Time course of effects of cardiac resynchronization therapy in chronic heart failure: benefits in patients with preserved exercise capacity

Objectives: To assess in patients with chronic heart failure the effect of cardiac resynchronization therapy (CRT) over 12 months' follow-up the time course of the changes in functional and neurohormonal indices and to identify responders to CRT.
Methods: Eighty-nine patients (74.1 ± 1 years, left ventricular ejection fraction [LVEF] < 35%), QRS complex duration >150 ms, in stable New York Heart Association (NYHA) class III or IV on optimal medical treatment were prospectively randomized either in a control (n = 45) or CRT (n = 44) group and underwent clinical evaluation, cardiopulmonary exercise testing (CPET), 2D-Echo, heart rate variability (HRV), carotid baroreflex (BRS), and BNP assessments before and at 6- and 12-month follow-up.
Results: In the CRT group, improvement of cardiac indices and BNP concentration were evident at medium term (over 6 months) follow-up, and these changes persisted on a longer term (12 months) (all P < 0.05). Instead CPET indices and NYHA class improved after 12 months associated with restoration of HRV and BRS (all P < 0.05). We identified 26 responders to CRT according to changes in LVEF and diameters. Responders presented less depressed hemodynamic (LVEF 25 ± 1.0 vs 22 ± 0.1%), functional (peak VO₂ 10.2 ± 0.2 vs 6.9 ± 0.3 ml/kg/min), and neurohormonal indices (HRV 203.6 ± 15.7 vs 147.6 ± 10.ms, BRS 4.9 ± 0.2 vs 3.6 ± 0.3 ms/mmHg) (all P < 0.05). In the multivariate analysis, peak VO₂ was the strongest predictor of responders.
Conclusions: Improvement in functional status is associated with restoration of neurohormonal reflex control at medium term. Less depressed functional status (peak VO₂) was the strongest predictor of responders to CRT.     

Cardiac Resynchronization Therapy:

In patients with heart failure and wide QRS complex, cardiac resynchronization therapy (CRT) is associated with improvement of symptoms and cardiac function. This study examined the effects of a 3-month period of CRT on left ventricular (LV) and right ventricular (RV) ejection fraction (EF) and on LV volumes, both at rest and during exercise. A CRT system was implanted in 15 patients with severe heart failure and wide QRS. Before implant and 3 months later, all patients underwent assessment of cardiac performance with equilibrium Tc⁹⁹ radionuclide angiography with imaging in the best septal left anterior oblique view. Exercise was performed on a bicycle ergometer. At 3 months, a significant improvement in New York Heart Association functional class was observed, and radionuclide angiography showed a significant decrease in LV volumes and a significant increase in LVEF at rest, as well as a significant increase in LVEF during exercise. The remodeling processes associated with CRT did not appear to include RV function, since RVEF did not improve, and changes in RVEF did not correlate with changes in LVEF, neither at rest nor during exercise.     

The benefits of biventricular pacing in heart failure patients with narrow QRS, NYHA class II and right ventricular pacing

OBJECTIVE: To identify subgroups of heart failure patients who might benefit from biventricular pacing. BACKGROUND: Cardiac resynchronization therapy (CRT) improves the quality of life, New York Heart Association (NYHA) functional class, and exercise capacity and decreases hospitalizations for heart failure for patients who have severe heart failure and a wide QRS. It is unclear if other populations of heart failure patients would benefit from CRT. METHODS: One hundred forty-four consecutive heart failure patients who underwent CRT and completed 3 months of follow-up were reviewed. Demographic, echocardiographic, electrocardiographic, and clinical outcome data were analyzed to assess the relationship of functional class and QRS duration before device implantation to postimplant outcomes. RESULTS: There were 20, 88, and 36 patients in NYHA functional class II, III, and IV, respectively. Thirty-four patients had right ventricular pacing and another 29 patients had a QRS duration < or = 150 ms. Patients who were in NYHA functional class II at baseline had significant improvement in left ventricular ejection fraction and indices of left ventricular remodeling after CRT. Similar significant findings were seen in the subgroup with right ventricular pacing at baseline after CRT. However, in the subgroup with a narrow QRS duration, there were no significant changes in the indices of left ventricular remodeling or in the NYHA functional class and there was a significant increase in the QRS duration. For the study cohort as a whole, an improvement in NYHA functional class after CRT correlated with a significant decrease in adverse clinical outcomes. CONCLUSIONS: Heart failure patients who were in NYHA functional class II and those with right ventricular pacing appeared to benefit from CRT.     

