of surgical outcomes and a lack of collaborative effort. We have formed an international coalition of centres to provide more robust investigations into this topic.
Cardiovascular Pathology, 2001
Expanded polytetrafluoroethylene (e-PTFE) sutures have been used with increasing frequency to rep... more Expanded polytetrafluoroethylene (e-PTFE) sutures have been used with increasing frequency to replace chordae tendineae in mitral valves prolapsing because of myxoid change. A case is reported where fibrosis and calcification of the endocardial overgrowth covering the synthetic chordae led to severe mitral regurgitation 7 years after plastic repair and required mechanical prosthetic valve implantation.
European Journal of Cardio-Thoracic Surgery, 2019
PubMed, 1981
Hyperbaric oxygenation was used in two patients with extensive neurologic damage from cerebral ai... more Hyperbaric oxygenation was used in two patients with extensive neurologic damage from cerebral air embolism occurring during open-heart surgery. One patient made a full recovery. The use of hyperbaric oxygenation produces the most direct relief of the mechanical obstruction and provides the definitive treatment for cerebral air embolism. First consideration must be given to the prevention of this complication, but once an embolus has occurred, hyperbaric treatment should be instituted promptly and early. Therefore every team engaged in open-heart operations should be familiar with the diagnosis and the therapy of air embolism.
American Journal of Cardiology, Aug 1, 1992
PubMed, Sep 1, 2000
We report the diagnosis of mammary artery graft dysfunction by high-resolution transthoracic Dopp... more We report the diagnosis of mammary artery graft dysfunction by high-resolution transthoracic Doppler and venous adenosine infusion. The patient was treated by percutaneous balloon angioplasty, with optimal angiographic results. Coronary flow reserve in the distal left anterior descending artery was abnormal before angioplasty, and recovered soon after the procedure. The utility of this new non-invasive technique in the diagnosis of flow-limiting stenoses and follow-up of coronary angioplasty is described.
The Journal of Thoracic and Cardiovascular Surgery, Oct 1, 2001
Hemodynamic and clinical performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus aortic ... more Hemodynamic and clinical performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus aortic valves (St Jude Medical, Inc, St Paul, Minn) were compared with those of 21-mm and 23-mm St Jude Medical standard cuff aortic valves in the first such multicenter, prospective, randomized study. Hemodynamic Plus valves are mechanical, bileaflet prostheses suitable for the small aortic anulus. Patients with 21-mm and 23-mm anulus diameters were randomized to receive either a Hemodynamic Plus or a standard cuff valve. Postoperatively and at 6 months after the operation, patients underwent 2-dimensional Doppler echocardiography. Ejection fraction, cardiac output, peak gradient, mean gradient, effective orifice area, effective area index, and performance index were calculated. Postoperative and 6-month echocardiographic measurements and their variations across observation times were analyzed statistically. Of the 140 patients enrolled, 5 died at operation and 1 died of aortic dissection during the follow-up period. Eight patients were lost to follow-up. A total of 125 patients completed the study. In 1 patient a sewing cuff escaped intraoperatively. At 6 months the 21-mm and 23-mm Hemodynamic Plus valves showed significantly lower peak gradients and mean gradients than those of the 21-mm and 23-mm standard cuff valves. The 21-mm Hemodynamic Plus valves had gradients similar to those of the 23-mm Hemodynamic Plus valves. The effective orifice area did not differ significantly between the Hemodynamic Plus and standard cuff valves at either measurement. No valve mismatch was found in the 4 groups of patients. A more enhanced decrease of peak gradients and mean gradients and a more enhanced increase of effective orifice areas, effective area indices, and performance indices were found across observation times for patients with Hemodynamic Plus valves compared with those with standard cuff valves. Clinical hemodynamic performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus valves correspond closely with those of standard cuff valves, and gradients are substantially better than those of standard cuff valves of the same diameter. Therefore, use of this valve may minimize the need for aortic anulus enlargement. Early follow-up results with the Hemodynamic Plus valves were excellent, although more time is required to confirm this outcome.
Journal of Cardiovascular Electrophysiology, Dec 1, 1987
Unexpected Discharge from an Implanted Automatic Defibrillator. The occurrence of inappropriate d... more Unexpected Discharge from an Implanted Automatic Defibrillator. The occurrence of inappropriate discharge from an implanted cardioverter-defibrillator is reported. The device was triggered by an episode of induced nonsustained ventricular tachycardia, and the shock was delivered 10 sec after spontaneous termination of the arrhythmia. This observation demonstrates that unexpected discharges from an implanted cardiaverter/defibrillator can occur while the patient is asymptomatic. In order to avoid such an adverse effect, improvement of the detection system of the device is advisable.
