Advanced Ischemic Cardiomyopathy Research Articles

Evaluation of Photobiomodulation on myocardial function of patients with advanced ischemic cardiomyopathy, A case series

BackgroundHeart failure is a growing cardiovascular disease burden with high mortality rates, primarily attributed to myocardial ischemia. Previous studies have shown promising effects of Photobiomodulation in heart failure treatment. In this study, we aimed to investigate the effect of Photobiomodulation on myocardial function of patients with advanced ischemic heart failure. MethodA non-randomized case series study involving 10 advanced heart failure patients was conducted. Patients received 15 sessions of transcutaneous and intravenous Photobiomodulation therapy using low-level red (658 nm) and infrared lasers (810 nm). All participants were evaluated by six-minute walk tests, dyspnea function classes, and echocardiography. 3 months after the sessions, the mentioned tests were reevaluated ResultThe study included ten cardiomyopathic patients, 90 % male and the mean age was 63.20±6.01 years. The six-minute walk test change and shortness of breath function class change has 0.852 (p-value=0.006) correlation and the correlation between the Six-minute walk test change and the Systolic ejection fraction rate change, was 0.73 (p-value=0.025). ConclusionBased on the results of the study, it can be concluded that interventions in cardiomyopathic patients have shown promising improvements in certain cardiac function parameters. Specifically, the significant enhancement in the six-minute walk test post-intervention (p = 0.013) suggests a positive impact on functional capacity. Although the increase in systolic ejection fraction rate was not statistically significant (p = 0.197), the correlations identified provide valuable insights into the interplay between variables such as shortness of breath function class and the six-minute walk test. These findings underscore the complexity of managing cardiomyopathy and highlight the importance of further research to elucidate the relationships between different clinical parameters and patient outcomes in this population.

Impact of Cardiac Magnetic Resonance Left Atrial Ejection Fraction in Advanced Ischemic Cardiomyopathy

BackgroundThe prognostic significance of cardiac magnetic resonance (CMR)-based left atrial ejection fraction (LAEF) is not well defined in the ischemic cardiomyopathy (ICM) cohort. ObjectivesThe authors sought to assess the prognostic impact of LAEF, when adjusted for left ventricular remodeling, myocardial infarct size (MIS), left atrial volume index, and functional mitral regurgitation (FMR), on outcomes in patients with advanced ICM. MethodsICM patients who underwent CMR were retrospectively evaluated (April 2001-December 2019). LAEF, left atrial volume index, MIS, left ventricular remodeling, and FMR were derived from CMR. The primary clinical endpoint was a composite of all-cause mortality and cardiac transplant. A baseline multivariable Cox proportional hazards regression model was constructed to assess prognostic power of LAEF. ResultsThere were 718 patients (416 primary events) evaluated, with a median duration of follow-up of 1,763 days (4.8 years) and a mean LAEF of 36% ± 15%. On multivariable analysis, higher LAEF was independently associated with reduced risk (HR: 0.24, 95% CI: 0.12-0.48, P < 0.001), even after adjusting for FMR and MIS. The highest adjusted risk was observed in patients with an LAEF <20% and an MIS of >30% (HR: 3.20, 95% CI: 1.73-5.93). The lowest risk was in patients within the comparator group with an LAEF of >50% and a MIS of <15% (HR: 1.07, 95% CI: 0.81-1.42). ConclusionsReduced LAEF is independently associated with increased mortality in ICM. Risk associated with declining LAEF is continuous and incremental to other risk factors for adverse outcomes in patients with ICM even after adjusting for MIS and FMR severity.

Programmatic approach to patients with advanced ischemic cardiomyopathy: Integrating microaxial support into strategies for the modern era.

