IGFBP7 and GDF-15, but not P1NP, are associated with cardiac alterations and 10-year outcome in an elderly community-based study.

BACKGROUND: Little is known about the clinical value of Insulin-like growth factor-binding protein-7 (IGFBP7), a cellular senescence marker, in an elderly general population with multiple co-morbidities and high prevalence of asymptomatic cardiovascular ventricular dysfunction. Inflammation and fibrosis are hallmarks of cardiac aging and remodelling. Therefore, we assessed the clinical performance of IGFBP7 and two other biomarkers reflecting these pathogenic pathways, the growth differentiation factor-15 (GFD-15) and amino-terminal propeptide of type I procollagen (P1NP), for their association with cardiac phenotypes and outcomes in the PREDICTOR study. METHODS: 2001 community-dwelling subjects aged 65-84 years who had undergone centrally-read echocardiography, were selected through administrative registries. Atrial fibrillation (AF) and 4 echocardiographic patterns were assessed: E/e' (> 8), enlarged left atrial area, left ventricular hypertrophy (LVH) and reduced midwall circumference shortening (MFS). All-cause and cardiovascular mortality and hospitalization were recorded over a median follow-up of 10.6 years. RESULTS: IGFBP7 and GDF-15, but not P1NP, were independently associated with prevalent AF and echocardiographic variables after adjusting for age and sex. After adjustment for clinical risk factors and cardiac patterns or NT-proBNP and hsTnT, both IGFBP7 and GDF-15 independently predicted all-cause mortality, hazard ratios 2.13[1.08-4.22] and 2.03[1.62-2.56] per unit increase of Ln-transformed markers, respectively. CONCLUSIONS: In a community-based elderly cohort, IGFBP7 and GDF-15 appear associated to cardiac alterations as well as to 10-year risk of all-cause mortality.

Circulating biomarkers and cardiac function over 3 years after chemotherapy with anthracyclines: the ICOS-ONE trial.

AIMS: A multicentre trial, ICOS-ONE, showed increases above the upper limit of normality of cardiac troponin (cTn) in 27% of patients within 12 months after the end of cancer chemotherapy (CT) with anthracyclines, whether cardiac protection with enalapril was started at study entry in all (prevention arm) or only upon first occurrence on supra-normal cTn (troponin-triggered arm). The aims of the present post hoc analysis were (i) to assess whether anthracycline-based treatment could induce cardiotoxicity over 36 month follow-up and (ii) to describe the time course of three cardiovascular biomarkers (i.e. troponin I cTnI-Ultra, B-type natriuretic peptide BNP, and pentraxin 3 PTX3) and of left ventricular (LV) function up to 36 months. METHODS AND RESULTS: Eligible patients were those prescribed first-in-life CT, without evidence of cardiovascular disease, normal cTn, LV ejection fraction (EF) >50%, not on renin-angiotensin aldosterone system antagonists. Patients underwent echocardiography and blood sampling at 24 and 36 months. No differences were observed in biomarker concentration between the two study arms, 'prevention' vs. 'troponin-triggered'. During additional follow-up 13 more deaths occurred, leading to a total of 23 (9.5%), all due to a non-cardiovascular cause. No new occurrences of LV-dysfunction were reported. Two additional patients were admitted to the hospital for cardiovascular causes, both for acute pulmonary embolism. No first onset of raised cTnI-Ultra was reported in the extended follow-up. BNP remained within normal range: at 36 months was 23.4 ng/L, higher (N.S.) than at baseline, 17.6 ng/L. PTX3 peaked at 5.2 ng/mL 1 month after CT and returned to baseline values thereafter. cTnI-Ultra peaked at 26 ng/L 1 month after CT and returned to 3 ng/L until the last measurement at 36 months. All echocardiographic variables remained stable during follow-up with a median LVEF of 63% and left atrial volume index about 24 mL/m2 . CONCLUSIONS: First-in-life CT with median cumulative dose of anthracyclines of 180 mg/m2 does not seem to cause clinically significant cardiac injury, as assessed by circulating biomarkers and echocardiography, in patients aged 51 years (median), without pre-existing cardiac disease. This may suggest either a 100% efficacy of enalapril (given as preventive or troponin-triggered) or a reassuringly low absolute cardiovascular risk in this cohort of patients, which may not require intensive cardiologic follow-up.

