Current era survival of patients with pulmonary arterial hypertension associated with congenital heart disease: a comparison between clinical subgroups.

AIMS: This study compared the clinical, functional, and haemodynamic characteristics and current era survival of subgroups of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD): Eisenmenger syndrome (ES); PAH-CHD associated with systemic-to-pulmonary shunts (SPs); PAH with small defects (SDs); and PAH after defect correction (CDs). METHODS AND RESULTS: Data from consecutive PAH-CHD patients referred to our centre from 1 January 1998 to 31 May 2011 were collected. A contemporary group of idiopathic PAH patients was utilized for comparison. Treatment was per PAH guidelines, including combination therapy, with approved PAH-specific drugs. Survival was assessed with Kaplan-Meier analysis from the first invasive haemodynamic confirmation of PAH and compared across subgroups by log-rank test. Of 192 patients (mean age 41 ± 17 years; 61% female), 90 had ES (aged 41 ± 16 years); 48 SP (aged 47 ± 18 years); 10 SD (aged 25 ± 21 years); and 44 CD (aged 36 ± 17 years). Patients with ES had the highest baseline pulmonary vascular resistance and the lowest exercise capacity. Seventy-eight per cent were treated with approved PAH-specific drugs, and 44% were treated with combination therapy. Kaplan-Meier survival estimates (95% confidence interval) at 20 years for ES, SP, and CD were 87% (77-93%), 86% (60-96%), and 36% (12-72%, P = 0.0001 vs. ES; P = 0.004 vs. SP), respectively, and at 15 years for SD was 66% (16-91%, P = 0.015 vs. ES; P = 0.016 vs. SP). The survival of the 278 patients with idiopathic PAH appeared to be worse when compared with the PAH-CHD subgroups. CONCLUSION: Relevant clinical, functional, haemodynamic, and survival differences were observed among subgroups. In particular, patients with CD and SD had the worst survival. These findings should be considered when planning medical or interventional treatment strategies in PAH-CHD patients.

Recent temporal trends for first-time hospitalization for acute myocardial infarction. Treatment patterns and clinical outcome in a large cohort study.

BACKGROUND: The objective was to report recent trends in the incidence, adoption of evidence-based treatment, and clinical outcomes for first-time hospitalization for acute myocardial infarction. METHODS: This is a large retrospective population-based cohort study using medical administrative data (International Classification of Diseases, Ninth Revision, Clinical Modification, codes) performed in the Emilia-Romagna Region of Italy (approximately 4.5 million inhabitants). We identified 60,673 patients with a first hospitalization for acute myocardial infarction from 2002 through 2009. RESULTS: The standardized incidence rate per 100,000 person-years of acute myocardial infarction increased from 173 cases in 2002 to a peak of 197 cases in 2004 and then decreased each year thereafter to 167 cases in 2009. The proportion of patients who underwent coronary angiography and angioplasty in the acute phase increased over time, respectively, from 45.4% and 27.1% to 72.3% and 57.2% (P < .001). Medication use within 12 months of discharge increased for aspirin, ß-blockers, and statins. A reduction in crude and adjusted in-hospital all-cause (16.1% in 2002 vs 12.8% in 2009, P < .001) and cardiovascular mortality (13.6% in 2002 vs 9.5% in 2009, P < .001) was observed over time. At 1 year after hospital discharge, no significant variations occurred in adjusted risk for all-cause mortality or cardiovascular mortality. Notably, crude and adjusted risk for in-hospital and postdischarge bleeding showed a significant increment. CONCLUSIONS: The utilization of evidence-based treatments in patients with myocardial infarction increased between 2002 and 2009. These changes in practice over time favored a reduction in early case fatality at the cost of a significant increase in bleeding.

Risk of stroke with percutaneous coronary intervention compared with on-pump and off-pump coronary artery bypass graft surgery: Evidence from a comprehensive network meta-analysis.

