One-Year Outcomes After MitraClip for Functional Mitral Regurgitation.

BACKGROUND: Secondary mitral regurgitation (SMR) occurs in the absence of organic mitral valve disease and may develop as the left ventricle dilates or remodels or as a result of leaflet tethering with impaired coaptation, most commonly from apical and lateral distraction of the subvalvular apparatus, with late annular dilatation. The optimal therapy for SMR is unclear. This study sought to evaluate the 1-year adjudicated outcomes of all patients with SMR undergoing the MitraClip procedure in the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) Investigational Device Exemption program, which is comprised of the randomized clinical trial, the prospective High-Risk Registry, and the REALISM Continued Access Registry (Multicenter Study of the MitraClip System). METHODS: Patients with 3+/4+ SMR enrolled in EVEREST II were stratified by non-high surgical risk (non-HR) and high surgical risk (HR) status (defined as Society of Thoracic Surgeons risk of mortality ≥12% or predefined risk factors). Clinical, echocardiographic, and functional outcomes at 1 year were evaluated. RESULTS: A total of 616 patients (482 HR, 134 non-HR; mean age, 73.3±10.5 years; Society of Thoracic Surgeons risk, 10.2±6.9%) with SMR underwent the MitraClip procedure. At baseline, 80.5% of patients were in New York Heart Association class III/IV. Major adverse events at 30 days included death (3.6%), stroke (2.3%), and renal failure (1.5%). At discharge, 88.8% had MR ≤2+. At 1 year, there were 139 deaths, and the Kaplan-Meier estimate of freedom from mortality was 76.8%. The majority of surviving patients (84.7%) remained with MR ≤2+ and New York Heart Association class I/II (83.0%). Kaplan-Meier survival at 1 year was 74.1% in HR patients and 86.4% in non-HR patients ( P=0.0175). At 1 year, both groups achieved comparable MR reduction (MR ≤2+, 84.0% versus 87.0%) and improvement in left ventricular end-diastolic volume (-8.0 mL versus -12.7 mL), whereas New York Heart Association class I/II was found in 80.1% versus 91.8% ( P=0.008) of HR and non-HR patients, respectively. In HR patients, the annualized rate of heart failure hospitalizations decreased from 0.68 to 0.46 in the 12 months before to 12 months after the procedure ( P<0.0001). CONCLUSIONS: Transcatheter mitral valve repair with the MitraClip in patients with secondary MR is associated with acceptable safety, reduction of MR severity, symptom improvement, and positive ventricular remodeling. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov . Unique identifiers: NCT00209274, NCT01940120, and NCT01931956.

Evolution of Echocardiographic Measures of Cardiac Disease From CKD to ESRD and Risk of All-Cause Mortality: Findings From the CRIC Study.

RATIONALE & OBJECTIVE: Abnormal cardiac structure and function are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD) and linked with mortality and heart failure. We examined changes in echocardiographic measures during the transition from CKD to ESRD and their associations with post-ESRD mortality. STUDY DESIGN: Prospective study. SETTING & PARTICIPANTS: We studied 417 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) who had research echocardiograms during CKD and ESRD. PREDICTOR: We measured change in left ventricular mass index, left ventricular ejection fraction (LVEF), diastolic relaxation (normal, mildly abnormal, and moderately/severely abnormal), left ventricular end-systolic (LVESV), end-diastolic (LVEDV) volume, and left atrial volume from CKD to ESRD. OUTCOMES: All-cause mortality after dialysis therapy initiation. ANALYTICAL APPROACH: Cox proportional hazard models were used to test the association of change in each echocardiographic measure with postdialysis mortality. RESULTS: Over a mean of 2.9 years between pre- and postdialysis echocardiograms, there was worsening of mean LVEF (52.5% to 48.6%; P<0.001) and LVESV (18.6 to 20.2mL/m2.7; P<0.001). During this time, there was improvement in left ventricular mass index (60.4 to 58.4g/m2.7; P=0.005) and diastolic relaxation (11.11% to 4.94% with moderately/severely abnormal; P=0.02). Changes in left atrial volume (4.09 to 4.15mL/m2; P=0.08) or LVEDV (38.6 to 38.4mL/m2.7; P=0.8) were not significant. Worsening from CKD to ESRD of LVEF (adjusted HR for every 1% decline in LVEF, 1.03; 95% CI, 1.00-1.06) and LVESV (adjusted HR for every 1mL/m2.7 increase, 1.04; 95% CI, 1.02-1.07) were independently associated with greater risk for postdialysis mortality. LIMITATIONS: Some missing or technically inadequate echocardiograms. CONCLUSIONS: In a longitudinal study of patients with CKD who subsequently initiated dialysis therapy, LVEF and LVESV worsened and were significantly associated with greater risk for postdialysis mortality. There may be opportunities for intervention during this transition period to improve outcomes.