Cardiologia (Rome, Italy), 1991
From January 1981 to January 1991, 40 patients underwent operation for acute ascending aorta diss... more From January 1981 to January 1991, 40 patients underwent operation for acute ascending aorta dissection (AAD, 14 patients), chronic ascending aorta dissection (CAD, 9 patients) or aortic ectasia (AE, 17 patients), with simultaneous aortic valve replacement in 30 cases (75%). Average age was 54 years with a 3:1 M/F ratio. In 20 cases (50%) a composite graft bearing a mechanical bileaflet valve was inserted with coronary artery reattachment (Bentall operation). In 16 cases (40%) the ascending aorta was replaced by a woven dacron graft alone (7 cases) or associated with aortic valve substitution (7 cases) or resuspension (2 cases). In 1 case (2.5%) a sutureless ring graft replacement of ascending aorta was carried out and 3 patients (7.5%) underwent aortoplasty with aortic valve substitution. Postoperative mortality rate was 21% for AAD group, 11% for CAD group and 6% for AE group. Non-fatal postoperative complications developed in 36% of AAD patients and in 78% and 29% of CAD and AE p...
The Journal of Thoracic and Cardiovascular Surgery, Sep 1, 2013
To determine whether the SYNTAX score can predict the outcomes of patients with left ventricular ... more To determine whether the SYNTAX score can predict the outcomes of patients with left ventricular dysfunction undergoing coronary artery bypass grafting. We studied a consecutive series of 191 patients (mean age, 67 ± 10 years) with a left ventricular ejection fraction of 40% or less who were undergoing isolated coronary artery bypass grafting. All patients were stratified according to their SYNTAX score, indicating coronary artery disease complexity: low, 0 to 22; intermediate, 23 to 32; and high, 33 or more. The primary outcome was all-cause mortality. Secondary outcomes included the late occurrence of major adverse cardiac and cerebrovascular events, left ventricular function, and New York Heart Association functional class. The mean SYNTAX score was 32 ± 13, and the mean preoperative left ventricular ejection fraction was 35% ± 6%. At a median follow-up of 43 months, the primary outcome had occurred in 46 of 191 patients (24%). Kaplan-Meier analysis showed a survival of 81% ± 15% for low, 77% ± 7% for intermediate, and 53% ± 7% for high coronary artery disease complexity (χ(2), 29.4; P = .001). The rate of major adverse cardiac and cerebrovascular events was significantly greater in patients with a SYNTAX score of 33 or more (P = .002). Greater degrees of left ventricular ejection fraction improvement were found in patients with a SYNTAX score of 32 or less (+15% ± 10% vs +4% ± 11%; P = .17) and translated into a better New York Heart Association functional class among patients with a lower SYNTAX score (P = .01). Receiver operating characteristic curve analysis showed the SYNTAX score (area under the curve, 0.70; 95% confidence interval, 0.63-0.77) to have the best predictive power for late mortality with respect to the preoperative left ventricular ejection fraction (area under the curve, 0.59; difference, P = .04) and incomplete revascularization (area under the curve, 0.55; difference, P = .02). The results of the present study have shown a direct relationship between coronary artery disease complexity and late outcomes of patients with left ventricular dysfunction who are undergoing coronary artery bypass grafting. Additional studies are needed to confirm these findings.
International Journal of Cardiology, 2019
Background: The modified Bentall procedure is still the treatment of choice for patients requirin... more Background: The modified Bentall procedure is still the treatment of choice for patients requiring combined replacement of the ascending aorta and aortic valve. We compared the long-term outcome of patients >65 years of age undergoing Bentall procedure with biological vs mechanical valved conduits in a multi institutional study. Methods: A total of 282 patients, undergoing a Bentall operation (January 1994-May 2015), with a biological (Group1, 173 patients) or a mechanical (Group2, 109 patients) conduit were reviewed, the primary outcome being analysis of late survival and freedom from major adverse events. Results: Hospital mortality was 5% (9 patients) and 2% (2 patients) for Group 1 and Group 2 (p=0.2). Median follow-up was 77 months (range Q1-Q3: 49-111) for Group 1 vs 107 months (range Q1-Q3: 63-145) for Group 2 (p< 0.001). A not statistically significant advantage in late survival was found in patients receiving mechanical valved conduits (36% for Group1 vs 58% for Group2 at 12 years; p=0.09), although freedom from major adverse events was similar between the 2 groups (33% in Group 1 vs 50% in Group 2 at 12 years; p=0.3). Conclusions: In conclusion, mechanical-valved conduits employed for the modified Bentall procedure show a trend towards an improved late survival in patients ≥65 years of age and particularly in those between 65 and 75 years, despite a higher incidence of major adverse events. Our results indicate the need for specific guidelines to better define the ideal age limit for each type of valved conduit.
