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.

Risk of stroke with coronary artery bypass graft surgery compared with percutaneous coronary intervention.

OBJECTIVES: This study sought to determine whether coronary artery bypass graft (CABG) surgery is associated with an increased risk of stroke compared with percutaneous coronary intervention (PCI). BACKGROUND: Some, but not all, randomized trials have reported increased rates of stroke with CABG compared with PCI. However, all these studies were powered insufficiently to examine differences in the risk of stroke reliably. METHODS: We performed a meta-analysis of 19 trials in which 10,944 patients were randomized to CABG versus PCI. The primary end point was the 30-day rate of stroke. We also determined the rate of stroke at the midterm follow-up and investigated whether there was an interaction between revascularization type and the extent of coronary artery disease on the relative risk of stroke. RESULTS: The 30-day rate of stroke was 1.20% after CABG compared with 0.34% after PCI (odds ratio: 2.94, 95% confidence interval: 1.69 to 5.09, p < 0.0001). Similar results were observed after a median follow-up of 12.1 months (1.83% vs. 0.99%, odds ratio: 1.67, 95% confidence interval: 1.09 to 2.56, p = 0.02). The extent of coronary artery disease (single vessel vs. multivessel vs. left main) did not affect the relative increase in the risk of stroke observed with CABG compared with PCI at either 30 days (p = 0.57 for interaction) or midterm follow-up (p = 0.08 for interaction). Similar results were observed when the outcomes in 33,980 patients from 27 observational studies were analyzed. CONCLUSIONS: Coronary revascularization by CABG compared with PCI is associated with an increased risk of stroke at 30 days and at the mid-term follow-up.

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.

The role of percutaneous balloon aortic valvuloplasty as a bridge for transcatheter aortic valve implantation.

AIMS: Many inoperable patients with severe aortic stenosis (AS) are not immediately eligible for transcatheter aortic valve implantation (TAVI). We evaluated the role of percutaneous balloon aortic valvuloplasty (BAV) in this setting. METHODS AND RESULTS: Among 210 consecutive patients referred to our institution for BAV, we identified three groups: immediately eligible for TAVI (n=65, 31%), excluded from TAVI (n=67, 32%), BAV as a bridge to TAVI (n=78, 37%). This last group comprised patients with low left ventricular ejection fraction, frailty or enfeebled status, symptoms of uncertain origin, critical conditions, moderate-to-severe mitral valve regurgitation, need of major non-cardiac surgery. Outpatient clinic visit and echocardiography were performed around one month after BAV to decide the final therapeutic strategy. Mean age was 81±8 years and the vast majority of patients had comorbidities and high-risk features. The incidence of periprocedural adverse events was 6.4%: 5.1% death (four patients: one procedural complication, three, natural disease progression), 1.3% minor stroke. After BAV, 46% of these patients were deemed eligible for TAVI, and 28% for cardiac surgery. Patients who underwent TAVI after bridge BAV showed 94% 30-day survival. CONCLUSIONS: BAV is a safe and effective tool to bridge selected patients to TAVI when indications are not obvious.

Left atrial size is a potent predictor of mortality in mitral regurgitation due to flail leaflets: results from a large international multicenter study.

BACKGROUND: Left atrium (LA) enlargement is common in organic mitral regurgitation (MR) and is an emerging prognostic indicator. However, outcome implications of LA enlargement have not been analyzed in the context of routine clinical practice and in a multicenter study. METHODS AND RESULTS: The Mitral Regurgitation International DAtabase (MIDA) registry enrolls patients with organic MR due to flail leaflets, diagnosed in routine clinical practice, in 5 US and European centers. We investigated the relation between LA diameter and mortality under medical treatment and after mitral surgery in 788 patients in sinus rhythm (64±12 years; median LA, 48 [43 to 52] mm). LA diameter was independently associated with survival after diagnosis (hazard ratio, 1.08 [1.04 to 1.12] per 1 mm increment). Compared with patients with LA <55 mm, those with LA ≥55 mm had lower 8-year overall survival (P<0.001). LA ≥55 mm independently predicted overall mortality (hazard ratio, 3.67 [1.95 to 6.88]) and cardiac mortality (hazard ratio, 3.74 [1.72 to 8.13]) under medical treatment. The association of LA ≥55 mm and mortality was consistent in subgroups. Similar excess mortality associated with LA ≥55 mm was observed in asymptomatic and symptomatic patients (P for interaction, 0.77). In patients who underwent mitral surgery, LA ≥55 mm had no impact on postoperative outcome (P>0.20). Mitral surgery was associated with greater survival benefit in patients with LA ≥55 mm compared with LA <55 mm (P for interaction, 0.008). CONCLUSIONS: In MR caused by flail leaflets, LA diameter ≥55 mm is associated with increased mortality under medical treatment, independent of the presence of symptoms or left ventricular dysfunction.

