Gabriele Giunti

Characterization of the Hyperpolarization-Activated Current, If, in Ventricular Myocytes From Human Failing Heart

BACKGROUND Disease-associated electrophysiological alterations may contribute to the increased predisposition to arrhythmias of the hypertrophied or failing myocardium. An I(f)-like current is expressed in rat left ventricular myocytes (LVMs), its amplitude being linearly related to the severity of cardiac hypertrophy. Here, we report the occurrence and electrophysiological properties of I(f) in human LVMs. METHODS AND RESULTS LVMs were isolated from hearts of three male patients undergoing cardiac transplantation for terminal heart failure due to ischemic dilated cardiomyopathy. The patch-clamp technique was used to record I(f), ie, a barium-insensitive, cesium-sensitive, time-dependent increasing inward current elicited on hyperpolarization. Membrane capacitance was 244 +/- 27 pF (n = 25). I(f) occurred in all cells tested; its density measured at -120 mV was 2.1 +/- 0.3 pA/pF. Activation curves of I(f) (n = 24) were fitted by a Boltzmann function; the threshold was -55 mV; midpoint, -70.9 +/- 2.1 mV; slope, -5.4 +/- 0.3 mV; and maximal specific conductance, 19.6 +/- 2.5 pS/pF. I(f) blockade by extracellular cesium was voltage dependent. Reducing extracellular potassium concentration from 25 to 5.4 mmol/L caused a shift of the reversal potential from -12.7 +/- 0.5 to -24.8 +/- 2.1 mV and a 64% decrease of current conductance. CONCLUSIONS I(f) is present in human LVMs. Its electrophysiological characteristics resemble those previously described in hypertrophied rat LVMs and suggest that I(f) could be an arrhythmogenic mechanism in patients with severe heart failure.

Does ministernotomy improve postoperative outcome in aortic valve operation? A prospective randomized study

BACKGROUND The aim of this study was to compare the postoperative outcome obtained in patients undergoing elective aortic valve operation, either through ministernotomy or conventional sternotomy. METHODS Between January 1999 and July 2001, 80 consecutive patients undergoing elective aortic valve replacement were randomly divided into two groups: group I (n = 40 patients) undergoing a ministernotomy approach (reversed-C or reversed-L), and group II (n = 40 patients) undergoing conventional sternotomy. RESULTS The length of skin incision was significantly shorter in group I than in group II (8.2+/-1.3 cm versus 23.7+/-2.6 cm, p < 0.001). No significant differences were found in cardiopulmonary bypass duration, associated procedures, or aortic cross-clamping times. Total operating time was 3.7+/-0.46 hours in group I compared with 3.4+/-0.6 hours in group II (p = 0.014). A similar incidence of cardiac, neurologic, infective, and renal complications between groups was found. Mean mediastinal drainage and mean blood transfusions (amount of blood transfused) per patient were greater in group II (p < 0.004 and p < 0.001, respectively). Twenty-five (62.5%) patients in group II and 15 (37.5%) patients in group I required postoperative blood transfusion (p = 0.04). Mechanical ventilation time was significantly longer in group II (6.2+/-1.8 hours versus 4.4+/-0.9 hours, p = 0.006). Five days after the surgical procedure, spirometric data analysis demonstrated a significantly lower total lung capacity and maximum inspiratory and expiratory pressures in group II compared with group I (p = 0.003, p = 0.007, and p < 0.001, respectively). CONCLUSIONS Our results showed that ministernotomy had not only important cosmetic advantages but also beneficial effects in blood loss and transfusion, postoperative pain, and probably in sternal stability. Ministernotomy also improved recovery of respiratory function and allowed earlier extubation and hospital discharge.