Relevance of Echocardiographic Evaluation of Right Ventricular Function in Patients Undergoing Cardiac Resynchronization Therapy

Aims: Right ventricular (RV) dysfunction is a marker of poor prognosis in heart failure (HF) patients. It is still unclear whether RV function might influence response to cardiac resynchronization therapy (CRT).
Methods: Forty-four consecutive patients with HF, large QRS, and either intraventricular or interventricular dyssynchrony underwent echocardiographic evaluation before, 1 month after, and 6 months after CRT. Response to CRT was considered in case of significant LV reverse remodeling, defined as the occurrence of LV end-systolic volume (LVESV) reduction ≥15% at 6 months.
Results: All echocardiographic indexes of baseline RV function and dimensions were significantly more impaired in nonresponders versus responders to CRT: tricuspid annular plane systolic excursion (TAPSE 15 ± 4 mm vs 20 ± 5 mm, P = 0.001), RV systolic pulmonary artery pressure (RVSP 39 ± 14 mmHg vs 27 ± 8 mmHg, P = 0.02), RV end-diastolic area (RVEDA 23 ± 6 cm² vs 16 ± 3 cm² P < 0.001), RV end-systolic area (RVESA 16 ± 6 cm² vs 8 ± 2 cm², P = 0.001), and RV fractional area change (30 ± 12% vs 48 ± 8%, P < 0.001). All the indexes of RV function significantly correlated with the percentage of LVESV reduction after CRT. Severe RV dysfunction was defined as TAPSE ≤14 mm and the population was stratified into two groups based on baseline TAPSE ≤ or > 14 mm. As compared to those with high TAPSE (n = 30), patients with low TAPSE (n = 14) were less likely to show LV reverse remodeling after CRT (76% vs 14%, P < 0.001).
Conclusions: Our study suggests that RV function significantly affects response to CRT. Poor LV reverse remodeling occurs after CRT in patients with HF having severe RV dysfunction at baseline.     

Left Ventricular Functional Recovery During Cardiac Resynchronization Therapy:

Cardiac resynchronization therapy (CRT) improves myocardial performance in patients with heart failure (HF) and left bundle-branch block (LBBB). Tissue Doppler echocardiography (TDE) has already been used to guide the selection of candidates for CRT. The objective of this study is to correlate the effects of CRT on left ventricular (LV) systolic function with wall motion synchrony assessed by TDE. High frame TDE data were obtained in 15 patients (mean age = 68.9 years, 11 men) with LBBB (QRS = 163 ± 13 ms) to derive temporal intraventricular horizontal asynchrony indexes, expressed as the time difference at the onset of shortening between the septum and the lateral (S-L) and antero-inferior (A-I) walls, and measure the amount of delayed longitudinal contraction (DLC) within the LV. All measurements were made at baseline, 24 hours after implantation, and at 1 year of follow-up. The results show that LV ejection fraction (EF) increased from 25 ± 6.2% at baseline to 36.9 ± 7.9% at 1 year, and was strongly related to DLC, expressed either by time duration (DLCd, r =−0.51; P < 0.0001) or percent of the basal segments (%DLC, r =−0.50; P < 0.001). New York Heart Association functional class, which decreased from 3.6 ± 0.5 to 2.3 ± 0.8, was correlated with %DLC (r = 0.50) and DLCd (r = 0.48, P < 0.001). Weaker correlations were found between LVEF and S-Li (r =−0.40) and between NYHA and S-Li (r = 0.40). It is concluded that DLC was the best among intraventricular asynchrony indexes in predicting increases in LVEF after CRT. DLC may be useful to identify responders to CRT.     