Patients with advanced ischemic cardiomyopathy manifesting as left ventricular dysfunction exist along a spectrum of severity and risk, and thus decision-making surrounding optimal management is challenging. Treatment pathways can include medical therapy as well as revascularization through percutaneous coronary intervention or coronary artery bypass grafting. Additionally, temporary and durable mechanical circulatory support, as well as heart transplantation, may be optimal for select patients. Given this spectrum of risk and the complexity of treatment pathways, patients may not receive appropriate therapy given their perceived risk, which can lead to sub-satisfactory outcomes. In this review, we discuss the identification of high-risk ischemic cardiomyopathy patients, along with our programmatic approach to patient evaluation and perioperative optimization. We also discuss our strategies for therapeutic decision-making designed to optimize both short- and long-term patient outcomes.

Abstract 13337: Left Atrial Ejection Fraction by Cardiac Magnetic Resonance Imaging as a Predictor of Adverse Outcomes in Patients With Advanced Ischemic Cardiomyopathy

Background: The prognostic significance of cardiac magnetic resonance (CMR) based left atrial ejection fraction (LAEF) is not well defined in the ischemic cardiomyopathy (ICM) cohort.We assess the additive effect of LAEF in a model to predict outcomes in patients with ICM. Methods: Patients with ICM, who underwent CMR between April 2001 and March 2019 were retrospectively included. Clinical characteristics and CMR parameters were collected and analyzed and LAEF was calculated in addition to myocardial infarct size (MIS) using late gadolinium enhancement (LGE) and CMR based mitral regurgitant fraction (MRF). The primary clinical endpoint was a composite of all-cause mortality and cardiac transplant. A multiple-variable Cox proportional hazards regression model which included established predictors of outcome was constructed, followed by the addition of LAEF. Four pre-specified interactions of LAEF with left ventricular end systolic volume index (LVESVi), MIS and mitral regurgitant fraction (MRF) were tested at a significance level of 0.05. RESULTS: LA functional data was measured in 718 patients. There were 416 deaths and/or transplants, with a median duration of follow up of 1763 days (4.8 years) The mean LA EF was 36 [2 ,74]. In univariate analysis, lower LAEF and higher LAVI were significant predictors of worse outcome, HR= 0.12, 95% CI [0.06, 0.25], p&lt;0.001; HR 1.008, (1.003-1.014) p = 0.003. After addition to the multivariable model, a normal LAEF was highly predictive of reduced risk, HR 0.24, (0.12, 0.48), p&lt;0.001. In the interaction between LAEF and MIS with MR Fraction, the highest risk was observed in patients with an LAEF &lt; 20% and an MIS of &gt; 30%, with MR Fraction of &gt;35%, HR of 3.2 (1.73-5.93), p= 0.009. The lowest risk was in patients with an LAEF of &gt;50% with an MIS of &lt;15 and MR Fraction of &lt;35%, HR 1.07 (0.81-1.42), p=0.009. Figure 1. CONCLUSION: Reduced LAEF is an important predictor of increased mortality in patients with ICM and additive to MIS and MR Fraction.

Nucleolar stress: Friend or foe in cardiac function?

Studies in the past decades have uncovered an emerging role of the nucleolus in stress response and human disease progression. The disruption of ribosome biogenesis in the nucleolus causes aberrant nucleolar architecture and function, termed nucleolar stress, to initiate stress-responsive pathways via nucleolar release sequestration of various proteins. While data obtained from both clinical and basic investigations have faithfully demonstrated an involvement of nucleolar stress in the pathogenesis of cardiomyopathy, much remains unclear regarding its precise role in the progression of cardiac diseases. On the one hand, the initiation of nucleolar stress following acute myocardial damage leads to the upregulation of various cardioprotective nucleolar proteins, including nucleostemin (NS), nucleophosmin (NPM) and nucleolin (NCL). As a result, nucleolar stress plays an important role in facilitating the survival and repair of cardiomyocytes. On the other hand, abnormalities in nucleolar architecture and function are correlated with the deterioration of cardiac diseases. Notably, the cardiomyocytes of advanced ischemic and dilated cardiomyopathy display impaired silver-stained nucleolar organiser regions (AgNORs) and enlarged nucleoli, resembling the characteristics of tissue aging. Collectively, nucleolar abnormalities are critically involved in the development of cardiac diseases.