BACKGROUND: Although some trials have reported that on-pump coronary artery bypass graft (CABG) surgery may be associated with higher rates of stroke than percutaneous coronary intervention (PCI), whether stroke is more common after off-pump CABG compared with PCI is unknown. We therefore sought to determine whether off-pump CABG is associated with an increased risk of stroke compared with PCI by means of network meta-analysis. METHODS: Randomized controlled trials (RCTs) comparing CABG vs PCI were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. RESULTS: Eighty-three RCTs with 22,729 patients randomized to on-pump CABG (n = 10,957), off-pump CABG (n = 7,119), or PCI (n = 4,653) were analyzed. Thirty-day rates of stroke were significantly lower in patients treated with PCI compared with either off-pump CABG (odds ratio [OR]; 0.39, 95% CI, 0.19-0.83) or on-pump CABG (OR, 0.26; 95% CI, 0.12-0.47). Compared with on-pump CABG, off-pump CABG was associated with significantly lower 30-day risk of stroke (OR, 0.67; 95% CI, 0.41-0.95). However, in sensitivity analyses restricted to high-quality studies, studies with more than either 100 or 1,000 patients, or studies with protocol definition or adjudication of stroke by a clinical events committee, the precision of the point estimate for the 30-day risk of stroke between off-pump vs on-pump CABG was markedly reduced. CONCLUSIONS: Percutaneous coronary intervention is associated with lower 30-day rates of stroke than both off-pump and on-pump CABG. Further studies are required to determine whether the risk of stroke is reduced with off-pump CABG compared with on-pump CABG.

Baseline white blood cell count is an independent predictor of long-term cardiovascular mortality in patients with non-ST-segment elevation acute coronary syndrome, but it does not improve the risk classification of the GRACE score.

OBJECTIVES: To investigate the prognostic significance of baseline white blood cell count (WBCc) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and its additive predictive value beyond the Global Registry of Acute Coronary Events (GRACE) score. METHODS: We included 1,315 consecutive NSTE-ACS patients. Patients were divided in quartiles according to the WBCc (cells per 1 mm(3)) i.e. Q1 <6,850, Q2 = 6,850-8,539, Q3 = 8,540-10,857 and Q4 ≥10,858. The study end point was 3-year cardiovascular death (CVD). RESULTS: The median age of the study population was 76 years. Overall, 335 patients (25.5%) died with 211 of these (16%) suffering from CVD. Patients in Q4 showed a higher cumulative probability of CVD compared to patients in Q1-Q3. On multivariable analysis, patients in Q4 were at higher risk of CVD [hazard ratio (HR) = 1.47, 95% confidence interval (CI) 1.09-1.98, p = 0.011]. WBCc as a continuous variable was also independently associated with the study end point (HR = 1.043; 95% CI 1.02-1.07; p = 0.001). However, the incorporation of WBCc into the GRACE score did not improve either prediction of risk (C-index = 0.796 for GRACE score with or without WBCc) or classification of risk [relative integrated discrimination improvement = 0.0154, 95% CI) -0.029 to 0.0618; continuous net reclassification improvement = -0.0676, 95% CI -0.2149-0.0738). CONCLUSIONS: WBCc was an independent predictor of 3-year CVD in patients with NSTE-ACS. However, it did not add prognostic information beyond the GRACE score.

Is balloon aortic valvuloplasty safe in patients with significant aortic valve regurgitation?

