Baseline Left Ventricular End-diastolic Volume Research Articles

Impact of baseline left ventricular volume on left ventricular reverse remodeling after cardiac resynchronization therapy.

Left ventricular (LV) dilatation may limit LV reverse remodeling after cardiac resynchronization therapy (CRT). The purpose of this study was to evaluate the impact of baseline LV volumes on LV reverse remodeling after CRT and whether this is associated with improved survival. Patients were stratified into quintiles according to baseline LV end-diastolic volume indexed for body surface area (LVEDVi). LV reverse remodeling was defined as ≥15% reduction in LV end-systolic volume at 6-month follow-up after CRT. Independent associates of LV remodeling were assessed and long-term mortality rates were compared between patients with and without LV reverse remodeling (across LVEDVi quintiles). A total of 864 patients were included (mean age 66 ± 10 years; 657 patients (76%) were male), of whom 101 (12%) were in quintile 1 (<65 mL/m2), 272 (32%) in quintile 2 (65-95 mL/m2), 247 (29%) in quintile 3 (95-125 mL/m2), 151 (18%) in quintile 4 (125-155 mL/m2), and 93 (11%) in quintile 5 (>155 mL/m2). Patients with larger baseline LVEDVi had worse survival after CRT (log-rank, P = .019). The cumulative 10-year survival was significantly better in patients with vs without LV reverse remodeling (48.7% vs 33.9%; P < .001). Significant LV reverse remodeling was observed in all LVEDVi quintiles. In addition, patients with LV reverse remodeling had superior survival than did patients without LV reverse remodeling, regardless of baseline LVEDVi quintile (log-rank, P < .05 for all). Many patients with larger baseline LV volumes still show significant LV reverse remodeling after CRT and had superior survival (regardless of baseline LV volumes) than did patients without LV reverse remodeling. Therefore, CRT should not be denied on the basis of severe LV dilatation.

MitraClip implantation in real-world: clinical relevance of different patterns of left ventricular remodeling

ObjectiveThe role of left ventricular (LV) volumes and ejection fraction (EF) in the selection of patients for the MitraClip procedure remains matter of debate. The goal of this study is to assess the pattern of LV remodeling and its clinical implications after MitraClip procedures, and to evaluate the role of LV ejection fraction (EF) in patient selection. MethodsComplete echocardiography was performed before, at discharge, 1,6, and 12-months in 45 patients treated with MitraClip for severe mitral regurgitation (MR) [age 78.2 ± 8.3 yrs, NYHA 3.74 ± 0.44, EF 36.5 ± 12.8%]. From baseline to 6-month, reverse and adverse LV-R were defined as a ≥15% decrease in LV end-systolic volume and a ≥10% increase in LV end-systolic volume, respectively. ResultsAt 6-month, sustained reduction of MR ≤ 2 was observed in all patients, but two; reverse, adverse, and no LV-R occurred in 51% (N = 23), 18% (N = 8), and 31% (N = 14) of patients, respectively. Baseline LV end-diastolic volume was an independent predictor of reverse LV-R [P = 0.004], whereas EF was not. During follow-up (17.5 ± 9.3 months) period, 50% of adverse/no LV-R patients were free of the composite endpoint (mortality and hospitalization for heart failure) compared to 95.7% of reverse LV-R patients (P = 0.006). In Cox analysis, adverse LV-R and adverse/no LV-R were associated with composite endpoint with adjusted hazard ratios of 5.6 (95% CI 1.65-19.00) and 10.08 (95% CI 1.29–78.6), respectively. ConclusionAfter MitraClip implantation, sustained adverse or no LV-R occurred in one-in-two patients and was associated with poor prognosis. Large LV volumes may help us to avoid the futility of the procedure.

QRS narrowing predicts left ventricular reverse remodelling after resynchronization therapy in patients with end-stage heart failure