“Stable” Asystole In A Patient With Left Ventricular Assist Device

The use of Left Ventricular assist devices (LVADs) for mechanical circulatory support has become a standard therapy for some patients with end-stage heart failure. Although presentation and consequences of ventricular arrhythmias (VA) in LVAD supported patients are well described and often stabilized by the mechanical support, presence of asystole is less commonly reported. Our patient is a 75-year-old male with advanced ischemic cardiomyopathy requiring cardiac resynchronization therapy-defibrillator (CRT-D) and ultimately HeartMate II LVAD. Post implantation, his CRT-D was abandoned after it reached the elective replacement indicator as he had no VAs and was not pacer dependent. He now presented with a new onset of low flow alarms that started earlier in the day. He appeared stable, pleasant and in a humorous mood. He reported lightheadedness but denied syncope. While in the ED, the patient was noted to be asystolic. His mean arterial pressure was in the 50s. Physical exam was unremarkable with the expected LVAD hum and lack of pulses. LVAD parameters revealed decreased Flow (2.5 from baseline 5.1) and Pulsatility Index (2.7 from baseline 4.9). Patient subsequently underwent implantation of a new battery with reactivation of his previously abandoned pacemaker leads with resultant hemodynamic improvement. Ultimately, he was discharged home in stable condition. Discussion: Very few cases of asystolic LVAD patients without immediate hemodynamic collapse are described. Similarly to ventricular arrhythmias, the hypothesized physiology for stability is this quasi-Fontan circulation, where low pulmonary vascular resistance with elevated central venous pressure allows pulmonary vasculature perfusion and left atrial filling. In this case, low flow alarms and decreased PI were due to decreased left ventricular preload in the setting of asystole. Ventricular arrhythmias remain common after LVAD implantation, asystole, as in the present case can equally be an issue. This is particularly true as many of LVAD supported patients have CRT-Ds implanted in the setting of pre-existent left bundle branch blocks, which can progress to complete heart block or asystole. Thus, It might not always be the case that LVAD supported patients don't benefit from maintaining ICD function. Conclusion: Traditionally unstable asystole and ventricular arrhythmia can be well tolerated in the LVAD population due to quasi-Fontan physiology. ICD role in LVAD patients is currently unclear, and should be a part of shared decision making with the patient. Yes, there may be such a thing as, "stable" asystole.

Abstract 12147: Prognostic Impact of Cardiac MRI Derived Left Atrial Volumetric and Functional Parameters in Patients With Advanced Ischemic Cardiomyopathy

Background: Left atrial (LA) size has been shown to be predictive of adverse outcomes in patients with various cardiac conditions. However, the significance of left atrial function (LAF) is not clearly defined in patients with advanced ischemic cardiomyopathy (ICM). We assess the effect of cardiac magnetic resonance imaging (CMR) based LA ejection fraction (LAEF), LA volume index (LAVi) and total LA strain(Las) on outcomes in patients with ICM. Methods: Patients with ICM, who underwent cardiac magnetic resonance (CMR) between January 2002 and January 2017, were included in our study. Clinical characteristics and CMR parameters were collected and analyzed. Maximum and minimum left atrial volume (LAV) and LAEF were calculated using the biplane area-length method. Multi-variable Cox proportional hazards models were then built to test whether LAEF, LAs, and LAVi predict all-cause mortality or time to transplant. The proportionality assumption test and supremum test for functional form were used to verify the model. Results: LA functional data on 656 patients were analyzed. Patients were followed for a median of 1900 days (5.2 years). There were 336 deaths and 17 transplants. LAEF and Las were significant predictors of outcome: HR=0.98, 95% CI [0.97, 0.99], p&lt;0.001 , HR=0.94, 95% CI [0.91, 0.96], p&lt;0.001) respectively. LAVi was not an independent predictor of survival after adjusting for the medical risk score (p=0.749). Multivariable Cox proportional analysis and ROC analysis for the prediction of death or transplant of the model within two years is shown in Figure 1. Conclusion: Left atrial function is a more powerful predictor of adverse outcome than left atrial size and ischemic mitral regurgitation. Further studies are needed to assess impact of treatment on LA function.

