Effective nonapical left ventricular pacing with quadripolar leads for cardiac resynchronization therapy.

BACKGROUND: Current guidelines recommend avoiding apical left ventricular (LV) pacing for cardiac resynchronization therapy (CRT). AIMS: We investigated the feasibility of nonapical pacing with the current quadripolar LV lead technology. METHODS: We analyzed consecutive patients who received CRT with an LV quadripolar lead. The post--implantation position of each electrode of the LV lead was designated as basal, mid, or apical. The pacing capture threshold (PCT) and phrenic nerve stimulation (PNS) threshold were assessed for each electrode. RESULTS: We enrolled 168 patients. A total of 8 CRT defibrillators were from Biotronik (with Sentus OTW QP leads), 98 were from Boston Scientific (with 21 Acuity X4 Spiral and 77 Acuity X4 Straight leads), and 62 from St. Jude Medical (with Quartet leads). The median (interquartile range) number of electrodes at nonapical segments per patient was 3 (1-4) with Biotronik Sentus leads, 4 (3-4) with spiral -design Boston Scientific leads, 4 (3-4) with straight Boston Scientific leads, and 3 (3-4) with St. Jude Medical Quartet leads (P = 0.045). Three patients (38%) with Biotronik Sentus leads, 21 (100%) with spiral -design Boston Scientific leads, 69 (90%) with straight -design Boston Scientific leads, and 49 (79%) with St. Jude Medical Quartet leads (P <0.001) had at least 1 electrode located at nonapical segments linked with a PNS -PCT safety margin of more than 2 V. During the 6-month follow -up, PNS was detected in 4 patients and was eliminated with reprogramming. No significant changes in PCT were detected during follow -up. CONCLUSIONS: Quadripolar leads allowed nonapical pacing with acceptable electrical parameters in the majority of CRT recipients, although differences were found among the currently available devices.

Risk stratification of ischaemic patients with implantable cardioverter defibrillators by C-reactive protein and a multi-markers strategy: results of the CAMI-GUIDE study.

AIMS: Patients at risk of sudden cardiac death (SCD) after myocardial infarction (MI) can be offered therapy with implantable cardioverter defibrillators (ICDs). Whether plasma biomarkers can help risk stratify for SCD and ventricular arrhythmias (VT/VF) is unclear. METHODS AND RESULTS: The primary objective of the CAMI-GUIDE study is to assess the predictive role of C-reactive protein for SCD or VT/VF in ischaemic patients with the ejection fraction <30% and ICDs. Secondary endpoints included all-cause mortality, hospitalizations, and death from heart failure. Additional analyses incorporated cystatin-C and NT-ProBNP in multi-marker approach for the prediction of adverse outcomes. A total of 300 patients were enrolled. All-cause mortality at 2 years was 22.6%, mortality from heart failure was 8.3%. Primary endpoint occurred in 17.3%. At a competing risk multivariable analysis adjusted for baseline variables, no significant difference in primary endpoint was found between patients with C-reactive protein ≤3 vs. >3 mg/L [heart rate (HR) 0.91 (0.50-1.64) P = 0.76], while C-reactive protein >3 mg/L was strongly associated with mortality due to heart failure [HR: 3.17 (1.54-6.54) P = 0.002]. NT-proBNP above median was significantly associated with the primary endpoint [adjusted HR: 1.46 (1.020-2.129) P = 0.042]. A risk function, including the three biomarkers, NYHA class and resting HR, allowed stratification of patient mortality risk from 5 to 50%. CONCLUSION: C-reactive protein >3 mg/L is not associated with SCD or fast VT/VF, however, is a strong predictor of HF mortality. Biomarkers combined with clinical markers allow an excellent risk stratification of mortality at 2 years.

Persistent atrial fibrillation worsens heart rate variability, activity and heart rate, as shown by a continuous monitoring by implantable biventricular pacemakers in heart failure patients.