Abstract Introduction Cardiac resynchronization therapy (CRT) is an established treatment for heart failure (HF) patients, however one-third of the patients fail to benefit from CRT. The relationship between the QRS duration, severity of mechanical dyssynchrony and efficacy of CRT is not completely understood. We determined if QRS duration shortening after CRT implantation was predictive of left ventricular reverse remodelling. Methods We retrospectively enrolled 227 patients undergoing CRT implantation between 2013 and 2020 according to the guidelines. 88 patients were included in our analysis, from whom all data were available, and these represent our sample. Clinical, electrocardiographic and echocardiographic parameters were evaluated at baseline and after 6 months of CRT implantation. Response to CRT was defined as a reduction in left ventricular end-diastolic volume (LVEDV) &amp;gt;15%. Linear regression models were used. Results 88 patients were included (mean age 69±10 years, 62.5% males, 36.4% ischemic etiology). Baseline left ventricular ejection fraction (LVEF) was 27,5±5,8% and LVEDV was 181±69 ml. After 6 months of CRT, 52 patients (59.1%) were considered responders. Baseline LVEDV was superior in responders when compared with non responders (199±85 ml vs 168±53 ml, p=0.038). No significant differences were noted in male gender (p=0.823), ischemic cardiomyopathy (p=0.065), LVEF (p=0.853), atrial fibrillation (p=0.390), left bundle branch block (p=0.950) or biventricular pacing (p=0.154) between them. QRS duration at baseline was similar between responders and non-responders (165±17 ms vs 163±17 ms, p=0.620). After 6 months of CRT, the reduction of QRS duration in responders was significantly higher than non-responders (p&amp;lt;0.001). QRS duration was reduced from 165±17 ms to 136±15 ms in responders vs 163±17 ms to 160±17 ms in non-responders, (p&amp;lt;0.001). The change in QRS duration positively correlated with the change in LVEDV (0. 654; p&amp;lt;0.001). Multi-linear regression analysis suggested that QRS duration shortening had a significant effect on LVEDV (y = 14,375 + 1.354 X, R2 0.337, p&amp;lt;0.001) Conclusion QRS duration shortening after CRT implantation was predictive of LV reverse remodelling in end-stage heart failure patients. Further prospective studies should be conducted to assess the prognostic value of QRS narrowing in response to CRT. Funding Acknowledgement Type of funding sources: None.

Left Ventricular Enlargement, Cardiac Resynchronization Therapy Efficacy, and Impact of MultiPoint Pacing.

Left ventricular (LV) epicardial pacing results in slowly propagating paced wavefronts. We postulated that this effect might limit cardiac resynchronization therapy efficacy in patients with LV enlargement using conventional biventricular pacing with single-site LV pacing, but be mitigated by LV stimulation from 2 widely spaced sites using MultiPoint pacing with wide anatomic separation (MPP-AS: ≥30 mm). We tested this hypothesis in the multicenter randomized MPP investigational device exemption trial. Following implant, quadripolar biventricular single-site pacing was activated in all patients (n=506). From 3 to 9 months postimplant, among patients with available baseline LV end-diastolic volume (LVEDV) measures, 188 received biventricular single-site pacing and 43 received MPP-AS. Patients were dichotomized by median baseline LVEDV indexed to height (LVEDVIMedian). Outcomes were measured by the clinical composite score (primary efficacy end point), quality of life, LV structural remodeling (↑EF >5% and ↓ESV 10%) and heart failure event/cardiovascular death. LVEDVIMedian was 1.1 mL/cm. Baseline characteristics differed in patients with LVEDVI>Median versus LVEDVI≤Median. Among patients with LVEDVI>Median, biventricular single-site pacing was less efficacious compared to patients with LVEDVI≤Median (clinical composite score, 65% versus 79%). In contrast, MPP-AS programming generated greater clinical composite score response (92% versus 65%, P=0.023) and improved quality of life (-31.0±29.7 versus -15.7±22.1, P=0.038) versus biventricular single-site pacing in patients with LVEDVI>Median. Reverse remodeling trended better with MPP-AS programming. In patients with LVEDVI>Median, heart failure event rate increased following the 3-month randomization point with biventricular single-site pacing (0.0150±0.1725 in LVEDVI>Median versus -0.0190±0.0808 in LVEDVI ≤Median, P=0.012), but no heart failure event occurred in patients with MPP-AS programming between 3 and 9 months in LVEDVI>Median. All measured outcomes did not differ in patients receiving MPP-AS and biventricular single-site pacing with LVEDVI≤Median. Conventional biventricular single-site pacing, even with a quadripolar lead, has reduced efficacy in patients with LV enlargement. However, the greatest response rate in patients with larger hearts was observed when programmed to MPP-AS pacing.

