Significant Improvement In Left Ventricular Function Research Articles

Assessment of the Heart's Left and Right Ventricles (EF and TAPSE) in CABG Surgery Patients before and after Cardiac Rehabilitation.

Post-coronary artery bypass grafting (post-CABG) is a beneficial procedure for cardiac patients. However, without an appropriate cardiac rehabilitation (CR) program, patient care may be inadequate, leading to recurrent hospitalizations and heart failure. This study aims to assess the effects of a CR program on left ventricular ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE) measures in post-CABG patients at Amir-almomenin, kordkuy Hospital, Golestan, Iran. This descriptive-analytic study included 100 patients who underwent post-CABG surgery in the second half of 2020, and whose complete information was available in their medical files. An echocardiologist assessed the LVEF and TAPSE of the patients. After one month of CR procedures, these measures were reevaluated and recorded. The CR program consisted of 5 to 10 sessions of physiotherapy per patient, with 2 or 3 sessions conducted per week. It involved a four-phase therapy that included light sports activities such as running and jogging on a treadmill at a CR clinic. Data analysis was performed using SPSS software version 18. The data analysis of this study suggests that implementing a CR program for post- CABG patients can have beneficial effects. CR significantly increased the patients' LVEF, but the increase in TAPSE was not statistically significant. Furthermore, both male and female patients showed improved LVEF after the CR program. There was a non-significant inverse relationship between hospitalization duration and LVEF. Statistically, older patients had a significantly longer duration of hospitalization compared to younger patients. Completion of a cardiac rehabilitation program leads to significant improvement in left ventricular function, while the improvement in right ventricular function is relatively modest. Moreover, a significant proportion of patients were able to resume their normal daily activities after completing the rehabilitation phase.

Three-Dimensional Echocardiography and Global Longitudinal Strain in Follow-Up After Multisystem Inflammatory Syndrome in Children: Six-Month, Single-Center, Prospective Study

To assess the potential long-term cardiac effects after multisystem inflammatory syndrome in children (MIS-C) with cardiovascular involvement in the acute phase. Our prospective study involved children consecutively diagnosed with MIS-C between October 2020 and February 2022 and followed 6 weeks and 6 months after the disease. In patients with severe cardiac involvement during the acute phase, an additional check-up after 3 months was scheduled. In all patients at all check-ups, 3D-echocardiography and global longitudinal strain were used to assess ventricular function. The study enrolled 172 children aged 1-17 years (median 8 years). The means of ejection fraction (EF) and global longitudinal strain (GLS) for both ventricles were within normal limits after 6 weeks with no relationship with initial severity: left ventricular ejection fraction (EF) 60 (59-63)%, left ventricular (LV) GLS -21.08 (-18.63 - -23.2)%, right ventricular (RV) EF 64 (62-67)%, and RV GLS -22.8 (-20.5 - -24.5)%. Further, statistically significant improvement of LV function was observed after 6 months - LVEF 63 (62-65)%, LV GLS -22.55 (-21.05 - -24.25)%; p<0.05, but RV function remained unchanged. The group with severe cardiac involvement showed LV function recovery pattern with no significant improvement between 6 weeks and 3 months after MIS-C, while still improving between 3 and 6 months after discharge. LV and RV function is within normal limits 6 weeks after MIS-C regardless of severity of cardiovascular involvement; LV function improves further between 6 weeks and 6 months after the disease. The long-term prognosis is optimistic with full recovery of cardiac function.

Reverse Cardiac Remodeling Response and Its Effect on Quality of Life After initiation of Sacubitril/valsartan in Heart Failure with Reduced Ejection Fraction

Objective: To evaluate if switching therapy from an angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) to sacubitril/valsartan induces incremental left ventricular (LV) reverse remodeling and the effect of switching on quality of life (QOL) in heart failure with reduced ejection fraction (HFrEF). Methodology: This prospective multicenter study included 100 patients with HFrEF. The patients were subdivided into two equal groups: Group one included patients who were switched to sacubitril/valsartan and group two included patients continued on ACEIs or ARBs as control group. The patients were subjected to medical history taking, clinical examination, heart failure related data, New York Heart Association (NYHA) functional classification, blood samples and chemistry, transthoracic echocardiography (TTE) and quality of life assessment. Results: There was marked improvement in all two dimensional (2D) echocardiography parameters, as left ventricular end-systolic volume (LVESVI), left ventricular end-diastolic volume index (LVEDVI) and left atrium volume index (LAVI) which significantly reduced after 3 months of therapy with significant improvement in LV function (P-value &lt; 0.05). Moreover, mitral regurgitation (MR) severity significantly decreased (P-value &lt; 0.05). Regarding quality of life, there was a significant improvement in QOL. KCCQ score was significantly improved after 3 months of treatment (P-value &lt; 0.05). Conclusion: In HFrEF patients, sacubitril/valsartan significantly improves LV function; furthermore, it induces incremental LV reverse remodeling as well as improves QOL.

