Cardiac resynchronization therapy and outcomes in patients with left ventricular assist devices: a systematic review and meta-analysis.

The impact of cardiac resynchronization therapy (CRT) on clinical outcome in patients with a continuous-flow left ventricular assist device (LVAD) is currently not well understood. We conducted a systematic literature review and meta-analysis with an intention to summarize all published clinical evidence. We searched MEDLINE and EMBASE databases through March 2018 for studies that compared the outcomes in patients with LVAD and CRT. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random-effects model, inverse variance method. The between-study heterogeneity was assessed using the Q statistic and I2. A total of seven studies that included 1157 (575 CRT; 582 non-CRT) patients were identified. Our meta-analysis did not demonstrate a significant difference in the risk of mortality (pooled OR = 1.21, 95% CI 0.90-1.63, P = 0.21), ventricular arrhythmia incidence (pooled OR = 1.36, 95% CI 0.99-1.86, P = 0.06), hospitalization (pooled OR = 1.36, 95% CI 0.59-3.14, P = 0.48), or implantable cardioverter defibrillator therapies (pooled OR = 1.08, 95% CI 0.51-2.30, P = 0.84) among the CRT group compared with the non-CRT group. There was high heterogeneity with an I2 of 75% for ICD therapies. Among LVAD patients, CRT combined did not significantly affect mortality, re-hospitalization, ventricular arrhythmia incidence, and ICD therapies.

Usefulness of Cardiac Resynchronization Therapy in Patients With Continuous Flow Left Ventricular Assist Devices.

The benefit of cardiac resynchronization therapy in patients supported by a left ventricular assist device (LVAD) is unknown. There are currently no guidelines regarding the continuation, discontinuation or pacemaker (PM) settings post-LVAD implant. The aim of the study was to assess the hemodynamic benefit of biventricular (BiV) pacing in LVAD patients. We studied 22 patients supported by LVADs (age 62 ± 9, 21 males) who had received a BiV PM before LVAD implant. A total of 123 complete sets of hemodynamics were obtained during BiV pacing (n = 54), right ventricular (RV) pacing (n = 54), and intrinsic rhythm (n = 15). There were no significant differences in right atrial (RA) pressure, mean pulmonary artery pressure (mPA), PCWP, cardiac output, PA saturation (PASat) and right ventricular stroke work index between BiV and RV pacing. Hemodynamics obtained during intrinsic rhythm in 15 non-PM-dependent patients were not significantly different compared with those obtained during BiV or RV pacing. Furthermore, hemodynamics were similar at different heart rates ranging 50 to 110 beats/min. Right ventricular stroke work index was significantly lower at the highest heart rate compared with baseline and lowest heart rates suggesting decreased RV performance at higher heart rate. In conclusion, BiV pacing does not have any acute hemodynamic benefit compared with RV pacing or intrinsic rhythm in LVAD patients. A lower heart rate may confer better RV performance.

Predictors and prognostic significance of atrial fibrillation developed during dobutamine stress echocardiography: A propensity score-matched comparison.

AIMS: Atrial fibrillation (AF) uncommonly occurs during dobutamine stress echocardiography (DSE). We aimed to characterize the predictors and long-term prognostic significance of AF during DSE. METHODS: The clinical, echocardiographic, and outcome data of patients in sinus rhythm who developed AF during DSE were reviewed and compared to a propensity score-matched group of controls. RESULTS: Atrial fibrillation developed in 73 (1% of 7026) patients (age 70±10 years, 58% men). Compared to 144 propensity score-matched controls without AF during DSE, those with AF were more likely to have had history of prior AF (23% vs 8%, P=.002), known coronary artery disease (CAD; 22% vs 10%, P=.037), enlarged left ventricle (LV; 27% vs 9%, P=.002), LV wall-motion abnormality (33% vs 12%, P<.0001), enlarged aortic root (22% vs 8%, P=.009), or dilated left atrium (52% vs 30%, P=.002). Multivariate logistic regression analysis identified prior history of AF (OR=3.7, 95% CI 1.5-9.0, P=.005), larger LV size (OR=3.1, 95% CI 1.3-7.3, P=.009), and lower LV ejection fraction (OR=-0.95, 95% CI -0.92 to -0.99, P=.02) as independent predictors of AF during DSE. At a mean follow-up period of 3.4 (0.5-7.3) years, those with AF during DSE were more likely to develop new coronary events (22% vs 10%, P=.0372), new-onset heart failure (19% vs 4%, P=.0003), or die from any cause (27% vs 6%, P<.0001). Kaplan-Meier curves demonstrated significantly lower event-free survival in patients compared to controls (P by log-rank test=.001) over the follow-up period. CONCLUSION: Dobutamine-induced AF occurs more commonly in those with prior history of AF and remodeled LV and is associated with unfavorable outcomes.

