Explore the vast range of titles available.

Angiotensin II type 1 receptor blockers have favourable effects on haemodynamic measurements, neurohumoral activity, and left-ventricular remodelling when added to angiotensin-converting-enzyme (ACE) inhibitors in patients with chronic heart failure (CHF). We aimed to find out whether these drugs improve clinical outcome. Between March, 1999, and November, 1999, we enrolled 2548 patients with New York Heart Association functional class II–IV CHF and left-ventricular ejection fraction 40% or lower, and who were being treated with ACE inhibitors. We randomly assigned patients candesartan (n=1276, target dose 32 mg once daily) or placebo (n=1272). At baseline, 55% of patients were also treated with β blockers and 17% with spironolactone. The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF. Analysis was done by intention to treat. The median follow-up was 41 months. 483 (38%) patients in the candesartan group and 538 (42%) in the placebo group experienced the primary outcome (unadjusted hazard ratio 0·85 [95% CI 0·75–0·96], p=0·011; covariate adjusted p=0·010). Candesartan reduced each of the components of the primary outcome significantly, as well as the total number of hospital admissions for CHF. The benefits of candesartan were similar in all predefined subgroups, including patients receiving baseline β blocker treatment. The addition of candesartan to ACE inhibitor and other treatment leads to a further clinically important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction. Published online Sept 1, 2003 http://image.thelancet.com/extras/03art7417web.pdf

Angiotensin-converting-enzyme (ACE) inhibitors improve outcome of patients with chronic heart failure (CHF). A substantial proportion of patients, however, experience no benefit from ACE inhibitors because of previous intolerance. We aimed to find out whether candesartan, an angiotensin-receptor blocker, could improve outcome in such patients not taking an ACE inhibitor. Between March, 1999, and March, 2001, we enrolled 2028 patients with symptomatic heart failure and left-ventricular ejection fraction 40% or less who were not receiving ACE inhibitors because of previous intolerance. Patients were randomly assigned candesartan (target dose 32 mg once daily) or matching placebo. The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF. Analysis was by intention to treat. The most common manifestation of ACE-inhibitor intolerance was cough (72%), followed by symptomatic hypotension (13%) and renal dysfunction (12%). During a median follow-up of 33·7 months, 334 (33%) of 1013 patients in the candesartan group and 406 (40%) of 1015 in the placebo group had cardiovascular death or hospital admission for CHF (unadjusted hazard ratio 0·77 [95% CI 0·67–0·89], p=0·0004; covariate adjusted 0·70 [0·60–0·81], p<0·0001). Each component of the primary outcome was reduced, as was the total number of hospital admissions for CHF. Study-drug discontinuation rates were similar in the candesartan (30%) and placebo (29%) groups. Candesartan was generally well tolerated and reduced cardiovascular mortality and morbidity in patients with symptomatic chronic heart failure and intolerance to ACE inhibitors. Published online Sept 1, 2003 http://image.thelancet.com/extras/03art7418web.pdf

Although single photon emission computed tomography (SPECT) and positron emission tomography (PET) myocardial perfusion imaging (MPI) have evolved considerably over the last decade, there is no recent comparison of diagnostic performance. This study was designed to assess relative image quality, interpretive confidence, and diagnostic accuracy by use of contemporary technology and protocols. By consensus and without clinical information, 4 experienced nuclear cardiologists interpreted 112 SPECT technetium-99m sestamibi and 112 PET rubidium-82 MPI electrocardiography (ECG)–gated rest/pharmacologic stress studies in patient populations matched by gender, body mass index, and presence and extent of coronary disease. The patients were categorized as having a low likelihood for coronary artery disease (27 in each group) or had coronary angiography within 60 days. SPECT scans were acquired on a Cardio-60 system and PET scans on an ECAT ACCEL scanner. Image quality was excellent for 78% and 79% of rest and stress PET scans, respectively, versus 62% and 62% of respective SPECT scans (both p < .05). An equal percent of PET and SPECT gated images were rated excellent in quality. Interpretations were definitely normal or abnormal for 96% of PET scans versus 81% of SPECT scans ( p = .001). Diagnostic accuracy was higher for PET for both stenosis severity thresholds of 70% (89% vs 79%, p = .03) and 50% (87% vs 71%, p = .003) and was higher in men and women, in obese and nonobese patients, and for correct identification of multivessel coronary artery disease. In a large population of matched pharmacologic stress patients, myocardial perfusion PET was superior to SPECT in image quality, interpretive certainty, and diagnostic accuracy.