Challenges of Treating Late Onset Severe Antibody Mediated Rejection Post Orthotopic Heart Transplant

<h3>Introduction</h3> Outcomes of severe antibody mediated rejection (AMR) post orthotopic heart transplant (OHT) are often poor & management a challenge. <h3>Case Report</h3> A 50-year-old multiparous female with stable donor specific antibodies (DSAs) presented with cardiogenic shock (CS) & severe left ventricular (LV) dysfunction 4 years post OHT. Maintenance immunosuppressants (IS) included tacrolimus, mycophenolate & prednisolone with good adherence. Urgent endomyocardial biopsy (EMB), coronary angiogram & right heart catheterisation were performed. Progression to SCAI Stage D shock necessitated venoarterial extracorporeal membrane oxygenation (VA ECMO) within 24 hrs. Based on clinical presentation, the patient was treated with methylprednisolone, intravenous immunoglobulin (IVIG) & IV thymoglobulin alongside hemodynamic & other organ support (dialysis, ventilation). EMB confirmed pAMR3 fulfilling criteria for severe AMR together with CS & raised DSAs. Within days the patient's cardiac output improved allowing removal of VA ECMO. Following MDT consensus given persistent graft dysfunction & DSAs an AMR specific regimen of plasmapheresis, IVIG & rituximab were administered resulting in significant improvement in LV function & DSAs. A serious consequence of high dose IS was severe CMV reactivation (CMV peak 18,000 copies/ml). Successful treatment with IV ganciclovir caused leukopenia requiring mycophenolate cessation. Fortunately our patient survived to discharge day 152 post admission with graft recovery & excellent functional capacity. Ongoing management remains a challenge due to severe CAV & balancing risks associated with high dose IS with AMR recurrence. <h3>Summary</h3> This case highlights the importance of urgent evaluation including EMB, hemodynamic support & targeted anti-rejection therapy in patients post OHT with severe allograft dysfunction. It exemplifies challenges when treating severe AMR illustrating the importance of a collaborative team approach for successful outcomes.

AMPK Activation Is Indispensable for the Protective Effects of Caloric Restriction on Left Ventricular Function in Postinfarct Myocardium

Simple SummaryImpaired coronary blood flow induces cardiac ischemia and can lead to myocardial infarction. Although revascularization therapy and medical treatment potentially restore cardiac function in ischemic hearts, loss of cardiomyocytes and replacement of the dead myocardium by a scar can lead to ischemic heart disease with impaired cardiac output, a condition called heart failure. Medical treatment of heart failure includes drugs such as ACE-inhibitors, beta-blockers, diuretics, mineralocorticoid receptor antagonists, and SGLT (sodium-glucose cotransporter) 2 inhibitors. In addition, dietary interventions may provide further benefits to slow down disease progression. Caloric restriction, the decrease in calorie intake without malnutrition, is a strategy for improving health and increasing lifespan. Caloric restriction reduces the risk factors for cardiovascular diseases, and it improves heart function in animals and humans. Our study investigated the impact of caloric restriction on heart failure progression in mice and rats with myocardial infarction. We show that caloric restriction inhibits progressive loss of heart function, even when started after heart failure is already established. Together, the findings help to deepen our understanding of the complex mechanisms involved in the cardioprotective effects of caloric restriction and how they could be therapeutically utilized to prevent disease progression.Background: Caloric restriction (CR) extends lifespan in many species, including mammals. CR is cardioprotective in senescent myocardium by correcting pre-existing mitochondrial dysfunction and apoptotic activation. Furthermore, it confers cardioprotection against acute ischemia-reperfusion injury. Here, we investigated the role of AMP-activated protein kinase (AMPK) in mediating the cardioprotective CR effects in failing, postinfarct myocardium. Methods: Ligation of the left coronary artery or sham operation was performed in rats and mice. Four weeks after surgery, left ventricular (LV) function was analyzed by echocardiography, and animals were assigned to different feeding groups (control diet or 40% CR, 8 weeks) as matched pairs. The role of AMPK was investigated with an AMPK inhibitor in rats or the use of alpha 2 AMPK knock-out mice. Results: CR resulted in a significant improvement in LV function, compared to postinfarct animals receiving control diet in both species. The improvement in LV function was accompanied by a reduction in serum BNP, decrease in LV proapoptotic activation, and increase in mitochondrial biogenesis in the LV. Inhibition or loss of AMPK prevented most of these changes. Conclusions: The failing, postischemic heart is protected from progressive loss of LV systolic function by CR. AMPK activation is indispensable for these protective effects.