OBJECTIVES: To assess safety and effectiveness of balloon aortic valvuloplasty (BAV) in patients with symptomatic severe aortic stenosis (AS) and significant aortic regurgitation. BACKGROUND: BAV is a palliative procedure that has possibly been underused in patients with symptomatic AS not suitable for surgical aortic valve replacement or transcatheter aortic valve implantation. Significant aortic regurgitation is commonly perceived as a contraindication to BAV. METHODS: Among 416 consecutive patients undergoing BAV at our Institution, 73 patients showed moderate or severe AR before the procedure. Demographics and baseline characteristics, as well as in-hospital clinical outcome, have been prospectively collected in a dedicated database. Transthoracic echocardiography was regularly performed in all patients undergoing BAV before the procedure and at hospital discharge. RESULTS: Patients had a high-risk profile, confirmed by advanced age (77.2 ± 11.8 years) and important comorbidity (logistic Euroscore 26.5 ± 16.3%). Advanced heart failure was present in 73.9%. Indication to BAV was cardiogenic shock in 9.6%, palliation in 31.5%, bridge in 58.9% of the patients. BAV was performed with standard retrograde approach. Aortic valve area increased from 0.62 ± 0.15 cm(2) at baseline to 0.83 ± 0.17 cm(2) before discharge (P < 0.001). The degree of AR was improved or unchanged in 65 patients (89%). In-hospital mortality was 6.9%, mainly limited to terminal patients. Symptomatic status at discharge was improved in all surviving patients. Acute AR occurred in seven patients; in five of them it was successfully resolved in the catheterization laboratory. CONCLUSIONS: When clinically indicated, BAV can be safely performed in patients with combined aortic stenosis and significant aortic regurgitation.

Prognostic and therapeutic implications of pulmonary hypertension complicating degenerative mitral regurgitation due to flail leaflet: a multicenter long-term international study.

AIMS: To determine the frequency, predictors, and outcome implications of pulmonary hypertension (PH) diagnosed by Doppler echocardiography in a large cohort of patients with the homogenous diagnosis of degenerative mitral regurgitation (MR) due to flail leaflets. METHODS AND RESULTS: The Mitral Regurgitation International DAtabase (MIDA) is a registry including patients with MR due to flail leaflets consecutively referred at tertiary centres in Europe and the USA. Between 1987 and 2004, pulmonary artery systolic pressure (PASP) was measured at baseline by Doppler echocardiography in 437 patients (age 67 ± 11 years; 66% men). Pulmonary hypertension (PASP > 50 mmHg) was observed in 102 patients (23%). Independent predictors of PH were age and left atrial size (P < 0.0001). During a mean follow-up of 4.8 ± 2.8 years, PH was a strong independent predictor of death [adjusted HR 2.03 (1.30-3.18) P = 0.002], cardiovascular death [CVD; adjusted HR 2.21 (1.30-3.76) P = 0.003], and heart failure [adjusted HR 1.70 (1.10-2.62) P = 0.018]. Mitral valve surgery at any time during follow-up (performed in 325 patients, 75%) was beneficial [adjusted HR for death 0.22 (0.14-0.36) P < 0.001], but PH was associated with the increased risk of postoperative death and CVD (P = 0.01). CONCLUSION: Pulmonary hypertension is a frequent complication of significant MR due to flail leaflet and is associated with major outcome implications, approximately doubling the risk of death and heart failure after diagnosis. Mitral valve surgery performed during follow-up is beneficial but does not completely abolish the adverse effects of PH once it is established and is particularly beneficial in patients without PH. These data support relieving PH secondary to MR due to flail leaflet, but also careful consideration for mitral surgery before PH is established.

Usefulness and limitations of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy.

PURPOSE: We previously reported in a small series of patients that (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy tested positive in transthyretin-related (TTR) (both mutant and wild-type) but not in primary (AL) amyloidotic cardiomyopathy (AC). We extended our study to a larger cohort of patients with AC. METHODS: We evaluated (1) 45 patients with TTR-related AC (28 mutant and 17 wild-type), (2) 34 with AL-related AC and (3) 15 non-affected controls. Myocardial uptake of (99m)Tc-DPD (740 MBq i.v.) was semiquantitatively and visually assessed at 5 min and at 3 h. RESULTS: Heart retention (HR) and heart to whole-body retention ratio (H/WB) of late (99m)Tc-DPD uptake were higher among TTR-related AC (HR 7.8%; H/WB 10.4) compared with both unaffected controls (HR 3.5%; H/WB 5.7; p < 0.0001) and AL-related AC (HR 4.0%; H/WB 6.1; p < 0.0001). For the diagnosis of TTR-related AC, positive and negative predictive accuracy of visual scoring of cardiac retention were: 80 and 100% (visual score ≥1); 88 and 100% (visual score ≥2); and 100 and 68% (visual score = 3). At adjusted linear regression analysis, TTR aetiology turned out to be the only positive predictor of increasing (99m)Tc-DPD uptake in terms of both HR [ß 2.5, 95% confidence interval (CI) 1.5-3.5; p < 0.0001] and H/WB (ß 3.5, 95% CI 2.1-4.9; p < 0.0001). CONCLUSION: While (99m)Tc-DPD scintigraphy was confirmed to be useful for differentiating TTR from AL-related AC, diagnostic accuracy was lower than previously reported due to a mild degree of tracer uptake in about one third of AL patients. (99m)Tc-DPD scintigraphy can provide an accurate differential diagnosis in cases of absent or intense uptake evaluated by visual score.