Atrial fibrillation (AF) may occur without symptoms. Little is known about demographic features and prognostic information in patients with asymptomatic AF. In the AFFIRM study, 4060 patients were randomized to either rhythm or rate control. At baseline, patients were identified as asymptomatic if they answered “no” to a 15-item questionnaire related to cardiac symptoms during AF in the 6 months before study entry. There were 481 (12%) asymptomatic patients at baseline. Compared with symptomatic patients, asymptomatic patients were more often men and had a lower incidence of coronary artery disease and congestive heart failure, but had more cerebrovascular events. Asymptomatic patients had a longer duration of AF, a lower maximum heart rate, and better left ventricular function. They received fewer cardiac medications and fewer therapies to maintain sinus rhythm. At 5 years, there was a trend for better survival in asymptomatic patients (81% vs 77%, P = .058), and they were more likely to be free from disabling stroke or anoxic encephalopathy, major bleeding, and cardiac arrest (79% vs 67%, P = .024). However, mortality and major events were similar after correction for baseline differences. Patients with asymptomatic AF have less serious heart disease but more cerebrovascular disease. Asymptomatic patients receive different therapies than symptomatic patients. However, the absence of symptoms and the differences in treatment does not confer a more favorable prognosis when differences in baseline clinical parameters are considered. Anticoagulation should be considered in these patients.

Long-term clinical outcomes of new-generation drug-eluting stents in complex anatomic and clinical settings are not well defined. This study assessed the impact of patient and lesion complexity on 2-year outcomes after coronary revascularization with ultrathin strut biodegradable-polymer (BP) sirolimus-eluting stents (SES) versus durable-polymer (DP) everolimus-eluting stents (EES). In a prespecified analysis of the BIOSCIENCE randomized trial (NCT01443104), complex patients (911 of 2,119; 43%) were defined by the presence of acute ST-elevation myocardial infarction (MI); left ventricular ejection fraction ≤30%; renal dysfunction; insulin-treated diabetes; treatment of ostial lesion, bypass graft, unprotected left main lesion; or 3-vessel intervention. The primary end point was target lesion failure (TLF), a composite of cardiac death, target vessel MI, and clinically indicated target lesion revascularization. At 2 years, complex compared with simple patients had a greater risk of TLF (14.5% vs 7.4%, risk ratio 2.05, 95% confidence interval 1.56 to 2.69; p <0.001). The difference was sustained beyond 1 year on landmark analysis. Complex patients had higher rates of the patient-oriented composite end point of death, any MI, or any revascularization (23% vs 14.4%; p <0.001) as well as definite stent thrombosis (1.6% vs 0.4%, p = 0.006). There were no differences in TLF and patient-oriented composite end point between the BP-SES versus DP-EES, consistently among simple and complex patients. In conclusion, patient and lesion complexity had a durable adverse impact on clinical outcomes throughout 2 years of follow-up in this all-comers randomized trial. Safety and efficacy of new-generation BP-SES and DP-EES were comparable, irrespective of complexity status.

Objectives This study reports the long-term follow-up of the randomised controlled HEBE trial. The HEBE study is a multicentre trial that randomised 200 patients with large first acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention to either intracoronary infusion of bone marrow mononuclear cells (BMMCs) (n=69), peripheral blood mononuclear cells (PBMCs) (n=66) or standard therapy (n=65). Methods In addition to 3–5 days, and 4 months after AMI, all patients underwent cardiac MRI after 2 years. A follow-up for 5 years after AMI was performed to assess clinical adverse events, including death, myocardial reinfarction and hospitalisation for heart failure. Results Of the 200 patients enrolled, 9 patients died and 12 patients were lost to follow-up at 5 years after AMI. BMMC group showed less increase in LV end-diastolic volume (LVEDV) (3.5±16.9 mL/m2) compared with (11.2±19.8 mL/m2, p=0.03) in the control group, with no difference between the PBMC group (9.2±20.9 mL/m2) and controls (p=0.69). Moreover, the BMMC group showed a trend for decrease in LV end systolic volume (−1.8±15.0 mL/m2) as compared with controls (3.0±16.3 mL/m2, p=0.07), with again no difference between PBMC (3.3±18.8 mL/m2) and controls (p=0.66). The combined endpoint of death and hospitalisation for heart failure was non-significantly less frequent in the BMMC group compared with the control group (n=4 vs n=1, p=0.20), with no difference between PBMC and controls (n=6 vs n=4, p=0.74). The composite endpoint of death or recurrent myocardial infarction was significantly higher in the PBMC group compared with controls (14 patients vs 3 patients, p=0.008), with no difference between the BMMC group and controls (2 vs 3 patients, p=0.67). Conclusions Long-term follow-up of the HEBE trial showed that increase in LVEDV was lower in the BMMC group. This study supports the long-term safety of intracoronary BMMC therapy. However, major clinical cardiovascular adverse events were significantly more frequent in the PBMC group. Trial registration number The Netherlands Trial Register #NTR166 (http://www.trialregister.nl) and the International Standard Randomised Controlled Trial, #ISRCTN95796863 (http://isrctn.org).