Hexarelin targets neuroinflammatory pathways to preserve cardiac morphology and function in a mouse model of myocardial ischemia-reperfusion

Acute myocardial ischemia and reperfusion injury (IRI) underly the detrimental effects of coronary heart disease on the myocardium. Despite the ongoing advances in reperfusion therapies, there remains a lack of effective therapeutic strategies for preventing IRI. Growth hormone secretagogues (GHS) have been demonstrated to improve cardiac function, attenuate inflammation and modulate the autonomic nervous system (ANS) in models of cardiovascular disease. Recently, we demonstrated a reduction in infarct size after administration of hexarelin (HEX), in a murine model of myocardial infarction. In the present study we employed a reperfused ischemic (IR) model, to determine whether HEX would continue to have a cardioprotective influence in a model of higher clinical relevance.Myocardial ischemia was induced by transient ligation of the left descending coronary artery (tLAD) in C57BL/6 J mice followed by HEX (0.3 mg/kg/day; n = 20) or vehicle (VEH) (n = 18) administration for 21 days, first administered immediately prior-to reperfusion. IR-injured and sham mice were subjected to high-field magnetic resonance imaging to assess left ventricular (LV) function, with HEX-treated mice demonstrating a significant improvement in LV function compared with VEH-treated mice. A significant decrease in interstitial collagen, TGF-β1 expression and myofibroblast differentiation was also seen in the HEX-treated mice after 21 days. HEX treatment shifted the ANS balance towards a parasympathetic predominance; combined with a significant decrease in cardiac troponin-I and TNF-α levels, these findings were suggestive of an anti-inflammatory action on the myocardium mediated via HEX.In this model of IR, HEX appeared to rebalance the deregulated ANS and activate vagal anti-inflammatory pathways to prevent adverse remodelling and LV dysfunction. There are limited interventions focusing on IRI that have been successful in improving clinical outcome in acute myocardial infarction (AMI) patients, this study provides compelling evidence towards the translational potential of HEX where all others have largely failed.

Observational study of left ventricular global longitudinal strain in ST-segment elevation myocardial infarction patients with extended pharmaco-invasive strategy: A six months follow-up study.

To evaluate left ventricular (LV) function by assessment of LV global longitudinal strain (GLS) in ST-segment elevation myocardial infarction (STEMI) patients who underwent delayed fibrinolysis and coronary intervention (extended pharmaco-invasive strategy), since LV function is one of the determinants of both immediate and long-term outcomes. Prospective study of consecutive STEMI patients who underwent extended pharmaco-invasive strategy. The LV function was estimated using LV GLS at baseline and at 6months. The study included eighty-seven STEMI patients who received delayed pharmaco-invasive therapy and coronary intervention. The primary aim of the study was to evaluate a change in LV function by assessment of GLS at 6months as compared to baseline. Prior to PCI, LV ejection fraction was 48.08±6.23% and GLS was -11.11±2.99%. Procedural success was achieved in all patients. LV ejection fraction after 6months of follow-up increased to 53.12±5.61% and the GLS improved to -13.03±3.06% In comparison to baseline, there was a significant improvement in both LV ejection fraction and GLS at 6months of follow-up (P<.001).The cardiac mortality was 1.1% at 6months. There is a significant improvement of LV function as assessed by GLS and ejection fraction at short-term follow-up. In a stable cohort of STEMI patients, extended pharmaco-invasive strategy is also a reasonable option if PCI cannot be performed within the first 24hours, due to logistic and infrastructural constraints.