Survival with cardiac-resynchronization therapy in mild heart failure.

BACKGROUND: The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) showed that early intervention with cardiac-resynchronization therapy with a defibrillator (CRT-D) in patients with an electrocardiographic pattern showing left bundle-branch block was associated with a significant reduction in heart-failure events over a median follow-up of 2.4 years, as compared with defibrillator therapy alone. METHODS: We evaluated the effect of CRT-D on long-term survival in the MADIT-CRT population. Post-trial follow-up over a median period of 5.6 years was assessed among all 1691 surviving patients (phase 1) and subsequently among 854 patients who were enrolled in post-trial registries (phase 2). All reported analyses were performed on an intention-to-treat basis. RESULTS: At 7 years of follow-up after initial enrollment, the cumulative rate of death from any cause among patients with left bundle-branch block was 18% among patients randomly assigned to CRT-D, as compared with 29% among those randomly assigned to defibrillator therapy alone (adjusted hazard ratio in the CRT-D group, 0.59; 95% confidence interval [CI], 0.43 to 0.80; P<0.001). The long-term survival benefit of CRT-D in patients with left bundle-branch block did not differ significantly according to sex, cause of cardiomyopathy, or QRS duration. In contrast, CRT-D was not associated with any clinical benefit and possibly with harm in patients without left bundle-branch block (adjusted hazard ratio for death from any cause, 1.57; 95% CI, 1.03 to 2.39; P=0.04; P<0.001 for interaction of treatment with QRS morphologic findings). CONCLUSIONS: Our findings indicate that in patients with mild heart-failure symptoms, left ventricular dysfunction, and left bundle-branch block, early intervention with CRT-D was associated with a significant long-term survival benefit. (Funded by Boston Scientific; ClinicalTrials.gov numbers, NCT00180271, NCT01294449, and NCT02060110.).

Cardiovascular events and hospital resource utilization pre- and post-transcatheter mitral valve repair in high-surgical risk patients.

MitraClip is an approved therapy for mitral regurgitation (MR); however, health care resource utilization pre- and post-MitraClip remains understudied. METHODS: Patients with functional and degenerative MR at high surgical risk in the EVEREST II High-Risk Registry and REALISM Continued-Access Study were linked to Medicare data. Pre- and post-MitraClip all-cause death, stroke, myocardial infarction, heart failure (HF), and bleeding hospitalizations were identified. Inpatient costs, adjusted to 2010 US dollars, were calculated, and event rate ratios and cost ratios were estimated with multivariable modeling. RESULTS: Among 403 linked patients, the mean age was 80 years, 60% were male, mean baseline left ventricular ejection fraction was 49.6%, 83.3% were New York Heart Association class III/IV, 78.2% were MR grade 3+/4+, and 63.3% had functional MR. All-cause hospitalization decreased from 1,854 to 1,435/1,000 person-years (P<.001). HF hospitalization decreased following MitraClip (749 vs 332/1000 person-years, P<.001), but bleeding increased (199 vs 298/1000 person-years, P<.001). Changes in stroke and myocardial infarction were not statistically significant. Overall mean Medicare costs per patient were similar pre- and post-MitraClip, although there was a significant decrease in mean costs among those that survived a full year after MitraClip ($18,131 [SD $25,130] vs $11,679 [SD $22,486], P=.02). CONCLUSIONS: MitraClip was associated with a reduced rate of all-cause and HF hospitalizations and an increased rate of bleeding hospitalizations. One-year Medicare costs were reduced in those who survived a full year after the MitraClip procedure. Payors and providers seeking to reduce HF hospitalizations and associated Medicare costs may consider MitraClip among appropriate patients likely to survive 1 year.

