Cardiomyopathy Patients Research Articles

Transthyretin amyloid cardiomyopathy in patients with unexplained increased left ventricular wall thickness

Amyloid cardiomyopathy (CA) was previously considered a rare disease; however, rapid advancements in imaging modalities have led to an increased frequency of its diagnosis. The aim of this prospective study was to assess the prevalence and clinical phenotype of transthyretin amyloidosis (ATTR) cardiomyopathy in patients exhibiting unexplained increased left ventricular (LV) wall thickness. From 2020 to 2022, we enrolled 100 consecutive adults with unexplained increased LV wall thickness in the study. The analysis included clinical data, electrocardiography, transthoracic echocardiography, single-photon emission computed tomography/computed tomography with 3,3-disphono-1,2-propanodicarboxylic acid, genetic testing. Overall, 18% of patients were diagnosed with CA, comprising 5% with light-chain amyloidosis, and 12% with ATTR. To evaluate associations with the ATTR diagnosis, a LOGIT model and multivariate analysis were applied. Notably, age, polyneuropathy, gastropathy, carpal tunnel syndrome, lumbar spine stenosis, low voltage, ventricular arrhythmia, LV mass, LV ejection fraction, global longitudinal strain (GLS), E/A, E/E′, right ventricle (RV) thickness, right atrium area, RV VTI, TAPSE, apical sparing, ground glass appearance of myocardium, thickening of interatrial septum, thickening of valves, and the “5–5–5” sign were found to be significantly associated with ATTR (p < 0.05). The best predictive model for ATTR diagnoses exhibited an area under the curve of 0.99, including LV mass, GLS and RV thickness. This study, conducted at a cardiology referral center, revealed that a very considerable proportion of patients with unexplained increased LV wall thickness may suffer from underlying CA. Moreover, the presence of ATTR should be considered in patients with increased LV mass accompanied by reduced GLS and RV thickening.

Impact of Functional Mitral Regurgitation on Left Ventricular Strain in Nonischemic Dilated Cardiomyopathy Patients with Type 2 Mellitus Diabetes: A Magnetic Resonance Feature Tracking Study

BackgroundThe impact of functional mitral regurgitation and type 2 mellitus diabetes (T2DM) on left ventricular (LV) strain in nonischemic dilated cardiomyopathy (NIDCM) patients remains unclear.PurposeTo evaluate the impact of mitral regurgitation severity on LV strain, and explore additive effect of T2DM on LV function across varying mitral regurgitation severity levels in NIDCM patients.Study TypeRetrospective.Population352 NIDCM (T2DM−) patients (49.1 ± 14.6 years, 67% male) (207, 85, and 60 no/mild, moderate, and severe mitral regurgitation) and 96 NIDCM (T2DM+) patients (55.2 ± 12.4 years, 77% male) (47, 30, and 19 no/mild, moderate, and severe mitral regurgitation).Field Strength/Sequence3.0 T/balanced steady‐state free precession sequence.AssessmentLV geometric parameters and strain were measured and compared among groups. Determinants of LV strain were investigated.Statistical TestStudent's t‐test, Mann–Whitney U test, one‐way ANOVA, Kruskal‐Wallis test, univariable and multivariable linear regression. P &lt; 0.05 was considered statistically significant.ResultsLV GLPS and longitudinal PDSR decreased gradually with increasing mitral regurgitation severity in NIDCM patients with T2DM(GLPS: −5.7% ± 2.1% vs. −4.3% ± 1.6% vs. −2.6% ± 1.3%; longitudinal PDSR:0.5 ± 0.2 sec−1 vs. 0.4 ± 0.2 sec−1 vs. 0.3 ± 0.1 sec−1). NIDCM (T2DM+) demonstrated decreased GCPS and GLPS in the no/mild subgroup, reduced LV GCPS, GLPS, and longitudinal PDSR in the moderate subgroup, and reduced GRPS, GCPS, GLPS, and longitudinal PDSR in the severe subgroup compared with NIDCM (T2DM−) patients. Multivariable regression analysis identified that mitral regurgitation severity (β = −0.13, 0.15, and 0.25 for GRPS, GCPS, and GLPS) and the presence of T2DM (β = 0.14 and 0.13 for GCPS and GLPS) were independent determinants of LV strains in NIDCM patients.Data ConclusionIncreased mitral regurgitation severity is associated with reduced LV strains in NIDCM patients with T2DM. The presence of T2DM exacerbated the decline of LV function across various mitral regurgitation levels in NIDCM patients, resulting in reduced LV strains.Level of Evidence3.Technical EfficacyStage 3.

Predictors of long-term success after successful explantation of continuous flow left ventricular assist device support.