Management of Peripartum Cardiomyopathy with Secondary Large Left Ventricular Apical Clot using Novel Oral Anticoagulants: A Case Report

Peripartum Cardiomyopathy (PPCM) is a major life-threatening complication of pregnancy, as only half of them or slightly more patients show improvement of Left Ventricular (LV) dysfunction. A 28-year-old woman with a history of gestational hypertension and diabetes during pregnancy, underwent full-term normal vaginal delivery. She started developing dyspnea, Class II which progressed to Class IV postpartum. Kidney and liver functions were found to be grossly deranged along with thrombocytopenia. Provisional diagnosis of Haemolysis, Elevated Liver Enzymes and Low Platelets (HELLP) was made. Electrocardiography (ECG) revealed the left anterior fascicular block. Eventually, bedside echocardiogram revealed severe LV dysfunction and the presence of a large soft LV apical clot with an Ejection Fraction (EF) of 30%. Adequate anticoagulation was achieved using Novel Oral Anticoagulants (NOAC). After six days and a 3-month follow-up, an echocardiogram demonstrated a significant improvement of LV function (EF-45%) and a complete resolution of LV apical clot, respectively.

Cell-Based Therapy in Cardiac Regeneration: An Overview.

Although pioneering preclinical research on the use of cell therapy for cardiac regeneration was conducted in the last quarter of the 20th century,1,2 a preponderance of advances have occurred in the 21st century, making this a relatively young field. In the first important clinical trial of cardiac cell therapy, begun in 2001, Menasche et al3 implanted autologous skeletal myoblasts into postinfarct scar at the time of coronary artery bypass surgery. Although the transplanted cells remained viable and exhibited contraction, they formed the nidus for serious ventricular tachyarrhythmias, which led to premature discontinuation of the trial. Despite this outcome, the trial energized the field, accelerating both preclinical and clinical research, albeit not with skeletal myoblasts. The extensive progress in cardiac regeneration is reviewed in this Compendium, and as occurs frequently in science, important observations have led to more questions and challenges (Table). View this table: Table. Important Challenges to Cell Therapy for Cardiac Regeneration Many cell types have been evaluated as candidates for cardiac regeneration. Among the earliest clinical trials, Zeiher’s group infused autologous bone marrow-derived progenitor cells into the coronary arteries of patients with acute,4 as well as healed myocardial infarction (MI)5 and reported improvements in left ventricular (LV) function. However, these results have not been fully confirmed by later studies, as pointed out in the review in the Compendium by Banarjee, Bolli, and Hare.6 Pittenger et al7 were among the first to direct attention to bone marrow-derived (stromal) mesenchymal stem cells (MSCs), emphasizing that these cells proliferated extensively in culture and suggesting that they could be attractive candidates for transplantation. In 2004, Chen et al8 reported that intracoronary infusion of autologous bone marrow-derived MSCs improved cardiac function. Zimmet and Hare pointed out that MSCs lack histocompatibility type II markers and elude rejection by …

Ventricular arrhythmias associated with left ventricular noncompaction: Electrophysiologic characteristics, mapping, and ablation

Left ventricular noncompaction (LVNC) is a primary cardiomyopathy that can present with recurrent ventricular arrhythmias (VAs). Data on the benefit of catheter ablation of VAs in LVNC are lacking. The purpose of this study was to describe the electrophysiologic features and outcomes of catheter ablation of VAs in LVNC. The cohort consisted of 9 patients (age 42 ± 15 years) with diagnosis of LVNC based on established criteria and VA (ventricular tachycardia [VT] in 3 and frequent premature ventricular contractions (PVCs) in 6) despite treatment with a mean of 2 ± 1 antiarrhythmic drugs. Ablation sites were identified using a combination of entrainment, activation, late/fractionated potential ablation, and pace-mapping. A total of 8 patients (89%) had left ventricular (LV) systolic dysfunction (mean ejection fraction 40% ± 13%). Patients who presented with VT had evidence of abnormal electroanatomic substrate involving the mid- to apical segments of the LV, which matched the noncompacted myocardial segments identified by preprocedural magnetic resonance imaging or echocardiography. In patients presenting with frequent PVCs, the site of origin was identified at the papillary muscles (50%) and/or basal septal regions (67%). After median follow-up of 4 years (range 1-11) and a mean of 1.8 ± 1.1 procedures, VAs recurred in 1 patient (11%). Significant improvement in LV function occurred in 4 of 8 cases (50%). No patients died or underwent heart transplantation. The VA substrate in patients with LVNC and VT typically involves the mid-apical LV segments, whereas focal PVCs often arise from LV basal-septal regions and/or papillary muscles. Catheter ablation is safe and effective in achieving good VA control over long-term follow-up in most patients.