European Journal of Internal Medicine, 2011
European Heart Journal, 2018
co-expression networks and classify cell types. RNA in situ hybridization analysis was conducted ... more co-expression networks and classify cell types. RNA in situ hybridization analysis was conducted to validate the spatial expression profiles of novel cell type-specific gene. Furthermore, we performed genetic ablation to dissect the molecular and functional properties of the cell type-specific gene. Results: Computational analysis of single-cell transcriptomes clearly separated non-CMs into 4 cell groups and revealed their distinct gene programs. By transcriptional network analysis, we identified high-temperature requirement factor A3 (HtrA3) as a novel cardiac fibroblast-specific gene. RNA in situ hybridization analysis revealed a marked increase of HtrA3-expressing cardiac fibroblasts in response to pressure overload. HtrA3 knockout mice show that HtrA3 in cardiac fibroblast is essential for preventing TGFβ signaling activation, interstitial fibrosis, and cardiac dysfunction after pressure overload. Biochemical assay confirmed that HtrA3 represses the activity of TGFβ signaling by promoting cleavage of TGFβ. We also demonstrated that HTRA3 expression in heart is up-regulated in patients with heart failure, and is down-regulated after mechanical unloading. Conclusion: Single-cell RNA-seq analysis of non-CMs from healthy and failing hearts revealed the transcriptional stress response and distinct gene programs specific for cell types. We further identified HtrA3 in cardiac fibroblasts as a critical regulator of cardiac homeostasis, providing a potential therapeutic target for heart failure.
AORTA, 2014
Alkaptonuria is an autosomal recessive trait resulting in an error of aromatic amino acids metabo... more Alkaptonuria is an autosomal recessive trait resulting in an error of aromatic amino acids metabolism. Heyde's syndrome is a condition clustering together aortic valve stenosis and gastrointestinal bleeding from colonic angiodysplasia. At present, there is no report describing the association of the latter two syndromes in the same patient. Here we present the case of a patient with severe aortic stenosis, alkaptonuria, and Heyde's syndrome. The patient underwent aortic valve replacement by means of a valvular bioprosthesis and the histological examination of the aortic cusps revealed calcific degeneration. This was associated with stromal degeneration characterized by extra-cellular deposition of granular, brownish-pigmented material along with macrophages and multiple foci of calfication showing the same brownish pigmentation. This configuration represents the typical pattern of homogentisic acid accumulation known as ochronosis. The postoperative course was uneventful and the echocardiographic follow-up at 6 months postoperatively showed good-functioning of the aortic valve bioprosthesis.
Journal of Cardiovascular Medicine, 2010
Preoperative renal function is an important risk factor in cardiac surgery for long-term and shor... more Preoperative renal function is an important risk factor in cardiac surgery for long-term and short-term outcomes. Renal function is best assessed by measuring or calculating the glomerular filtration rate (GFR). Several algorithms using the endogenous marker serum creatinine have been developed to estimate renal function. These include the Cockcroft and Gault and the modification of diet in renal disease (MDRD) formulae. The aim of this study was to compare the predictive power of the two formulae towards short-term outcomes after cardiac surgery, such as the length of intensive care unit (ICU) stay, the length of mechanical ventilation time, and the length of in-hospital stay. One hundred and fifty patients undergoing cardiac surgery and not affected by renal failure were followed up until hospital discharge. We collected data before, during and after surgery. Before surgery data consisted of date of birth, sex, height, weight, plasma creatinine level; during surgery data consisted of type of intervention (including number of bypasses, if any), cardiopulmonary bypass time and aortic cross-clamp time; after surgery data consisted of length of ICU stay, mechanical ventilation time, length of in-hospital stay after intensive-care discharge (ward stay), incidence of acute renal failure (expressed as the need for dialysis) and mortality. The dataset was analyzed using Cox regression. The average mechanical ventilation time, ICU stay and ward stay were 11 h, 49 h and 10 days, respectively. After having adjusted for chronic obstructive pulmonary disease, diabetes and postsurgical dialysis, the GFR calculated with the Cockcroft and Gault formula appeared to be a predictor of ICU stay and mechanical ventilation time with very strong evidence (P = 0.002 and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001, respectively) and a predictor of ward stay with some evidence (P = 0.062). After an identical case-mix adjustment, the GFR calculated with the MDRD formula appeared to be a predictor of ICU stay with strong evidence (P = 0.007), a predictor of mechanical ventilation time with some evidence (P = 0.075) and it has shown no evidence of predicting ward stay (P = 0.197). There is an indication that the Cockcroft and Gault formula could be more powerful than the MDRD formula for the preoperative prediction of early postoperative clinical outcomes in cardiac surgery, in patients not affected by renal failure. Further research is needed to confirm this result.