Predictors and evaluations of continuous flow left ventricular assist device (cf-LVAD) explantation in recovered patients remains under discussion due to lack of evidence on long-term safety and efficacy. This study summarized our experiences regarding cf-LVAD explantation in non-ischaemic dilated cardiomyopathy patients and estimated a predictor for sufficient myocardial recovery allowing LVAD explant. We retrospectively identified 135 adult patients with cf-LVAD therapy as bridge to heart transplant due to non-ischaemic dilated cardiomyopathy. Of those, 13 patients underwent device explantation (recovery group) after myocardial recovery. 12 (92%) of the explanted patients were evaluated using our weaning protocol, and underwent surgical explantation. Meanwhile, the remaining 122 continued with cf-LVAD therapy (non- recovery group). Multivariate logistic regression analysis revealed time interval between the first heart failure event and cf-LVAD implantation as an independent predictor for successful explantation. The optimal time interval cutoff value to predict cf-LVAD explantation was 7 months, with a sensitivity of 91.0% and specificity of 84.6%. Echocardiography in patients with successful cf-LVAD explantation showed significant improvement of left ventricular function and dimensions at six months postoperatively. The 13 explanted patients are currently alive at a median of 30 (IQR; 18-58) months after explantation. The survival rate free from rehospitalization due to heart failure following explantation was 100%. Left ventricular function and remodelling after explantation were also preserved. In non-ischaemic dilated cardiomyopathy patients with a short interval between the first heart failure event and cf-LVAD therapy, left ventricular myocardium may recover in an early phase after device implantation.

Programmed ventricular stimulation for risk stratification in hypertrophic cardiomyopathy patients.

Programmed ventricular stimulation for risk stratification in hypertrophic cardiomyopathy patients.

Evaluation of mavacamten in patients with hypertrophic cardiomyopathy.

We aimed to comprehensively assess the safety and efficacy of mavacamten in hypertrophic cardiomyopathy (HCM) patients. A systematic review and meta-analysis was conducted, and efficacy [changes in postexercise left ventricular outflow tract (LVOT) gradient, left ventricular ejection fraction (LVEF), peak oxygen consumption (pVO 2 ), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS), and the proportion of patients exhibiting an improvement of at least one New York Heart Association (NYHA) functional class from baseline)], safety (total count of treatment-emergent adverse events and SAEs, as well as the proportion of patients experiencing at least one adverse event or SAE), and cardiac biomarkers (NT-proBNP and cTnI) outcomes were evaluated. We incorporated data from four randomized controlled trials, namely EXPLORER-HCM, VALOR-HCM, MAVERICK-HCM, and EXPLORER-CN. Mavacamten demonstrated significant efficacy in reducing the postexercise LVOT gradient by 49.44 mmHg ( P = 0.0001) and LVEF by 3.84 ( P < 0.0001) and improving pVO 2 by 0.69 ml/kg/min ( P = 0.4547), KCCQ CSS by 8.11 points ( P < 0.0001), and patients with at least one NYHA functional class improvement from baseline by 2.20 times ( P < 0.0001). Importantly, mavacamten increased 1.11-fold adverse events ( P = 0.0184) 4.24-fold reduced LVEF to less than 50% ( P = 0.0233) and 1.06-fold SAEs ( P = 0.8631). Additionally, mavacamten decreased NT-proBNP by 528.62 ng/l ( P < 0.0001) and cTnI by 8.28 ng/l ( P < 0.0001). Mavacamten demonstrates both safety and efficacy in patients with HCM, suggesting its potential as a promising therapeutic strategy for this condition. Further research is warranted to confirm these results and explore its long-term effects.

Myocardial contractility characteristics of hypertrophic cardiomyopathy patients with and without sarcomere mutation.

Hypertrophic cardiomyopathy (HCM) patients with sarcomere mutationshave an increased riskof heart failure and left ventricular (LV)systolicdysfunction. We hypothesize that sarcomere mutation carriers have abnormal myocardial contractility before LV dysfunction. Therefore, we aimed to associate myocardial contractility with identified sarcomere mutations and predict genotyped HCM patients with sarcomere mutation bythree-dimensional speckle tracking imaging (3D-STI). A retrospective analysis of 117 HCM patients identified 32 genotype-positive (G +) and 85 genotype-negative (G-) patients. Genotype-positive patients had higher globe circumferential strain (GCS), globe longitudinal strain (GLS), and globe radial strain (GRS) (p < 0.05), and multivariate logistic regression revealed that these variables were associated with a positive genetic status (p < 0.05). After the propensity matches other possible influencing factors, we developed three models, named Model GCS, Model GLS, and Model GRS, which could identified genotype-positive HCM patients with excellent performance (AUC of 0.855, 0.833, and 0.870 respectively, all p < 0.001). Genotype-positive HCM patients show a higher myocardial hyper-contractility status than patients without sarcomere mutations. When combined with clinical and echocardiographic markers, the 3D-STI parameters can effectively identify the likelihood of genotype-positive HCM.

Reversible acute heart failure induced by thyrotoxic cardiomyopathy: A case report.