Larger End-Diastolic Volume Associates With Response to Cell Therapy in Patients With Nonischemic Dilated Cardiomyopathy

ObjectiveTo investigate the association of left ventricular end-diastolic volume (LVEDV) and the response to cell therapy in patients with nonischemic dilated cardiomyopathy (NICM). Patients and MethodsFive-year registry data from 133 consecutive patients with NICM who underwent CD34+ cell treatment were analyzed. All patients received granulocyte-colony stimulating factor; CD34+ cells were collected by apheresis and delivered by transendocardial injections. Patients with baseline LVEDV less than 200 mL (group A; n=72) and patients with LVEDV 200 to 370 mL (group B; n=54) were included. Patients with LVEDV greater than 370 mL were excluded (n=7). Favorable ejection fraction response was pre-defined by improvement in left ventricular ejection fraction (LVEF) greater than or equal to 5% at 1 y post-cell therapy. ResultsAt baseline, groups A and B were comparable with regards to age (52±11 y in group A vs 53±10 y in group B; P=.95), sex (male: 79% vs 83%, respectively; P=.55), creatinine (1.07±0.28 mg/dL vs 1.03±0.21 mg/dL, respectively; P=.21), or N-terminal probrain natriuretic peptide (1454±1658 pg/mL vs 1589±1338 pg/mL, respectively; P=.80). Baseline LVEF was higher in group A (32.8±8.7%) than in group B (30.2±8.7%; P=.03). During follow-up, there were four deaths in group A (5.6%), and 2 in group B (3.7%, P=.63). At 1-year post-cell therapy, LVEDV decreased significantly in group B (-56±30 mL; P=.003), but not in group A (+12±97 mL; P=.13). On multivariate analysis, baseline LVEDV was an independent correlate of favorable response in LVEF to therapy (P=.02). ConclusionLarger LVEDV was associated with more pronounced increase in LVEF after transendocardial CD34+ cell therapy in NICM patients, informing target individuals with the highest likelihood of regenerative response. Trial Registrationclinicaltrials.gov identifier: NCT02445534

ST-Segment Resolution and Global Longitudinal Strain as Predictors of LV Remodeling in Patients with ST-Segment Elevation Myocardial Infarction (STEMI)

left ventricular (LV) remodeling after acute myocardial infarction (AMI) is a feared prognostic sequence. Objectives: our goal was to study the possibility of using speckle tracking imaging (STI), especially, global longitudinal strain in predicting LV remodeling. Methods: A total of 82 AMI patients were included in this study. During the first hospital admission after first AMI and at a 6-month follow-up, two-dimensional echocardiography was done. The data was analyzed offline. LV remodeling was defined as ≥15% increase from the baseline LV end-diastolic volume. Results: 34.1% with LV remodeling at 6-month follow-up had similar baseline clinical and echocardiographic characteristics to those without remodeling, except for a predominance of the anterior wall MI (P<0.01), decreased ejection fraction (P<0.05), increased end-systolic volume (P<0.05), and decreased global systolic Ls (P<0.05). Multivariable logistic regression analysis proved that systolic Ls is an independent predictor of remodeling after AMI. Conclusions. Our work has shown that LV longitudinal strain measured by STI is an efficient predictor of LV remodeling after AMI.

Predictors of Left Ventricular Remodeling After Myocardial Infarction in Patients With a Patent Infarct Related Coronary Artery After Percutaneous Coronary Intervention (from the Post-Myocardial Infarction Remodeling Prevention Therapy [PRomPT] Trial)

Left ventricular (LV) remodeling after myocardial infarction (MI) is a strong predictor of heart failure and mortality. The predictors of long-term remodeling after MI have been incompletely studied. We therefore examined the correlates of LV remodeling in patients with large ST-segment elevation myocardial infarction and a patent infarct artery after percutaneous 2coronary intervention (PCI) from the randomized Post-Myocardial Infarction Remodeling Prevention Therapy trial. Peri-infarct pacing had a neutral effect on long-term remodeling in patients with large first MI. The present analysis includes 109 patients in whom an open artery was restored after PCI, and in whom LV end-diastolic volume (LVEDV) at baseline and 18 months was assessed by transthoracic echocardiography. Multivariable models were fit to identify the independent predictors of LVEDV at baseline and 18 months. By multivariable analysis, male sex (p = 0.004) and anterior MI location (p = 0.03) were independently associated with baseline LVEDV. The following variables were independent predictors of increased LVEDV at 18 months: younger age (p = 0.01), male sex (p = 0.03), peak creatine phosphokinase (p = 0.03), shorter time from MI to baseline transthoracic echocardiography (p = 0.04), baseline LVEDV (p < 0.0001), and lack of statin use (p = 0.03). In conclusion, patients with large MI and an open infarct artery after PCI, anterior MI location, and male sex were associated with greater baseline LVEDV, but MI location was not associated with 18-month LVEDV. In contrast, younger age, peak creatine phosphokinase, male sex, baseline LVEDV, and lack of statin use were associated with long-term LV remodeling.