BACKGROUND: Atrial fibrillation (AF) induces loss of atrial contribution, heart rate irregularity, and fast ventricular rate. OBJECTIVES: The objectives of the study were to accurately measure AF incidence and to investigate the mutual temporal patterns of AF and heart failure (HF) in patients indicated to cardiac resynchronization therapy. METHODS: Four hundred ten consecutive patients (70% male, age 69 +/- 11) with advanced HF (NYHA = 3.0 +/- 0.6), low ejection fraction (EF = 27 +/- 9%), and ventricular conduction delay (QRS = 165 +/- 29 ms) received a biventricular pacemaker. Enrolled patients were divided into two groups: G1 = 249 patients with no AF history, G2 = 161 patients with history of paroxysmal/persistent AF. RESULTS: In a median follow-up of 13 months, AF episodes longer than 5 minutes occurred in 105 of 249 (42.2%) G1 patients and 76 of 161 (47.2%) G2 patients, while AF episodes longer than one day occurred in 14 of 249 (5.6%) G1 patients and in 36 of 161 (22.4%) G2 patients. Device diagnostics monitored daily values of patient activity, night heart rate (NHR), and heart rate variability (HRV). Comparing 30-day periods before AF onset and during persistent AF, significant (P < 0.0001) changes were observed in patient activity, which decreased from 221 +/- 13 to 162 +/- 12 minutes, and in NHR, which increased from 68 +/- 3 to 94 +/- 7 bpm. HRV significantly decreased (from 75 +/- 5 ms before AF onset to 60 +/- 6 ms after AF termination). NHR during AF was significantly (P < 0.01) and inversely correlated (R(2)= 0.73) with activity, with a significant lower activity associated with NHR >or= 88 bpm. CONCLUSION: AF is frequent in HF patients. Persistent AF is associated with statistically significant decrease in patient activity and HRV and NHR increase.

Effectiveness of cardiac resynchronisation therapy in patients with echocardiographic evidence of mechanical dyssynchrony.

OBJECTIVE: Cardiac resynchronisation therapy has proven to be effective in refractory heart failure (HF) patients with QRS >120-130 ms. Therefore, the aim of our study was to verify the long-term effectiveness of cardiac resynchronisation therapy in HF patients with echocardiographic evidence of mechanical asynchrony regardless of QRS duration. METHODS: One hundred and six patients with New York Heart Association class II-IV HF and echocardiographic documentation of interventricular and intraventricular asynchrony underwent biventricular stimulation. A clinical and functional evaluation was performed at baseline, 1, 3, 6 months, and every 6 months thereafter. RESULTS: After a median follow-up of 16 months, a significant improvement was noted in ejection fraction, left ventricular diameters, mitral regurgitation jet area, interventricular and intraventricular echocardiographic indexes of asynchrony, and the 6-min walking distance (P < 0.001 for all). Death rates for all causes and for cardiac causes were 18.2 (95% confidence interval 12.8-25.9) and 13.5 (95% confidence interval 9.0-20.3) per 100 person-years, respectively. Patients in New York Heart Association class IV had an almost three-fold increase in risk of dying as compared to class II-III (hazard ratio 2.97, 95% confidence interval 1.30-6.79). CONCLUSIONS: Interventricular and intraventricular asynchrony at echocardiography may be useful in identifying HF patients suitable for cardiac resynchronisation therapy, with results comparable to those obtained with QRS duration selection criteria.

Cardiac resynchronization therapy: gender related differences in left ventricular reverse remodeling.

AIM: Gender related differences in epidemiology, treatment, and prognosis of heart failure (HF) have been reported. We examined the sex influence in patients treated with cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Out of 334 consecutive HF patients (19.7% women) who underwent CRT, 195 patients reached clinical and echocardiographic evaluation at six and 12 months and were selected for analysis. A reduction in left ventricular (LV) end-diastolic volume/m(2) (EDVi) and end systolic volume/m(2) (ESVi) was evident in the overall population at six months (P < 0.001) and from six to 12 months (P < 0.001). Compared to men, women showed significantly greater changes in LV volumes at mid (P < 0.05) and long-term (P < 0.001) follow-up and a significantly higher LV ejection fraction (EF) (40.8 +/- 12.3 vs 34.1 +/- 10.1, P < 0.01) at one year. Multiple regression analysis, including several demographic and clinical parameters, revealed that female gender is independently associated with greater reduction in LV ESVi. At the 12-month follow-up, the proportion of responders (defined in terms of ESV reduction by at least 10%) was higher in women than in men (76.1% vs 59.3%, P < 0.05). CONCLUSIONS: CRT induced a gender specific LV remodeling response.

Results of the SCART study: selection of candidates for cardiac resynchronisation therapy.