Hepatic portal vein gas detected by point of care ultrasound.

IntroductionPortal venous gas is a rare finding in adults and is typically associated with underlying intestinal ischemia. Portal venous gas can be detected by a bedside point of care ultrasound (POCUS) examination in adult patients in critical care units (CCU). Findings include echogenic bubbles flowing centrifugally throughout the portal venous system.Case presentationWe present the case of a 73-year-old female with advanced ischemic cardiomyopathy and cardiorenal syndrome who was managed in the CCU. She developed vague abdominal pain and respiratory depression requiring intubation and dialysis during her course of treatment in the CCU. Her findings were consistent with portal venous gas upon POCUS, prompting computed tomography of her abdomen and surgical consultation. She was ultimately found to have nonobstructive mesenteric ischemia.Clinical discussionPVG is an ominous radiological sign and reflects intestinal ischemia in up to 72% of cases. Acute mesenteric ischemia of the small bowel could be due to occlusive or nonocclusive obstruction of the arterial blood supply or obstruction of venous outflow. Nonocclusive obstruction accounts for 5% to 15% of patients with acute mesenteric ischemia.ConclusionWith the increasing use of POCUS, critical care physicians should be aware of findings consistent with portal venous gas as a bedside tool for directing the treating physician toward an ominous diagnosis in patients with shock.

Ventricular remodeling in ischemic heart failure stratifies responders to stem cell therapy.

Response to stem cell therapy in heart failure is heterogeneous, warranting a better understanding of outcome predictors. This study assessed left ventricular volume, a surrogate of disease severity, on cell therapy benefit. Small to large infarctions were induced in murine hearts to model moderate, advanced, and end‐stage ischemic cardiomyopathy. At 1 month postinfarction, cardiomyopathic cohorts with comparable left ventricular enlargement and dysfunction were randomized 1:1 to those that either received sham treatment or epicardial delivery of cardiopoietic stem cells (CP). Progressive dilation and pump failure consistently developed in sham. In comparison, CP treatment produced significant benefit at 1 month post‐therapy, albeit with an efficacy impacted by cardiomyopathic stage. Advanced ischemic cardiomyopathy was the most responsive to CP‐mediated salvage, exhibiting both structural and functional restitution, with proteome deconvolution substantiating that cell therapy reversed infarction‐induced remodeling of functional pathways. Moderate cardiomyopathy was less responsive to CP therapy, improving contractility but without reversing preexistent heart enlargement. In end‐stage disease, CP therapy showed the least benefit. This proof‐of‐concept study thus demonstrates an optimal window, or “Goldilocks principle,” of left ventricular enlargement for maximized stem cell‐based cardiac repair. Disease severity grading, prior to cell therapy, should be considered to inform regenerative medicine interventions.

Circulatory support and stem cell therapy in the management of advanced heart failure: a concise review of available evidence.

Stem cell therapy utilizing bone marrow mononuclear cells (BMC's) is a potential strategy to treat heart failure patients with improvement in symptom profile and cardiac function. We describe a rationale for concurrent BMC and left ventricular assist device therapy in selected heart failure patients. This combination therapy has demonstrated improved myocardial perfusion and cardiac function in patients with advanced ischemic cardiomyopathy. Moreover, preclinical data support improved cell retention with left ventricular unloading. The beneficial effects of BMC's are likely through a paracrine mechanism initiating a 'cardiac-repair' process. Combination therapy of BMC's and a left ventricular assist device may exhibit a synergistic effect with improved engraftment of BMC's through left ventricular unloading.