Intracardiac Echocardiography-Guided Cardiac Resynchronization Therapy: Technique and Clinical Application

Background: We undertook a pilot investigation to evaluate the feasibility of a novel technique using intracardiac echocardiography (ICE) for intraoperative assessment of cardiac resynchronization therapy (CRT).
Methods: We evaluated ICE intraoperative imaging of left ventricular (LV) function and aortic valvular flow as well as safety of implementation. ICE was used to guide CRT system lead placement, assess impact of pacing modes, and optimization of device programming.
Results: Twenty-three patients underwent ICE imaging. ICE showed global hypokinesis in six patients, regional wall motion abnormality only in 10 patients, and both in seven patients. Optimized CRT modes included mean atrioventricular (AV) interval of 170 ms and interventricular timing using simultaneous right ventricular (RV)-LV pacing (five patients), LV pacing only (one patient), and sequential LV to RV stimulation (15 patients) or RV to LV stimulation (two patients). ICE-guided CRT acutely improved mean left ventricular ejection fraction (LVEF) from 24 ± 9% to 41 ± 1% (P < 0.00001). During follow-up of 3–24 (mean 11) months, New York Heart Association class improved in all patients from a mean of 3.2 ± 0.4 at implant to 1.6 ± 0.7 (P < 0.0001), with improvement of LVEF from 19 ± 7% to 34 ± 12% (P = 0.0001). Actuarial survival was 83% at 12 months.
Conclusions: (1) ICE imaging is reliable and safe for continuous intraoperative imaging of LV wall motion, and assesses baseline status and impact of CRT interventions. (2) Intraoperative ICE-guided CRT optimization resulted in an increase in LVEF acutely and consistent improvement in heart failure. (3) Sequential biventricular pacing and longer AV interval programming were more often used in ICE-guided CRT.     

Recent advances in cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is an integral component of modern heart failure therapy for patients with severe symptoms (New York Heart Association [NYHA] class III or IV), a reduced ejection fraction (≤ 35%), and a wide QRS complex (> 120 ms). Results from recent trials have provided ample evidence that CRT may also reduce morbidity and mortality in patients with mildly symptomatic heart failure (NYHA class II). As a result, the 2010 European guidelines now recommend CRT for this patient population (level of evidence I, class A). This review summarizes and critically evaluates the landmark Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE), Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT), and Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT) studies, which comprise the suite of randomized controlled trials available today on this matter. Furthermore, we discuss the rationale and available evidence for other emerging indications for CRT, including its use in patients with a mildly reduced left ventricular ejection fraction (> 35%), in those with a narrow QRS complex (≤ 130 ms), or in patients with concomitant bradyarrhythmic pacemaker indications.     

Long-Term Outcomes of CRT-PM Versus CRT-D Recipients

Objective: To compare the rates of all-cause mortality in recipients of cardiac resynchronization therapy devices without (CRT-PM) versus with defibrillator (CRT-D).
Methods: Between February 1999 and July 2004, 233 patients (mean age = 69 ± 8 years, 180 men) underwent implantation of CRT-PM or CRT-D devices. New York Heart Association (NYHA) heart failure functional class II was present in 11%, class III in 69%, and class IV in 20% of patients; mean left ventricle ejection fraction (LVEF) was 26.5 ± 6.5 %, 48% presented with idiopathic dilated cardiomyopathy and 49% with ischemic heart disease. Cox multiple variable regression analysis was performed in search of predictors of death.
Results: The clinical characteristics of the 117 CRT-PM and 116 CRT-D recipients were similar, except for LVEF (28.2 ± 6.2% vs 25.0 ± 6.5%, respectively; P < 0.001), and ischemic versus nonischemic etiology of heart failure (41% vs 56%, respectively P = 0.02). Over a mean follow-up of 58 ± 15 months, no significance difference in overall mortality rate was observed between the two study groups. Male sex, NYHA functional class IV, and atrial fibrillation at implant were significant predictors of death.
Conclusions: There was no difference in long-term survival rate among patients with CRT-D versus CRT-PM, although CRT-D more effectively lowered the sudden death rate. Male sex, NYHA functional class IV, and atrial fibrillation predicted the worst prognosis.     