Idiopathic thrombocytopenic purpura and coronary artery disease: comparison between coronary artery bypass grafting and percutaneous coronary intervention.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by a low platelet count and an increased risk of bleeding. At the same time, ITP patients present an increased risk of thrombosis and atherosclerosis related to the high presence of haemostatic factors and chronic steroid therapy. Although relatively rare, the association of ITP and coronary artery disease represents a complex therapeutic challenge. In particular, no recommendations exist regarding the best management approach. We reviewed the literature making a comparison between coronary artery bypass grafting and percutaneous coronary intervention.

Prognostic significance of mean platelet volume on admission in an unselected cohort of patients with non ST-segment elevation acute coronary syndrome.

Mean platelet volume (MPV) has been proposed as a marker of platelet reactivity and cardiovascular risk. Its prognostic significance has not been thoroughly investigated in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). We included 1,041 consecutive patients with NSTE-ACS. Patients were divided in quartiles according to the MPV value on admission (fl) i.e. Q1<7.5; Q2=7.5-8.0; Q3=8.1-8.8; Q4≥8.9. The primary study endpoint was the composite of cardiovascular death and re-myocardial infarction (MI) at one year. Secondary study endpoints were individual cardiovascular death and re-MI. Patients in Q4 were older, had a higher prevalence of previous MI, peripheral artery disease and advanced Killip class compared to patients in Q1-Q3. Elevated MPV levels (Q4) was independently associated with gender, smoking status, platelet count and creatinine level. Overall, 210 patients (20.2%) reached the primary endpoint, 124 (12.1%) died from cardiovascular causes and 125 (12.0%) suffered from re-MI. On multivariable analysis patients in Q4 were at higher risk of primary endpoint (HR=1.41; 95%CI 1.06-1.89; p=0.02) whilst the association with cardiovascular death and re-MI was attenuated. MPV as continuous variable was independently associated with both primary endpoint (HR=1.19; 95%CI 1.06-1.33; p=0.003) and cardiovascular death (HR=1.23; 95%CI 1.06-1.42, p=0.006). The incorporation of MPV into a comprehensive model of risk significantly increased the likelihood ratio chi-square for prediction of both the composite endpoint (p=0.004) and cardiovascular death (p=0.009). Therefore, MPV may be useful to improve risk stratification in NSTE-ACS patients and should be included in future prospective studies evaluating the role of platelet function in promoting cardiovascular events.

Implante transcateter de prótese valvular aórtica: perfil clínico e evolução de uma série consecutiva de 75 casos do registro conjunto Universidade de Bolonha/Hospital Sírio-Libanês / Transcatheter implantation of aortic valve prosthesis: clinical profile and course of a consecutive series of 75 cases of the Bologna University/Hospital Sírio-Libanês joint registry