Jeopardized Myocardium Defined by Late Gadolinium Enhancement Magnetic Resonance Imaging Predicts Survival in Patients With Ischemic Cardiomyopathy: Impact of Revascularization.

BackgroundThe prognostic impact of jeopardized myocardium (JM) in patients with advanced ischemic cardiomyopathy (ICM) is unclear. We hypothesized that JM is an independent predictor of mortality in patients with advanced ICM.Methods and ResultsPatients with ICM who underwent cardiac magnetic resonance imaging between January 2002 and January 2013 were included in our study. JM was identified as a vascular territory with <50% myocardial scarring on cardiac magnetic resonance imaging and with >70% stenosis in a major coronary vessel that was not subsequently revascularized. A propensity score was developed for revascularization. A multivariable Cox proportional hazards model was used to evaluate the association of JM with all‐cause mortality. We evaluated 631 patients over a mean follow‐up of 5.1 years. Overall, 336 patients underwent subsequent revascularization during the follow‐up period, among whom 23% had remaining JM, while 295 patients were medically treated (57% with JM). There were 204 deaths (32%). On multivariable analysis, JM (hazard ratio, 1.88; 95% confidence interval, 1.38–2.55 [P<0.001]) was independently associated with all‐cause mortality after adjusting for multiple other factors. The risk associated with the presence of JM increased by 5% for every 10‐unit increase in left ventricular end‐systolic volume index.Conclusions JM is an independent and incremental predictor of mortality in patients with advanced ICM. Patients undergoing revascularization with residual JM had similar risk of mortality compared with medically treated patients with JM. The risk associated with JM significantly increased in the presence of worsening adverse left ventricular remodeling. Cardiac magnetic resonance viability assessment may provide important risk stratification in patients with ICM.

Initial Slovenian experience with MitraClip therapy : Careful selection of patients is crucial for optimal outcome.

MitraClip is a percutaneous mitral repair technology increasingly used for high surgical risk patients with primary or secondary mitral regurgitation. We describe initialSlovenian experiencewith MitraClip and discuss the importance of identifying the suitable candidates for this procedure. We retrospectively analyzed the first 10 patients (mean age 75.6± 6.9 years, logistic Euroscore 28.4± 10.9%) with severe and moderate to severe mitral regurgitation (8secondary, 1primary and 1mixed etiology) who underwent a MitraClip procedure between January 2015 and February 2017. Acute reduction of mitral regurgitation was achieved in all but one patient (90%). There were no periprocedural mortalities and at short to mid-term follow-up (median 12months, interquartile range3-15 months). In eight patients improvement of functional class was observed at discharge. No functional improvement was achieved in apatient with advanced ischemic cardiomyopathy, and in apatient with degenerative mitral disease in whom the MitraClip procedure had failed necessitating mitral valve surgery. One patient experienced late leaflet detachment and was effectively managed with a second MitraClip procedure. There were two vascular complications at the access site and one percutaneous closure of an iatrogenic atrial septal defect. Our initial experiences with asmall number of patients indicate that percutaneous mitral repair with MitraClip is afeasible and safe method in high-risk patients. Special attention should be paid to careful patient selection including detailed echocardiographic evaluation of mitral valve anatomy, technical performance and final result, particularly at the beginning of the learning curve in order to reduce the rate of serious complications.

Predictors of Mortality in Patients With Severe Ischemic Cardiomyopathy Undergoing Surgical Mitral Valve Intervention.