Cardiac surgery with cardiopulmonary bypass is associated with the development of a systemic inflammatory response, which can lead to myocardial damage. However, knowledge concerning the time course of ventricular performance deterioration and restoration after correction of a congenital heart defect (CHD) in pediatric patients is sparse. Therefore, the authors perioperatively quantified left ventricular (LV) and right ventricular (RV) performance using echocardiography. Their study included 141 patients (ages 0–18 years) undergoing CHD correction and 40 control subjects. The study assessed LV systolic performance (fractional shortening) and diastolic performance (mitral Doppler flow) in combination with RV systolic performance [tricuspid annular plane systolic excursion (TAPSE)] and diastolic performance (tricuspid Doppler flow). Additionally, systolic (S′) and diastolic (E′, A′, E/E′) tissue Doppler imaging (TDI) measurements were obtained at the LV lateral wall, the interventricular septum, and the RV free wall. Echocardiographic studies were performed preoperatively, 1 day postoperatively, and at hospital discharge after 9 ± 5 days. Although all LV echocardiographic measurements showed a deterioration 1 day after surgery, only LV TDI measurements were impaired in patients at discharge versus control subjects (S′: 5.7 ± 2.0 vs 7.1 ± 2.7 cm/s; E′: 9.8 ± 3.9 vs 13.7 ± 5.1 cm/s; E/E′: 12.2 ± 6.4 vs 8.8 ± 4.3; p  < 0.05). In the RV, TAPSE and RV TDI velocities also were impaired in patients at discharge versus control subjects (TAPSE: 9 ± 3 vs 17 ± 5 mm; S′: 5.2 ± 1.7 vs 11.4 ± 3.4 cm/s; E′: 7.3 ± 2.5 vs 16.3 ± 5.2 cm/s; E/E′: 12.5 ± 6.8 vs 4.8 ± 1.9; p  < 0.05). Furthermore, longer aortic cross-clamp times were associated with more impaired postoperative LV and RV performance ( p  < 0.05). In conclusion, both systolic and diastolic biventricular performances were impaired shortly after CHD correction. This impairment was detected only by TDI parameters and TAPSE. Furthermore, a longer-lasting negative influence of cardiopulmonary bypass on myocardial performance was suggested.

Background Transient ischemic dilation (TID) of the left ventricle in myocardial perfusion SPECT (MPS) has been shown to be a clinically useful marker of severe coronary artery disease (CAD). However, TID has not been evaluated for 99mTc-sestamibi rest/stress protocols (Mibi-Mibi). We aimed to develop normal limits and evaluate diagnostic power of TID ratio for Mibi-Mibi scans. Methods TID ratios were automatically derived from static rest/stress MPS (TID) and gated rest/stress MPS from the end-diastolic phase (TID ed ) in 547 patients who underwent Mibi-Mibi scans [215 patients with correlating coronary angiography and 332 patients with low likelihood (LLk) of CAD]. Scans were classified as severe (≥70% stenosis in proximal left anterior descending (pLAD) artery or left main (LM), or ≥90% in ≥2 vessels), mild to moderate (≥90% stenosis in 1 vessel or ≥70%-90% in ≥1 vessel except pLAD or LM), and normal (<70% stenosis or LLk group). Another classification based on the angiographic Duke prognostic CAD index (DI) was also applied: DI ≥ 50, 30 ≤ DI < 50 and DI < 30 or LLk group. Results The upper normal limits were 1.19 for TID and 1.23 for TID ed as established in 259 LLk patients. Both ratios increased with disease severity ( P  < .0001). Incidence of abnormal TID increased from 2% in normal patients to >36% in patients with severe CAD. Similarly, when DI was used to classify disease severity, the average ratios showed significant increasing trend with DI increase ( P  < .003); incidence of abnormal TID also increased with increasing DI. The incidence of abnormal TID in the group with high perfusion scores significantly increased compared to the group with low perfusion scores (stress total perfusion deficit, TPD < 3%) ( P  < .0001). The sensitivity for detecting severe CAD improved for TID when added to mild to moderate perfusion abnormality (3% ≤ TPD < 10%): 71% vs 64%, P  < .05; and trended to improve for TID ed /TID es : 69% vs 64%, P  = .08, while the accuracy remained consistent if abnormal TID was considered as a marker in addition to stress TPD. Similar results were obtained when DI was used for the definition of severe CAD (sensitivity: 76% vs 66%, P  < .05 when TID was combined with stress TPD). Conclusion TID ratios obtained from gated or ungated Mibi-Mibi MPS and are useful markers of severe CAD.