Respiratory dysfunction after coronary artery bypass grafting employing bilateral internal mammary arteries: the influence of intact pleura

OBJECTIVE To evaluate the role of intact pleurae regarding the postoperative respiratory functional status in patients undergoing coronary revascularization employing both internal mammary arteries (IMAs), according to the pedunculated or skeletonized technique (SKT) with opened or intact pleurae. MATERIALS AND METHODS Using both IMAs, 299 patients underwent elective coronary revascularization. They were randomized and divided into group I (n=82, undergoing IMA harvesting according to the SKT without opening the pleurae); group II (n=186, undergoing IMA harvesting according the pedunculated technique with open pleurae); and group III (n=31, undergoing IMA harvesting according the SKT with incidentally opened pleurae). There were no differences regarding the preoperative patient characteristics and the anaesthetic and surgical management. RESULTS There were two deaths in group I versus seven in group II and one in group III (P=ns). The number of total arterial myocardial revascularization and arterial composite grafts was significantly higher in groups I and III than in group II, (P<0.001 and P<0.005, respectively). The incidence of postoperative complications was similar between groups. Blood loss of >1000 ml was significantly higher in group II than group I (P<0.028); but the incidence of re-thoracotomy and blood transfusion was similar between groups. The mechanical ventilation time was significantly higher in groups II and III versus group I (P<0.018 and P<0.02, respectively). The incidence of prolonged ventilation (>24 h), pleural effusion, thoracocentesis and atelectasis, resulted in being significantly higher in group II than group I. The incidence of thoracocentesis was significantly higher in group III than group I. The pain score and analgesic requirements at 1-12 h after awakening were significantly higher in groups II and III versus group I, becoming similar after the chest tubes were removed. PaO(2) was significantly higher, and PaCO(2) and FiO(2) were significantly lower in group I than groups II and III at 1 and 4 h before extubation and at 1 and 4 h after extubation. PaO(2) and PaCO(2) became similar between groups at the 5th postoperative day. CONCLUSIONS According to our results, we may conclude that pleural integrity has beneficial effects on the respiratory functional status after coronary revascularization using both IMAs. A meticulous and more careful IMA harvesting approach significantly reduces the postoperative morbidity regarding the pulmonary functional status, and as a consequence, reduces the hospital costs.

Repair of congenital malformations of the mitral valve: early and midterm results.

BACKGROUND The aims of this study were to determine early and midterm survival and freedom from reoperation, and to identify the predictors for poor postoperative outcome in children undergoing mitral valve (MV) repair owing to congenital malformations of the mitral valve. METHODS Between January 1990 and February 2001, 94 consecutive children with congenital MV disease underwent valve repair. The mean age was 5.2+/-3.3 years (range 20 days to 15 years). Twenty-five (26.6%) children were less than 1 year old. Isolated MV disease was found in 21 (22.4%) patients. MV stenosis was the predominant lesion in 21 (22.4%) patients with a mean left atrial to left ventricle diastolic peak gradient of 24.5+/-9.2 mm Hg. MV regurgitation was the predominant pathophysiology in 73 (77.6%) patients with a mean regurgitation grade of 3.3+/-0.7. RESULTS The hospital mortality was 8.5% (8 of 94). Three patients required permanent pacemaker implantation owing to complete atrioventricular block. Two patients underwent mediastinal exploration for significant bleeding. Postoperatively the echocardiography color Doppler study demonstrated a significantly lower mean end diastolic left atrium to left ventricle gradient 8.7+/-2.2 mm Hg (p < 0.001) in patients with MV stenosis and a mean regurgitation grade of 0.9+/-0.6 (p < 0.001) in patients with MV regurgitation. Actuarial survival and actuarial reoperation-free survival were 89.2% and 76.3%, respectively. Multivariate analysis demonstrated that age less than 1 year (p = 0.035), hammock MV (p = 0.0093), cardiothoracic ratio greater than 0.6 (p < 0.0001), and associated cardiac anomalies (p = 0.003) were strong predictors for poor overall freedom from reoperation and midterm survival. CONCLUSIONS Mitral valve repair for congenital mitral valve disease yields acceptable early and midterm mortality and reoperation rates. Strong predictors for poor overall freedom from reoperation and midterm survival were age less than 1 year, hammock MV, cardiothoracic ratio greater than 0.6, and associated cardiac anomalies.