BackgroundIschemic mitral regurgitation is associated with substantial risk of death. Although surgical mitral valve intervention (MVi) may improve symptoms, it has not been shown to improve survival. The aim of this study was to identify predictors of mortality in patients with ischemic mitral regurgitation and MVi.Methods and ResultsWe evaluated 117 consecutive patients (age, 65±10 years) with advanced ischemic cardiomyopathy who underwent cardiac magnetic resonance and subsequent MVi between January 1, 2002 and January 1, 2012. Cardiac magnetic resonance was used to assess left ventricular remodeling and myocardial scarring. The effective regurgitant orifice area was calculated from the proximal isovelocity surface area by echocardiography. There were 43 deaths (37%) during follow‐up (median, 62 months). On multivariable analysis, age ≥70 years (P=0.013), diabetes mellitus (P=0.001), dyslipidemia (P=0.012), papillary muscle scar (P=0.010), incomplete revascularization (P=0.001), and total scar %×effective regurgitant orifice area ≥0.20 cm2 (P=0.005) were each independently associated with all‐cause mortality. Although patients with effective regurgitant orifice area <0.2 cm2 at baseline demonstrated an increased hazard ratio of 3.3 for every 10% increase in scar, the hazard ratio increased to 9 for every 10% increase in scar in those with baseline effective regurgitant orifice area ≥0.20 cm2. Mortality also was significantly higher in patients with incomplete revascularization compared with those with vascularized viable myocardium (61% versus 28%; P<0.001).ConclusionsIncreased total scar burden and the presence of incomplete revascularization are powerful predictors of mortality in patients with advanced ischemic cardiomyopathy undergoing MVi. Viability assessment with cardiac magnetic resonance imaging can identify which patients with ischemic mitral regurgitation are at highest risk for mortality after surgical MVi.

Sustained Placental Growth Factor-2 Treatment Does Not Aggravate Advanced Atherosclerosis in Ischemic Cardiomyopathy.

Angiogenic growth factor therapy for ischemic cardiovascular disease carries a risk of stimulating atherosclerotic plaque growth. We evaluated risk benefit ratio of sustained administration of recombinant human placental growth factor (rhPlGF)-2 in mice with advanced atherosclerosis and chronic ischemic cardiomyopathy. We maintained apolipoprotein E-deficient mice on a high cholesterol diet and induced myocardial infarction by transient ligation at 4weeks. At 8weeks, we assessed left ventricular (LV) function and randomized mice to receive rhPlGF-2 or vehicle (VEH) subcutaneously for 28days. Administration of rhPlGF-2 significantly increased PlGF plasma levels without adverse hemodynamic or systemic inflammatory effects. RhPlGF-2 did not increase plaque area, composition, or vulnerability in the aortic arch. RhPlGF-2 significantly improved contractile function and reduced LV end-systolic and end-diastolic volume indices with a concomitant increase in capillary and arteriolar density in ischemic myocardium. RhPlGF-2 may represent a promising therapeutic strategy in chronic ischemic cardiomyopathy.

Predictors and Prognostic Impact of Progressive Ischemic Mitral Regurgitation in Patients With Advanced Ischemic Cardiomyopathy: A Multimodality Study.

Ischemic mitral regurgitation (IMR) is associated with poor outcomes. It is unknown what factors contribute to progression of IMR and how progressive IMR affects outcomes. We sought to determine imaging predictors of IMR progression and to determine if progressive IMR is an independent predictor of survival in patients with advanced ischemic cardiomyopathy. Consecutive advanced ischemic cardiomyopathy patients who underwent cardiac magnetic resonance and echocardiograms at baseline with echocardiographic follow-up were studied. Cardiac magnetic resonance was used to assess left ventricular volumes, infarct size, and mitral valve geometry. The effective regurgitant orifice area (EROA) was calculated from the proximal isovelocity surface area by echocardiography. Repeated measures mixed effects and Cox proportional hazards regression models were built to identify predictors of IMR progression and survival. We evaluated 336 patients (age, 62±11 years) over a median follow-up time of 54 months: 154 patients were subsequently revascularized, and 182 patients were medically treated. Ninety-eight patients (29%) demonstrated an increase in EROA values of ≥0.1 cm(2). There were 87 adverse events (death or transplant). On multivariable analysis, infarct size (P<0.001), progression in IMR (P=0.008), age (P=0.003), and baseline EROA (P=0.010) were independently associated with adverse events. Independent predictors of IMR progression were as follows: baseline EROA (P<0.001), left ventricular end-systolic volume index (P=0.014), and total scar (P=0.036). IMR frequently increases in severity, and progression is independently associated with adverse left ventricular remodeling and infarct size, as assessed by cardiac magnetic resonance. Furthermore, IMR progression is a powerful independent predictor of adverse events, even after controlling for the severity of IMR at baseline.