Left ventricular end-diastolic volume as early indicator of trastuzumab-related cardiotoxicity in HER2+ breast cancer patients: results from a single-center retrospective study.

Adjuvant trastuzumab therapy increases survival rates in patients with early HER2-positive breast cancer, although it can be potentially cardiotoxic. The aim of this study was to evaluate the prevalence of left ventricular (LV) systolic dysfunction; and the relationship between the presence of cardiovascular risk factors, cardiac therapy and/or echocardiographic parameters of systolic function at baseline and the development of cardiotoxicity in such patients. A total of 227 patients were retrospectively reviewed. Cardiotoxicity was defined as a decrease in LV ejection fraction (EF) below 50% or an absolute decrease of >10 points below the baseline value or any indication of heart failure. Each patient underwent echocardiography at baseline and at follow-up every three months. The prevalence of cardiotoxicity was 17.6% (15.4% asymptomatic, 2.2% symptomatic). Patients developing LV dysfunction presented hypertension (P=0.041) and diabetes (P=0.01) and used cardiac therapy at baseline more frequently. Smoke habit, age >50 and use of angiotensin-converting enzyme (ACE)-inhibitors, were independent predictors of cardiac damage. Furthermore, patients with LV dysfunction showed baseline LV end-diastolic volume (EDV) higher than those who did not and baseline EDV (OR=1.02; 95% CI: 1.00-1.04; P=0.027) independently predicted cardiotoxicity with 58 mL/m2 as best cut-off point (AUC=0.65, 95% CI: 0.55-0.75]). The prevalence of trastuzumab-related cardiotoxicity in patients with HER2-positive early breast cancer is relatively frequent, although asymptomatic in most cases. Baseline EDV resulted as independent predictor of cardiotoxicity suggesting that EDV may be more reliable than LVEF to identify patients at higher risk of developing cardiac damage.

Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial.

AimsCardiopoietic cells, produced through cardiogenic conditioning of patients’ mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort.Methods and resultsThis multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein–Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann–Whitney estimator 0.54, 95% confidence interval [CI] 0.47–0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200–370 mL (60% of patients) (Mann–Whitney estimator 0.61, 95% CI 0.52–0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death.ConclusionThe primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.

Improved patient selection for cardiac resynchronization therapy by normalization of QRS duration to left ventricular dimension.

This study evaluates the relative importance of two components of QRS prolongation, myocardial conduction velocity and travel distance of the electrical wave front (i.e. path length), for the prediction of acute response to cardiac resynchronization therapy (CRT) in left bundle branch block (LBBB) patients. Thirty-two CRT candidates (ejection fraction <35%, LBBB) underwent cardiac magnetic resonance (CMR) imaging to provide detailed information on left ventricular (LV) dimensions. Left ventricular end-diastolic volume (LVEDV) was used as a primary measure for path length, subsequently QRSd was normalized to LV dimension (i.e. QRSd divided by LVEDV) to adjust for conduction path length. Invasive pressure-volume loop analysis at baseline and during CRT was used to assess acute pump function improvement, expressed as LV stroke work (SW) change. During CRT, SW improved by +38 ± 46% (P < 0.001). The baseline LVEDV was positively related to QRSd (R = 0.36, P = 0.044). Despite this association, a paradoxical inverse relation was found between LVEDV and SW improvement during CRT (R = -0.40; P = 0.025). Baseline unadjusted QRSd was found to be unrelated to SW changes during CRT (R = 0.16; P = 0.383), whereas normalized QRSd (QRSd/LVEDV) yielded a strong correlation with CRT response (R = 0.49; P = 0.005). Other measures of LV dimension, including LV length, LV diameter, and LV end-systolic volume, showed similar relations with normalized QRSd and SW improvement. Since normalized QRSd reflects myocardial conduction properties, these findings suggest that myocardial conduction velocity rather than increased path length mainly determines response to CRT. Normalizing QRSd to LV dimension might provide a relatively simple method to improve patient selection for CRT.