Venous Stenosis After Transvenous Lead Placement: A Study of Outcomes and Risk Factors in 212 Consecutive Patients.

BACKGROUND: Venous stenosis is a common complication of transvenous lead implantation, but the risk factors for venous stenosis have not been well defined to date. This study was designed to evaluate the incidence of and risk factors for venous stenosis in a large consecutive cohort. METHODS AND RESULTS: A total of 212 consecutive patients (136 male, 76 female; mean age 69 years) with existing pacing or implantable cardioverter-defibrillator systems presented for generator replacement, lead revision, or device upgrade with a mean time since implantation of 6.2 years. Venograms were performed and percentage of stenosis was determined. Variables studied included age, sex, number of leads, lead diameter, implant duration, insulation material, side of implant, and anticoagulant use. Overall, 56 of 212 patients had total occlusion of the subclavian or innominate vein (26%). There was a significant association between the number of leads implanted and percentage of venous stenosis (P=0.012). Lead diameter, as an independent variable, was not a risk factor; however, greater sum of the lead diameters implanted was a predictor of subsequent venous stenosis (P=0.009). Multiple lead implant procedures may be associated with venous stenosis (P=0.057). No other variables approached statistical significance. CONCLUSIONS: A significant association exists between venous stenosis and the number of implanted leads and also the sum of the lead diameters. When combined with multiple implant procedures, the incidence of venous stenosis is increased.

Impact of clinical predictors and routine coronary artery disease testing on outcome of patients admitted to chest pain decision unit.

BACKGROUND: Chest pain decision unit (CDU) evaluation of patients with acute chest pain (ACP) and nondiagnostic electrocardiogram (ECG) usually includes noninvasive testing for coronary artery disease (CAD). HYPOTHESIS: CAD evaluation will not improve clinical outcome in low-risk ACP patients. METHODS: We studied 459 adults admitted to CDU with ACP and no troponin release who underwent noninvasive CAD testing (stress testing in 396 and coronary computed tomographic angiography in 63). Multivariate logistic regression was used to determine predictors of adverse outcome over a 3-year follow-up period. RESULTS: Initial noninvasive test was normal in 367 (80%) and abnormal (positive or indeterminate) in 92 (20%). A total of 42 (9%) patients underwent invasive coronary angiography, and 16 (3.5%) underwent revascularization. During follow-up, 33 patients had a total of 36 major clinical events: 12 revascularizations, 9 myocardial infarctions, and 15 deaths. Multivariate logistic regression analysis identified abnormal ECG (odds ratio [OR]: 2.7, P = 0.03), typical chest pain (OR: 3.8, P = 0.002), diabetes (OR: 4.1, P = 0.001), and known CAD (OR: 2.3, P = 0.03) as independent predictors for adverse outcome, but not noninvasive test result. Thus, in 187 patients with no high-risk features (41% of the cohort), the annualized event rate was 0.5%. In 272 patients with at least 1 high-risk feature, annualized event rates were 2.8% and 5.7% when noninvasive test was normal or abnormal, respectively (P = 0.04). CONCLUSIONS: Clinical risk stratification allows identification of patients at low risk of adverse outcome over an intermediate period of follow-up. Noninvasive testing is not warranted in such patients.

Dobutamine-induced myocardial ischemia and ST-segment elevation in collateral-dependent myocardium.