Analysis of polymorphisms Leiden Factor V G1691A and prothrombin G20210A as risk factors for acute myocardial infarction.

Thrombotic risk increases in elderly, therefore, the understanding of the genetic predisposition of hypercoagulability could make the difference in the prevention of venous and/or arterial thrombotic events. Laboratory evaluation of hyperfibrinogenemia, increased Factor VII levels, antiphospholipid antibodies presence and hyperhomocysteinemia are considered to have a consistent high predictivity for arterial thrombophilic diseases. Anyway, a large debate exists on the validity of testing Leiden Factor V (FV) G1691A and/or prothrombin (FII) G20210A polymorphisms in patients affected by arterial thrombotic diseases, despite of the several observations described. Here we report data strongly suggesting that at least the FII G20210A polymorphism might be considered an important risk factor for acute myocardial infarction in aged patients (55-80 years old). On the other hand, in spite of a not different genotypic and allelic distribution for the Leiden FV G1691A mutation, the presence of one or both the two polymorphisms is significantly higher among cases than in controls. In conclusion, our data suggest that FII G20210A and/or Leiden FV might be involved as risk factor for arterial disorders in about 5% of old subjects, justifying the opportunity of a genetic screening and an eventual preventive treatment, in particular in old subjects in which other and major risk factors, as hypertension and atherosclerosis, are detected.

Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types.

BACKGROUND: Most studies of amyloidotic cardiomyopathy consider as a single entity the 3 main systemic cardiac amyloidoses: acquired monoclonal immunoglobulin light-chain (AL); hereditary, mutated transthyretin-related (ATTRm); and wild-type transthyretin-related (ATTRwt). In this study, we compared the diagnostic/clinical profiles of these 3 types of systemic cardiac amyloidosis. METHODS AND RESULTS: We conducted a longitudinal study of 233 patients with clear-cut diagnosis by type of cardiac amyloidosis (AL, n=157; ATTRm, n=61; ATTRwt, n=15) at 2 large Italian centers providing coordinated amyloidosis diagnosis/management facilities since 1990. Average age at diagnosis was higher in AL than in ATTRm patients; all ATTRwt patients except 1 were elderly men. At diagnosis, mean left ventricular wall thickness was higher in ATTRwt than in ATTRm and AL. Left ventricular ejection fraction was moderately depressed in ATTRwt but not in AL or ATTRm. ATTRm patients less often displayed low QRS voltage (25% versus 60% in AL; P<0.0001) or low voltage-to-mass ratio (1.1+/-0.5 versus 0.9+/-0.5; P<0.0001). AL patients appeared to have greater hemodynamic impairment. On multivariate analysis, ATTRm was a strongly favorable predictor of survival, and ATTRwt predicted freedom from major cardiac events. CONCLUSIONS: AL, ATTRm, and ATTRwt should be considered 3 different cardiac diseases, probably characterized by different pathophysiological substrates and courses. Awareness of the diversity underlying the cardiac amyloidosis label is important on several levels, ranging from disease classification to diagnosis and clinical management.

Management of acute left ventricular dysfunction after primary percutaneous coronary intervention for ST elevation acute myocardial infarction.