Remission of left ventricular systolic dysfunction and of heart failure symptoms after cardiac resynchronization therapy: temporal pattern and clinical predictors.

BACKGROUND: The aim of the study was to determine whether cardiac resynchronization therapy (CRT) may induce a heart failure (HF) remission phase (recovery to New York Heart Association functional class I-II and regression of left ventricular [LV] dysfunction: LV ejection fraction [EF] > or = 50%) and to define the incidence and predictors of such a process. METHODS: Cardiac resynchronization therapy devices were successfully implanted in 520 consecutive HF patients from 1999 to 2006 (mean age 66 years, 82% male sex, New York Heart Association class > or = II, LVEF 28%, QRS 164 milliseconds, 6-minute hall walk distance 302 m) at our institution. Follow-up data were prospectively collected every 3 to 6 months. Continuous variables were stratified in tertiles. RESULTS: Over a median follow-up of 28 months, 26% of patients achieved LV remission (rate: 16 per 100 person-years). At univariate analysis, female sex (P = .032), non-coronary artery disease (CAD) etiology (P < .001), mitral regurgitation < 2/4 (P = .022), higher EF tertile (P < .001), lower diameter and volume tertiles (both P < .001), previous conventional right ventricle pacing (P = .029), and post-CRT-paced QRS (P = .008) predicted remission. At multivariate analysis, non-CAD etiology, LVEF 30% to 35%, and LV end-diastolic volume < 180 mL were strongly associated with HF remission phase (all P < .001). Concomitance of these 3 factors yielded a significantly higher remission rate compared with either no or only 1 factor (respectively, 60 vs 7 and 11 per 100 person-years, P < .001). CONCLUSIONS: Cardiac resynchronization therapy induces HF remission phase in 26% of patients, even after 3 years. Non-CAD etiology and moderately compromised LV function at baseline may easily predict this process.

Insulin-treated type 2 diabetes is associated with a decreased survival in heart failure patients after cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves cardiac performance and survival in patients with congestive heart failure. Recent observations suggest that diabetes is associated with a worse outcome in these patients. The aim of the study was to investigate the effect of diabetes and insulin treatment on outcome after CRT. METHODS: Diabetic status and insulin treatment were assessed in 447 patients who underwent CRT (males 80.8%, mean age 65.7 +/- 9.7 years, ejection fraction 29.9 +/- 6.11%). Patients were stratified in three groups according to the presence or absence of diabetes and insulin treatment. RESULTS: Nondiabetic patients were 366 (79.6%), noninsulin-treated diabetic patients 62 (13.9%), insulin-treated diabetic patients 29 (6.5%). The estimated death rate was 5.15 per 100 patients-year in the nondiabetic group, 8.63 in noninsulin-treated diabetics (HR 1.59, P = 0.240), and 15.84 in insulin-treated diabetics (HR 3.05, P = 0.004). Cardiac mortality accounted for 81% of deaths in nondiabetic patients and for 56% of deaths in diabetic patients. Diabetic patients tended to have a worse recovery of left ventricular ejection fraction over time (P = 0.057) and of the distance at 6-minute walking test (6MWT) (P = 0.018). CONCLUSIONS: Insulin-treated diabetes is associated with a worse functional recovery and a higher mortality in patients with advanced heart failure after CRT. While cardiac death accounts for the majority of deaths in nondiabetic patients, a relevant proportion of the mortality in diabetic patients seem to result from noncardiac causes.

Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial.