Cardiac Resynchronization Therapy in Patients with Mildly Impaired Left Ventricular Function

Aims: We sought to determine the unknown effects of cardiac resynchronization therapy (CRT) in patients with a left ventricular ejection fraction (LVEF) >35%. Because of its technical limitations, echocardiography (Echo) may underestimate LVEF, compared with cardiovascular magnetic resonance (CMR).
Methods: Of 157 patients undergoing CRT (New York Heart Association [NYHA] functional class III or IV, QRS ≥ 120 ms), all of whom had a preimplant Echo-LVEF ≤35%, 130 had a CMR-LVEF ≤35% (Group A, 19.7 ± 7.0%[mean ± standard deviation]) and 27 had a CMR-LVEF >35% (Group B, 43.6 ± 7.7%). All patients underwent a CMR scan at baseline and a clinical evaluation, including a 6-minute walk test and a quality of life questionnaire, at baseline and after CRT.
Results: Both groups derived similar improvements in NYHA functional class (A =−1.3, B =−1.2, [mean]), quality of life scores (A =−21.6, B =−33.0; all P < 0.0001 for changes from baseline), and 6-minute walking distance (A = 64.5, B = 70.1 m; P < 0.001 and P < 0.0001, respectively). Symptomatic response rates (increase by ≥1 NYHA classes or 25% 6-minute walking distance) were 79% in group A and 92% in group B. Over a maximum follow-up period of 5.9 years for events, patients in group A were at a higher risk of death from any cause, hospitalization for major cardiovascular events (P = 0.0232), or cardiovascular death (P = 0.0411). There were borderline differences in the risk of death from any cause (P = 0.0664) and cardiovascular death or hospitalization for heart failure (P = 0.0526).
Conclusions: This observational study suggests that the benefits of CRT extend to patients with a LVEF > 35%.     

Marked Improvement in Left Ventricular Function and Significant Reverse Left Ventricular Remodeling within 3 Months of Cardiac Resynchronization Therapy in Patients with Dilated Cardiomyopathy

We monitored reverse left ventricular (LV) remodeling and LV function during the first 6 months of cardiac resynchronization therapy (CRT) in 34 patients (mean age = 55.3 ± 13.6 years, 28 men) with dilated cardiomyopathy (DCM), left bundle branch block, in stable New York Heart Association class III, and on fixed drug regimen who underwent implantation of CRT systems with or without cardioverter defibrillator back-up. QRS-complex duration was reduced from 169.69 ± 19.6 ms (SD) to 144.1 ± 23.4 ms during CRT. Parasternal M-mode and apical 2D-echocardiography was performed before and 3 and 6 months after device implantation. LV enddiastolic (EDD) and endsystolic (ESD) diameters were measured, and biplane LV enddiastolic (EDV), and endsystolic (ESV) volumes and ejection fractions (EF) were calculated using a modified Simpson formula. Significant decreases in LVEDD (P = 0.0064 at 3 months and P = 0.021 at 6 months), LVESD (P = 0.023 at 3 months, and P = 0.003 at 6 months), and LVESV (P = 0.006 resp. P = 0.007), and increases in LVEF (P = 0.003 at 3 months and P < 0.001 at 6 months) were observed. Mean LVEF increased from 23% at baseline to 39% at 6 months. CRT induced prominent reverse LV remodeling and significantly increased LVEF within a few months in patients with DCM.     

Resynchronization: What if the Left Ventricular Lead Cannot Reach the Lateral or Posterolateral Wall?