Primary percutaneous coronary intervention (PCI) decreases myocardial damage and reduces the occurrence of mechanical complications and acute heart failure in patients with ST elevation myocardial infarction (STEMI). Nevertheless, left ventricular (LV) dysfunction remains the leading cause of in-hospital mortality in all subsets of patients and particularly for those in whom primary PCI fails to reopen the infarct-related artery. The clinical scenarios of acute LV failure are heart failure and cardiogenic shock, both conditions being associated with extremely poor outcomes. It has been estimated that LV failure accounts for >75% of the cases of shock complicating acute STEMI. As compared to similar situations, the decision-making process in these patients can potentially benefit from the known coronary anatomy and, in many instances, from the immediate implantation of an intraaortic balloon pump at the time of PCI in selected groups of patients. A thorough clinical and instrumental evaluation is mandatory to discriminate patients who will likely recover (either spontaneously or with further conventional procedures) from those who have irreversible myocardial injury and should be screened for LV assist devices and/or emergent heart transplantation. In this review, we provide a practical diagnostic and therapeutic algorithm that may be helpful for the clinical management of patients with acute LV failure after primary PCI.

Long-term follow-up of patients with syncope evaluated by head-up tilt test.

BACKGROUND: Clinicians may be tempted to consider a positive head-up tilt test (HUTT) an unfavorable prognostic indicator. We investigated whether results of routine HUTT predict long-term recurrence of syncope. METHODS: We analyzed syncope recurrence at long-term among 107 patients (mean age 51 +/- 20 years) receiving HUTT for diagnostic evaluation of unexplained/suspected neurocardiogenic syncope in our Institute. RESULTS: HUTT was positive in 76 patients (vasodepressive response, n = 58; cardioinhibitory, n = 5; mixed, n = 13). During a median follow-up of 113 months (range, 7-161), 34 (32%) patients experienced recurrence (24 [32%] with positive HUTT during 110 months (7-159); 10 [32%] with negative HUTT during 120 [22-161] months). Actuarial freedom from recurrence at 10 years did not significantly differ for patients with positive/negative test results (after passive/active phases) or with different positive response patterns (vasodepressive, cardioinhibitory, mixed). By contrast, history of >4 syncopes in the 12 months preceding HUTT stratified risk of recurrence, irrespective of HUTT positivity/negativity. At Cox proportional hazards analysis, history of >4 syncopes in the 12 months preceding HUTT was the single independent risk factor for recurrence both in the overall study population (HR, 1.7; 95% CI, 1.07-2.69) and within the subset of patients who tested positive (HR, 1.83; 95% CI, 1.07-3.17). CONCLUSIONS: This long-term follow-up study reinforces the concept that a positive HUTT should not be considered an unfavorable prognostic indicator; frequency of recent occurrences may be a more valid predictor.

Interventricular delay optimization: a comparison among three different echocardiographic methods.

AIM OF THE STUDY: To compare three different methods for obtaining interventricular-(VV) interval optimization. METHODS: A total of 30 patients undergoing cardiac resynchronization therapy (CRT) were enrolled. All the patients underwent VV-interval optimization performed with three different echocardiographic methods at seven different settings: simultaneous right (RV) and left (LV) ventricular pacing, LV stimulation only, LV preexcitation (LV+20,+40,+60 ms, respectively), RV preexcitation (RV+20 and+40 ms, respectively). Optimal VV delay was selected by: (1) measuring the aortic velocity time integral (VTI method); (2) measuring the time to maximum delay between septal and lateral longitudinal motion in the four-chamber view (velocity method); and (3) measuring the segment with maximal temporal difference of peak circumferential strain in short-axis view at papillary muscles level, (strain method). Velocity and strain methods measurements were obtained relying on two-dimensional ultrasound border tracking algorithm thus providing angle-independent measurements. RESULTS: Immediately after CRT, VTI, maximum peak circumferential strain delay and maximum septal-to-lateral delay were significantly improved (P < 0.001). Particularly, VV-interval optimization determined a further improvement of these indices as compared to the other VV settings (P < 0.001). Furthermore, a substantial concordance was found between the optimal VV interval obtained according to the VTI method and velocity method (k = 0.68), between the optimal VV interval obtained according to the VTI method and strain method (k = 0.63); and between the optimal VV interval obtained according to the velocity method and strain method (k = 0.71). CONCLUSIONS: VV-interval optimization was shown to determine a further benefit beyond CRT. A significant concordance was present between VV programming based on different echocardiographic methods.