BACKGROUND: Troponin changes over time have been suggested to allow for an early diagnosis of cardiac injury ensuing cancer chemotherapy; cancer patients with troponin elevation may benefit of therapy with enalapril. It is unknown whether a preventive treatment with enalapril may further increase the benefit. METHODS: The International CardioOncology Society-one trial (ICOS-ONE) was a controlled, open-label trial conducted in 21 Italian hospitals. Patients were randomly assigned to two strategies: enalapril in all patients started before chemotherapy (CT; 'prevention' arm), and enalapril started only in patients with an increase in troponin during or after CT ('troponin-triggered' arm). Troponin was assayed locally in 2596 blood samples, before and after each anthracycline-containing CT cycle and at each study visit; electrocardiogram and echocardiogram were done at baseline, and at 1, 3, 6 and 12-month follow-up. Primary outcome was the incidence of troponin elevation above the threshold. FINDINGS: Of the 273 patients, 88% were women, mean age 51 ± 12 years. The majority (76%) had breast cancer, 3% had a history of hypertension and 4% were diabetic. Epirubicin and doxorubicin were most commonly prescribed, with median cumulative doses of 360 [270-360] and 240 [240-240] mg/m2, respectively. The incidence of troponin elevation was 23% in the prevention and 26% in the troponin-triggered group (p = 0.50). Three patients (1.1%) -two in the prevention, one in the troponin-triggered group-developed cardiotoxicity, defined as 10% point reduction of LV ejection fraction, with values lower than 50%. INTERPRETATION: Low cumulative doses of anthracyclines in adult patients with low cardiovascular risk can raise troponins, without differences between the two strategies of giving enalapril. Considering a benefit of enalapril in the prevention of LV dysfunction, a troponin-triggered strategy may be more convenient.

Clinical predictors of marked improvement in left ventricular performance after cardiac resynchronization therapy in patients with chronic heart failure.

BACKGROUND: Previous studies have shown that cardiac resynchronization therapy (CRT) improves cardiac performance and decreases mortality and hospital admission rates. However, it is not yet clear which patients will benefit from the procedure the most. The purpose of the study was to identify the pre-implant characteristics that better predict which patients will have the best outcome after CRT. METHODS: In this observational study, 156 patients were studied with echocardiography and a 6-minute walking test at baseline and 12 months after CRT. RESULTS: After CRT, we observed an increase in left ventricular ejection fraction (+29.6%, P < .0001), a decrease in left ventricular end systolic volume (-26.4%, P < .0001), in the proportion of patients with grade 2-4 mitral regurgitation (from 47.1% to 34.0%, P = .002), and with NYHA functional class III-IV (from 83.2% to 11.6%, P < .0001), an increase in exercise tolerance (+31.1%, P < .0001). Sixty-two patients had a marked increase in left ventricular ejection fraction (> 10 units); the only independent predictor of a marked effect of CRT was the nonischemic etiology of heart failure. In patients with ischemic cardiomyopathy, the benefit on ejection fraction correlates inversely with the extension of the ischemic damage. CONCLUSIONS: CRT improves left ventricular function and exercise tolerance in the long term. The nonischemic etiology of the cardiomyopathy is the only independent predictor of a marked effect of CRT; this is probably due to the absence of ischemic, nonviable scar tissue in these patients.

Correlation between serial measurements of N-terminal pro brain natriuretic peptide and ambulatory cardiac filling pressures in outpatients with chronic heart failure.

BACKGROUND: Serial measurements of N-terminal pro brain natriuretic peptide (NT-proBNP) have been suggested for the management of outpatients with chronic heart failure (CHF). The relationship between NT-proBNP plasma levels and central haemodynamic parameters in this setting is not known. METHODS: In 19 outpatients with CHF, NT-proBNP was related to central haemodynamic information, continuously measured with an implanted haemodynamic monitor (IHM) during 24 h of daily living activities ("24 h") and during supine rest ("rest"). In 13 patients, three to seven serial measurements were obtained with a mean time interval of 39 days (range 19-113). RESULTS: At the first visit (n=19), NT-proBNP plasma levels were dispersed over a wide range of filling pressures and not correlated with the 24 h median of the right ventricular systolic pressure (RVSP) and the estimated pulmonary artery pressure (ePAD). However, in the individual patient, serial measurements yielded significant positive correlations between NT-proBNP and RVSP (p=0.006) and ePAD (p=0.001). During "24 h" compared with "rest", the median RVSP and ePAD were elevated by 20+/-16% and 32+/-18%, respectively, and corresponded better with NT-proBNP (p<0.05). CONCLUSION: In outpatients with CHF, single measurements of NT-proBNP are not correlated with cardiac filling pressures. However, serial measurements of NT-proBNP in each individual patient show a significant positive correlation with central haemodynamic parameters and reflect changes in the haemodynamic state over time.

Comparison of low and high initial tacrolimus dosing in primary heart transplant recipients: a prospective European multicenter study.