Myocardial Hemorrhage After Acute Reperfused ST-Segment-Elevation Myocardial Infarction: Relation to Microvascular Obstruction and Prognostic Significance.

The success of coronary reperfusion therapy in ST-segment-elevation myocardial infarction (MI) is commonly limited by failure to restore microvascular perfusion. We performed a prospective cohort study in patients with reperfused ST-segment-elevation MI who underwent cardiac magnetic resonance 2 days (n=286) and 6 months (n=228) post MI. A serial imaging time-course study was also performed (n=30 participants; 4 cardiac magnetic resonance scans): 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. Myocardial hemorrhage was taken to represent a hypointense infarct core with a T2* value of <20 ms. Microvascular obstruction was assessed with late gadolinium enhancement. Adverse remodeling was defined as an increase in left ventricular end-diastolic volume ≥20% at 6 months. Cardiovascular death or heart failure events post discharge were assessed during follow-up. Two hundred forty-five patients had evaluable T2* data (mean±age, 58 [11] years; 76% men). Myocardial hemorrhage 2 days post MI was associated with clinical characteristics indicative of MI severity and inflammation. Myocardial hemorrhage was a multivariable associate of adverse remodeling (odds ratio [95% confidence interval]: 2.64 [1.07-6.49]; P=0.035). Ten (4%) patients had a cardiovascular cause of death or experienced a heart failure event post discharge, and myocardial hemorrhage, but not microvascular obstruction, was associated with this composite adverse outcome (hazard ratio, 5.89; 95% confidence interval, 1.25-27.74; P=0.025), including after adjustment for baseline left ventricular end-diastolic volume. In the serial imaging time-course study, myocardial hemorrhage occurred in 7 (23%), 13 (43%), 11 (33%), and 4 (13%) patients 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. The amount of hemorrhage (median [interquartile range], 7.0 [4.9-7.5]; % left ventricular mass) peaked on day 2 (P<0.001), whereas microvascular obstruction decreased with time post reperfusion. Myocardial hemorrhage and microvascular obstruction follow distinct time courses post ST-segment-elevation MI. Myocardial hemorrhage was more closely associated with adverse outcomes than microvascular obstruction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02072850.

Impact on Left Ventricular Function and Remodeling and on 1-Year Outcome in Patients With Left Bundle Branch Block After Transcatheter Aortic Valve Implantation

Conflicting results have been reported about the prognostic impact of left bundle branch block (LBBB) after transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the impact of LBBB after TAVI on left ventricular (LV) function and remodeling and on 1-year outcomes. Of 101 TAVI patients, 9 were excluded. All complications were evaluated according to the Valve Academic Research Consortium 2 definition. Of 92 patients, 34 developed LBBB without more advanced myocardial damage or inflammation biomarkers in comparison with patients without LBBB. The only predictor of new LBBB was larger baseline LV end-diastolic volume. LBBB plus advanced atrioventricular block was strongly correlated with permanent pacemaker implantation (p <0.0001). Patients with LBBB had a higher rate of permanent pacemaker implantation at 30 days (59% vs 19%, p <0.0001) and less recovery of LV systolic function and a trend toward a lower rate of LV reverse remodeling at 1 year. The development of acute kidney injury and the logistic European System for Cardiac Operative Risk Evaluation score were associated with poor outcomes (all-cause mortality and heart failure) (hazard ratio 6.86, 95% confidence interval 2.51 to 18.74, p <0.0001, and hazard ratio 1.04, 95% confidence interval 1.01 to 1.08, p = 0.021, respectively), but not LBBB. In conclusion, after TAVI, 37% of patients developed new LBBB without more advanced myocardial damage or inflammation biomarkers. LBBB was associated with a higher rate of permanent pacemaker implantation, which negatively affected the recovery of LV systolic function. The development of acute kidney injury, rather than LBBB, increases the 1-year risk for mortality and hospitalization for heart failure.

Trial occlusion to assess the risk of persistent pulmonary arterial hypertension after closure of a large patent ductus arteriosus in adolescents and adults with elevated pulmonary artery pressure.