OBJECTIVE: To prospectively determine whether prespecified electrocardiographic, echocardiographic and tissue Doppler imaging (TDI) selection criteria may predict a positive response to cardiac resynchronisation therapy (CRT). METHODS: In this multicentre, prospective, non-randomised study, 96 heart failure patients with New York Heart Association class III-IV symptoms, an ejection fraction of < or =35%, and at least one marker of ventricular dyssynchrony according to prespecified electrocardiographic, echocardiographic or TDI criteria were enrolled. The primary endpoint was an improvement in the clinical composite score at 6 months. RESULTS: At enrolment, 70 patients fulfilled the electrocardiographic criterion (QRS duration > or =150 ms), 77 patients showed echocardiographic signs of dyssynchrony, and 37 patients met the TDI dyssynchrony criteria. The overall responder rate was 78/96 (81%). In particular, the primary endpoint was reached in 68 patients who fulfilled the echocardiographic criteria as compared with 10 patients who did not (88 vs. 53%, P = 0.001). The patients who met the echocardiographic criteria showed a significant greater reduction in left ventricular end-systolic diameter (P = 0.029) and a higher improvement in quality of life (P = 0.017) than patients who did not. Neither electrocardiographic nor TDI criteria seemed to predict a positive response to CRT. CONCLUSIONS: In our patient population, mechanical indexes of dyssynchrony as assessed by echocardiography appeared to identify CRT responders. Although TDI is useful for evaluating ventricular dyssynchrony after CRT, the prespecified TDI inclusion criteria adopted in this investigation did not increase the number of CRT responders.

Efficacy of cardiac resynchronization therapy in very old patients: the Insync/Insync ICD Italian Registry.

AIMS: To assess the effects of cardiac resynchronization therapy (CRT) in > or =80-year-old patients vs. patients <80 years, in terms of clinical, functional, and echocardiographic parameters after 12 month of CRT, survival, and incidence of arrhythmic events. METHODS AND RESULTS: The study population consisted of 1181 CRT patients (85 were > or =80 years old). They were enrolled in a national observational registry and underwent baseline evaluation and periodical follow-up visits. In the overall population, New York Heart Association class and ejection fraction (EF) improved and ventricular diameters decreased. Similar changes were observed in the two groups. In the study population, 157 patients died, 144 (13%) in the <80 years group and 13 (15%) in the > or =80 years group. There was a higher all-cause mortality (log-rank test, P = 0.015) among > or =80 years patients, with a trend towards higher sudden cardiac death (SCD) (P = 0.057), but similar non-SCD (P = 0.293). Using the combined endpoint of SCD or appropriate shock from a defibrillator for ventricular fibrillation, no significant differences resulted between groups (P = 0.455). In both groups, lower EF was associated with higher mortality. CONCLUSION: Cardiac resynchronization therapy demonstrated similar efficacy in patients aged > or =80 years and in those under 80, in terms of clinical and functional parameters and reverse remodelling. Similarly, CRT resulted in comparable effects on death for heart failure and on SCD.

Prognostic role of post-infarction C-reactive protein in patients undergoing implantation of cardioverter-defibrillators: design of the C-reactive protein Assessment after Myocardial Infarction to GUide Implantation of DEfibrillator (CAMI GUIDE) study.

BACKGROUND: Patients at risk of sudden cardiac death (SCD) after myocardial infarction (MI) can currently be offered effective means of prevention, such as implantable cardioverter-defibrillators (ICD). However, predictors of SCD able to identify those patients who are at higher risk are still lacking. Whether C-reactive protein (CRP), a serum inflammatory marker with established prognostic accuracy after MI, can also be a predictor of SCD is unclear. METHODS: The CAMI GUIDE study is designed to evaluate the prognostic role of CRP in patients undergoing ICD implantation after MI according to MADIT II criteria (i.e. left ventricular ejection fraction

Prediction of response to cardiac resynchronization therapy: the selection of candidates for CRT (SCART) study.

BACKGROUND: The aim of this study was to evaluate the ability of baseline clinical and echocardiographic parameters to predict a positive response to CRT. METHODS: We analyzed 6-month data from the first 133 consecutive patients enrolled in a multicenter prospective study. These patients had symptomatic heart failure (HF) refractory to pharmacological therapy (NYHA class II-IV), left ventricular ejection fraction (LVEF) < or =35%, and prespecified electrocardiographic, echocardiographic or tissue Doppler imaging markers of left ventricular (LV) dyssynchrony. RESULTS: After a follow-up period of 6 months, 1 patient died and 13 were hospitalized for worsening HF. There were significant (P < 0.01) clinical, functional, and echocardiographic improvements that included: New York heart Association Class, Quality-of-Life Score, QRS duration, LVEF, LV end-diastolic and end-systolic diameter (LVESD), and severity of mitral regurgitation A positive response was documented in 90/133 (68%) patients who presented an improved clinical composite score associated to an increase in LVEF > or = 5 units. A multivariate analysis identified that a smaller LVESD (OR = 0.957, 95% CI 0.920-0.996; P = 0.030) and longer interventricular mechanical delay (IVMD) (OR = 1.017, 95% CI 1.005-1.029, P = 0.007) as independent predictors of a positive response. Receiver-operating curve analysis showed that a positive response to CRT may be predicted in patients with IVMD > 44 ms (with a sensitivity of 66% and a specificity of 55%) or with LVESD < 60 mm (with a sensitivity of 66% and a specificity of 61%). CONCLUSIONS: Our results confirm the limited value of QRS duration in the selection of patients for CRT. A less-advanced stage of disease and echocardiographic evidence of interventricular dyssynchrony demonstrated to predict response to CRT, while intraventricular dyssynchrony did not predict response.