AVJ-514 Trial　- Baseline Characteristics and 30-Day Outcomes Following MitraClip® Treatment in a Japanese Cohort.

BACKGROUND: The MitraClip®system is a transcatheter-based therapeutic option for patients with chronic mitral regurgitation (MR) who are at high risk for surgery. A prospective, multicenter, single-arm study was initiated to confirm the transferability of this system to Japan.Methods and Results:Patients with symptomatic chronic moderate-to-severe (3+) or severe (4+) functional or degenerative MR with a Society of Thoracic Surgery (STS) score ≥8%, or the presence of 1 predefined risk factor were enrolled. Patients with left ventricular (LV) ejection fraction (EF) <30% were excluded. MR severity and LV function were assessed by an independent echocardiography core lab. Primary outcome included major adverse events (MAE) at 30 days and acute procedural success (APS). A total of 30 patients (age: 80±7 years; STS score: 10.3%±6.6%) were treated with the MitraClip®. At baseline, all patients had MR 3+/4+ with 53%/47% patients with degenerative/functional etiology with mean LVEF of 50.2±12.8%, and 37% of patients were NYHA class III/IV. APS was achieved in 86.7% with no occurrence of MAE. At 30 days, 86.7% of patients had MR ≤2+ and 96.7% were NYHA class I/II. CONCLUSIONS: The MitraClip®procedure resulted in clinically meaningful improvements in MR severity, function and quality of life measures, and low MAE rates. These early results suggest the transferability of this therapy to appropriately selected Japanese patients. (Trial Registration: clinicaltrials.gov Identifier NCT02520310.).

Left ventricular ejection fraction normalization in cardiac resynchronization therapy and risk of ventricular arrhythmias and clinical outcomes: results from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) trial.

BACKGROUND: Appropriate guideline criteria for use of implantable cardioverter-defibrillators (ICDs) do not take into account potential recovery of left ventricular ejection fraction (LVEF) in patients treated with CRT-defibrillator. METHODS AND RESULTS: Patients randomized to CRT-defibrillator from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) trial who survived and had paired echocardiograms at enrollment and at 12 months (n=752) were included. Patients were evaluated by LVEF recovery in 3 groups (LVEF ≤35% [reference], 36%-50%, and >50%) on outcomes of ventricular tachyarrhythmias (VTAs), VTA ≥200 bpm, ICD shock, heart failure or death, and inappropriate ICD therapy by multivariable Cox models. A total of 7.3% achieved LVEF normalization (>50%). The average follow-up was 2.2±0.8 years. The risk of VTA was reduced in patients with LVEF >50% (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.07-0.82; P=0.023) and LVEF of 36% to 50% (HR, 0.44; 95% CI, 0.28-0.68; P<0.001). Among patients with LVEF >50%, only 1 patient had VTA ≥200 bpm (HR, 0.16; 95% CI, 0.02-1.51), none were shocked by the ICD, and 2 died of nonarrhythmic causes. The risk of HF or death was reduced with improvements in LVEF (LVEF >50%: HR, 0.29; 95% CI, 0.09-0.97; P=0.045; and LVEF of 36%-50%: HR, 0.44; 95% CI, 0.28-0.69; P<0.001). For inappropriate ICD therapy, no additional risk reduction for LVEF>50% was seen compared with an LVEF of 36% to 50%. A total of 6 factors were associated with LVEF normalization, and patients with all factors present (n=42) did not experience VTAs (positive predictive value, 100%). CONCLUSIONS: Patients who achieve LVEF normalization (>50%) have very low absolute and relative risk of VTAs and a favorable clinical course within 2.2 years of follow-up. Risk of inappropriate ICD therapy is still present, and these patients could be considered for downgrade from CRT-defibrillator to CRT-pacemaker at the time of battery depletion if no VTAs have occurred. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

Pregnancy-related cardiovascular deaths in California: beyond peripartum cardiomyopathy.