In patients with obstructive coronary artery disease, electrocardiographic (ECG) ST-segment elevation (STE) is frequently seen during dobutamine stress echocardiography (DSE) in leads overlying previous transmural left ventricular (LV) myocardial infarction. The mechanism of occasional STE during DSE in LV region with inducible myocardial ischemia and no previous myocardial infarction has not been well delineated. We retrospectively identified 28 adults (age 51 to 83 years [69 ± 8]; 82% men) with STE (>1 mm at ≥80 ms after J point in ≥2 contiguous leads without pathologic Q waves) and inducible myocardial ischemia in the same territory during DSE. STE occurred in inferior (n = 16), inferolateral (n = 8), anterior (n = 1), lateral (n = 2), or anterolateral (n = 1) leads and was associated with ischemic symptoms in 17 patients (61%). Inducible LV wall motion abnormality developed in LV segments corresponding to ECG STE in all patients. Coronary arteriography (within 1 week of the index DSE) showed severe luminal narrowing in the major epicardial coronary artery supplying the region with DSE STE and ischemia (90% to 99% in 9 patients [32%] and 100% in 19 patients [68%]). The ischemic region was supplied by ipsilateral (n = 4 [14%]), contralateral (n = 21 [75%]), or both ipsilateral and contralateral (n = 3 [11%]) collateral branches. In conclusion, dobutamine-induced ECG STE in LV segments with normal baseline wall motion is a highly reliable marker of viable collateral-dependent myocardium.

Impact of ß(1)- and ß(2)-adrenergic receptor gene single nucleotide polymorphisms on heart rate response to metoprolol prior to coronary computed tomographic angiography.

A slow, steady heart rate (HR) is necessary for optimal image quality during coronary computed tomographic angiography. Beta blockers are often used, but the goal HR is not achieved in some patients. The aim of this study was to examine the influence of single-nucleotide polymorphisms (SNPs) of the ß(1) (codons 49 and 389) and ß(2) (codons 16, 27, and 164) adrenergic receptor (AR) genes on HR response to metoprolol in 200 adults (mean age 56 ± 11 years) referred for coronary computed tomographic angiography (using a 64-slice scanner). Oral and intravenous (IV) metoprolol was given to achieve a goal HR of <60 beats/min. Overall, 37 patients (18.5%) did not reach the goal HR despite the administration of oral (181 ± 116 mg) and IV (4.2 ± 9.4 mg) metoprolol. Patients with the ß(1)-AR Ser49Gly or Gly49Gly genotype (n = 49) more often failed to reach an optimal HR compared to those with the Ser49Ser genotype (n = 151) (29% vs 15%, p = 0.04), despite receiving higher doses of oral (210 ± 115 vs 172 ± 115 mg, p = 0.048) and IV (7 ± 13 vs 3 ± 8 mg, p = 0.02) metoprolol. Similarly, patients with the ß(1)-AR Gly389Gly genotype (n = 11) more often failed to reach an optimal HR compared to those with the Arg389Arg and Arg389Gly genotypes (n = 189) (45% vs 17%, p = 0.02), despite receiving higher doses of IV (13 ± 15 vs 4 ± 9 mg, p = 0.002) but not oral (162 ± 105 vs 182 ± 117 mg, p = 0.50) metoprolol. Multivariate analysis identified ß(1)-AR SNPs at codons 49 and 389 and ß(2)-AR SNP at codon 27 as independent predictors of suboptimal HR response. In conclusion, these data indicate that the selected SNPs of ß(1)-AR and ß(2)-AR genes influence HR response to metoprolol in patients who undergo coronary computed tomographic angiography.

Improved diabetic control in advanced heart failure patients treated with left ventricular assist devices.