Paroxetine‐mediated GRK2 Inhibition Reverses Cardiac Dysfunction and Remodeling Post‐Myocardial Infarction

Heart failure (HF) is a disease of epidemic proportion associated with exceedingly high healthcare costs. Data shows that G protein‐coupled receptor (GPCR) kinase 2 (GRK2) plays a critical role in HF progression, promoting dysfunctional adrenergic signaling and myocyte death. We found that the selective serotonin reuptake inhibitor, paroxetine, could selectively inhibit GRK2. In this study wild‐type mice underwent myocardial infarction (MI) and following 2 weeks of injury, underwent 4 weeks of treatment with paroxetine or control SSRI, fluoxetine. All post‐MI mice exhibited similar left ventricular (LV) dysfunction prior to treatment; however, in contrast to continuing degradation of function, paroxetine produced significant improvement in LV function and structure. Paroxetine enhanced hemodynamic function, blocking the ~2.5 fold increase in LV end diastolic pressure (LVEDP). Paroxetine restored βAR membrane density, returned serum catecholamine and GRK2 levels to baseline, and prevented induction of the fetal gene program. Importantly, the beneficial effects persisted after termination of treatment and were markedly greater than β‐blocker therapy, a current standard of care. These data demonstrate that paroxetine‐mediated inhibition of GRK2 improves cardiac function post‐MI and potentially represents novel re‐purposing as well as a starting point for innovative small molecule inhibitor development.

Left Ventricular Functional Recovery and Remodeling in Low-Flow Low-Gradient Severe Aortic Stenosis after Transcatheter Aortic Valve Implantation

Speckle-tracking-derived global longitudinal strain (GLS) is a more sensitive method of detecting left ventricular (LV) functional recovery after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis. However, it remains unknown whether LV function improves in patients with low-flow, low-gradient severe aortic stenosis (LFLGSAS) after TAVI. The aim of the present was to evaluate LV functional recovery and remodeling after TAVI in patients with LFLGSAS. Sixty-eight patients (57% men; mean age, 79.1 ± 7.1 years) with LFLGSAS treated with TAVI were evaluated. LV function and remodeling were investigated before TAVI and at 6 and 12 months after TAVI. All echocardiographic data were prospectively collected, and GLS was retrospectively analyzed. Among patients with LFLGSAS, 35 (52%) had low LV ejection fraction (LVEF) (<50%), and 33 (48%) had preserved LVEF (≥50%). The low-LVEF group had significantly more impaired GLS than the group with preserved LVEF (-8.3 ± 2.6% vs -13.3 ± 3.5%, P < .001). LV systolic function improved after TAVI in both groups. Although in the group of patients with low LVEF, all functional parameters improved, in the group of patients with preserved LVEF, only strain-derived parameters significantly improved. There were significant decreases in absolute LV wall thickness and relative wall thickness and a trend toward decreased LV mass index in both LVEF groups. LV volumes decreased significantly in those with low LVEF but not in those with preserved LVEF. Baseline GLS but not LVEF group was independently associated to GLS improvement at 12 months after TAVI. Patients with LFLGSAS with low and preserved LVEF had a significant improvement in LV function after TAVI, as assessed by GLS. Absolute and relative LV wall thickness decreased in both groups of patients, but only those with low LVEF had reductions in LV volumes.

Aortic Regurgitation and Left Ventricular Remodeling After Transcatheter Aortic Valve Implantation

Aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) has been associated with poor outcomes, but little is known about how it evolves over time. We evaluated left ventricular (LV) function, remodeling, and the occurrence and evolution of AR after TAVI by using cardiac MRI. Forty-three patients treated with transfemoral TAVI underwent cardiac MRI 1 week and 6 months after TAVI. LV volumes and function were assessed by using standard cine MRI sequences. Phase-contrast imaging was performed to quantify the degree of AR. The mean age of the evaluated patients was 80 years, and 65% of patients were women. At baseline MRI, the median LV ejection fraction was 58.1%, which improved significantly at follow-up to 63.4% (P<0.0001). A significant reduction of LV end-diastolic volume (149.7 ± 41.4-140.1 ± 43.9 mL; P=0.014) and of LV mass (156.3 ± 32.8-142.7 ± 39.3 g; P<0.001) was observed. Over time, aortic regurgitant fraction increased slightly but significantly from 5.2% to 7.8% (P=0.04). Subgroup analysis revealed that significant changes of LV ejection fraction, volumes, and mass only occurred in patients with no or mild AR at baseline MRI, whereas those parameters remained unchanged in patients with AR more than or equal to grade II. By using cardiac MRI in patients with TAVI, a significant improvement of LV function, volume, and mass can be documented. Mild-to-moderate AR is commonly seen, and AR shows a small increase over time. More-than-mild AR seems to prevent LV functional and structural recovery after TAVI.