Should Mild‐to‐Moderate and Moderate Ischemic Mitral Regurgitation Be Corrected in Patients with Impaired Left Ventricular Function Undergoing Simultaneous Coronary Revascularization?

Introduction: Mitral valve regurgitation (MR) occurring as a result of myocardial ischemia and global left ventricular (LV) dysfunction predicts poor outcome. This study assessed the feasibility of mitral valve (MV) surgery concomitant with coronary artery bypass grafting (CABG) in patients with mild‐to‐moderate and moderate ischemic MR and impaired LV function. Materials and Method: From January 1996 to July 2000, 49 patients (group 1) and 50 patients (group 2) with grade II and grade III ischemic MR and LV ejection fraction (EF) between 17% and 30% underwent combined MV surgery and CABG (group 1) or isolated CABG (group 2). LVEF (%), LV end‐diastolic diameter (EDD) (mm), LV end‐diastolic pressure (EDP) (mmHg), and LV end‐systolic diameter (ESD) (mm) were 27.5 ± 5, 67.7 ± 7, 27.7 ± 4, and 51.4 ± 7, respectively in group 1 versus 27.8 ± 4, 67.5 ± 6, 27.5 ± 5, and 51.2 ± 6, respectively in group 2. Groups 1 and 2 were divided into Groups 1A and 2A with mild‐to‐moderate MR (22 [45%] and 28 [56%] patients, respectively) and groups 1B and 2B with moderate MR (27 [55%] and 22 [46%], respectively). In group 1, MV repair was performed in 43 (88%) patients and MV replacement in 6 (12%) patients. Results: Preoperative data analysis did not reveal any difference between groups. Five (10%) patients in group 1 died versus 6 (12%) in group 2 (p = ns). Within 6 months after surgery, LV function and its geometry improved significantly in group 1 versus group 2 (LVEF, p < 0.001; LVEDD, p = 0.002; LVESD, p = 0.003; and LVEDP (p < 0.001) improved significantly in group 1 instead of a mild improvement in Group 2). The regurgitation fraction decreased significantly in group 1 patients after surgery (p < 0.001). There was an inverse strong correlation between postoperative forward cardiac output and regurgitation fraction (p < 0.001). LVEF and LVESD improved significantly in group versus group 2 patients (p = 0.04 and p = 0.02, respectively). The cardiac index increased significantly in group 1 and 2 (p < 0.001 and p = 0.03, respectively). LV function and geometry improved significantly postoperatively in group 1B versus group 2B (LVEDD, p = 0.027; LVESD, p = 0.014; LVEDP, p = 0.034; and LVEF, p = 0.02), instead of a mild improvement in group 1A versus group 2A (LVESD, p = 0.015; LVEF, p = 0.046; and LVEDD and LVEDP, p = 0.05). At follow‐up, 4 (67%) of 6 patients undergoing MV replacement died versus 5 (11.59/0) of patients undergoing MV repair in group 1 (p = 0.007). The overall survival at 3 years in Group 2 was significantly lower than group 1 (p < 0.009). Conclusion: MV repair and replace‐ ment‐preserving subvalvular apparatus in patients with impaired LV function offered acceptable outcomes in terms of morbidity and survival. Surgical correction of mild‐to‐moderate and moderate MR in patients with impaired LV function should be taken into consideration since yields better survival and improved LV function.