Thyrotoxic cardiomyopathy is a rare but severe complication of thyrotoxicosis, leading to episodes of acute heart failure. This case report highlights a rare presentation of thyrotoxic cardiomyopathy with low-output heart failure, emphasizing the importance of early diagnosis and comprehensive management. The report aims to increase awareness among clinicians about the potential reversibility of this condition and the effective strategies for managing such complex cases. This patient presented with dyspnea and chest constriction, without any antecedent predisposing factors. Subsequently, the patient abruptly manifested symptoms indicative of acute heart failure during outpatient consultation. Electrocardiography revealed rapid atrial fibrillation with type A preexcitation syndrome, whereas cardiac ultrasonography demonstrated global cardiac enlargement with a diminished ejection fraction (EF). After a comprehensive evaluation, the patient was diagnosed with thyrotoxic cardiomyopathy, acute heart failure, and atrial fibrillation with preexcitation syndrome. Immediate interventions comprised diuretic administration, oxygen therapy, and antiarrhythmic agents, addressing acute heart failure concomitant with preexcitation syndrome. Following a fortnight of comprehensive therapeutic measures, the patient was discharged with a prescription for oral medications, notably methimazole. Following the intervention, the patient showed significant improvement with the resolution of heart failure symptoms and dyspnea, restoration of sinus rhythm, improved left ventricular ejection fraction (LVEF improved from 36% to 45%), and normalization of thyroid function. These outcomes underscore the efficacy of the intervention strategy and offer a hopeful prognosis for similar cases. Thyrotoxicosis may cause cardiomyopathy in patients with heart failure that manifests as dilated cardiac chambers. Clinicians should carefully screen patients for this reversible condition. Diagnosis requires a comprehensive assessment of various tests, and the therapeutic goal is to restore normal thyroid function.

Single-center experience with His bundle lead implantation: success rate, implantation method optimization, and lessons learned in 426 patients

Abstract Background Conduction system pacing (CSP) is increasingly used to avoid the development of pacing-induced cardiomyopathy in patients who require a high amount of ventricular pacing. His bundle pacing (HBP) is considered as ideal to achieve the narrowest paced QRS and optimal synchronization in patients with intrinsic narrow QRS or right bundle branch block but also as difficult at implantation. Purpose We analyzed our experience with HBP in terms of time and effort, pacing and sensing results, success rate, and lessons learned for optimization over a time period of 7 years. Methods All consecutive patients in whom HBP was attempted between 6/2016 and 11/2023 were included in this analysis. Implantations were performed using a pacing system analyzer (PSA) with high-resolution electrograms (EGMs). Data on implantation success [selective or non-selective HBP, left bundle branch area pacing (LBBAP)], sensing and pacing parameters, achievement of His bundle current of injury (coi), duration of implantation and fluoroscopy were collected prospectively. These results were compared for the 1st, 2nd, 3rd and 4th quartile of implantations and reasons for improvement or deterioration were analyzed. Results HBP was attempted in 426 patients (78±11 years, 38% female, 90% AV block, left ventricular ejection fraction 54±10 %, 81 single-, 286 dual-, 46 triple-chamber pacemakers, 2 dual- and 11 triple-chamber ICDs) and was successful in 404 patients (95%): 182 non-selective HBP, 206 selective HBP, and 16 LBBAP. R wave amplitude was 4.5±3.5 mV, pacing threshold 1.1 ± 0.6V/1.0 ms. In 16% of patients, a ventricular back-up lead was implanted. A His bundle coi was achieved in 61% of patients. The implantation duration was 92±43 min, fluoroscopy duration 10±8 min. Success rate increased from 89% in the 1st to 99% in the 4th quartile. Improved implantation success was associated with using a stiff 3D steerable sheath, implantation site at the distal His bundle, and an increased number of screw-in turns until a His bundle coi was visible. Conclusions Establishing an implantation routine with 1) a PSA and high-resolution EGMs, 2) use of a stiff 3D steerable sheath, 3) implantation at the distal His bundle with myocardial capture (non-selective HBP) as a back-up, and 4) an increased number of screw-in turns of the lead tip until a His bundle coi is achieved, HBP implantation can be facilitated and results optimized to a highly acceptable implantation effort and a success rate &amp;gt;95%.