BACKGROUND: The purpose of this prospective, randomized, open-label, phase II, multicenter study was to optimize the initial oral dose of tacrolimus. METHODS: A total of 113 patients were randomly assigned to initial low-dose (0.075 mg/kg/day, n=55) or high-dose (0.15 mg/kg/day, n=58) oral tacrolimus and followed for 3 months. Target whole-blood trough levels were 10 to 20 ng/mL. Prophylactic use of corticosteroids and azathioprine was identical in both groups, and antibody induction was mandatory. The primary endpoint was the time to and incidence of the initial oral tacrolimus dose adjustment because of toxicity or rejection, or withdrawal before initial dose change. Efficacy was assessed by the occurrence of biopsy-proven rejection (International Society for Heart and Lung Transplantation grade > or =1B). RESULTS: In the primary endpoint, no significant difference was observed between the low- and high-dose groups. After 3 months, there was no difference in freedom from initial oral tacrolimus dose change because of rejection, toxicity, or withdrawal (89.0% vs. 87.6%; not significant [NS]). In both groups, dose adjustments were mainly required to achieve and maintain target blood levels (80.0% vs. 82.8%; NS). Patient survival was 92.7% and 98.3% (NS). There was no significant difference between groups regarding freedom from biopsy-proven acute rejection (57.1% vs. 66.3%; NS). The overall safety profiles indicated a tendency toward better tolerability in the low-dose group. CONCLUSIONS: Although low-dose and high-dose tacrolimus had similar efficacy, low-dose tacrolimus was associated with a more favorable safety profile. Therefore we recommend starting tacrolimus therapy after antibody induction at 0.075 mg/kg and adjust dose according to whole-blood trough levels.

Prognostic value of contractile response during high-dose dipyridamole echocardiography test in heart transplant recipients.

BACKGROUND: Coronary allograft vasculopathy (CAV) remains a main factor limiting long-term survival after heart transplantation (HTX). The diagnosis of CAV is still based on serial coronary angiography. In this study, we evaluated the prognostic value of high-dose dipyridamole echocardiography in HTX. METHODS: Sixty-eight patients underwent dipyridamole echocardiography within 48 hours of their scheduled annual coronary angiography. Coronary allograft vasculopathy was defined as CAV 1 (focal or diffuse stenosis <50%) or CAV 2 (focal or diffuse stenosis >or=50%). Wall-motion score index (WMSI) was evaluated at rest and after dipyridamole administration. RESULTS: Results of coronary angiography were normal in 43 patients (63%), showed CAV 1 in 11 (16%), and showed CAV 2 in 14 (21%). Rest wall motion was normal in 39 patients and abnormal in 29. After dipyridamole administration, wall motion remained normal in all 39 (Group 1, no CAV in 34 and CAV 1 in 5). Of 29 patients with rest wall-motion abnormalities, all reversed to normal after dipyridamole in 8 patients (Group 2, no CAV in 7 and CAV 1 in 1) and remained or worsened in 21 (Group 3, CAV 2 in 14 and no CAV or CAV 1 in 7). During follow-up (6 +/- 3 years), 15 patients had major cardiac events: 11 occurred in Group 3, whereas 4 occurred in Groups 1 and 2. Wall motion at rest and after dipyridamole administration and CAV were independent predictors for cardiac events; only dipyridamole WMSI >1 remained significant (p < 0.0001) at multivariate analysis. CONCLUSIONS: Dipyridamole echocardiography is a simple, non-invasive test that after HTX may identify patients with altered wall motion who deserve stricter surveillance.

A population-based study on overt heart failure in Lombardy (survey of hospitalization in 1996 and 1997).