No method is available to predict whether patients with patent ductus arteriosus (PDA) and severe pulmonary arterial hypertension (PAH) will show persistent postprocedural PAH (PP-PAH) after PDA closure. This study evaluated the usefulness of trial occlusion for predicting PP-PAH after transcatheter PDA closure in patients with severe PAH. Trial occlusion was performed in 137 patients (age ≥12 years) with PDA and severe PAH. All patients undergoing trial occlusion had a mean pulmonary artery pressure ≥45 mm Hg, pulmonary:systemic flow (Qp/Qs) ratio >1.5, and pulmonary:systemic resistance (Rp/Rs) ratio <0.7. A total of 135 patients (98%) showing stable hemodynamics during occlusion trial underwent successful device closure. Linear correlation analysis revealed weak or moderate relationships between the baseline and post-trial pulmonary artery pressures and pulmonary:systemic pressure (Pp/Ps) ratios. Patients were followed up for 1 to 10 years (median: 5 years). PP-PAH (systolic pulmonary artery pressure >50 mm Hg by Doppler echocardiography) was detected in 17 patients (13%), who displayed no significant differences in sex and age compared with patients without PP-PAH. According to discriminant analysis, the strongest discriminators between patients with and without PP-PAH were the baseline left ventricular end-diastolic volume and the baseline and post-trial systolic Pp/Ps ratios. In particular, a post-trial systolic Pp/Ps ratio >0.5 correctly classified 100% of the PP-PAH and non-PAH patients. Trial occlusion is a feasible method to predict PP-PAH in patients with PDA and severe PAH. A post-trial systolic Pp/Ps ratio >0.5 indicates a high risk of PP-PAH occurrence after device closure.

Clinical and Procedural Characteristics of Acute Hemodynamic Responders Undergoing Triple-Site Ventricular Pacing for Advanced Heart Failure

The advantages of triple-site ventricular pacing (Tri-V) compared to conventional biventricular site pacing (Bi-V) have been reported. We sought to identify the predictors of acute hemodynamic Tri-V responders. Acute hemodynamic studies were performed in 32 patients with advanced heart failure during Tri-V implantation. After the right ventricular (RV) and left ventricular (LV) leads were implanted for a conventional Bi-V system, an additional pacing lead was implanted in the RV outflow tract for Tri-V. The LV peak +dP/dt and tau were measured during AAI, Bi-V, and Tri-V pacing. A Tri-V responder was defined as a patient whose percentage of increase in the peak +dP/dt during Tri-V was >10% compared to of that during Bi-V. The baseline clinical variables and RV outflow tract lead location were analyzed to identify the characteristics of the Tri-V responders. Of the 32 patients, 10 (31%) were classified as Tri-V responders. The LV end-diastolic volume was greater (246 ± 48 vs 173 ± 53 ml, p <0.01), and the RV outflow tract lead was implanted at a greater outflow tract portion (p <0.05) in the Tri-V responders. Multivariate analysis revealed that only the baseline LV end-diastolic volume (per 50-ml greater) predicted the Tri-V response (odds ratio 2.87, 95% confidence interval 1.03 to 8.00, p <0.05). The area under the receiver operating characteristic curve for the LV end-diastolic volume was 0.84 (p <0.01) and an LV end-diastolic volume of >212 ml had a sensitivity of 80% and specificity of 77% to distinguish Tri-V responders. In conclusion, Tri-V provides greater hemodynamic effect for patients with a larger LV end-diastolic volume owing to its resynchronization effects on the LV anterior wall.

Dilated versus nondilated cardiomyopathy in the elderly population treated with guideline-based medical therapy for systolic chronic heart failure

Background Although the process by which the left ventricular (LV) remodels in response to an injury generally leads to dilatation, in patients with heart failure (HF) the recognition of a small or mildly dilated left ventricle is not uncommon. We investigated the prevalence and the characteristics of elderly patients with traditional dilated and nondilated cardiomyopathy (CMP). We also assessed the response to the guideline-based medical therapy and the prognosis based on LV dilatation in this population. Methods and results We selected 243 patients >70 years of age with HF and LV ejection fraction <40% who underwent clinical and echocardiographic evaluations at baseline and after 12 months. They were subdivided into 2 groups according to baseline LV end-diastolic volume (LVEDV) (values ≤78 mL/m 2 identified nondilated CMP). Nondilated CMP was recognized in 64 patients (26%) who showed at baseline better clinical status, less severe mitral regurgitation, and higher LV ejection fraction than those with dilated CMP. At the final evaluation, favorable changes in clinical and echocardiographic parameters could be detected in both groups. The magnitude of these variations did not differ between the groups. The risk of hospitalization for worsening HF was 2.4-fold higher in patients with nondilated than dilated CMP. Mortality was 11% and 20%, respectively ( P = .06). Statistical analysis revealed a direct, approximately linear relationship between LVEDV and outcomes in this population. Conclusions A total of 1 of 4 elderly patients with systolic HF had a nondilated left ventricle. These patients had a better clinical presentation than did counterparts with dilated left ventricles. After HF therapy is optimized, the likelihood of improvement is independent of LV size in this population, whereas the risk of death or worsening HF linearly increases with LV dilatation.