Percutaneous left atrial appendage closure for stroke prevention in hypertrophic cardiomyopathy patients with atrial fibrillation

BackgroundPercutaneous left atrial appendage closure (LAAC) is an effective alternative strategy for stroke prevention in patients with atrial fibrillation (AF) at high risk for bleeding with anticoagulation (AC). Efficacy of this strategy in hypertrophic cardiomyopathy (HCM) remains uncertain. ObjectiveThe study aimed to compare risk of stroke in HCM-AF patients treated with LAAC with those treated with AC. MethodsBy use of the TriNetX Global Research Network, HCM-AF patients from 2015 to 2024 were assigned to categories of treatment with LAAC and treatment solely with AC and observed for 3 years for ischemic stroke, systemic embolism, and all-cause mortality. Propensity score matching was used to limit confounders. ResultsOf 14,867 HCM-AF patients identified, 364 (2.5%) were treated with LAAC vs 14,503 (97.5%) treated with AC. HCM LAAC patients were older (72 vs 67 years; P < .001) and had more comorbidities and more prior bleeding events, including higher rate of prior gastrointestinal bleeding (68% vs 18%; P < .001), compared with HCM patients treated solely with AC. After propensity score matching, there was no baseline difference between groups including prior bleeding events (P > .05). During follow-up, HCM patients treated with LAAC had higher rates of ischemic stroke (13% vs 8%; hazard ratio, 1.9; P = .006) and systemic embolism (14% vs 9%; hazard ratio, 1.8; P = .006) but no difference in mortality compared with matched HCM patients receiving AC. ConclusionThese real-world data do not support percutaneous LAAC in HCM-AF patients as the primary treatment strategy during long-term AC to reduce stroke risk. However, LAAC may remain a reasonable option for HCM-AF patients who are unable to tolerate AC because of prohibitive bleeding risk.

Clinical impact of ICD implantation in octogenarians: a longitudinal cohort study

Abstract Background The implantation of defibrillators (ICDs) in patients over 80 years old is becoming increasingly common; however, evidence-based data regarding the actual clinical benefit in this population remain limited and contradictory. While age seems not to affect mortality and arrhythmia risk in octogenarians undergoing secondary prevention, the mortality reduction benefit given by ICD implantation for primary prevention appears to decrease with advancing age, likely due to the high number of non-arrhythmic deaths. Purpose This study aims to assess the long-term incidence of ventricular arrhythmias and mortality in a real-world cohort of octogenarian patients undergoing ICD implants. Methods This was an observational, retrospective, longitudinal cohort study. Demographic, clinical, and radiological data were collected for all patients undergoing ICD implantation between 2014 and 2021. Deaths from all causes and significant arrhythmic events (sustained ventricular tachycardias and ventricular fibrillation) detected during routine device controls and remote monitoring were recorded. Then was performed an univariate Kaplan-Meier analysis, stratifying the population by age in relation to the two study endpoints: ventricular arrhythmias and all-cause mortality. Results Out of a total of 700 patients, 512 underwent ICD implantation before the age of 80 (mean age at implantation 64±12), while 188 underwent ICD implantation after the age of 80 (mean age at implantation 82±3.2). No significant differences were found between these two groups in terms of gender (82% vs. 83% male; p 0.12), indication for implantation (74% vs. 75% primary prevention; p 0.79), and the presence of late gadolinium enhancement (LGE) on cardiac MRI (68% vs. 77%; p 0.14). Octogenarians were more frequently affected by ischemic heart disease (54% vs. 65%; p 0.01) and were more frequently treated with Amiodarone (17% vs. 24%; p 0.02). At the end of the average 8-year follow-up, octogenarians had significantly higher all-cause mortality than younger patients (HR=2.35 [1.88-3.16]; p&amp;lt;0.05), with survival curves diverging from 3 years after implantation. However, ventricular arrhythmic events were significantly reduced in octogenarian patients (HR=0.88 [0.87-0.89]; p&amp;lt;0.05). Conclusions In a real-world population of octogenarian patients, the clinical benefit of ICD implantation for primary prevention appears diminished, considering the trade-off between ventricular arrhythmias and mortality, in both ischemic and non-ischemic cardiomyopathy patients.

Non-invasive electrocardiographic assessment of arrhythmic risk in ischaemic cardiomyopathy patients undergoing revasularisation