BACKGROUND: The aim of this study was to get updated information about the incidence and outcome of heart failure hospital admission in the whole population of the largest Italy region. METHODS: The Lombardy regional database of hospital records (Information System and Quality Control Bureau) provided the requested information: all the heart failure cases admitted to all the institutions of the region were selected by the ICD9 code of congestive heart failure (428-) as the principal or secondary diagnosis. The available data included: diagnosis and surgical procedures (up to four), date of birth, dates of admission and discharge, outcome, DRG code, discharge unit code, gender. The data so obtained concern the hospital discharges in 1996 and 1997. RESULTS: 32,093 cases were selected. The mean ages were 74.1 +/- 11.5 years for males and 80.6 +/- 10.7 for females in 1996, and 71.8 +/- 11.7 for males and 78.3 +/- 10.6 for females in 1997. Most of the cases were classified as appertaining to DRG 127--pure heart failure (56.7%). Heart failure associated with myocardial infarction accounted for 7.3% of cases. The remaining cases (36.0%) were classified as appertaining to heterogeneous medical and surgical DRGs. In 1997, the in-hospital mortality was 14.7% for patients aged > 80 years; 9.7% for patients aged between 71 and 80 years; 7.4% for patients aged between 61 and 70 years and 6.9% for patients < 61 years of age with the exclusion of pediatric cases. The in-hospital mortality was different between discharge units: 2.8% of in-patients discharged from cardiology units, and 10.3% of in-patients discharged from general medicine units. The readmission rate at 1 month was 5.49% whereas that within 1 year was 14.3%. CONCLUSIONS: Heart failure mortality differences between hospital units are not explained by age and by comorbidity. The readmission rate was lower than in previous reports.

[CircuLite Synergy ventricular assist device: a new approach to end-stage congestive heart failure]. / Sistema di assistenza ventricolare CircuLite Synergy: un nuovo approccio all'insufficienza cardiaca terminale.

BACKGROUND: The Synergy system, a miniature partial circulatory support device, is implanted by an off-pump, minimally invasive surgical approach. The system has been optimized to improve performance in an EU clinical trial for chronic ambulatory heart failure. This therefore offers the possibility of treating elderly chronic heart failure patients who might not usually be considered for long-term circulatory support. METHODS: From June 2007 to December 2012, 63 patients were implanted with the Synergy system (12 patients ≥70 years) using four different releases of the device. Briefly, the system draws blood through the inflow cannula from the left atrium into the micro-pump (placed in a right subclavicular pocket) and pumps it through an outflow graft to the right subclavian artery. In this paper, we present an intermediate analysis of the clinical trial as performed on April 30, 2013, leading to the placing of the CE mark. RESULTS: Mean duration of support is ongoing at 230 days (range 23-1387). Follow-up showed improved hemodynamic response, with additional improvements in 6-min walk distance (299 ± 144 to 420 ± 119 m) and Minnesota Living with Heart Failure Questionnaire (69.5 ± 20.4 to 49.2 ± 24.3). Older patients had longer mean durations of support (337 vs 188 days). On average, elderly and younger patients showed similar improvements in hemodynamics and 6-min walk distance (107 ± 120 vs 130 ± 121 m). Major adverse cardiac events included bleeding (n=4) with one bleeding related to renal failure resulting in death. CONCLUSIONS: Clinical use of the Synergy device was associated with a significant functional improvement. Very low adverse event rates were reported with the latest device release. Older patients had smaller body sizes and worse renal function than younger patients. Both groups experienced similar hemodynamic benefits and functional improvements. The risk of bleeding and renal dysfunction appears to be increased in the elderly, though still within acceptable ranges compared to other full support devices. Minimally invasive long-term circulatory support devices, like Synergy, offer a new treatment option that might be available even for the elderly chronic heart failure population.

[Gender differences of at risk patients with overt heart failure in the real world of general practice. Data from the GIPSI (Gestione Integrata Progetto Scompenso in Italia) registry]. / Differenze tra la popolazione maschile e femminile a rischio ed affetta da insufficienza cardiaca nel mondo reale della medicina generale. I dati del registro GIPSI (Gestione Integrata Progetto Scompenso in Italia).

BACKGROUND: Controlled clinical trials have defined the characteristics of specialized world populations, different from the real world population. On this basis, the GIPSI registry was created, aiming to collect data from heart failure populations managed by general practitioners, focusing on gender differences. METHODS: The registry was based on family history, clinical and laboratory data collection from general practitioners. Patients were considered as being at risk for heart failure if data applied to stage A/B, or presenting overt heart failure if data applied to stage C/D of the American College of Cardiology/American Heart Association classification. RESULTS: From June 2006 to October 2007, 757 consecutive patients (475 male, 62.7%) were enrolled from 260 general practitioner's practices; 227 patients (143 male, 63.0%) had overt heart failure. In the female population at risk, higher systolic and diastolic blood pressure values were observed, whereas males showed more frequently ischemic heart disease, hypercholesterolemia and hypertriglyceridemia, and were more often prescribed with statins and antiplatelet drugs. There were more heart failure females with diabetes and of advanced age. Moreover, females showed a higher pulse pressure and a significantly lower estimated glomerular filtration rate (by simplified MDRD equation) than males. CONCLUSIONS: The data collected in a real world population show that heart failure has significantly different gender characteristics, especially for risk factors, age, blood pressure and renal function. This kind of investigation should be extended to larger patient populations for a better understanding of the disease.