Abstract Rationale Patients with pulmonary hypertension due to left heart disease (PH-LHD) and a diastolic pulmonary vascular pressure gradient ≥7 mm Hg, representing PH out of proportion to pulmonary arterial wedge pressure, have pulmonary vascular disease and increased mortality. Little information exists on this condition, recently labeled as “combined pre- and post-capillary PH” (Cpc-PH). Objectives To investigate epidemiology, risk factors, right ventricular function, and outcomes in patients with chronic heart failure and Cpc-PH. Methods The study population was identified from a retrospective chart review of a clinical database of 3,107 stable patients who underwent first diagnostic right heart catheterization and from a prospective cohort of 800 consecutive patients at a national university-affiliated tertiary center. Measurements and Main Results The retrospective cohort had 664 patients with systolic heart failure (SHF) and 399 patients with diastolic heart failure (DHF), 12% of whom were classified as Cpc-PH. The prospective cohort had 172 patients with SHF (14% Cpc-PH) and 219 patients with DHF (12% Cpc-PH). Chronic obstructive pulmonary disease (P = 0.034) and the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio (P = 0.015) predicted Cpc-PH in SHF. Younger age (P = 0.004), valvular heart disease (P = 0.046), and the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio predicted Cpc-PH in DHF (P = 0.016). Right ventricular–pulmonary vascular coupling was worse in Cpc-PH patients (end-systolic elastance to effective arterial elastance [Ees/Ea]: SHF: 1.05 ± 0.25; P = 0.002; DHF: 1.17 ± 0.27; P = 0.027) than in those with isolated post-capillary PH (Ees/Ea: SHF: 1.52 ± 0.51; DHF: 1.45 ± 0.29). Conclusions Cpc-PH is rare in chronic heart failure. Right ventricular–pulmonary vascular coupling is poor in Cpc-PH and could be one explanation for dismal outcomes.

Background Different diagnostic criteria limit comparisons between populations in the prevalence of diastolic left ventricular (LV) dysfunction. We aimed to compare across populations age-specific echocardiographic criteria for diastolic LV dysfunction as well as their correlates and prevalence. Methods We measured the E and A peaks of transmitral blood flow by pulsed wave Doppler and the e' and a' peaks of mitral annular velocities by tissue Doppler imaging (TDI) in 2 cohorts randomly recruited in Belgium ( n = 782; 51.4% women; mean age, 51.1 years) and in Italy, Poland and Russia ( n = 476; 55.7%; 44.5 years). Results In stepwise regression, the multivariable-adjusted correlates of the transmitral and TDI diastolic indexes were similar in the 2 cohorts and included sex, age, body mass index, blood pressure and heart rate. Similarly, cut-off limits for the E/A ratio (2.5th percentile) and E/e' ratio (97.5th percentile) in 338 and 185 reference subjects free from cardiovascular risk factors respectively selected from both cohorts were consistent within 0.02 and 0.26 units (median across 5 age groups). The rounded 2.5th percentile of the E/A ratio decreased by ~0.10 per age decade in these apparently healthy subjects. The reference subsample provided age-specific cut-off limits for normal E/A and E/e' ratios. In the 2 cohorts combined, diastolic dysfunction groups 1 (impaired relaxation), 2 (possible elevated LV filling pressure) and 3 (elevated E/e' and abnormally low E/A) encompassed 114 (9.1%), 135 (10.7%), and 40 (3.2%) subjects, respectively. Conclusions The age-specific criteria for diastolic LV dysfunction were highly consistent across the study populations with an age-standardized prevalence of 22.4% vs. 25.1%.