Abstract Background Ventricular arrhythmias are a leading cause of death in patients with ischaemic cardiomyopathy (ICM). Ischaemia is thought to increase arrhythmic risk and coronary revascularisation is frequently undertaken to reduce this risk, although the recent REVIVED-BCIS2 trial did not show a difference in the incidence of death, device therapies or sustained arrhythmias in patients assigned to have percutaneous coronary intervention (PCI) compared to optimal medical therapy alone(1). Purpose We assessed the mechanistic effects of revascularisation on arrhythmic risk in patients with ICM using non-invasive electrocardiographic imaging (ECGi). Methods Patients were eligible if they had a left ventricular ejection fraction (LVEF) &amp;lt;40%, extensive coronary disease (BCIS Jeopardy Score≥6) and were scheduled to undergo revascularisation with coronary artery bypass grafting or PCI. ECGi assessment was performed using a 252-electrode vest with anatomical co-registration using a CT thorax. Patients underwent stress perfusion cardiac magnetic resonance (CMR) imaging; both ECGi and CMR were conducted at baseline and 3 months post revascularisation(Figure 1). The primary outcome measure was dispersion of repolarisation measured using global activation recovery interval (ARI) dispersion. Secondary outcome measures included repolarisation time (RT) dispersion, mean ARI and LV ARI dispersion. We also assessed the relationship between ARI dispersion, revascularisation and left ventricular scar burden. Data are presented as mean ± SD or median [IQR]. Results Thirty patients were recruited between 2020-2023; age 67±11 years, 90% male, BMI 28±5 and baseline LVEF was 29±8%. Twelve patients underwent CABG, 18 (60%) had PCI. The BCIS jeopardy score was 10 [9-11] at enrolment and decreased to 2 [0-4] after revascularisation. The LV scar burden at baseline was 15.1±6.5% and the change at 3 months was -0.5±5% (p=0.70). ARI dispersion and LV ARI dispersion were correlated with LV scar burden (r=0.62,p=0.01 and 0.71,p=0.002 respectively). No differences were seen in ARI dispersion (44.5 vs 44.1, p=0.86) or secondary outcome measures before and after revascularisation (RT dispersion: 45.5 vs 44.7, p=0.49; Mean ARI: 281.3 vs 282.6, p=0.74; ARI dispersion: 44.5 vs 44.1, p=0.86; LV ARI dispersion: 38.4 vs 36.7, p=0.39)(Figure 2). The LVEF change on CMR at 3 months was +6.9±10%; no relationship was seen between change in LVEF and ARI dispersion. Conclusion Arrhythmic risk assessed by non-invasive ECGi was not altered by coronary revascularisation. LV ARI dispersion was highly correlated with scar burden, which is not altered by revascularisation. Future work includes analysis of perfusion data. Our results support the findings of the REVIVED arrhythmia study that revascularisation does not reduce arrhythmic risk in patients with ICM(1). ECGi derived LV ARI dispersion correlates with scar and may represent a non-invasive arrhythmic risk assessment tool.Figure 1Figure 2

Prevalence of diabetic cardiomyopathy in patients with type 2 diabetes in a large academic medical center

BackgroundDiabetic cardiomyopathy (DbCM) is characterized by asymptomatic stage B heart failure (SBHF) caused by diabetes-related metabolic alterations. DbCM is associated with an increased risk of progression to overt heart failure (HF). The prevalence of DbCM in patients with type 2 diabetes (T2D) is not well established. This study aims to determine prevalence of DbCM in adult T2D patients in real-world clinical practice.MethodsRetrospective multi-step review of electronic medical records of patients with the diagnosis of T2D who had echocardiogram at UC San Diego Medical Center (UCSD) within 2010–2019 was conducted to identify T2D patients with SBHF. We defined “pure” DbCM when SBHF is associated solely with T2D and “mixed” SBHF when other medical conditions can contribute to SBHF. “Pure” DbCM was diagnosed in T2D patients with echocardiographic demonstration of SBHF defined as left atrial (LA) enlargement (LAE), as evidenced by LA volume index ≥ 34 mL/m2, in the presence of left ventricular ejection fraction (LVEF) ≥ 45%, while excluding overt HF and comorbidities that can contribute to SBHF.ResultsOf 778,314 UCSD patients in 2010–2019, 45,600 (5.9%) had T2D diagnosis. In this group, 15,182 T2D patients (33.3%) had echocardiogram and, among them, 13,680 (90.1%) had LVEF ≥ 45%. Out of 13,680 patients, 4,790 patients had LAE. Of them, 1,070 patients were excluded due to incomplete data and/or a lack of confirmed T2D according to the American Diabetes Association recommendations. Thus, 3,720 T2D patients with LVEF ≥ 45% and LAE were identified, regardless of HF symptoms. In this group, 1,604 patients (43.1%) had overt HF and were excluded. Thus, 2,116 T2D patients (56.9% of T2D patients with LVEF ≥ 45% and LAE) with asymptomatic SBHF were identified. Out of them, 1,773 patients (83.8%) were diagnosed with “mixed” SBHF due to comorbidities such as hypertension (58%), coronary artery disease (36%), and valvular heart disease (17%). Finally, 343 patients met the diagnostic criteria of “pure” DbCM, which represents 16.2% of T2D patients with SBHF, i.e., at least 2.9% of the entire T2D population in this study.ConclusionsOur findings provide insights into prevalence of DbCM in real-world clinical practice and indicate that DbCM affects a significant portion of T2D patients.

Alternating low-rank tensor reconstruction for improved multiparametric mapping with cardiovascular MR Multitasking.