A meta-analysis of randomized controlled trials in pulmonary arterial hypertension.

AIMS: There is no cure for pulmonary arterial hypertension, but current approved treatment options include prostanoids, endothelin-receptor antagonists, and phosphodiesterase type-5 inhibitors. The effect on survival of these compounds has not been appropriately assessed in individual trials because of small sample size and short duration. We performed a meta-analysis of all randomized controlled trials with drugs published in this condition. METHODS AND RESULTS: Trials were searched in the Medline database from January 1990 to October 2008. The primary analysis included only studies with a placebo comparator arm, the sensitivity analysis also included studies comparing two active treatment arms. The main outcome measure was all-cause mortality. Twenty-one trials were included in the primary analysis (3140 patients) and two additional studies (59 patients) were included in the sensitivity analysis. Average duration of the trials was 14.3 weeks. All-cause mortality rate in the control group was 3.8%. Active treatments were associated with a reduction in mortality of 43% (RR 0.57; 95% CI 0.35-0.92; P = 0.023); the sensitivity analysis confirmed a reduction in mortality of 38% (RR 0.62; 95% CI 0.39-1.00; P = 0.048). CONCLUSION: The results of this meta-analysis suggest an improvement of survival in the patients treated with the targeted therapies approved for pulmonary arterial hypertension.

Exercise stress echocardiography is superior to rest echocardiography in predicting left ventricular reverse remodelling and functional improvement after cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) improves functional capacity and survival in heart failure. However, one-third of patients fail to respond to CRT. Resting left ventricular (LV) dyssynchrony assessed by echocardiography (ECHO) showed discordant results in identifying CRT responders. LV dyssynchrony can totally change during exercise. Aim of this study was to evaluate whether exercise dyssynchrony could select responders to CRT. METHODS AND RESULTS: Sixty-four patients scheduled for CRT implantation performed bicycle exercise ECHO in semi-supine position on an exercise tilting table before and 6 months after CRT implantation. Tissue Doppler imaging (TDI) was acquired both at rest and during exercise to detect LV mechanical dyssynchrony. Predictive values for CRT response were 70% for rest TDI and 89% for exercise TDI (P = 0.01). Exercise LV dyssynchrony was the only parameter independently associated with follow-up improvement of rest ejection fraction and LV volume during multivariable analysis (P < 0.001). Functional improvement at 6-min walking test was statistically higher in patients with exercise dyssynchrony (P = 0.005), and not different considering rest dyssynchrony (P = 0.30). CONCLUSION: Exercise intraventricular dyssynchrony assessed by exercise TDI ECHO is a strong independent predictor of CRT response. It could be used to select candidates for CRT, thus reducing ineffective implantations of biventricular pacemakers.

Long-term effectiveness of early administration of glycoprotein IIb/IIIa agents to real-world patients undergoing primary percutaneous interventions: results of a registry study in an ST-elevation myocardial infarction network.