Background: The recommended left ventricular (LV) lead position for cardiac resynchronization therapy (CRT) is at the lateral or posterolateral wall. However, LV leads cannot always be implanted at this site. The objective of our study was to compare the clinical response to CRT when the LV lead could be implanted or not at the lateral or posterolateral wall.
Methods: In consecutive patients implanted with a CRT device, we documented the final position achieved by the tip of the LV lead in the left anterior oblique projection. Patients were prospectively followed for 6 months after implantation. They were defined as responders if they were alive, had gained 1 New York Heart Association (NYHA) functional class, and had not been hospitalized for heart failure.
Results: The study population consisted of 77 patients (56 men, 71 ± 10 years, 62 NYHA class III, 15 NYHA class IV). The LV lead was implanted at the lateral or posterolateral wall in 54 patients (group A) and at the anterior or anterolateral wall in 23 patients (group B). At 6 months, seven patients (9%) died (all in group A). There were 37 responders (69%) in group A as compared to 22 (96%) in group B.
Conclusions: The responder rate was not inferior when the LV lead was implanted at the anterior or anterolateral wall. Thus, in case of failed implantation at the lateral or posterolateral wall, positioning the LV lead in a more anterior location appears to be a reasonable alternative. Further studies are required to confirm these findings.     

Biventricular upgrading in patients with conventional pacing system and congestive heart failure: results and response predictors

BACKGROUND: There are few studies on cardiac resynchronization therapy (CRT) in heart failure (HF) patients with preexisting right ventricular (RV) pacing. The purpose of this study was to determine the efficacy of CRT upgrading in RV-paced patients and the predictivity of electromechanical dyssynchrony parameters (EDP) evaluated by standard echocardiography (ECHO) and tissue Doppler imaging (TDI). METHODS: Thirty-eight consecutive patients with HF [New York Heart Association (NYHA) class III or IV, LVEF < 35%], prior continuous RV pacing, and absence of atrial fibrillation were enrolled in the presence of a paced QRS > or = 150 ms and evaluated by ECHO and TDI. A responder was defined as a patient with a favorable change in NYHA class and neither HF hospitalization nor death, plus an absolute increase of LVEF > or = 10 units. RESULTS: At six-months follow-up, the whole study population had significant improvement in symptoms, systolic function, and QRS duration (P < 0.001); 32 (84%) patients had a favorable clinical outcome, 25 (66%) were considered responders according to the previous definition. Postimplant QRS was similarly reduced in both responders and nonresponders, whereas EDP had a significant improvement only in responders (P < 0.05). Using EDP, 23 (79%) patients were responders compared with 2 (22%) patients without mechanical dyssynchrony (P = 0.002). CONCLUSIONS: In HF patients with previous RV pacing, CRT is effective to improve clinical, functional outcome, and LV performance and to reduce electromechanical dyssynchrony in a large proportion of patients. Dyssynchrony evaluated by standard and TDI ECHO can be useful for CRT selection of paced patients.     

Determinants of mortality in patients undergoing cardiac resynchronization therapy: baseline clinical, echocardiographic, and angioscintigraphic evaluation prior to resynchronization