To develop a novel low-rank tensor reconstruction approach leveraging the complete acquired data set to improve precision and repeatability of multiparametric mapping within the cardiovascular MR Multitasking framework. A novel approach that alternated between estimation of temporal components and spatial components using the entire data set acquired (i.e., including navigator data and imaging data) was developed to improve reconstruction. The precision and repeatability of the proposed approach were evaluated on numerical simulations, 10 healthy subjects, and 10 cardiomyopathy patients at multiple scan times for 2D myocardial T1/T2 mapping with MR Multitasking and were compared with those of the previous navigator-derived fixed-basis approach. In numerical simulations, the proposed approach outperformed the previous fixed-basis approach with lower T1 and T2 error against the ground truth at all scan times studied and showed better motion fidelity. In human subjects, the proposed approach showed no significantly different sharpness or T1/T2 measurement and significantly improved T1 precision by 20%-25%, T2 precision by 10%-15%, T1 repeatability by about 30%, and T2 repeatability by 25%-35% at 90-s and 50-s scan times The proposed approach at the 50-s scan time also showed comparable results with that of the previous fixed-basis approach at the 90-s scan time. The proposed approach improved precision and repeatability for quantitative imaging with MR Multitasking while maintaining comparable motion fidelity, T1/T2 measurement, and septum sharpness and had the potential for further reducing scan time from 90 s to 50 s.

Mortality risk score for patients with Chagas cardiomyopathy and pacemaker.

Prognosis of Chronic Chagasic Cardiomyopathy (CCC) patients depends on functional and clinical factors. Bradyarrhythmia requiring pacemaker is a common complication. Prognosis of these patients is poorly studied, and mortality risk factors are unknown. We aimed to identify predictors of death and to define a risk score for mortality in a large cohort of CCC patients with pacemaker. It was an observational, unicentric and prospective study. The endpoint was all-cause mortality. Cox regression was used to identify predictors of death and to define a risk score. Bootstrapping method was used to internal score validation. We included 555 patients and after a mean follow-up of 3.7±1.5 years, 100 (18%) deaths occurred. Predictors of death were: right ventricular dysfunction (HR [hazard ratio] 2.24; 95%CI 1.41-3.53; P = 0.001); heart failure class III or IV (HR 2.16; 95% confidence interval [95%CI] 1.16-4.00; P = 0.014); renal disease (HR 2.14; 95%CI 1.24-3.68; P = 0.006); left ventricular end-systolic diameter > 44mm (HR 1.97; 95%CI 1.26-3.05; P = 0.003); atrial fibrillation (HR 1.94; 95%CI 1.25-2.99; P = 0.003) and cardiomegaly on X-ray (HR 1.87; 95%CI 1.10-3.17; P = 0.020). The score identified patients with: low (0-20 points), intermediate (21-30 points) and high risk (>31points). The optimism-corrected C-statistic of the predictive model was 0.751 (95% CI 0.696-0.806). Internal validation with bootstrapping revealed a calibration slope of 0.946 (95% CI 0.920-0.961), reflecting a small degree of over-optimism and C-statistic of 0.746 (95% CI 0.692-0.785). This study identified predictors of mortality in CCC patients with pacemaker defining a simple, validated and specific risk score.

A Comparison of the Association of Septal Scar Burden on Responses to LBBAP-CRT and BVP-CRT

BackgroundLeft bundle branch area pacing (LBBAP) is an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). However, despite the presence of left bundle branch block, whether cardiac substrate may influence the effect between the 2 strategies is unclear. ObjectivesThis study aims to assess the association of septal scar on reverse remodeling and clinical outcomes of LBBAP compared with BVP. MethodsWe analyzed patients with nonischemic cardiomyopathy who had CRT indications undergoing preprocedure cardiac magnetic resonance examination. Changes in left ventricular ejection fraction (LVEF) and echocardiographic response (ER) (≥5% absolute LVEF increase) were assessed at 6 months. The clinical outcome was the composite of all-cause mortality, heart failure hospitalization, or major ventricular arrhythmia. ResultsThere were 147 patients included (51 LBBAP and 96 BVP). Among patients with low septal scar burden (below median 5.7%, range: 0% to 5.3%), LVEF improvement was higher in the LBBAP than the BVP group (17.5% ± 10.9% vs 12.3% ± 11.8%; P = 0.037), with more than 3-fold increased odds of ER (OR: 4.35; P = 0.033). In high sepal scar subgroups (≥5.7%, range: 5.7%-65.9%), BVP trended towards higher LVEF improvement (9.2% ± 9.4% vs 6.4% ± 12.4%; P = 0.085). Interaction between septal scar burden and pacing strategy was significant for ER (P = 0.002) and LVEF improvement (P = 0.011) after propensity score adjustment. During median follow-up of 33.7 (Q1-Q3: 19.8-42.1) months, the composite clinical outcome occurred in 34.7% (n = 51) of patients. The high-burden subgroups had worse clinical outcomes independent of CRT method. ConclusionsRemodeling response to LBBAP and BVP among nonischemic cardiomyopathy patients is modified by septal scar burden. High septal scar burden was associated with poor clinical prognosis independent of CRT methods.

Pathophysiology and Advances in the Therapy of Cardiomyopathy in Patients with Diabetes Mellitus.