Role of ventricular Autocapture function in increasing longevity of DDDR pacemakers: a prospective study.

AIMS: Autocapture is an algorithm for automatic adaptation of ventricular output to capture threshold. The aim of this prospective study was to estimate the effects of ventricular Autocapture algorithm on DDD-DDDR pacemaker longevity. METHODS AND RESULTS: Eighty-three patients implanted with a DDD-DDDR pacemaker (Affinity or Entity; St Jude Medical, USA) were enrolled and the Autocapture function was activated pre-discharge. Ventricular pulse duration was randomly programmed at 0.3 or 0.4 ms, with a cross-over at 8-12 weeks and again at 13-14 months. Diagnostic data were retrieved from device memory and by calculating battery current drain from long-term threshold recordings; device longevity was estimated at the following settings: Autocapture with a pulse duration of 0.3 and 0.4 ms, respectively, standard output (3.5 V, 0.4 ms) and conventional low output programming (2.5 V, 0.4 ms). According to a series of assumptions, Autocapture was associated with a 55-60% increase in estimated device longevity compared with standard output programming and a 6-7% increase in longevity compared with low output programming. No significant differences were found between Autocapture programmed with a pulse duration of 0.3 or 0.4 ms. In projections to a 10-year follow-up, use of the Autocapture function resulted in a 42% reduction in pacing-related estimated costs compared with standard output programming at 3.5 V, 0.4 ms. CONCLUSION: Pacing with constant adaptation of ventricular output in dual-chamber devices has the potential to increase generator longevity and to reduce sizeably pacing-related costs compared with standard programming.

[Cardiac resynchronization therapy for heart failure]. / La terapia di resincronizzazione cardiaca per il trattamento dello scompenso cardiaco.

The short-term prognosis of advanced refractory heart failure is extremely poor and closely correlated with progressive left ventricular dysfunction. The identification of the negative effects of conduction delay on cardiac performance, observed in almost 50% of heart failure patients, disclosed a new research field addressing the correction of electrical abnormalities in order to achieve an improvement in myocardial function. Biventricular stimulation, or cardiac resynchronization therapy, corrects the atrioventricular, inter- and intraventricular mechanical asynchrony and, to date, is indicated (class IIA, level of evidence A) for patients with NYHA class III-IV refractory heart failure regardless of its etiology, QRS interval > or = 130 ms, left ventricular end-diastolic diameter > or = 55 mm, and ejection fraction < or = 35%. To date, the completed trials demonstrated in patients undergoing biventricular pacing a significant improvement in left ventricular performance, quality of life and NYHA class with no significant effects on total mortality. The identification of non-responders (approximately 20-30% of the patient population in completed trials) represents an unresolved issue of cardiac resynchronization therapy. Tissue Doppler imaging evaluation of left ventricular dyssynchrony, which is being addressed by non-randomized prospective studies, should drastically decrease the percentage of these patients.

Long-term effectiveness of dual site left ventricular cardiac resynchronization therapy in a patient with congestive heart failure.

This article describes a case of cardiac resynchronization therapy (CRT) performed with dual site left ventricular pacing. The main clinical and functional long-term results are in agreement with the most recent data regarding traditional CRT. Furthermore, this innovative pacing modality allowed optimal inter- and intraventricular resynchronization.

Long-term effectiveness of cardiac resynchronization therapy in patients with refractory heart failure and "narrow" QRS.