OBJECTIVE: Maternal mortality rates rose markedly from 2002 to 2006 in California, prompting an in-depth maternal mortality review in a state that comprises one twelfth of the US birth cohort. Cardiovascular disease has emerged as the leading cause of pregnancy-related death in the United States. The primary aim of this analysis was to describe the incidence and type of cardiovascular disease as a cause of pregnancy-related mortality in California. The secondary aims were to describe racial/ethnic and socioeconomic disparities, risk factors, birth outcomes, timing of death and diagnosis, and signs and symptoms of cardiovascular disease and identify contributing factors. STUDY DESIGN: The California Pregnancy-Associated Mortality Review retrospectively examined a case series of 64 cardiovascular pregnancy-related deaths from 2002 through 2006. Two cardiologists independently reviewed complete inpatient and outpatient medical records including laboratory, radiology, electrocardiogram, chest X-ray, echocardiograms, and autopsy findings for each cardiovascular death and classified cause of death by type of cardiovascular disease. Demographic data, racial disparities, risk factors, signs and symptoms, timing of diagnosis and death, birth outcomes, and contributing factors were analyzed using bivariate comparisons with noncardiovascular pregnancy-related deaths and population-based data. RESULTS: Among 2,741,220 California women who gave birth, 864 died while pregnant or within 1 year of pregnancy; 257 of the deaths were deemed pregnancy related, and of these, 64 (25%) were attributed to cardiovascular disease. There were 42 deaths caused by cardiomyopathy, and the pregnancy-related mortality rate from cardiomyopathy was 1.54 per 100,000 births. Dilated cardiomyopathy existed in 29 cases, of which 15 met the definition of peripartum cardiomyopathy. Women with cardiovascular disease were more likely than women who died from noncardiovascular causes to be African-American (39.1% vs 16.1%; P < .01) and more likely to use illicit substances (23.7% vs 9.4%; P < .01). Thirty-seven percent were obese and 20% had a concomitant diagnosis of hypertension or preeclampsia during pregnancy. Health care decisions in the diagnosis or treatment of cardiovascular disease during and after pregnancy contributed to the fatal outcomes. CONCLUSION: African-American race, substance use, and obesity were risk factors for pregnancy-related cardiovascular disease mortality. Chronic disease prevention and better recognition and response to cardiovascular disease during pregnancy are needed to reduce maternal mortality.

Echocardiographic evaluation in transposition of the great arteries in the adult.

Transposition of the great arteries is marked by ventriculo-arterial discordance and occurs in 2 distinct subtypes. Echocardiography is the primary method of evaluating this condition in the adult. Key elements of the echocardiographic exam include confirming the diagnosis, evaluating ventricular size and function, assessing valvular regurgitation, identifying atrial baffle leaks or obstruction, estimating pulmonary artery pressures, and ruling out residual shunts.

Relationship between the magnitude of reduction in mitral regurgitation severity and left ventricular and left atrial reverse remodeling after MitraClip therapy.

BACKGROUND: MitraClip has been shown to reduce mitral regurgitation (MR) severity safely but to a lesser degree than surgery. No data exist on the magnitude of MR reduction necessary to reverse left ventricular (LV) and left atrial (LA) dilation in patients with severe MR. Therefore, an analysis was performed to evaluate the relationship between MR reduction and LV and LA volumes after MitraClip therapy. METHODS AND RESULTS: A total of 801 patients treated with MitraClip and 80 patients treated surgically were included. All patients had severe (3-4+) MR. MR severity, LV volumes at end-diastole and end-systole, and LA volumes were measured at baseline, discharge, 30 days, 6 months, and 1 year by an independent echocardiographic core laboratory. A linear repeated measures model was developed to determine the relationship between MR severity and time of measurement postindex procedure on longitudinal LV and LA volumes. Separate models were fit for functional MR and degenerative MR. In both degenerative and functional MR, reduction in LV volumes at end-diastole was associated with degree of residual MR at 12 months (P<0.0001). LV volumes at end-systole was significantly reduced in functional MR but not degenerative MR. LA volumes were significantly related to reduction of MR severity in both groups. CONCLUSIONS: Reduction of LV volumes at end-diastole and LA volumes, but not LV volumes at end-systole in degenerative MR, is consistent with correction of volume overload from primary MR. Reduction of all 3 measurements in functional MR demonstrates reverse remodeling when MR severity is reduced to either 1+ or 2+ by MitraClip therapy. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00209274.