Early and long-term outcome in patients undergoing aortic root replacement with composite graft according to the Bentall's technique

OBJECTIVE The aims of this study were: (i) to evaluate the early and long-term outcome in patients undergoing aortic root replacement (ARR) with a composite graft; (ii) to identify the predictors for poor overall survival in this pool of patients. MATERIAL AND METHODS Between January 1989 and December 2000, 212 patients underwent ARR with a CG. Mean age was 56+/-14 years, ranging from 16 to 77. Annuloaortic ectasia was the most frequent cause of aortic disease in this series, 81 (38%) patients, followed by atherosclerotic aneurysm 57 (27%) and type A acute aortic dissection 52 (24.5%). Marfans syndrome was present in 37 (17.5%) patients. Duration of follow-up ranged from 1 to 120 months, mean 59+/-35 months. RESULTS The overall hospital mortality was 16 (7.5%) patients. Eight of them had aortic dissection and four Marfan syndrome. The most frequently found complication resulted to be renal failure in 22 (10%) patients and low cardiac output in 15 (7%) patients. The incidence of perioperative myocardial infarction, neurological complications, respiratory complications, renal failure and coagulopathy incidence were significantly higher in patients with cardiopulmonary bypass (CPB) time >170 min, CA >40 min, and total aortic arch replacement. The actuarial survival at 1, 3 and 5 years resulted to be 91.8, 86 and 81.5%, instead the actuarial survival without re-operation resulted to be 89, 82 and 78%. The actuarial survival in patients with aortic dissection was significantly lower versus non-dissection (P=0.022). The multivariate analysis revealed the aortic dissection (P=0.03), age >65 years (P=0.014), associated coronary artery disease (P=0.002), NYHA functional class>/=3 (P=0.027), LVEF <35% (P=0.002) and total arch reconstruction (P=0.003) as strong predictors for poor overall survival in patients undergoing ARR. CONCLUSIONS The ARR with a CG offers acceptable early and long-term outcome. The predictors for poor overall survival in patients undergoing ARR seems to be preoperative aortic dissection extended into the aortic arch, older age, depressed left ventricular function and associated coronary artery disease.

Does On-Pump/Beating-Heart Coronary Artery Bypass Grafting Offer Better Outcome in End-Stage Coronary Artery Disease Patients?

Abstract  Objectives: The purpose of our study was to evaluate in a cohort of end‐stage coronary artery disease (ESCAD) patients the effects of on‐pump/beating‐heart versus conventional coronary artery bypass grafting (CABG) requiring cardioplegic arrest. We report early and midterm survival, morbidity, and improvement of left ventricular (LV) function. Methods: Between January 1992 and October 1999,107 (Group I) ESCAD patients underwent on‐pump/beating‐heart surgery and 191 (Group II) ESCAD patients underwent conventional CABG requiring cardioplegic arrest. Mean age in Group I was 65.8 ± 6.5 years (58–79 years); New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) classifications were 3.2 ± 0.4 and 3.3 ± 0.5, respectively. LV ejection fraction (LVEF) was 24.8% ± 4%, LV end diastolic pressure (LVEDP) was 28.2 ± 3.8 mmHg, and LV end diastolic diameter (LVEDD) was 69.6 ± 4.6 mm. Mean age in Group II was 64.1 ± 5 years (57–76 years), NYHA class was 3 ± 0.6, CCS class was 3.4 ± 0.4, LVEF was 26.2% ± 4.3%, LVEDP was 27.2 ± 3.4 mmHg, and LVED was 68 ± 4.2 mm. Results: Preoperatively, Group I patients versus Group II patients had a markedly depressed LV function (LVEF, p = 0.006; LVEDP, p = 0.02; LVEDD, p = 0.003; and NYHA class, p = 0.002), older age (p = 0.012), and higher incidences of multiple acute myocardial infarction (AMI; p = 0.004), cardiovascular disease (CVD; p = 0.008), and chronic renal failure (CRH, p = 0.002). Cardiopulmonary bypass (CPB) time was longer in Group II patients (p = 0.028). The mean distal anastomosis per patient was similar between groups (p = NS). Operative mortality between Groups I and II was 7 (6.5%) and 19 (10%), respectively (p = NS). Perioperative AMI (p = 0.034), low cardiac output syndrome (LCOS; p = 0.011), necessity for ultrafiltration (p = 0.017), and bleeding (p = 0.012) were higher in Group II. Improvement of LV function within 3 months after the surgical procedure was markedly higher in Group I, demonstrated by increased LVEF (p = 0.035), lower LVEDP (p = 0.027), and LVEDD (p = 0.001) versus the preoperative data in Group II. The actuarial survivals at 1, 3, and 5 years were 95%, 86%, and 73% in Group I and 95%, 84%, and 72% in Group II (p = NS). Conclusions: ESCAD patients with bypassable vessels to two or more regions of reversible ischemia can undergo safe CABG with acceptable hospital survival and mortality and morbidity. In higher risk ESCAD patients, who may poorly tolerate cardioplegic arrest, on‐pump/beating‐heart CABG may be an acceptable alternative associated with lower postoperative mortality and morbidity. Such a technique offers better myocardial and renal protection associated with lower postoperative complications.