A Randomized Study of the Beneficial Effects of Aldosterone Antagonism on LV Function, Structure, and Fibrosis Markers in Metabolic Syndrome

The purpose of this study was to identify the effects of spironolactone on left ventricular (LV) structure and function, and serological fibrosis markers in patients with metabolic syndrome (MS) taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Myocardial fibrosis may be an important contributor to myocardial impairment in MS, and aldosterone antagonism may reduce fibrosis. Eighty patients (age 59 ± 11 years) with MS, already being treated with angiotensin II inhibition, were randomized to spironolactone 25 mg/day or placebo for 6 months. Each patient underwent baseline and follow-up conventional echocardiography and color tissue Doppler imaging. Raw data files were used to measure calibrated integrated backscatter and to calculate radial and longitudinal strain. Blood was obtained at baseline and follow-up to measure fibrosis markers (procollagen type III amino-terminal propeptide and procollagen type I carboxy-terminal propeptide [PICP]). The spironolactone group showed significant improvement of LV function, myocardial reflectivity, and LV hypertrophy, with a parallel decrease in levels of PICP and procollagen type III amino-terminal propeptide. No analogous changes were seen in the placebo group. Baseline strain (β = 0.47, p < 0.0001), spironolactone therapy (β = -0.38, p < 0.0001), and change in PICP level (β = -0.19, p < 0.03) were independently associated with LV systolic function improvement (increase in strain). Correlates of LV diastolic function improvement (increase in early diastolic mitral annular velocity) were baseline early diastolic mitral annular velocity (β = 0.47, p < 0.0001), spironolactone therapy (β = -0.21, p < 0.03), change in PICP level (β = -0.23, p < 0.02), and age (β = 0.22, p < 0.04). Favorable effects of spironolactone on cardiac function were not demonstrated in patients with less fibrosis (the lower baseline PICP tertile) or preserved function (the upper baseline strain tertile). Addition of spironolactone to standard angiotensin II inhibition improved myocardial abnormalities and decreased fibrotic markers in MS. The magnitude of benefit on cardiac performance is determined mainly by baseline LV dysfunction and collagen turnover as well its response to intervention.

Effects of myocardial fibrosis and ventricular dyssynchrony on response to therapy in new-presentation idiopathic dilated cardiomyopathy: insights from cardiovascular magnetic resonance and echocardiography

To determine whether the extent of myocardial fibrosis by late-gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR), and echocardiographic ventricular dyssynchrony are independently associated with response to medical therapy in patients with newly diagnosed idiopathic dilated cardiomyopathy (DCM). Myocardial fibrosis and ventricular dyssynchrony are frequent findings in DCM. Previous studies focused on patients with established cardiomyopathy; however, the degree of myocardial fibrosis and ventricular dyssynchrony at presentation and their role in perpetuating left ventricular (LV) dysfunction in DCM remains unclear. Those studies of individuals with long-standing DCM did not characterize patients early in the disease course, and may not have included those with significant improvement in LV function. Thus factors contributing to LV recovery are uncertain. Consecutive patients with a new diagnosis of DCM [LV ejection fraction (EF) ≤45%] made within the preceding 2 weeks were recruited. Patients underwent LGE-CMR, echocardiography, 6-minute walk testing, cardiopulmonary exercise testing, and blood sampling for measurement of serum amino-terminal pro-brain natiuretic peptide (NT-pro-BNP) concentration at baseline. Baseline patient characteristics were compared with a cohort of healthy volunteers. Myocardial fibrosis by LGE-CMR was quantified, identified by experienced observers blinded to patient outcome. Left ventricular systolic function was reassessed after 5 months of optimal medical therapy. Sixty-eight patients with DCM and 19 healthy volunteers were studied. DCM patients were studied a median 12.5 days following diagnosis. Compared with healthy controls, DCM patients exhibited greater inter- and intra-ventricular dyssynchrony. Twenty-four per cent of DCM patients exhibited LGE at diagnosis. Among DCM patients with LGE, the mean fibrosis mass was 2.2 ± 1.3 g. On multivariate analysis, strain dyssynchrony index, and fibrosis mass were independently associated with change in the LVEF over time (P≤ 0.001). Late-gadolinium enhancement cardiovascular magnetic resonance conferred additive value for modelling change in the LVEF beyond clinical and echocardiographic dyssynchrony parameters. The extent of myocardial fibrosis is independently associated with lack of response to medical therapy in new-presentation DCM, and LGE-CMR may thus be an important risk-stratifying investigation in these patients. Accurate risk stratification may permit more targeted pharmacological and device therapies for patients with newly diagnosed DCM.