Percutaneous repair or surgery for mitral regurgitation.

BACKGROUND: Mitral-valve repair can be accomplished with an investigational procedure that involves the percutaneous implantation of a clip that grasps and approximates the edges of the mitral leaflets at the origin of the regurgitant jet. METHODS: We randomly assigned 279 patients with moderately severe or severe (grade 3+ or 4+) mitral regurgitation in a 2:1 ratio to undergo either percutaneous repair or conventional surgery for repair or replacement of the mitral valve. The primary composite end point for efficacy was freedom from death, from surgery for mitral-valve dysfunction, and from grade 3+ or 4+ mitral regurgitation at 12 months. The primary safety end point was a composite of major adverse events within 30 days. RESULTS: At 12 months, the rates of the primary end point for efficacy were 55% in the percutaneous-repair group and 73% in the surgery group (P=0.007). The respective rates of the components of the primary end point were as follows: death, 6% in each group; surgery for mitral-valve dysfunction, 20% versus 2%; and grade 3+ or 4+ mitral regurgitation, 21% versus 20%. Major adverse events occurred in 15% of patients in the percutaneous-repair group and 48% of patients in the surgery group at 30 days (P<0.001). At 12 months, both groups had improved left ventricular size, New York Heart Association functional class, and quality-of-life measures, as compared with baseline. CONCLUSIONS: Although percutaneous repair was less effective at reducing mitral regurgitation than conventional surgery, the procedure was associated with superior safety and similar improvements in clinical outcomes. (Funded by Abbott Vascular; EVEREST II ClinicalTrials.gov number, NCT00209274.).

Sudden death due to nonarrhythmic cause in a patient with L-TGA.

We report a case of sudden death in a clinically stable adult with l-transposition of the great arteries (l-TGA). Sudden death has been reported to be the leading cause of death in l-TGA and is often attributed to arrhythmias in the absence of another identifiable cause. However, the contribution of nonarrhythmic causes to the burden of sudden death in this population is unknown. Comprehensive postmortem investigation, including autopsy and pacemaker interrogation, demonstrated that the cause of death was massive pulmonary hemorrhage due to stenosis of the patient's mechanical tricuspid (systemic AV) valve. This report highlights the important contribution of nonarrhythmic causes of sudden death in this population and the value of autopsy and device interrogation in determining true cause of death.

Acute effects of withdrawal of cardiac resynchronization therapy on left and right ventricular function, dyssynchrony, and contractile function in patients with New York Heart Association functional class I/II heart failure: MADIT-CRT.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves left ventricular (LV) function, size, mitral regurgitation, and clinical outcomes. Whether these improvements are due to the short-term effects of improvement in synchrony or contractile performance, or to long-term improvement in ventricular structure and function remains insufficiently elucidated. METHODS AND RESULTS: We used echocardiographic data from 63 patients enrolled in the MADIT-CRT trial who, after 1 year of CRT therapy, underwent echocardiographic evaluation with CRT turned both on and off within minutes. LV volumes, LV ejection fraction, left atrial (LA) volumes, and right ventricular function were assessed at baseline and in the on and off modes within a 5-minute time-frame at 12 months. Speckle-tracking strain analysis was used to assess LV dyssynchrony and contractile function. Interruption of long-term CRT resulted in acute deterioration of LV and RV function and acute increase in LV and LA volumes, although not to baseline. Acute withdrawal was also associated with increased dyssynchrony (SD time to peak transverse strain 178 ± 68 ms vs 195 ± 62 ms; P = .16; and SD time to peak longitudinal strain 108 ± 46 ms vs 125 ± 55 ms; P = .046). However, there was no deterioration in contractile function (global longitudinal strain), which had improved with CRT (-9.8 ± 4.3% vs -10.0 ± 3.7%; P = .93). CONCLUSIONS: Despite substantial LV reverse remodeling with CRT, interruption of long-term CRT after 12 months resulted in an acute worsening of LV size and function, LA volumes, and right ventricular function, with concomitant worsening of ventricular synchrony despite minimal change to the observed improvement in LV strain measures of contractile function. These findings suggest that the beneficial reverse remodeling associated with CRT may be mostly dependent on active pacing, although intrinsic improvements in contractile function may persist beyond termination of pacing.