Men and Women Remodel Differently in Chronic Systolic Heart Failure: Analyses from MIRACLE and MIRACLE-ICD

Background: Predictors of ventricular remodeling are well established in hypertensive heart disease and transmural infarction. Less is known about clinically relevant predictors of remodeling in chronic systolic heart failure. We tested the hypothesis that specific baseline characteristics would predict progressive left ventricular enlargement in a large cohort of patients with chronic systolic heart failure. Methods: MIRACLE (Multicenter InSync Randomized Clinical Evaluation) and MIRACLE-ICD were prospective, double-blind, randomized clinical trials designed to test the efficacy and safety of CRT and combined CRT/ICD therapy in outpatients with chronic systolic heart failure. We combined these studies into a single cohort since the inclusion criteria, mode of CRT, and timing of endpoint assessments were similar. Out of 1008 randomized participants, 776 underwent quantitative echocardiography at baseline and at six months. We used univariate and stepwise multivariable linear regression to determine which baseline characteristics predicted an increase or decrease in left ventricular end diastolic volume (LVEDV) over the subsequent six months. Results: LVEDV increased in 308 (40%) and decreased in 468 (60%) patients. In multivariable models, male gender, severity of mitral regurgitation, and plasma BNP levels were independent predictors of ventricular enlargement after adjustment for baseline LVEDV and randomization to CRT (all p<0.01; see Table for predicted changes in LVEDV). CRT was an independent predictor of a decrease in LVEDV, with greater reduction among patients with longer baseline QRS. In our final model, age and beta-blocker use did not independently predict change in LVEDV. Conclusion: Male gender, mitral regurgitation, and plasma BNP are independent predictors of left ventricular enlargement in chronic systolic heart failure. These findings emphasize the importance of volume load, caused by regurgitant valve lesions or manifested by increased BNP, in mediating ventricular remodeling. Moreover, they demonstrate that men and women may remodel differently, with men showing a higher likelihood of progressive LV enlargement. Further studies are indicated to determine genetic and gender-specific modifiers of ventricular remodeling. Tabled 1 Predicted Change in LVEDV (mL) at Six Months (CRT OFF) Gender MR index Plasma BNP (pg/mL) Male Female 0.1 0.3 100 500 1000 4.5 −19 −0.2 9.1 −6.3 1.1 4.2 Open table in a new tab

Cardiac atrophy after bed-rest deconditioning: a nonneural mechanism for orthostatic intolerance.

The cardiovascular adaptation to bed rest leads to orthostatic intolerance, characterized by an excessive fall in stroke volume (SV) in the upright position. We hypothesized that this large fall in SV is due to a change in cardiac mechanics. We measured pulmonary capillary wedge pressure (PCWP), SV, left ventricular end-diastolic volume (LVEDV), and left ventricular mass (by echocardiography) at rest, during lower-body negative pressure, and after saline infusion before and after 2 weeks of bed rest with -6 degrees head-down tilt (n=12 subjects aged 24+/-5 years). Pressure (P)-volume (V) curves were modeled exponentially by P=ae(kV)+b and logarithmically by P=-Sln[(Vm-V)/(Vm-V0)], where V0 indicates volume at P=0, and the constants k and S were used as indices of normalized chamber stiffness. Dynamic stiffness (dP/dV) was calculated at baseline LVEDV. The slope of the line relating SV to PCWP during lower-body negative pressure characterized the steepness of the Starling curve. We also measured plasma volume (with Evans blue dye) and maximal orthostatic tolerance. Bed rest led to a reduction in plasma volume (17%), baseline PCWP (18%), SV (12%), LVEDV (16%), V0 (33%), and orthostatic tolerance (24%) (all P<.05). The slope of the SV/PCWP curve increased from 4.6+/-0.4 to 8.8+/-0.9 mL/mm Hg (P<.01) owing to a parallel leftward shift in the P-V curve. Normalized chamber stiffness was unchanged, but dP/dV was reduced by 50% at baseline LVEDV, and cardiac mass tended to be reduced by 5% (P<.10). Two weeks of head-down-tilt bed rest leads to a smaller, less distensible left ventricle but a shift to a more compliant portion of the P-V curve. This results in a steeper Starling relationship, which contributes to orthostatic intolerance by causing an excessive reduction in SV during orthostasis.