HMGB1 Attenuates Cardiac Remodelling in the Failing Heart via Enhanced Cardiac Regeneration and miR-206-Mediated Inhibition of TIMP-3

AimsHMGB1 injection into the mouse heart, acutely after myocardial infarction (MI), improves left ventricular (LV) function and prevents remodeling. Here, we examined the effect of HMGB1 in chronically failing hearts.Methods and ResultsAdult C57 BL16 female mice underwent coronary artery ligation; three weeks later 200 ng HMGB1 or denatured HMGB1 (control) were injected in the peri-infarcted region of mouse failing hearts. Four weeks after treatment, both echocardiography and hemodynamics demonstrated a significant improvement in LV function in HMGB1-treated mice. Further, HMGB1-treated mice exhibited a ∼23% reduction in LV volume, a ∼48% increase in infarcted wall thickness and a ∼14% reduction in collagen deposition. HMGB1 induced cardiac regeneration and, within the infarcted region, it was found a ∼2-fold increase in c-kit+ cell number, a ∼13-fold increase in newly formed myocytes and a ∼2-fold increase in arteriole length density. HMGB1 also enhanced MMP2 and MMP9 activity and decreased TIMP-3 levels. Importantly, miR-206 expression 3 days after HMGB1 treatment was 4-5-fold higher than in control hearts and 20–25 fold higher that in sham operated hearts. HMGB1 ability to increase miR-206 was confirmed in vitro, in cardiac fibroblasts. TIMP3 was identified as a potential miR-206 target by TargetScan prediction analysis; further, in cultured cardiac fibroblasts, miR-206 gain- and loss-of-function studies and luciferase reporter assays showed that TIMP3 is a direct target of miR-206.ConclusionsHMGB1 injected into chronically failing hearts enhanced LV function and attenuated LV remodelling; these effects were associated with cardiac regeneration, increased collagenolytic activity, miR-206 overexpression and miR-206 -mediated inhibition of TIMP-3.

Telephone Titration of Heart Failure Medications

In clinical practice, heart failure (HF) medications are underused and prescribed at lower than recommended doses. Telephone care is an option that could help to titrate HF medication in a timely manner. We describe our experience of a nurse-run, cardiologist- or nurse practitioner-supervised clinic to up-titrate HF medications via telephone. Patients with the diagnosis of HF, New York Heart Association classes I to III, were referred to a registered nurse-run, cardiologist-/nurse practitioner-supervised HF medication titration clinic. Clinical and medication data collected at enrollment to the clinic and at 3 to 6 months after optimization of HF medications in patients who did or did not reach the target doses were compared. Effect on left ventricular (LV) function was also evaluated. There were 79 patients in the evaluation: 64 with HF and LV systolic dysfunction (LVSD) and the remaining 15 with HF and preserved ejection fraction (EF). Seventy-two percent of patients with LVSD were on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), and 61% were on a β-blocker at baseline, and this increased to 98% and 97%, respectively, after optimization. Target doses was achieved in 50% of patients for ACEI or ARB, and in 41% for β-blockers. The median time to optimization was 54 days (interquartile range, 20-97 days). The average number of phone calls at the time of optimization were 5.4 (SD, 3.7), and the average number of clinic visits was 1.9 (SD, 1.3). Reasons for not reaching the target doses included hypotension, hyperkalemia, and renal dysfunction for ACEI and bradycardia for β-blockers. Overall, the EF increased by 10% (SD, 10%) after 6 months, and 35% or greater in 42% of patients whose baseline EF was less than 35%. There were no adverse events related to the dose up-titration. Telephonic titration of HF medications was feasible and safe and was achieved in 97% patients on ACEI/ARB and β-blockers. Medication titration was associated with significant improvement in LV function, avoiding the need for device therapy in many patients.