Right Y-graft, a new surgical technique using mammary arteries for total myocardial revascularization

BACKGROUND We report a new technique that consists of a right Y-graft using only skeletonized internal mammary arteries (IMA) for total arterial myocardial revascularization. METHODS This technique consists of anastomosing the in situ left IMA (LIMA) and right IMA (RIMA) to the left anterior descending and obtuse marginal artery, via the transverse sinus, respectively. The distal free LIMA was anastomosed to the right coronary artery and afterwards in a Y fashion to the RIMA stem. Eleven patients with triple-vessel disease underwent coronary artery bypass grafting using this technique. Postoperatively and at follow-up all patients underwent color Doppler contrast-enhanced transthoracic echocardiography (TTE) before and after an adenosine provocation test. RESULTS Overall, 33 IMA-coronary anastomoses were made and 11 right Y-grafts were constructed. At 1 week after operation color Doppler contrast-enhanced TTE before and after the adenosine provocation test, respectively, showed an increase in LIMA stem diameter of 0.31 mm and in mean flow 62 mL/min. Coronary flow reserve (CFR) was 2+/-0.3. The increase in RIMA stem diameter was 0.2 mm and in mean flow was 121.7 mL/min. Coronary flow reserve was 2.5+/-0.4. Only 1 patient demonstrated an anomalous Doppler pattern, suggesting a partial Y-graft closure. CONCLUSIONS Such a technique permits total myocardial revascularization using only mammary arteries and left ventricular perfusion from both IMAs simultaneously. The color Doppler contrast-enhanced TTE is a rapid, accurate, and noninvasive test allowing a good assessment of IMA patency.

Perioperative and clinical-angiographic late outcome of total arterial myocardial revascularization according to different composite original graft techniques.