Echocardiographic predictors of single versus dual MitraClip device implantation and long-term reduction of mitral regurgitation after percutaneous repair.

OBJECTIVES: To describe predictors of the number of MitraClip devices implanted during percutaneous repair of mitral regurgitation (MR), and the long-term reduction in MR. BACKGROUND: In the EVEREST trials, one or two MitraClip devices were implanted to reduce MR, as needed. METHODS: Preprocedural transthoracic echocardiograms (TTE) and transesophageal echocardiograms (TEE) of 233 subjects who received 1 or 2 MitraClip devices in the EVEREST II Randomized Trial and High-Risk Study were analyzed. TEEs were reviewed for etiology of MR and pathoanatomic features of the valve, valve apparatus, and the regurgitant jet. Follow-up MR was assessed by TTE postprocedure and at 12 months. RESULTS: Ninety-seven subjects (42%) had two MitraClip devices implanted. Subjects with quantitatively more severe MR were more likely to receive two devices [mean regurgitant volume (RV) 45.9 ± 21.9 vs. 36.3 ± 18.5 mL, P <0.001]. On multivariate analysis, increased anterior leaflet thickness (OR 1.7 per mm, P = 0.007) and greater baseline RV (OR 1.21 per 10 mL, P = 0.01) were associated with increased odds of implanting two devices. The frequency of 2+ MR or less at discharge was similar regardless of the number of devices implanted. After propensity matching, patients had quantitatively similar MR at twelve-month follow-up, regardless of whether one or two MitraClip devices were implanted (P = 0.6). CONCLUSIONS: Subjects with thicker anterior mitral leaflets and more severe MR were more likely to receive two MitraClip devices. Immediate and long-term reduction in MR was similar regardless of the number of devices implanted at the time of the procedure.

CMR assessment of right ventricular function in patients with combined pulmonary stenosis and insufficiency after correction of tetralogy of Fallot.

BACKGROUND: Tetralogy of Fallot (TOF) is one of the most common types of congenital heart disease and requires prompt surgical correction. Post-correction pulmonary insufficiency (PI) often ensues in adulthood. At times, the PI is accompanied by residual pulmonary stenosis (PS). Little is known regarding right ventricular (RV) function in the setting of combined PS and PI. PURPOSE: To compare cardiac magnetic resonance (CMR) parameters for the assessment of RV function between patients with combined pulmonary stenosis and pulmonary insufficiency (PSPI) and isolated PI following surgical repair of TOF. MATERIAL AND METHODS: Retrospective review of patients with comparable corrected TOF and similar PI was performed. Seventeen patients (median age, 24 years; range, 10-52 years) had combined PSPI and 30 patients (median age, 30 years; range, 6-70 years) had isolated PI. Cine magnetic resonance (MR) images (Philips Medical Systems, Best, The Netherlands) in the short-axis plane were used to calculate end-systolic, end-diastolic, and stroke volumes (RVESV, RVEDV, RVSV) and to measure RV wall thickness. Velocity-encoded cine MR images were used to measure pulmonary regurgitation fraction (PRF) by calculating the ratio of backward flow and total forward flow, obtained from the main pulmonary flow analysis. Peak pressure gradient across the pulmonary valve was obtained from spectral Doppler echocardiography. RESULTS: RVEF was 51 ± 8% in the PSPI patients and 39 ± 11%, in the patients with isolated PI (P = 0.001). Additionally, RV wall thickness was 5.2 ± 0.8 mm in the PSPI patients compared to 2.6 ± 0.9 mm in the isolated PI patients (P = 0.001). RVESVi and RVEDVi were significantly lower (P < 0.05) in patients with combined PSPI (60 ± 21 mL/m(2), 121 ± 35 mL/m(2), respectively) compared to the patients with isolated PI (95 ± 48 mL/m(2), 152 ± 61 mL/m(2), respectively). CONCLUSION: RV function is preserved in patients with PSPI when compared to patients with PI following surgical repair of TOF.