Introdução: O implante transcateter de prótese valvular aórtica (ITVA) tem sido utilizado em nosso meio e em diversos países do mundo como alternativa ao tratamento conservador em pacientes com estenose aórtica grave e elevado risco cirúrgico. Objetivou-se descrever o perfil clínico basal e a mortalidade a curto e médio prazos de uma série consecutiva de casos tratados com ITVA em dois centros localizados, respectivamente, na Itália e no Brasil. Métodos: A população de estudo foi composta pelos primeiros 75 pacientes consecutivos com estenose valvar aórtica grave tratados com a prótese Medtronic CoreValve TM Revalving System (MCV – Medtronic, Minneapolis, Estados Unidos). Tipicamente, a indicação para o ITVA foi motivada pelo alto risco cirúrgico. A média de idade era de 82 anos, 55% eram mulheres, um terço apresentava doença pulmonar grave e 95% apresentavam insuficiência cardíaca sintomática. Resultados: Após o ITVA, houve redução significativa do gradiente transvalvar aórtico máximo (basal: 95,8 + 32,3 mmHg; pós-procedimento: 18,5 + 6,1 mmHg) e médio (basal: 45,9 + 16,9 mmHg; pós-procedimento: 10,4 + 5,2 mmHg) (P < 0,01 para ambos). Insuficiência aórtica moderada ou acentuada foi evidenciada em 7% dos casos após ITVA. A taxa de sobrevida global aos 30 dias foi de 91,6% e aos 12 meses, de 79%. Conclusões: O ITVA surge como um método terapêutico de grande relevância para portadores de estenose aórtica de alto risco cirúrgico. As taxas de sobrevida precoce e a médio prazo indicam o benefício potencial do novo procedimento também para pacientes tratados no chamado mundo real.

Background: Transcatheter aortic valve implantation (TAVI) has been used in our country and in several differentcountries worldwide as an alternative to conservative treatment for patients with severe aortic stenosis and high surgicalrisk. This paper aimed at describing the baseline clinical profile and the short and medium-term mortality of a consecutive series of cases treated with TAVI in two centers in Italy and Brazil, respectively. Methods: The study population included the first 75 consecutive patients with severeaortic stenosis treated with the Medtronic CoreValveTM Revalving System (MCV – Medtronic, Minneapolis, USA). Typically, the indication for TAVI was motivated by high surgical risk. Mean age was 82 years, 55% were females, a third had severe lung disease, and 95% had symptomaticheart failure. Results: TAVI was associated with a significant reduction of peak (baseline: 95.8 + 32.3 mmHg; postprocedure: 18.5 + 6.1 mmHg) and mean (baseline: 45.9 + 16.9 mmHg; post-procedure: 10.4 + 5.2 mmHg) transaortic gradient (P < 0.01 for both). Moderate or severe aortic insufficiencywas observed in 7% of the cases. The overall survival rate at 30 days was 91.6% and at 12 months it was 79%.Conclusions: TAVI emerges as an important therapeutic option for high risk patients with aortic stenosis. The short and mediumterm survival rates suggest that the new procedure might beof benefit for patients treated in the real world context.

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.

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.

Role of drugs and devices in patients at risk of sudden cardiac death.

The search for effective treatment for preventing sudden cardiac death (SCD) initially started with anti-arrhythmic agents in high-risk patients, but the use of randomized controlled trials clearly led to the conclusion that an approach based on anti-arrhythmic agents is not useful, and sometimes potentially harmful (the risk of arrhythmic death was increased up to 159% in CAST study). Today the approach to SCD prevention includes considering both the setting of patients who have already presented a cardiac arrest or a malignant ventricular tachyarrhythmias (secondary prevention of SCD) and the much broader setting of primary prevention in patients at variable degrees of identifiable risk. For secondary prevention of SCD, implantable cardioverter defibrillation is now the standard of care (the risk of overall mortality may be reduced by 20-31%), and anti-arrhythmic agents, specifically amiodarone, have only a complementary role (for reducing device activations or for preventing atrial fibrillation). For primary prevention of SCD in high-risk patients, cardioverter defibrillators have nowadays specific indications in patients with left ventricular dysfunction (often in combination with cardiac resynchronization therapy), where the risk of overall mortality may be reduced by 23-54%. For the large number of subjects who have some risk of SCD, but are not identified as at high risk of SCD, a series of drugs could exert a favorable effect (beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blocker agents, statins, omega-3 fatty acids and aldosterone antagonists), and for some of them evidence is emerging, from subgroup analysis, of possible SCD prevention capabilities.

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.

Lower long-term mortality within a regional system of care for ST-elevation myocardial infarction.