Hemodynamic changes before acute heart failure episodes in patients with advanced systolic left ventricular dysfunction.

AIM: We sought to verify which changes in right ventricular pressures occur before acute heart failure (HF) in patients with advanced systolic left ventricular (LV) dysfunction. In patients with chronic HF, continuous hemodynamic monitoring by implantable devices may detect increases in pulmonary pressures before the onset of symptoms. METHODS: A device which allowed monitoring of right ventricular systolic (RVSP) and diastolic pressure (RVDP) and an estimate of pulmonary artery diastolic pressure (ePAD) was implanted in 10 patients with advanced LV systolic dysfunction and frequent cardiovascular hospitalizations [mean age 56.8 years; New York Heart Association (NYHA) classes IIIb-IV; LV ejection fraction at echocardiography 21 +/- 2%]. RESULTS: During a follow-up period of 15 +/- 12 months, 18 hospitalizations due to acute HF were recorded; 10 episodes were characterized by symptoms due to low-cardiac output (LCO) and eight episodes were characterized by symptoms due to pulmonary congestion. RVSP and ePAD increased before six hospitalizations and decreased before three episodes; RVDP increased before 10 hospitalizations and decreased before one. The extent of RVDP increase was 16 +/- 24% before pulmonary congestion episodes and 29 +/- 32% before LCO episodes. CONCLUSION: An increase in RVDP was the most frequent hemodynamic change detected by the implantable hemodynamic monitor before hospitalizations due to acute HF in patients having advanced systolic LV dysfunction.

Three years of cardiac resynchronization therapy: could superior benefits be obtained in patients with heart failure and narrow QRS?

AIM OF THE STUDY: To examine the long-term effects of cardiac resynchronization therapy (CRT) in patients presenting with heart failure (HF) and QRS 120 ms in the remaining 331 patients. The baseline characteristics of the 2 groups were similar. We evaluated indices of cardiac function, percentage of responders, and survival rates over a mean 28-month follow-up. RESULTS: Both groups experienced similar long-term increases in 6-MHW, and decreases in New York Heart Association functional class and LV end-systolic volume (all comparisons P < 0.0001 in both groups). Time interaction of changes in LVEF and percentage of responders were significantly different (P = 0.03 and P = 0.004, respectively), in favor of the narrow QRS group, where the changes were sustained and persisted at 2 and 3 years. The long-term death rate from HF was lower in the group with narrow than in the group with wide QRS complex (P = 0.04; log-rank test). CONCLUSIONS: CRT confers considerable long-term clinical, functional, and survival benefits in patients presenting with HF and narrow QRS, not preselected by echocardiographic criteria of dyssynchrony. Caution is advised before denying CRT to these patients on the basis of QRS width only.

Relief of drug refractory angina by biventricular pacing in heart failure.

Since cardiac resynchronization therapy (CRT) improves LV function at the cost of low energetic expenditure, the authors hypothesized that it may increase the threshold of drug refractory angina in selected patients with CHF and CAD who are not amenable to myocardial revascularization. From October 1999 to April 2002, 75 patients with CHF and CAD were treated with CRT. Drug refractory angina occurred nearly daily in 8 of the 75 patients. The mean age of these eight men was 71 years, mean NYHA functional Class 3.4 +/- 0.5, mean QRS duration (QRSd) 168 +/- 20 ms, and mean left ventricular ejection fraction (LVEF) 0.29 +/- 0.4. Diffuse CAD not amenable to myocardial revascularization was confirmed on angiography. At baseline, no patient was able to complete a 6-minute walk test because of angina. In the 6 months before CRT, the mean number of hospitalizations per patient for management of CHF or angina was 3.1 +/- 0.3. All patients underwent successful CRT. Mean QRSd decreased to 141 +/- 16 ms (P = 0.01 vs baseline). After 9 +/- 6.1 months, LVEF increased to 0.317 +/- 0.028 (P = 0.03 vs baseline), while the NYHA class decreased to 2.6 +/- 0.5 (P = 0.02 vs baseline). All patients also experienced a marked decrease in angina episodes, from a mean of 8.3 +/- 11.6 to 0.6 +/- 1.3 episodes/week (P < 0.05), and completed a 6-minute walk test, covering a mean distance of 337 +/- 68 m (vs 237 +/- 136 m at baseline, P = 0.007). No further hospitalization was necessary. The beneficial effects of CRT on overall cardiac function may include a better control of angina in severely symptomatic patients.