New Method of Posterior Scallop Augmentation for Ischemic Mitral Regurgitation

We report a new method of posterior middle scallop (P2) augmentation for ischemic mitral regurgitation to achieve deep coaptation. First, P2 was divided straight at the center and partially detached from the annulus in a reverse Tshape. A narrow pentagon-shaped section of pericardium was sutured to the divided P2 and annular defect. The tip of the pentagon was attached directly to the papillary muscle, thus creating a very large P2 scallop. A standard-sized ring was placed. We adopted this technique in 2 patients with advanced ischemic cardiomyopathy, and no mitral regurgitation was observed during a 1-year follow-up.

Abstract 12437: Prediction of Mitral Regurgitation Progression With Advanced Ischemic Cardiomyopathy - A Multi-Modality Study

Introduction: Ischemic mitral regurgitation (IMR) is associated with poor outcomes. Determining risk for the presence and progression of IMR may be critical for risk stratification. Hypothesis: We hypothesize that a multi-modality approach can evaluate the progression of IMR in patients with advanced ischemic cardiomyopathy (ICM) and create a risk model for the prediction of IMR progression. Methods: Consecutive ICM patients who underwent cardiac magnetic resonance (CMR) and echocardiograms at baseline with echocardiographic follow-up were included. CMR was used to assess global and regional left ventricular (LV) remodeling, myocardial scarring, and mitral valve geometry. The effective regurgitant orifice area (EROA) was calculated from the proximal isovelocity surface area by echocardiography. We identified the best performing model for prediction of worsening IMR based on the c-index. Results: We evaluated 693 patients (age 62±11). The following factors were independently predictive of an increased EROA at baseline (n=693): higher total scar% (p=0.002) and higher ESVi (p&lt;0.001). In regards to progression of IMR over time, the following variables were independently predictive (n=481): older age (p=0.015), lower GFR (p&lt;0.001), higher EROA at baseline (p&lt;0.001), lower tenting area (p=0.008), higher ESVi (p=0.001), and the interaction of total scar % and treatment type (medical vs revascularization vs valve surgery, Figure) (p=0.001). The c-index for worsened IMR prediction for the ICM was 0.730 from our training sample (n=164). Conclusions: The variables which predict IMR at baseline and progression of IMR over time slightly differ. Higher total scar% and higher ESVi are independently associated with increasing IMR at baseline. However, higher EROA at baseline, lower tenting area, higher ESVi and total scar% * treatment type were associated with progression of IMR over time. The risk model of IMR progression was moderately predictive in this cohort.

Infarct characterization and quantification by delayed enhancement cardiac magnetic resonance imaging is a powerful independent and incremental predictor of mortality in patients with advanced ischemic cardiomyopathy.