INTRODUCTION: Organization of regional systems of care (RSC) with an emphasis on pre-hospital triage and primary percutaneous coronary intervention (PCI) has been recommended to implement guidelines and improve clinical outcome in ST-segment elevation myocardial infarction (STEMI). PATIENTS AND METHODS: All STEMI patients (n = 1,823) admitted to any of the 13 hospitals of the province of Bologna, Italy, before (pre-RSC, n = 858) and after (RSC, n = 965) the implementation of a RSC were enrolled in the study. Primary evaluation was mortality. Secondary outcomes included death, myocardial infarction, stroke, and coronary revascularization procedures up to three-year follow-up. RESULTS: Among patients admitted <12 h from symptom onset, reperfusion was performed in 68.7% pre-RSC versus 89.8% RSC, P <0.001. Within the RSC, primary PCI became the main reperfusion treatment (34.5% pre-RSC versus 85.9% RSC; P <0.001 for both), and one-year mortality was lower (23.9% pre-RSC versus 18.8% RSC; P = 0.0015). At three-year, this advantage was maintained and actually increased (31.7% pre-RSC versus 24.8% RSC; P = 0.0031). Independent predictors of mortality at three-years were RSC, age, heart failure, cerebrovascular disease, renal disease, shock, peripheral vascular disease, and malignancies. CONCLUSIONS: In this study, RSC for the treatment of STEMI was associated with increased rates of reperfusion and reduction of long-term mortality.

Transthyretin-related amyloidoses and the heart: a clinical overview.

A nonhereditary form of systemic amyloidosis associated with wild-type transthyretin causes heart involvement predominantly in elderly men (systemic senile amyloidosis, or SSA). However, hereditary transthyretin-related amyloidosis (ATTR) is the most frequent form of familial systemic amyloidosis, a group of severe diseases with variable neurological and organ involvement. ATTR remains a challenging and widely underdiagnosed condition, owing to its extreme phenotypic variability: the clinical spectrum of the disease ranges from an almost exclusive neurologic involvement to a strictly cardiac presentation. Such heterogeneity principally results from differential effects of the various reported transthyretin mutations, the geographic region the patient is from and, in the case of the most common mutation, Val30Met, whether or not large foci of cases occur (endemic versus nonendemic aggregation). Genetic or environmental factors (such as age, sex, and amyloid fibril composition) also contribute to the heterogeneity of ATTR, albeit to a lesser extent. The existence of exclusively or predominantly cardiac phenotypes should lead clinicians to consider the possibility of ATTR in all patients who present with an unexplained increase in left ventricular wall thickness at echocardiography. Assessment of such patients should include an active search for possible red flags that can point to the correct final diagnosis.

How many patients with severe symptomatic aortic stenosis excluded for cardiac surgery are eligible for transcatheter heart valve implantation?

OBJECTIVE: We sought to assess what proportion of patients with severe symptomatic aortic stenosis who are excluded from cardiac surgery are eligible for transcatheter aortic valve implantation (TAVI). METHODS: Between July 2007 and December 2008, 98 patients with severe symptomatic aortic stenosis judged inoperable were referred to our institution for percutaneous aortic balloon valvuloplasty (PABV). They entered a screening for TAVI with the CoreValve Revalving System or the Edwards-Sapien valve, comprising general clinical evaluation, echocardiogram, coronary angiography, angiography and angio-CT scan of thoracic aorta and ilio-femoral axes. RESULTS: Mean patients' age was 82 +/- 7 years; the vast majority presented relevant comorbidities. Mortality risk predicted by the logistic European System for Cardiac Operative Risk Evaluation was on average 25.3 +/- 14.5%. Overall, 45 (45.9%) patients met the criteria for TAVI: 29.6% for percutaneous transfemoral access, 6.1% for trans-subclavian and 10.2% for transapical approaches. Reason for exclusion was severe noncardiac comorbidity in around half of the cases. PABV allowed re-classification of several patients with very poor left ejection fraction and severe mitral regurgitation. Among the 39 patients undergoing TAVI after the screening, in-hospital mortality was 3.7% for transfemoral and 0 for trans-subclavian and transapical approaches. CONCLUSIONS: TAVI represents a viable therapeutic option for elderly patients with severe symptomatic aortic stenosis who are not candidates for surgical aortic valve replacement. However, presently less than half of them actually fulfil the criteria for these procedures.