BACKGROUND: In dilated cardiomyopathy (DCM) patients (pts) with cardiac resynchronization therapy (CRT) for ventricular dyssynchrony, long-term predictors of mortality and morbidity remain poorly investigated. METHOD AND RESULTS: We reviewed data of 102 pts, 68 +/- 10 years, NYHA Class II-IV (14 Class II, 67 Class III, 21 Class IV), who benefited from CRT (69 CRT, 33 CRT-ICD). Fifty-two patients had an ischemic DCM, 36 a previously implanted conventional PM/ICD, 29 a permanent atrial fibrillation, and 19 needed dobutamine in the month preceding implant. QRS duration was 187 +/- 35 ms, left ventricular end-diastolic diameter 72 +/- 10 mm, mitral regurgitation severity 1.9 +/- 0.8, echographic aorto-pulmonary electromechanical delay 61.5 +/- 25 ms and septo-lateral left intraventricular delay 86 +/- 56 ms, pulmonary artery pressure (PAP) 43 +/- 11 mmHg, angioscintigraphic left ventricular ejection fraction (EF) 20 +/- 9%, and right ventricular EF 30.5 +/- 14%. Over a mean follow-up of 23 +/- 20 months, 26 pts died (18 heart failures (HFs), 1 arrhythmic storm, 7 noncardiac deaths). Positive univariate predictors of death from any cause were NYHA Class IV (P < 0.001), and need for dobutamine the month preceding CRT (P < 0.008), while use of beta-blocking agents (P < 0.08) and left ventricular EF (P < 0.09) were negative ones. NYHA Class IV was the only independent predictor at multivariate analysis (P < 0.01). Survival at 24 months was 85% in Class II, 80% in Class III, and 37% in Class IV (II vs III, P = ns; III vs IV, P < 0.001). When using a composite endpoint of death from any cause and unplanned rehospitalization for a major cardiovascular event, there were 48 events (14 HF deaths, 3 noncardiac deaths, 26 HF rehospitalizations, 2 paroxysmal atrial fibrillation, 2 sustained ventricular tachycardia, 1 nonfatal pulmonary embolism). Predictors of death from any cause/unplanned rehospitalization for a major cardiovascular event in the follow-up were NYHA Class IV (P < 0.001), need for dobutamine during the month preceding CRT (P < 0.002), and PAP (<0.02). NYHA Class IV was the only independent predictor at multivariate analysis (P < 0.05). Event-free proportion at 24 months was 70% in Class II, 64% in Class III, and 37% in Class IV (II vs III, P = ns; III vs IV, P < 0.01). When considering determinants of mortality only in NYHA Class IV patients, no variable was significantly correlated to mortality. Need for dobutamine during the last month preceding CRT did not add an adjunctive mortality risk. CONCLUSION: Baseline NYHA Class IV at implantation appears as the most important determinant of a poor clinical outcome in terms of both mortality and morbidity. No predictive criteria seem available for NYHA Class IV patients, in order to discriminate who will die after CRT and who will not. NYHA Class IV strongly influences the clinical outcome, suggesting that, in future studies planned on mortality and rehospitalization as major endpoints, baseline NYHA Class IV should be separately taken into account.     

Treatment of heart failure with decreased left ventricular ejection fraction

Original Article Class I recommendations for treating patients with current or prior symptoms of heart failure with reduced left ventricular ejection fraction (LVEF) include using diuretics and salt restriction in individuals with fluid retention. Use angiotensin-converting enzyme (ACE) inhibitors, beta blockers, and angiotensin II receptor blockers if intolerant to ACE inhibitors because of cough or angioneurotic edema. Nonsteroidal anti-inflammatory drugs, most antiarrhythmic drugs, and calcium channel blockers should be avoided or withdrawn. Exercise training is recommended. Implant cardioverter-defibrillator (ICD) is recommended in individuals with a history of cardiac arrest, ventricular fibrillation, or hemodynamically unstable ventricular tachycardia. ICD is indicated in patients with ischemic heart disease for at least 40 d post-myocardial infarction or nonischemic cardiomyopathy, an LVEF of 30% or less, New York Heart Association (NYHA) class II or III symptoms on optimal medical therapy, and an expectation of survival of at least 1 yr. Cardiac resynchronization therapy should be used in individuals with an LVEF of 35% or below, NYHA class III or IV symptoms despite optimal therapy, and a QRS duration greater than 120 ms. An aldosterone antagonist can be added in selected patients with moderately severe to severe symptoms of heart failure who can be carefully monitored for renal function and potassium concentration (serum creatinine should be ≶2.5 mg/dL in men and ≶2.0 mg/dL in women; serum potassium should be <5.0 mEq/L).     

Long-Term Follow-Up of Biventricular Pacing Using a Totally Endocardial Approach in Patients with End-Stage Cardiac Failure