Predictors of response to cardiac resynchronization therapy in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT).

BACKGROUND: We hypothesized that combined assessment of factors that are associated with favorable reverse remodeling after cardiac resynchronization-defibrillator therapy (CRT-D) can be used to predict clinical response to the device. METHODS AND RESULTS: The study population comprised 1761 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). Best-subset regression analysis was performed to identify factors associated with echocardiographic response (defined as percent reduction in left ventricular end-diastolic volume 1 year after CRT-D implantation) and to create a response score. Cox proportional hazards regression analysis was used to evaluate the CRT-D versus defibrillator-only reduction in the risk of heart failure or death by the response score. Seven factors were identified as associated with echocardiographic response to CRT-D and made up the response score (female sex, nonischemic origin, left bundle-branch block, QRS ≥150 milliseconds, prior hospitalization for heart failure, left ventricular end-diastolic volume ≥125 mL/m(2), and left atrial volume <40 mL/m(2)). Multivariate analysis showed a 13% (P<0.001) increase in the clinical benefit of CRT-D per 1-point increment in the response score (range, 0-14) and a significant direct correlation between risk reduction associated with CRT-D and response score quartiles: Patients in the first quartile did not derive a significant reduction in the risk of heart failure or death with CRT-D (hazard ratio=0.87; P=0.52); patients in the second and third quartiles derived 33% (P=0.04) and 36% (P=0.03) risk reductions, respectively; and patients in the upper quartile experienced a 69% (P<0.001) risk reduction (P for trend=0.005). CONCLUSION: Combined assessment of factors associated with reverse remodeling can be used for improved selection of patients for cardiac resynchronization therapy. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

Cardiac-resynchronization therapy for the prevention of heart-failure events.

BACKGROUND: This trial was designed to determine whether cardiac-resynchronization therapy (CRT) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms, a reduced ejection fraction, and a wide QRS complex. METHODS: During a 4.5-year period, we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms. Patients were randomly assigned in a 3:2 ratio to receive CRT plus an implantable cardioverter-defibrillator (ICD) (1089 patients) or an ICD alone (731 patients). The primary end point was death from any cause or a nonfatal heart-failure event (whichever came first). Heart-failure events were diagnosed by physicians who were aware of the treatment assignments, but they were adjudicated by a committee that was unaware of assignments. RESULTS: During an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 patients in the CRT-ICD group (17.2%) and 185 of 731 patients in the ICD-only group (25.3%) (hazard ratio in the CRT-ICD group, 0.66; 95% confidence interval [CI], 0.52 to 0.84; P=0.001). The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy. The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more. CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction. There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups. CONCLUSIONS: CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex. (ClinicalTrials.gov number, NCT00180271.)

Impaired regional left ventricular strain after repair of tetralogy of Fallot.

PURPOSE: To test the potential of magnetic resonance imaging (MRI) in early detection of left ventricular (LV) dysfunction in patients with pulmonary regurgitation and normal LV ejection fraction after repair of tetralogy of Fallot. MATERIALS AND METHODS: Patients (n = 18) with repaired tetralogy of Fallot and pulmonary regurgitation were prospectively recruited. Healthy volunteers (n = 10) were used as control. Tagging MR images were acquired at the base, mid, and apical LV levels for assessing segmental rotation and circumferential strain. Cine MR images and velocity-encoded MR images were also acquired for assessment of biventricular volumes and biventricular function and pulmonary regurgitant fraction, respectively. Mean values were compared between groups using unpaired Student's t-test. RESULTS: Patients presented with preserved global LV function (LVEF of 59 ± 5%). A significant decrease in LV peak circumferential strain was seen in patients compared with normal volunteers at the basilar (-15.6 ± 4.5% vs. -17.6 ± 4.4%; P < 0.01) and apical (-14.4± 6.1% vs. -17.3± 5.1%, P < 0.01) slices. LV peak rotation was also delayed in patients compared with volunteers at the basilar (6.1 ± 2.6° vs. 4.2 ± 0.6°; P < 0.01) and mid (8.0 ± 1.7° vs. 4.9 ± 1.0°; P < 0.01) slices. CONCLUSION: MRI can detect early regional LV dysfunction in patients with preserved LVEF after repair of tetralogy of Fallot. MR may be a useful technique for guiding clinical decisions in these patients in order to prevent future global LV deterioration.