The Journal of Thoracic and Cardiovascular Surgery, 2009
International Journal of Cardiology, 2003
International Journal of Cardiology, 1997
We aimed at investigating contractile changes after hypoxia-reoxygenation and dobutamine challeng... more We aimed at investigating contractile changes after hypoxia-reoxygenation and dobutamine challenge in superfused human atrial pectinate muscle to see whether high versus low stimulation rate during hypoxia might account for outcome differences compatible with the definition of an in vitro model of myocardial stunning and whether pretreatment with the dihydropyridine Ca2+ entry blocker felodipine might afford protection. Human right atrial trabeculae obtained from adult patients were superfused in an organ bath with oxygenated (O2 content 16 ml/l) and modified (NaHCO3 25.7 mmol/l) Tyrode&amp;#39;s solution at 37 degrees C. Dobutamine (1 nmol/l to 10 micromol/l) was superfused in 10 oxygenated preparations to select the optimal drug concentration to be used in another 22 which were randomized. Group (A) consisted of time-related controls (Tyrodes&amp;#39;s solution for 225 min at cycle length (CL) 1600 ms and no dobutamine). There were two test groups, respectively: (B) low (1600 ms CL) and (C) high (400 ms CL) stimulation rate. After 60 min of stabilization, in groups B and C, hypoxic superfusion (O2 content 5 ml/l) lasted 60 min, then reoxygenation (60 min) and dobutamine challenge (1 micromol/l, 15 min) were performed. Analysis of variance for repeated measures with the Greenhouse-Geisser correction, and a repeated measures model with structured covariance (preparation mass, length, width and time-varying time to peak tension) matrices were used whereby grouping (G), time (T) and G x T interaction were weighted. Force-frequency relationship and post-pausal potentiation were studied after each phase. Electrophysiology, histomorphometry and electron microscopy were carried out (n=6). Felodipine (0.1 micromol/l, n=5) pretreatment (15 min before hypoxia) was given in parallel experiments. Time-related controls showed approximately 10% per hour decrease of developed tension and the Paradise test provided approximately 80% of control values. In test groups (as compared to baseline values) contractility was decreased approximately 65% after hypoxia-reoxygenation and it increased approximately 25% after dobutamine (G, 0.0065&amp;lt;P&amp;lt;0.0155; T, P=0.00005; G x T, P=0.00005). High stimulation rate during hypoxia worsened hypoxia-reoxygenation contractile changes, whereas reversibility after dobutamine was less. In both B and C groups during hypoxia, contractility decreased quite rapidly, although by 10 min or so a plateau (approximately 50%) was reached in group B, whereas in group C contractility decreased to &amp;lt;20%. None of the covariates contributed significantly to predict the dependent variables investigated. Force-frequency relationship and post-pausal potentiation were repeatable, paralleled overall changes due to hypoxia, reoxygenation and dobutamine challenge and were useful to discriminate Ca2+-related diastolic processes thus helping index myocardial contractile reserve. Force-frequency relationship was negative at high stimulation rates, concomitant to an abrupt change of shape and duration of action potential with little time for Ca2+-related Ca2+ release and ensuing systolic processes. Felodipine pretreatment enabled an unblunted response to dobutamine. Histomorphometry showed an unexpected &amp;#39;fibrotic core&amp;#39;. At electron microscopy, subendocardial and deep part of the same pectinate muscles showed identical degrees of degenerative lesions. Superfused samples showed, unexpectedly, less anoxic lesions than preparations fixed within 15 min from surgical explant, although lesions were higher than in samples fixed immediately after explant. This might be a relevant model, whereby pharmacological or physical interventions are tested. Native human atrial trabeculae might be used without dissection and/or preservatives. If high stimulation rate during hypoxia is used the power of hypothesis testing is maximized. Future studies with this material will be easier and comparatively smaller series might be investigated. Felo
European Journal of Cardio-Thoracic Surgery, 2013
OBJECTIVE: A number of factors limit the effectiveness of current aortic arch studies in assessin... more OBJECTIVE: A number of factors limit the effectiveness of current aortic arch studies in assessing optimal neuroprotection strategies, including insufficient patient numbers, heterogenous definitions of clinical variables, multiple technical strategies, inadequate reporting of surgical outcomes and a lack of collaborative effort. We have formed an international coalition of centres to provide more robust investigations into this topic.
Cardiovascular Pathology, 2001
Expanded polytetrafluoroethylene (e-PTFE) sutures have been used with increasing frequency to rep... more Expanded polytetrafluoroethylene (e-PTFE) sutures have been used with increasing frequency to replace chordae tendineae in mitral valves prolapsing because of myxoid change. A case is reported where fibrosis and calcification of the endocardial overgrowth covering the synthetic chordae led to severe mitral regurgitation 7 years after plastic repair and required mechanical prosthetic valve implantation.