Background: Besides standard left ventricular (LV) stimulation via the coronary sinus, a transseptal approach allows left ventricular endocardial stimulation. We report our long-term observations with biventricular stimulation, using a strictly endocardial system for patients presenting with severe congestive heart failure .
Methods: Six patients with nonischemic cardiomyopathy (mean age = 60 ± 9.6 years, women) in New York Heart Association (NYHA) functional class III (n = 5) or IV, despite optimal drug therapy, and a mean LV ejection fraction of 24 ± 3%, underwent implantation of biventricular stimulation systems between April 1998 and March 1999. All presented with left bundle branch block and an increased LV end-diastolic diameter (mean = 66 ± 5 mm). In all patients, a bipolar pacing lead was implanted in the lateral LV wall using a direct transseptal approach. After implantation, all patients received oral anticoagulation.
Results: QRS duration decreased from 184 ± 22 ms to 108 ± 11 ms. NYHA functional class decreased to II in all patients within 1 month. Over a 85 ± 5 month follow-up, two patients underwent cardiac transplantation, 2 and 4 years after device implantation, respectively; two patients died of end-stage heart failure 4 years after system implantation; and two patients were alive in functional class II. One patient, who experienced syncope due to fast ventricular, underwent implantation of an ICD. One transient ischemic attack occurred in a patient whose anticoagulation was temporarily interrupted .
Conclusions: Long-term endocardial biventricular stimulation via a transseptal approach was safe and effective in this small population. This approach needs to be further compared with conventional epicardial pacing via the coronary sinus     

SPECT and Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) has proven benefits in patients with refractory heart failure including improved symptoms, exercise capacity, quality of life, and left ventricular (LV) function, and mortality benefits. At present, CRT is recommended in patients with severe refractory heart failure (New York Heart Association class III or IV), LV ejection fraction ≤ 35%, QRS duration ≥ 120 ms, and sinus rhythm. When selected based on these standard indications, 20% to 40% of patients fail to respond to CRT. Important parameters for predicting CRT response, such as LV mechanical dyssynchrony, myocardial scar, and LV pacing lead position, have been studied using phase analysis of gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). This review aims to describe the role of gated SPECT MPI for the comprehensive assessment of those parameters for selection of patients for CRT.     

Segmental Wall Motion Abnormality Analyzed by Equilibrium Radionuclide Angiography and Improvement in Ventricular Function by Cardiac Resynchronization Therapy

Introduction: The purpose of this study was to determine the impact of the left ventricular (LV) segmental wall motion abnormalities detected by equilibrium radionuclide angiography (ERNA) on the improvement in LV and right ventricular (RV) function during biventricular (BIV) stimulation .
Results: We studied 28 patients in NYHA functional classes III or IV and QRS duration >150 ms on resting electrocardiogram. ERNA was performed before and during BIV stimulation at a 6-month follow-up. A significant shortening of QRS duration was observed during BIV stimulation (165 ± 5 ms before vs 133 ± 6 ms during, P < 0.01). Wall motion abnormalities (WMA) were observed in 16 patients (10 with nonischemic cardiomyopathies). In this group, LV and RV ejection fractions (EF) did not increase during BIV stimulation (LVEF = 22 ± 2% vs 20 ± 1.6%, ns; RVEF = 34 ± 3% vs 37 ± 3.8%, ns). Significant increases in RVEF (23 ± 3.2 %→ 38 ± 2.9%, P = 0.001) and LVEF (20 ± 2.5 %→ 30 ± 3%, P = 0.01) were observed in the group of patients without segmental WMA and with global hypokinesia (GH). In this group, a significant decrease in the dispersion in the phase of RV contraction was observed (SD = 39 ± 5 vs 26 ± 2 ms; P < 0.01). WMA predicted an increase in LVEF, in contrast to a baseline 6-minute-walk test, maximal oxygen consumption and LVEF, or amount of QRS shortening.
Conclusions: BIV stimulation increased in LV and RV EF in patients with ventricular dyssynchrony in absence of segmental WMA. ERNA was reliable in the selection of candidates for CRT.     