AIMS: To evaluate the clinical impact of early administration of glycoprotein IIb/IIIa agents (IIb/IIIa agents) in the context of a dedicated hub and spoke network allowing very prompt pharmacological/mechanical interventions. METHODS AND RESULTS: Using a prospective database, we conducted a cohort study of ST-elevation myocardial infarction (STEMI) patients (n = 1124) undergoing primary percutaneous coronary interventions (PPCIs) and IIb/IIIa agents administration (period, 2003-2006). Comparisons were planned between patients receiving early IIb/IIIa agents administration (in hub/spoke centre emergency departments or during ambulance transfer; early group, n = 380) or delayed administration (in the catheterization laboratory; late group, n = 744). The primary outcome measure was long-term overall mortality/re-infarction. Baseline characteristics of the two groups were largely comparable. Angiographically, early group patients more often achieved pre-PPCI TIMI Grade 2-3 and TIMI Grade 3 flow. Clinically, the early administration group experienced lower 2-year risk of unadjusted mortality/re-infarction (17 vs. 23%; P = 0.01). After adjustment for potential confounders, early administration was associated with favourable outcome in the overall population (HR = 0.71, P = 0.03) and in high-risk subgroups (TIMI risk index >25, HR = 0.64, P = 0.02; Killip class >1, HR = 0.54, P = 0.01). CONCLUSION: In patients treated by PPCI within a STEMI network setting, early administration of IIb/IIIa agents may provide long-term clinical benefits. Notably, these results appeared magnified in high-risk patients.

Is cardiac resynchronization therapy cost-effective?

Cardiac resynchronization therapy (CRT) is a treatment of proven efficacy for selected patients with heart failure and associated conduction disturbances. The increasing financial burden that healthcare systems face has increased the interest in cost-effectiveness and cost-utility estimates, focused on devices with defibrillation capabilities (CRT-D), with a high upfront cost, as well as on simpler devices providing only biventricular pacing (CRT-P). Available economic estimates are largely dependent on data source, assumptions, modelling technique, time horizon, and perspective, leading to some variability in cost-effectiveness and cost-utility estimates. As a whole, cost-effectiveness and cost-utility estimates of both CRT-P and CRT-D improve as the time horizon examined is lengthened and appear to be below US$50,000 per quality-adjusted life-year, a threshold value commonly adopted for coverage of healthcare interventions in the USA and quite comparable with similar thresholds used within Europe. Limited data are available on the comparative cost-effectiveness or cost-utility of CRT-P and CRT-D devices. Moreover, more data on the effectiveness and long-term benefits of CRT-D and CRT-P are needed in order to estimate better the value of these treatments in the 'real world, as well as for attempts to improve cost-effectiveness through improved patient selection.

Clinical implications of left superior vena cava persistence in candidates for pacemaker or cardioverter-defibrillator implantation.

Persistence of a left superior vena cava (LSVC) has been reported in 0.3%-0.4% of candidates for pacemaker (PM) or cardioverter-defibrillator (ICD) implantation. The aim of the study was to evaluate the clinical implications of LSVC persistence for proper device performance. We observed the prevalence of LSVC during a 15-year period. A total of 2077 consecutive patients underwent PM implantation over a 15-year period: 7 had persistent LSVCs (0.34%). Among 599 patients undergoing ICD implantation, 4 LSVCs (0.66%) were observed. Overall LSVC persistence was found in 11/2676 (0.41%) patients. The right superior vena cava was absent in 4/11 (36%) patients. The leads were placed from the left subclavian approach in 5/7 PM patients: 2 received an elective right sided approach due to physician preference. All ICD patients had the device placed left pectoral with a single-coil lead: defibrillation therapy was effective in the long term in all but one patient, who required the addition of a subcutaneous array. Left superior vena cava persistence in PM/ICD patients is similar to the general population (0.41% in our study). The left-sided implant may be skill-demanding during lead placement; however, this task can be accomplished in the majority of cases, with a reliable outcome in the short term and appropriate device performance at follow-up.

Predictive value of high sensitivity C-reactive protein in patients with ST-elevation myocardial infarction treated with percutaneous coronary intervention.