Diabetes mellitus (DM) is known as the first non-communicable global epidemic. It is estimated that 537 million people have DM, but the condition has been properly diagnosed in less than half of these patients. Despite numerous preventive measures, the number of DM cases is steadily increasing. The state of chronic hyperglycaemia in the body leads to numerous complications, including diabetic cardiomyopathy (DCM). A number of pathophysiological mechanisms are behind the development and progression of cardiomyopathy, including increased oxidative stress, chronic inflammation, increased synthesis of advanced glycation products and overexpression of the biosynthetic pathway of certain compounds, such as hexosamine. There is extensive research on the treatment of DCM, and there are a number of therapies that can stop the development of this complication. Among the compounds used to treat DCM are antiglycaemic drugs, hypoglycaemic drugs and drugs used to treat myocardial failure. An important element in combating DCM that should be kept in mind is a healthy lifestyle-a well-balanced diet and physical activity. There is also a group of compounds-including coenzyme Q10, antioxidants and modulators of signalling pathways and inflammatory processes, among others-that are being researched continuously, and their introduction into routine therapies is likely to result in greater control and more effective treatment of DM in the future. This paper summarises the latest recommendations for lifestyle and pharmacological treatment of cardiomyopathy in patients with DM.

Pathology of explanted pediatric hearts: An 11-year study. Population characteristics and implications for outcomes.

As more pediatric patients become candidates for heart transplantation (HT), understanding pathological predictors of outcome and the accuracy of the pretransplantation evaluation are important to optimize utilization of scarce donor organs and improve outcomes. The authors aimed to investigate explanted heart specimens to identify pathologic predictors that may affect cardiac allograft survival after HT. Explanted pediatric hearts obtained over an 11-year period were analyzed to understand the patient demographics, indications for transplant, and the clinical-pathological factors. In this study, 149 explanted hearts, 46% congenital heart defects (CHD), were studied. CHD patients were younger and mean pulmonary artery pressure and resistance were significantly lower than in cardiomyopathy patients. Twenty-one died or underwent retransplantation (14.1%). Survival was significantly higher in the cardiomyopathy group at all follow-up intervals. There were more deaths and the 1-, 5- and 7-year survival was lower in patients ≤10 years of age at HT. Early rejection was significantly higher in CHD patients exposed to homograft tissue, but not late rejection. Mortality/retransplantation rate was significantly higher and allograft survival lower in CHD hearts with excessive fibrosis of one or both ventricles. Anatomic diagnosis at pathologic examination differed from the clinical diagnosis in eight cases. Survival was better for the cardiomyopathy group and patients >10 years at HT. Prior homograft use was associated with a higher prevalence of early rejection. Ventricular fibrosis (of explant) was a strong predictor of outcome in the CHD group. We presented several pathologic findings in explanted pediatric hearts.

IF1 Knockout Protects Against Doxorubicin-Induced Cardiac Dysfunction by Improving Cardiomyocyte Energetics

Doxorubicin (DOX), a member of the Anthracycline antibiotics class, has been used as a potent chemotherapy agent against solid tumors. However, its use is limited by its cardiotoxicity. It is well-documented that mitochondrial dysfunction is one of the main mechanisms of DOX-induced cardiotoxicity. ATP synthase inhibitory subunit 1 (ATPIF1, or IF1) is an endogenous inhibitor of mitochondrial ATP synthase. Recent studies indicate that IF1 may suppress mitochondrial respiration via inhibiting ATP synthase. Others and our previous studies demonstrated that IF1 inactivation exerts hepatic and cardiac protective effects. We hypothesize that the absence of IF1 protects the heart from DOX-induced cardiotoxicity by improving mitochondrial energy metabolism. We first investigate the impact of IF1 KO on mitochondrial respiration using the high-resolution respirometer (OROBOROS) on freshly isolated cardiac mitochondria from IF1 KO and WT mice. IF1 KO mitochondria did show substantially increased state 2, state 3, and state 4 respiration rates compared with those of WT. We then investigated if WT and IF1 KO mice respond differently to DOX treatment. WT and IF1 KO mice at the ages of 12-16 weeks either received DOX 3mg/kg/every other day or vehicle intraperitoneally for two weeks. In vivo, cardiac function was evaluated using the VEVO F2 Echocardiographic system (Visual Sonic) 4 and 6 weeks after initiation of DOX and vehicle administration. Compared with the vehicle-treated WT mice, left ventricular ejection fraction (LVEF) was substantially decreased in DOX-treated WT mice compared with vehicle-treated WT mice. In contrast, LVEF in DOX-IF1 KO mice was substantially less reduced compared with vehicle-treated IF1 KO mice. We next investigated if improving cellular energetics is the critical mechanism underlying the protective effects of IF1 KO. Mouse neonatal cardiomyocyte (NMCM) isolated from WT and IF1 KO mice were cultured and treated with 0.5 and 1mM Dox for 24 hours. Cellular energetics were measured with the Mito stress assay using the Seahorse Bioanalyzer (96Xpro, Agilent). Basal, maximal, and ATP production-linked oxygen consumption rates were markedly decreased in DOX-treated-NMCM but not in DOX-treated IF1 KO NMCM compared with Vehicle-treated NMCM. In summary, the above in vivo and in vitro investigations support that IF1 inactivation is protective against DOX cardiac toxicity, at least partly, via improving cellular energetics; therefore, inactivating IF1 may be a potential therapeutic target to prevent and mitigate DOX-induced cardiomyopathy in patients. This research was supported by project number 5R01HL160969 from the National Heart Lung and Blood Institute at the NIH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sarcoplasmic reticulum (SR)-mitochondria tethering is lost in human heart failure