Effects of Cardiac Resynchronization Therapy on Diastolic Function: Evaluation by Radionuclide Angiography

While the beneficial effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) systolic function have been demonstrated, no information is available regarding its effects on LV diastolic function during exercise. Using radionuclide angiography, we prospectively evaluated the effects of CRT on diastolic function at rest and during exercise in 15 patients consecutively referred for CRT. All patients underwent equilibrium Tc⁹⁹ radionuclide angiography with bicycle exercise performed (1) at baseline; (2) immediately after CRT implantation, in spontaneous rhythm and during CRT; and (3) after 3 months of biventricular stimulation. Diastolic function was assessed by measurements of peak filling rate (PFR). At baseline, activation of biventricular stimulation influenced PFR neither at rest (1.06 ± 0.34 vs 1.07 ± 0.50 mL/s during spontaneous rhythm, P = 0.9) nor during exercise (1.45 ± 0.62 vs 1.33 ± 0.48 mL/s, P = 0.3). At 3 months, improvements were observed in New York Heart Association functional class and systolic function. By contrast, no improvement in diastolic function was observed either at rest (PFR = 1.11 ± 0.45 vs 1.07 ± 0.50 mL/s in spontaneous rhythm at baseline, P = 0.6) or during exercise (1.23 ± 0.50 vs 1.33 ± 0.48 mL/s, P = 0.2). These observations indicate that the intermediate benefits conferred by CRT on LV systolic function at rest and during exercise were not accompanied by similar improvements in diastolic function .     

Effects of Cardiac Resynchronization Therapy on Heart Rate Turbulence

Background: Cardiac resynchronization therapy (CRT) improves the clinical status of patients with heart failure (HF), though its effects on heart rate turbulence (HRT) are unknown.
Methods: We measured HRT indices in 58 recipients of CRT systems (mean age = 56 ± 9 years, 41 men) in New York Heart Association HF functional class III–IV, and with a left ventricular (LV) ejection fraction ≤35%. At 6 months of follow-up, 42 patients were responders and 13 nonresponders to CRT, and three patients died suddenly. The HRT indices turbulence onset (TO%) and turbulence slope (TS ms/RR interval) were calculated from digital 24-hour electrocardiogram before and after 6 months of CRT. TO ≥ 0% and TS ≤ 2.5 ms/RR interval were considered abnormal.
Results: Mean TO in the entire population was 0.4 ± 1.5 before CRT, and decreased to −0.8 ± 7.0 during the 6 months of CRT (ns). TS increased significantly from 2.0 ± 1.7 at baseline, to 3.9 ± 3.1 (P < 0.05), and a significantly lower proportion of patients had abnormal HRT indices at 6 months. In contrast to the significant increase observed in responders, not significant change in TS was observed among the nonresponders.
Conclusions: During 6 months of CRT, improvements in HRT indices and a decrease in the proportion of patients with abnormal HRT were observed. CRT may have beneficial effects on baroreflex sensitivity.     

Male gender and chronic obstructive pulmonary disease predict a poor clinical response in patients undergoing cardiac resynchronisation therapy

Aims: Current guidelines advocate cardiac resynchronisation therapy (CRT) in patients with class III/IV New York Heart Association (NYHA) heart failure, depressed left ventricular function and a broad QRS. However, a significant proportion of patients do not derive any benefit from CRT. The aim of this study was to identify clinical, electrocardiographic and echocardiographic predictors of response to CRT. Methods: A retrospective analysis of patients undergoing CRT in our institution was performed. A favourable clinical response to CRT was defined as an improvement in NYHA Heart failure class of ≥ 1 and lack of hospitalisation with heart failure. Comparisons were made between responders and non‐responders in terms of baseline characteristics and potential predictors of CRT response (QRS width, presence of left bundle branch block, atrial fibrillation, evidence of mechanical dyssynchrony on echocardiography and LV lead position). Results: A total of 164 patients had full follow‐up data. The mean follow‐up was 293 days. Of patients undergoing CRT, 90 (58.9%) had a favourable clinical response to CRT. Predictors of a lack of clinical response to CRT were male gender (p = 0.012) and chronic obstructive pulmonary disease (COPD) (0.008). Pre‐implant echocardiographic dyssynchrony assessment appeared not to predict response to CRT (p = 0.87); however, there was a trend towards a positive response in those patients with significant dyssynchrony (p = 0.09) defined as interventricular delay > 40 ms or maximal LV delay of > 80 ms. Conclusion: Male gender and coexisting COPD were shown to be independent predictors of non‐response to CRT in this cohort of patients fulfilling current criteria for CRT.