Total arterial myocardial revascularization (TAMR) is advisable because of the excellent long-term patency of arterial conduits. We present early and midterm outcomes of five different surgical configurations for TAMR. Between January 1998 and May 2004, 112 patients (aged 56.5 ± 4.5 years, 20% female) with three-vessel disease underwent TAMR. The internal mammary arteries (IMAs) were harvested in a sketelonized fashion. The surgical techniques for TAMR consisted in Y or T composite grafts (n = 88, 78%) constructed between the in situ right IMA (RIMA) and the free left IMA (LIMA) graft (n = 58) or the radial artery (n = 30) (RA) in three different configurations. The other techniques consisted in T- and inverted T-graft (n = 24, 22%) constructed between the RA conduit and the free LIMA graft in two different configurations. The mean follow-up time was 40 ± 23 months. Postoperative angiographic control was performed in 76/111 (70%) patients. Overall, 472 arterial anastomoses (average 4.2 per patient) were performed. One (0.9%) patient, undergoing the inverted T-graft technique, died on postoperative day 2. Another patient (0.9%), undergoing the λ-graft technique using both IMAs and RA, suffered a new myocardial infarction probably due to RA conduit vasospasm. One week after surgery, after the transthoracic echocardiographic Doppler with adenosine provocative test, the coronary flow reserve (CFR) at the LIMA and RIMA main stems were 2 ± 0.4 and 2.4 ± 0.3, respectively. At 12-month follow-up, after adenosine provocative test, the CFRs at the LIMA and RIMA stems were significantly higher than the values at 1 week after surgery within the same group; LIMACFR (1 week) 2.4 ± 0.3 (12 months) vs 2 ± 04 (1 week), P = 0.002; RIMACFR 2.58 ± 0.4 vs 2.4 ± 0.3, P = 0.001. The CFR at the RIMA main stem was higher in all measurements within the same group than in the LIMA main stem, but not significantly. In one patient undergoing the λ-graft technique using both IMAs, the RIMA was found to have a string sign. Postoperative angiography in 50 patients showed that the patency rate for the LIMA was 100%, for the RIMA 97.3%, and for the RA 96.7%. Angiography at 3-year follow-up in 76 patients documented excellent patency rates of the LIMA (97.4%), RIMA (95%), and RA (87%). Survival at 7 years was 92.5%, event-free survival 89.3%, and freedom from angina 94%. Total arterial myocardial revascularization using different surgical configurations is safe and effective. The use of composite arterial grafts provides excellent clinical and angiographic results, with a low rate of angina recurrence and late cardiac events. These configurations allow for complete arterial revascularization.

λ graft with the radial artery or free left internal mammary artery anastomosed to the right internal mammary artery: flow dynamics

BACKGROUND The aim of this study was to evaluate the outcome and flow dynamics of the lambda graft configuration, relative to a second arterial graft. METHODS From 1998 to 2000, 47 patients (mean age 55.5 +/- 4.7 years) with triple-vessel disease underwent arterial revascularization using the lambda graft. The in situ left internal mammary artery (LIMA) and right internal mammary artery (RIMA) were anastomosed to the left anterior descending (LAD) and obtuse marginal arteries, respectively. In 21 patients (group I) presenting proximal or middle-third LAD or right coronary (RC) arterial stenoses, the lambda graft was constructed by anastomosing the distal LIMA, as a free LIMA graft, to the RC and proximally to the in situ RIMA. In the other 26 patients (group II) presenting with middle-distal third LAD or RC arterial stenoses, the radial artery (RA) was used to construct the lambda graft. All patients underwent transthoracic echo color Doppler before and after an adenosine test at 1 week and 3 months after operation. RESULTS There were no hospital deaths. Overall, 47 lambda grafts were constructed. There was no difference between baseline and maximal flows and coronary flow reserve (CFR) between groups. CFR at IMA stems increased in both groups within 3 months versus 1 week [(LIMA)CFR = 2 +/- 0.3 vs 2.3 +/- 0.3 (p = 0.002) and (RIMA)CFR = 2.2 +/- 0.4 vs 2.5 +/- 0.3 (p = 0.009) in group I, and (LIMA)CFR = 2.12 +/- 0.33 vs 2.4 +/- 0.35 (p = 0.005) and (RIMA)CFR = 2.17 +/- 0.32 vs 2.52 +/- 0.26 (p = 0.001) in group II]. At 3 months versus 1 week, the (RIMA)diameter(i) (mm) at rest was 1.69 +/- 0.32 versus 1.48 +/- 0.2 (p = 0.015) in group I and 1.66 +/- 0.3 versus 1.47 + 0.2 (p = 0.01) in group II. At 6 +/- 2.4 months, all patients were free of angina. CONCLUSIONS These data, almost identical for free LIMA and RA to RIMA using the lambda graft, demonstrate that RIMA flow reserve is adequate for multiple coronary anastomoses irrespective of the second arterial graft.