AIMS: Left ventricular assist devices (LVADs) are increasingly used as therapeutic options for patients with advanced congestive heart failure (CHF), many of whom suffer from diabetes mellitus (DM). The aim of this study was to evaluate the effect of restoration of normal cardiac output using LVAD support on diabetes control in patients with advanced CHF. METHODS AND RESULTS: A retrospective chart review of all clinic patients supported with long-term LVADs between July 2008 and July 2009 at Columbia University Medical Center was performed. Patients with DM diagnosed prior to device implantation were included in this analysis. Clinical and laboratory data within 1 month preceding and 6 months following LVAD implantation were collected. Of 43 LVAD patients followed in our clinic during the study period, 15 had a diagnosis of DM. Thirteen of the 15 patients were male, mean age was 63 ± 11 years, and the pre-LVAD left ventricular ejection fraction (LVEF) was 16.5 ± 5.7%. Fasting glucose levels, HbA1c, and daily insulin requirement within 1 month before and an average of 4.0 ± 2.3 months after LVAD placement were 157.7 ± 50.6 vs. 104.1 ± 21.4 mg/dL, 7.7 ± 0.9 vs. 6.0 ± 0.8.%, and 53.3 ± 51.7 vs. 24.2 ± 27.2 IU, respectively (P < 0.05 for all comparisons). Six of the 15 patients were completely free of antidiabetic medications and had blood glucose < 126 mg/dL as well as HbA1c < 6% after LVAD. Body mass index (BMI) was slightly increased after LVAD (28.7 ± 5.3 vs. 30.2 ± 4.1 kg/m², P NS). CONCLUSION: Restoration of normal cardiac output after LVAD implantation improves diabetic control in patients with advanced CHF. Additional studies are warranted to determine the mechanisms that worsen or possibly induce DM in patients with advanced CHF.

Mediastinal radiation and adverse outcomes after heart transplantation.

Orthotopic heart transplantation (OHT) may represent the only treatment option for patients with end-stage cardiovascular disease due to mediastinal radiation therapy (MRT). The primary aim of this study was to evaluate the safety and efficacy of OHT in this patient population. We conducted a retrospective, single-center cohort study of patients with MRT-associated cardiovascular disease who underwent OHT between January 1987 and September 2008. Nine patients (3 men), aged 46 +/- 11 years at the time of their OHT, were identified. Time from MRT to OHT was 26 +/- 11 years. Lymphoma was the indication for MRT in all patients. Five patients had non-ischemic dilated cardiomyopathy, 2 had ischemic cardiomyopathy and 2 had constrictive pericarditis. Three patients expired in the peri-operative period, whereas another patient died 3 years post-transplant from lung carcinoma. Two additional patients developed a secondary malignancy post-transplant. Five patients are still alive at a mean follow-up of 10 +/- 8 years. Early survival rate is poor in patients who undergo OHT for MRT-associated end-stage cardiovascular disease. In addition, long-term follow-up shows an elevated incidence of malignancies. Our results raise concern about the safety and efficacy of performing OHT in patients with MRT-associated cardiovascular disease.

Heart transplantation in human immunodeficiency virus-positive patients.

BACKGROUND: Human immunodeficiency virus (HIV) infection is widely considered a contraindication for cardiac transplantation. However, with the newer anti-retroviral drugs, the estimated 10-year survival after seroconversion is exceeds 90%. This case series describes the intermediate range outcome of HIV-positive cardiac transplant recipients. METHODS: A retrospective analysis of 1679 cardiac transplant patients was undertaken to identify HIV-positive recipients. RESULTS: Seven patients were identified. Five (4 men) were diagnosed with HIV before transplantation and 2 patients seroconverted after transplantation. Dilated cardiomyopathy was the indication for transplant in all patients. The 5 HIV recipients were aged 42 +/- 8 years, and time after HIV seroconversion averaged 9.5 years. All underwent cardiac transplantation as high-risk candidates. The CD4 count was 554 +/- 169 cells/microl, and viral load was undetectable in all patients at the time of transplantation. Two patients seroconverted to HIV-positive status at 1 and 7 years after transplant. No AIDS-defining illness was observed in any patient before or after transplant. Six patients received highly active anti-retroviral therapy. Viral load remained low in the presence of immunosuppression. All patients are alive with a follow-up from transplant of 57 +/- 78.9 months. CONCLUSION: Excellent intermediate term outcome is noted in carefully selected HIV-positive patients. No significant AIDS-related infections or complications occurred.