OBJECTIVES: The aim of the study was to evaluate the effectiveness of cardiac resynchronization therapy (CRT) in patients with refractory heart failure (HF) and incomplete left bundle branch block ("narrow" QRS), together with echocardiographic evidence of interventricular and intraventricular asynchrony. BACKGROUND: Cardiac resynchronization therapy has been proven effective in patients with HF and wide QRS by ameliorating contraction asynchrony. METHODS: Fifty-two patients with severe HF received biventricular pacing. The patients were eligible in the presence of echocardiographic evidence of interventricular and intraventricular asynchrony, regardless of QRS duration. The patient population was divided into group 1 (n = 38), with a QRS duration >120 ms, and group 2 (n = 14), with a QRS duration < or =120 ms. RESULTS: The baseline parameters considered in the study were similar in both groups. At follow-up, CRT determined narrowing of the QRS interval in the entire population and in group 1 (p < 0.001), whereas a small increase in QRS duration was observed in group 2 (p = NS); in all patients and within groups, we observed improvement of New York Heart Association functional class (p < 0.001 in all), left ventricular ejection fraction (p < 0.001 in all), left ventricular end-diastolic and end-systolic diameter (p < 0.05 within groups), mitral regurgitation area (p < 0.001 in all), interventricular delay (p < 0.001 in all), and deceleration time (group 1: p < 0.001, group 2: p < 0.05), with no significant difference between groups. The 6-min walking test improved in both groups (group 1: p < 0.001; group 2: p < 0.01). CONCLUSIONS: Cardiac resynchronization therapy determined clinical and functional benefit that was similar in patients with wide or "narrow" QRS. Cardiac resynchronization therapy may be helpful in patients with echocardiographic evidence of interventricular and intraventricular asynchrony and incomplete left bundle branch block.

Functional and echocardiographic improvement following multisite biventricular pacing for congestive heart failure.

BACKGROUND: Heart failure remains a major cause of morbidity and mortality despite advances in pharmacological treatment. Recently, multisite biventricular pacing has been used in the treatment of patients with heart failure. OBJECTIVES AND METHODS: The short and medium term effects of this treatment modality were assessed, and the association between baseline clinical characteristics and the positive response to treatment was investigated. Consecutive patients who received this treatment modality were included. They underwent comprehensive clinical and echocardiographic assessment including a 6 min walk at baseline, one month and three months. RESULTS: Between January 1998 and June 1999, 95 patients received multisite biventricular pacing therapy in the three participating hospitals. In 63 patients with complete three-month follow-ups, there were improvements from baseline to three-month follow-up in New York Heart Association heart failure (3.3 +/- 0.5 to 2.2 +/- 0.6, P<0.001) and 6 min walk (305 +/- 120 to 403 +/- 113 m, P<0.001). Significant salutary changes in echocardiographic measurements were also observed in left ventricular (LV) diastolic dimension, ejection fractions (EFs), interventricular contraction delay and severity of mitral regurgitation (MR). The 63 patients were categorized into responders (n=42) and nonresponders (n=21) based on the clinical response. Clinical characteristics were similar between the two groups. The responders had a more pronounced decrease in QRS width. An increase in LVEF and a reduction in LV diastolic dimension, interventricular mechanical delay and severity of MR were observed in the responders but not in the nonresponders. Furthermore, there was a positive association between the reduction in QRS width and the increase in LVEF. CONCLUSIONS: Cardiac resynchronization by means of multisite pacing appears to be a promising therapy in the treatment of heart failure. The salutary clinical response is associated with echocardiographic improvement.

Comparison of two different methods for the evaluation of left ventricular ejection fraction in patients with coronary artery disease.

The evaluation of left ventricular ejection fraction (LVEF) may be troublesome in difficult clinical settings in patients with coronary artery disease (CAD). The aim of this study was to compare 2 simple geometrical and nongeometrical methods of LVEF evaluation that could overcome the typical technical limitations of ultrasound examination. The authors studied 26 patients with proven CAD (63+/-10 years) who underwent left ventricular (LV) catheterization and coronary angiography during the hospital stay. A complete 2D-Doppler echocardiography was performed and LVEF was evaluated with the formula by Wyatt (W-LVEF), which relates the left ventricle to a biplane ellipsoidal figure, and by the myocardial performance index (MPI) formula (MPI-LVEF), MPI being an index of systodiastolic function. Mean MPI-LVEF was 41+/-8% and was significantly lower with respect to contrast angiography (52+/-14%, p = 0.0003) and to W-LVEF (49+/-13%, p = 0.0009). There was no statistically significant correlation between MPI-LVEF and geometric (either angiographic or ultrasound) LVEF. Bland-Altman analysis showed lack of agreement between MPI-LVEF and any other method evaluated in the study. MPI-LVEF may not be reliable and accurate for the evaluation of systolic function in patients with CAD. Nonetheless, the evaluation of global LV function by means of MPI may represent a valuable and affordable alternative to expensive and time-consuming methods, especially in the presence of difficult technical settings.