Evidence of myocardial dysfunction in Bartter's syndrome.

Bartter's syndrome (BS) is characterized by arterial normohypotension despite biochemical and hormonal abnormalities generally associated with hypertension. An abnormal intracellular calcium homeostasis due to a reduced capacity to increase intracellular calcium has been demonstrated by us in BS and proposed as the main pathophysiological factor of the vascular hyporeactivity in BS. The present study was designed to assess whether this altered intracellular calcium homeostasis could also impair contractile recruitment at the myocyte level. Left-ventricular function of patients with BS and normal subjects (C) were studied by quantitative 2-D echocardiography at rest and by postextrasystolic potentiation (PESP), an inotropic stimulus able to recruit the maximal contractile reserve. A group of patients with hypokalemia other than BS (PB) was also included in the study to evaluate the effect of hypokalemia on myocardial contractile recruitment. Baseline left-ventricular end-diastolic volume (EDV) and ejection fraction (EF) did not differ in the 3 groups: EDV: 62 +/- 6 vs. 64 +/- 9 and 60 +/- 12 ml/m2; EF: 64 +/- 9 vs. 67 +/- 8 and 64 +/- 8%. PESP determines an increase of EF in C and PB: 82 +/- 5%, p < 0.01 and 76 +/- 6%, p < 0.01, while in BS it is unchanged: 69 +/- 9% and is reduced in comparison with the increment of myocardial function shown by C and PB (p < 0.01). This study is the first demonstration in BS of a depressed inotropic recruitment causing an exercise-induced left-ventricular dysfunction likely due to an abnormal intracellular calcium homeostasis in the myocytes.

Influence of posture and abdominal pressure on the hemodynamic effects of Mueller's Maneuver

Respiratory distress due to airway obstruction is usually associated with decreased mean intrathoracic pressure, which increases the afterload of the left ventricle. In normal subjects, Mueller's maneuver has been used to study left ventricular volume responses to controlled decreases in intrathoracic pressure. However, reported left ventricular responses have not been uniform. Using first-pass radionuclide ventriculography (RVG), we explored sources of variability, including experimental technique, posture, abdominal pressure, and heart rate in the cardiocirculatory response to Mueller's maneuver (pleural pressure change, −40 to −55 cm H 2O) in normal male volunteers. Individual responses to Mueller's maneuver were highly variable. In seven subjects, compared with the supine posture, the upright posture was associated with increased baseline heart rate and decreased baseline left ventricular end-diastolic volume (LVEDV). During Mueller's maneuver in both postures there was a significant increase in heart rate but no significant change in LVEDV, left ventricular end-systolic volume (LVESV), or left ventricular ejection fraction. In a separate group of seven subjects, Mueller's maneuver was performed in two different ways. The change in mouth pressure was the same, but in one maneuver, abdominal pressure was kept constant and in the other, it was increased. Left ventricular afterload, expressed as arterial minus pleural pressure increased by 36 torr when abdominal pressure increased and increased by 24 torr when abdominal pressure did not change ( P < .01). However, there was no associated difference in the left ventricular responses to Mueller's maneuver. In seven patients, pairs of RVGs were performed serially with no other intevention. For both ejection fraction and LVEDV, there were no significant differences between the first and second RVGs. The range of repeat measurements was far less than that associated with Mueller's maneuver. Although there were no differences in the reponses of LVEDV to Mueller's maneuver for the groups as a whole, when the data were pooled, LVEDV was found to be inversely correlated with change in heart rate during the maneuver (y = 1.1× + 20.8; r = .44; P < .04). We conclude that, in normals, (1)individualleft ventricular responses to Mueller's maneuver are highly variable, (2) little of this variability is inherent in making serial measurements using our techniques, (3) an important source of variability of the left ventricular volume response is the change in heart rate during the maneuver, and (4) neither changes in posture nor changes in abdominal pressure in the range studied are significant determinants of the left ventricular volume response to Mueller's maneuver.