Impact of left ventricular systolic function on clinical and echocardiographic outcomes following transcatheter aortic valve implantation for severe aortic stenosis

This study aimed to evaluate the impact of baseline left ventricular (LV) systolic function on clinical and echocardiographic outcomes following transcatheter aortic valve implantation (TAVI). Survival of patients undergoing TAVI was also compared with that of a population undergoing surgical aortic valve replacement. One hundred forty-seven consecutive patients (mean age=80±7 years) undergoing TAVI in 2 centers were included. Mean follow-up period was 9.1±5.1 months. At baseline, 34% of patients had impaired LV ejection fraction (LVEF) (<50%) and 66% had normal LVEF (≥50%). Procedural success was similar in these 2 groups (94% vs 97%, P=.41). All patients achieved improvement in transvalvular hemodynamics. At follow-up, patients with a baseline LVEF<50% showed marked LV reverse remodeling, with improvement of LVEF (from 37%±8% to 51%±11%). Early and late mortality rates were not different between the 2 groups, despite a higher rate of combined major adverse cardiovascular events (MACEs) in patients with a baseline LVEF<50%. The predictors of cumulative MACEs were baseline LVEF (HR=0.97, 95% CI=0.94-0.99) and preoperative frailty (HR=4.20, 95% CI=2.00-8.84). In addition, long-term survival of patients with impaired or normal LVEF was comparable with that of a matched population who underwent surgical aortic valve replacement. TAVI resulted in significant improvement in LV function and survival benefit in high-risk patients with severe aortic stenosis, regardless of baseline LVEF. Patients with a baseline LVEF<50% were at higher risk of combined MACEs.

Myocardial Contrast Echocardiography Versus Single Photon Emission Computed Tomography for Assessment of Hibernating Myocardium in Ischemic Cardiomyopathy: Preliminary Qualitative and Quantitative Results

Single photon-emission computed tomography (SPECT) is widely used for the assessment of hibernating myocardium (HM). The aim of this study was to test the hypothesis that myocardial contrast echocardiography (MCE), because of its better spatial and temporal resolution, would be superior to SPECT for the detection of HM. Thirty-nine consecutive patients with symptomatic ischemic cardiomyopathy underwent rest and vasodilator SPECT and MCE. Of these, 23 survived to undergo assessment 3 months after revascularization for the recovery of left ventricular (LV) function (spontaneous recovery or dobutamine induced), which is the definition of HM. Of the 214 dysfunctional segments, 156 segments demonstrated HM in the 23 patients, of whom 16 showed significant improvement in LV function. Logistic regression analysis showed that both qualitative and quantitative MCE were independent predictors for the detection of HM (P < .0001 vs P = .06 for qualitative MCE vs qualitative SPECT, respectively, and P < .01 vs P = .25 for all quantitative myocardial contrast echocardiographic parameters vs quantitative SPECT, respectively). Using clinical and LV functional data, SPECT, and MCE for predicting the recovery of LV function, MCE was the only independent predictor (P = .03). MCE was superior to SPECT for the assessment of HM in ischemic cardiomyopathy.

A Prospective Randomized Evaluation of VV Delay Optimization in CRT‐D Recipients: Echocardiographic Observations from the RHYTHM II ICD Study

All current cardiac resynchronization therapy (CRT) devices allow the programming of the atrioventricular (AV/PV) delays and the sequential stimulation of the ventricles via the inter ventricular (VV) delay. This post hoc analysis of the RHYTHM II study was conducted to compare the reverse remodeling associated with VV delay optimization in patients randomly assigned to simultaneous (SIM) biventricular stimulation versus patients assigned to optimized VV delay programming (OPT) (1:3 randomization scheme). The analysis included 14 patients assigned to the SIM group and 34 patients to the OPT group who completed the 6-month follow-up period with paired echocardiographic recordings. In both study groups, changes consistent with left ventricular (LV) remodeling were observed between baseline and 6 months, with significant improvements in LV function and decrease in LV dimensions. In the OPT group, there was also a decrease in left atrial diameter and mitral valve closure to opening time. At 6 months, the overall proportion of echocardiographic responders (> or =10% decrease in LV end-systolic volume or > or =5% absolute increase in LV ejection fraction) was similar in both groups. The optimal AV/VV delays, evaluated by maximization of LV outflow tract velocity time integral, changed over time. Ventriculo-ventricular delay optimization was associated with better immediate hemodynamic function than simultaneous biventricular stimulation, though did not promote additional reverse remodeling at 6 months and did not increase the proportion of echocardiographic responders to CRT. Optimization of both the AV and VV intervals was patient-specific and optimal values changed over time.