Is the left ventricular lateral wall the best lead implantation site for cardiac resynchronization therapy?

Short-term hemodynamic studies consistently report greater effects of cardiac resynchronization therapy (CRT) in patients stimulated from a LV lateral coronary sinus tributary (CST) compared to a septal site. The aim of the study was to compare the long-term efficacy of CRT when performed from different LV stimulation sites. From October 1999 to April 2002, 158 patients (mean age 65 years, mean LVEF 0.29, mean QRS width 174 ms) underwent successful CRT, from the anterior (A) CST in 21 patients, the anterolateral (AL) CST in 37 patients, the lateral (L) CST in 57 patients, the posterolateral (PL) CST in 40 patients, and the middle cardiac vein (MCV) CST in 3 patients. NYHA functional class, 6-minute walk test, and echocardiographic measurements were examined at baseline, and at 3, 6, and 12 months. Comparisons were made among all pacing sites or between lateral and septal sites by grouping AL + L + PL CST as lateral site (134 patients, 85%) and A + MC CST as septal site (24 patients, 15%). In patients stimulated from lateral sites, LVEF increased from 0.30 to 0.39 (P < 0.0001), 6-minute walk test from 323 to 458 m (P < 0.0001), and the proportion of NYHA Class III-IV patients decreased from 82% to 10% (P < 0.0001). In patients stimulated from septal sites, LVEF increased from 0.28 to 0.41 (P < 0.0001), 6-minute walk test from 314 to 494 m (P < 0.0001), and the proportion of NYHA Class III-IV patients decreased from 75% to 23% (P < 0.0001). A significant improvement in cardiac function and increase in exercise capacity were observed over time regardless of the LV stimulation sites, either considered singly or grouped as lateral versus septal sites.

Is the outcome of cardiac resynchronization therapy related to the underlying etiology?

This study was designed to examine the importance of the underlying cardiac pathology on outcome of cardiac resynchronization therapy (CRT), hypothesizing that myocardial infarction scar and other noncontractile segments represent limitations to the ability to resynchronize cardiac contraction in patients with congestive heart failure associated with dilated cardiomyopathy. From October 1999 to April 2002, 158 patients (mean age 65 years, 121 men) were included in a single center, longitudinal, comparative study. All patients had dilated cardiomyopathy and indications for CRT with a mean QRS duration of 174 ms. The patient population was divided into a coronary artery disease (CAD) group that included patients with significant CAD, and no indication, or a contraindication for revascularization, and a non-CAD group that included patients with nonischemic dilated cardiomypopathy. Follow-up data were collected at 3, 6, and 12 months, and yearly thereafter. The median follow-up was 11.2 months. In the CAD group, the LVEF increased from 0.29 to 0.34 (P < 0.0001), the 6-minute walk test distance increased from 310 to 463 m (P < 0.0001), and the percentage of patients in NYHA functional Class III-IV decreased from 83% to 23% (P = 0.04). In the non-CAD group, LVEF increased from 29% to 42% (P < 0.0001), the 6-minute walk test distance increased from 332 to 471 m (P < 0.0001), and the percentage of patients in NYHA functional Class III-IV decreased from 79% to 5%, (P < 0.0001). Comparison of the two groups showed that patients in the non-CAD group had a significantly greater increase in LVEF (P = 0.007) and decrease in NYHA class (P < 0.05). Patients with CAD or non-CAD significantly improved clinically during CRT. Non-CAD patients had a greater increase in LVEF and decrease in NYHA functional class than patients with CAD.