Survival implication of left ventricular end-systolic diameter in mitral regurgitation due to flail leaflets a long-term follow-up multicenter study.

OBJECTIVES: This study analyzed the association of left ventricular end-systolic diameter (LVESD) with survival after diagnosis in organic mitral regurgitation (MR) due to flail leaflets. BACKGROUND: LVESD is a marker of left ventricular function in patients with organic MR but its association to survival after diagnosis is unknown. METHODS: The MIDA (Mitral Regurgitation International Database) registry is a multicenter registry of echocardiographically diagnosed organic MR due to flail leaflets. We enrolled 739 patients with MR due to flail leaflets (age 65 +/- 12 years; ejection fraction: 65 +/- 10%) in whom LVESD was measured (36 +/- 7 mm). RESULTS: Under conservative management, 10-year survival and survival free of cardiac death were higher with LVESD <40 mm versus > or =40 mm (64 +/- 5% vs. 48 +/- 10%; p < 0.001, and 73 +/- 5% vs. 63 +/- 10%; p = 0.001). LVESD > or =40 mm independently predicted overall mortality (hazard ratio [HR]: 1.95, 95% confidence interval [CI]: 1.01 to 3.83) and cardiac mortality (HR: 3.09, 95% CI: 1.35 to 7.09) under conservative management. Mortality risk increased linearly with LVESD >40 mm (HR: 1.15, 95% CI: 1.04 to 1.27 per 1-mm increment). During the entire follow-up (including post-surgical), LVESD > or =40 mm independently predicted overall mortality (HR: 1.86, 95% CI: 1.24 to 2.80) and cardiac mortality (HR: 2.14, 95% CI: 1.29 to 3.56), due to persistence of excess mortality in patients with LVESD > or =40 mm after surgery (HR: 1.86, 95% CI: 1.11 to 3.15 for overall death, and HR: 1.81, 95% CI: 1.05 to 3.54 for cardiac death). CONCLUSIONS: In MR due to flail leaflets, LVESD > or =40 mm is independently associated with increased mortality under medical management but also after mitral surgery. These findings support prompt surgical rescue in patients with LVESD > or =40 mm but also suggest that best preservation of survival is achieved in patients operated before LVESD reaches 40 mm.

Phrenic stimulation: a challenge for cardiac resynchronization therapy.

BACKGROUND: Phrenic stimulation (PS) may hinder left ventricular (LV) pacing. We prospectively observed its prevalence in consecutive patients with cardiac resynchronization therapy (CRT) devices. METHODS AND RESULTS: In the years 2003 to 2006, 197 patients received a CRT device. PS and LV threshold measurements were carried out at implantation and at 6-month follow-up. LV reverse remodeling was assessed by echocardiography before implantation and at follow-up. LV lead placement was lateral/posterolateral in 86% of patients. Both PS and LV reverse remodeling occurred most frequently at the lateral/posterolateral LV pacing sites (P<0.001). PS was detected in 73 (37%) of patients and was clinically relevant in 41 (22%). The detection of PS at implantation had a poor sensitivity, as it occurred only in left lateral or sitting position in 27 patients. Ten patients (5%) underwent repeated surgery and 4 (2%) had their CRT turned off because of PS. At follow-up, we could manage PS noninvasively in 32 patients with a small PS-LV threshold difference: in 20 by cathode programmability (3 also thanks to automatic management of LV output) and in 12 (without cathode programmability) by programming the LV output as threshold +1 V. CONCLUSIONS: PS may seriously hinder CRT. A bipolar LV lead and cathode programmability are mandatory to avoid PS by changing the LV pacing vector at target sites for CRT. LV stability at target sites despite PS should also be pursued by these means. The automatic adjustment of LV pacing output is complementary in patients with a small PS-LV threshold difference.

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.