Relationship between improvement in left ventricular dyssynchrony and contractile function and clinical outcome with cardiac resynchronization therapy: the MADIT-CRT trial.

AIMS: To assess long-term effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) dyssynchrony and contractile function, by two-dimensional speckle-tracking echocardiography, compared with implantable cardioverter defibrillator (ICD) only in MADIT-CRT. METHODS AND RESULTS: We studied 761 patients in New York Heart Association I/II, ejection fraction ≤30%, and QRS ≥130 ms [n = 434, CRT-defibrillator (CRT-D), n = 327, ICD] with echocardiographic studies available at baseline and 12 months. Dyssynchrony was determined as the standard deviation of time to peak transverse strain between 12 segments of apical four- and two-chamber views, and contractile function as global longitudinal strain (GLS) by averaging longitudinal strain over these 12 segments. We compared changes in LV dyssynchrony and contractile function between treatment groups and assessed relationships between these changes over the first year and subsequent outcomes (median post 1-year follow-up = 14.9 months). Mean changes in LV dyssynchrony and contractile function measured by GLS in the overall population were, respectively, -29 ± 83 ms and -1 ± 2.9%. However, both LV dyssynchrony (CRT-D: -47 ± 83 ms vs. ICD: -6 ± 76 ms, P < 0.001) and contractile function (CRT-D: -1.4 ± 3.1% vs. ICD: -0.4 ± 2.5%, P < 0.001) improved to a greater extent in the CRT-D group compared with the ICD-only group. A greater improvement in dyssynchrony and contractile function at 1 year was associated with lower rates of the subsequent primary outcome of death or heart failure, adjusting for baseline dyssynchrony and contractile function, treatment arm, ischaemic status, and change in LV end-systolic volume. Each 20 ms decrease in LV dyssynchrony was associated with a 7% reduction in the primary outcome (P = 0.047); each 1% improvement in GLS over the 12-month period was associated with a 24% reduction in the primary outcome (P < 0.001). CONCLUSION: Cardiac resynchronization therapy resulted in a significant improvement in both LV dyssynchrony and contractile function measured by GLS compared with ICD only and these improvements were associated with better subsequent outcomes.

Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: multicenter automatic defibrillator implantation trial: cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) plus implantation of an implantable cardioverter defibrillator (ICD) reduced the risk of death or heart failure event in patients with mildly symptomatic heart failure, left ventricular dysfunction, and wide QRS complex compared with an ICD only. We assessed echocardiographic changes in patients enrolled in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation Trial: Cardiac Resynchronization Therapy) to evaluate whether the improvement in outcomes with CRT plus an ICD was associated with favorable alterations in cardiac size and function. METHODS AND RESULTS: A total of 1,820 patients were randomly assigned to CRT plus an ICD or to an ICD only in a 3:2 ratio. Echocardiographic studies were obtained at baseline and 12 months later in 1,372 patients. We compared changes in cardiac size and performance between treatment groups and assessed the relationship between these changes over the first year, as well as subsequent outcomes. Compared with the ICD-only group, the CRT-plus-ICD group had greater improvement in left ventricular end-diastolic volume index (-26.2 versus -7.4 mL/m(2)), left ventricular end-systolic volume index (-28.7 versus -9.1 mL/m(2)), left ventricular ejection fraction (11% versus 3%), left atrial volume index (-11.9 versus -4.7 mL/m(2)), and right ventricular fractional area change (8% versus 5%; P<0.001 for all). Improvement in end-diastolic volume at 1 year was predictive of subsequent death or heart failure, with adjustment for baseline covariates and treatment group; each 10% decrease in end-diastolic volume was associated with a 40% reduction in risk (P<0.001). CONCLUSIONS: CRT resulted in significant improvement in cardiac size and performance compared with an ICD-only strategy in patients with mildly symptomatic heart failure. Improvement in these measures accounted for the outcomes benefit. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.