AIMS: To evaluate the predictive value of high sensitivity (hs) C-reactive protein levels on long-term survival in patients with ST-elevation myocardial infarction (STEMI) treated with primary PCI. METHODS AND RESULTS: We conducted a retrospective analysis of 758 STEMI patients (from January 2003 to December 2005), with STEMI onset <12 h and hs-C-reactive protein determination on admission. Patients were classified into four groups [I (hs-C-reactive protein < 0.48 mg/dL), II (hs-C-reactive protein > or = 0.48 to <1.2 mg/dL), III (hs-C-reactive protein > or = 1.2 to <3.1 mg/dL), IV (hs-C-reactive protein > or = 3.1 mg/dL)] according to quartiles of hs-C-reactive protein serum level. The IV quartile hs-C-reactive protein group had a higher incidence of in-hospital mortality and cumulative adverse events. At a mean follow-up of 724 +/- 376 days (range 0-1393), the IV quartile hs-C-reactive protein group showed lower estimated survival, lower estimated myocardial infarction-free survival and lower estimated event-free survival. At multivariable analysis hs-C-reactive protein appeared to be an independent predictor of long-term mortality (HR: 1.04, 95% CI: 1.01-1.07, P = 0.003), long-term mortality and re-infarction (HR: 1.03, 95% CI: 1.01-1.06, P = 0.008) and adverse events (HR: 1.03, 95% CI: 1.01-1.05, P = 0.03). CONCLUSION: Evaluation of hs-C-reactive protein on admission in STEMI patients undergoing primary PCI allows reliable risk stratification of these patients.

Mechanical simulator of the cardiovascular system.

To devise and to build a mechanical simulator of the cardiovascular system of increasing complexity is a fascinating experience for a medical Physicist. We did it, and the effort to match the solutions with the objectives forced us to deepen the knowledge of the physiological aspects, to devise different solutions and to compare their results. This paper describes the final solution and shows the results, discussing the theoretical and practical aspects of the different choices. The ventricle is simulated by a pumping syringe with an external pulsing chamber to accomplish the Frank-Starling mechanism; the coronary circulation by a nonlinear hydraulic resistance device; the aorta by different wall thickness rubber tubes; the arterial vascular resistance by a thin, variable length tube; the venous reservoir by a variable volume chamber connected to a reservoir simulating the atrium. The simulator was mainly devoted to teaching purposes, but the possibility to modify the mechanical characteristics of the single components moved it to be used also for research, with an unexpected satisfaction.

Sildenafil citrate therapy for pulmonary arterial hypertension.

BACKGROUND: Sildenafil inhibits phosphodiesterase type 5, an enzyme that metabolizes cyclic guanosine monophosphate, thereby enhancing the cyclic guanosine monophosphate-mediated relaxation and growth inhibition of vascular smooth-muscle cells, including those in the lung. METHODS: In this double-blind, placebo-controlled study, we randomly assigned 278 patients with symptomatic pulmonary arterial hypertension (either idiopathic or associated with connective-tissue disease or with repaired congenital systemic-to-pulmonary shunts) to placebo or sildenafil (20, 40, or 80 mg) orally three times daily for 12 weeks. The primary end point was the change from baseline to week 12 in the distance walked in six minutes. The change in mean pulmonary-artery pressure and World Health Organization (WHO) functional class and the incidence of clinical worsening were also assessed, but the study was not powered to assess mortality. Patients completing the 12-week randomized study could enter a long-term extension study. RESULTS: The distance walked in six minutes increased from baseline in all sildenafil groups; the mean placebo-corrected treatment effects were 45 m (+13.0 percent), 46 m (+13.3 percent), and 50 m (+14.7 percent) for 20, 40, and 80 mg of sildenafil, respectively (P<0.001 for all comparisons). All sildenafil doses reduced the mean pulmonary-artery pressure (P=0.04, P=0.01, and P<0.001, respectively), improved the WHO functional class (P=0.003, P<0.001, and P<0.001, respectively), and were associated with side effects such as flushing, dyspepsia, and diarrhea. The incidence of clinical worsening did not differ significantly between the patients treated with sildenafil and those treated with placebo. Among the 222 patients completing one year of treatment with sildenafil monotherapy, the improvement from baseline at one year in the distance walked in six minutes was 51 m. CONCLUSIONS: Sildenafil improves exercise capacity, WHO functional class, and hemodynamics in patients with symptomatic pulmonary arterial hypertension.