Infarct heterogeneity has been shown to be independently associated with adverse outcomes in previous smaller studies. However, it is unknown whether infarct characterization is an independent predictor of all-cause mortality in patients with advanced ischemic cardiomyopathy, after adjusting for clinical risk factors, severity of ischemic mitral regurgitation, incomplete revascularization, and device therapy. A total of 362 patients with ischemic cardiomyopathy (left ventricular dysfunction with >70% stenosis in ≥1 epicardial coronary artery) underwent delayed hyperenhancement-magnetic resonance imaging and coronary angiography between 2002 and 2006. Total myocardial scar and peri-infarct (PI) area were measured using various threshold techniques. Multivariate survival analysis (primary end point of all-cause mortality) was conducted. One hundred fifty-seven deaths occurred during a mean 5.4-year follow-up (mean left ventricular ejection fraction, 23±9%; mean end-systolic volume index, 113±48 mL; mean total myocardial scar %, 25.5±16.0%; mean PI%, 5.7±2.9%). PI% (β=2.07; P<0.001) was an independent predictor of survival, independent of age, end-systolic volume, sex, mitral regurgitation, diabetes mellitus, dyslipidemia, coronary artery disease severity, implantable cardioverter defibrillator, and incomplete revascularization. PI% using 2 to 3 SD technique yielded the highest incremental prognostic power (χ(2) score 149). In advanced ischemic cardiomyopathy, PI% is a powerful independent and incremental predictor of all-cause mortality. Infarct heterogeneity offers substantial further risk stratification when compared with quantification of total myocardial scar % alone even after adjusting for clinical risk factors, end-systolic volume index, mitral regurgitation, incomplete revascularization, and implantable cardioverter defibrillator implantation.

Extent of Coronary and Myocardial Disease and Benefit From Surgical Revascularization in LV Dysfunction

BackgroundPatients with ischemic left ventricular dysfunction have higher operative risk with coronary artery bypass graft surgery (CABG). However, those whose early risk is surpassed by subsequent survival benefit have not been identified. ObjectivesThis study sought to examine the impact of anatomic variables associated with poor prognosis on the effect of CABG in ischemic cardiomyopathy. MethodsAll 1,212 patients in the STICH (Surgical Treatment of IsChemic Heart failure) surgical revascularization trial were included. Patients had coronary artery disease (CAD) and ejection fraction (EF) of ≤35% and were randomized to receive CABG plus medical therapy or optimal medical therapy (OMT) alone. This study focused on 3 prognostic factors: presence of 3-vessel CAD, EF below the median (27%), and end-systolic volume index (ESVI) above the median (79 ml/m2). Patients were categorized as having 0 to 1 or 2 to 3 of these factors. ResultsPatients with 2 to 3 prognostic factors (n = 636) had reduced mortality with CABG compared with those who received OMT (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.56 to 0.89; p = 0.004); CABG had no such effect in patients with 0 to 1 factor (HR: 1.08; 95% CI: 0.81 to 1.44; p = 0.591). There was a significant interaction between the number of factors and the effect of CABG on mortality (p = 0.022). Although 30-day risk with CABG was higher, a net beneficial effect of CABG relative to OMT was observed at >2 years in patients with 2 to 3 factors (HR: 0.53; 95% CI: 0.37 to 0.75; p<0.001) but not in those with 0 to 1 factor (HR: 0.88; 95% CI: 0.59 to 1.31; p = 0.535). ConclusionsPatients with more advanced ischemic cardiomyopathy receive greater benefit from CABG. This supports the indication for surgical revascularization in patients with more extensive CAD and worse myocardial dysfunction and remodeling. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595)

Endomyocardial implantation of autologous bone marrow mononuclear cells in advanced ischemic heart failure: a randomized placebo-controlled trial (END-HF).

Prior studies suggest that endomyocardial implantation of autologous bone marrow (BM) mononuclear cell therapy improves symptoms and left ventricular (LV) function in patients with refractory angina; however, the therapeutic efficacy in patients with ischemic cardiomyopathy is unclear. In a randomized, double-blind, placebo-controlled trial, 28 patients with advanced ischemic cardiomyopathy [New York Heart Association III-IV, LV ejection fraction (LVEF) <40%] were assigned in 2:1 ratio to receive endomyocardial injection of BM cells (100 million, n = 19) or placebo (n = 9), guided by electroanatomical mapping. After 6months, there was no significant difference between the two groups in LV ejection fraction (LVEF) and LV end-systolic volume (LVESV), LV infarct volume, and LV peri-infarct ischemic volume as determined by cardiac magnetic resonance imaging or exercise capacity. In conclusion, endomyocardial implantation of autologous BM mononuclear cells did not improve LV function or remodeling in patients with advanced ischemic cardiomyopathy.