Sarcoplasmic reticulum (SR)-mitochondria (SR-mito) tethering facilitates communication between these organelles and regulates many physiological processes critical for cardiomyocyte function. Recent evidence suggests that alterations in SR-mito tethering impacts cardiac metabolism and calcium handling which contributes to cardiovascular pathologies, such as heart failure (HF). To characterize SR-mito apposition in cardiac disease we obtained electron microscopy (EM) images of individual cardiomyocytes freshly isolated from failing hearts explanted from ischemic (ICM), ischemic-dilated (ICM-DCM) and dilated cardiomyopathy (DCM) patients undergoing transplantation and nonfailing control hearts. Topographical EM analysis revealed a significant increase in the mean SR-Mito distance, as well as an increase in the minimum SR-mito distance (closest approximation of any single mitochondrion to SR) in ICM, ICM-DCM and DCM cardiomyocytes, compared to nonfailing controls. Results from the EM analysis also revealed that in DCM there was a decrease in mean mitochondrion perimeter in contact with the SR, as well as a decrease in SR in approximation with mitochondria at a distance &lt;50-nm. In agreement, nonfailing hearts had a greater length of outer mitochondrial membrane in close contact (&lt;20-nM) with the SR, as compared to failing cardiomyocytes. ICM and DCM cardiomyocytes displayed an overall reduction in mitochondrion perimeter and circularity, suggesting smaller and more fragmented mitochondria. Surprisingly, failing cardiomyocytes exhibited an overall increase in mitochondrial area compared to nonfailing controls. To define the molecular changes that may underlie loss of SR-mito tethering, we evaluated the expression of several proposed linkers. qPCR analysis of left ventricular samples revealed that mRNA expression of mitofusin 2 is significantly decreased in both hypertrophic cardiomyopathy (HCM) and DCM. Further, other proposed tethering components including FUNDC1, BAP31, DJ-1 and VAPB demonstrated decreased mRNA expression in HCM, DCM and ischemic HF samples, compared to nonfailing controls. IP3R1 displayed increased mRNA expression in HCM and DCM human HF samples, whereas IP3R2 and VDAC1 displayed increases in expression in HCM and ICM. These results highlight that transcriptional remodeling of the components mediating SR-mito tethering and communication may contribute to the observed structural changes in inter-organelle approximation in cardiomyocytes. These studies provide rationale for causal interrogation of the structural mechanisms regulating SR-mito communication in the context of HF progression. Fellowship in Biomedical Sciences, Lewis Katz School of Medicine. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Efficacy of catheter ablation for ventricular tachycardia in ischemic cardiomyopathy patients without an ICD implantation

BackgroundThe implantable cardioverter-defibrillator (ICD) prevents sudden cardiac death in patients with ischemic cardiomyopathy (ICM). Catheter ablation has been shown to effectively reduce ventricular tachycardia (VT) recurrence, yet its efficacy in patients without an ICD implantation remains uncertain. ObjectiveWe aimed to investigate the outcomes of ablation for VT in patients with ICM without a backup ICD. MethodsPatients with ICM who received ablation for VT without an ICD implantation were included in this study. Ablation was guided by either activation mapping or substrate mapping. Endocardial ablation was the primary strategy; epicardial access was considered when endocardial ablation failed. The primary end point was VT recurrence during follow-up; secondary end points included cardiovascular rehospitalization, all-cause mortality, and a composite of these events. ResultsA total of 114 patients were included, with the mean age of 58.2 ± 11.1 years, 102 of whom (89.5%) were male. Twelve patients (10.5%) underwent endo-epicardial ablation, whereas the rest received endocardial ablation. With a median follow-up of 53.8 months (24.8–84.2 months), VT recurred in 45 patients (39.5%), and 6 patients (5.3%) died, including 2 sudden cardiac deaths. The recurrence rate of VT was significantly lower in patients undergoing endo-epicardial ablation than in those with endocardial ablation only (8.3% vs 43.1%; log-rank P = .032). After multivariate adjustment, epicardial ablation remained associated with a reduced risk of VT recurrence (hazard ratio, 0.14; 95% confidential interval, 0.02–0.98; P = .048). ConclusionPatients with ICM undergoing VT ablation without a backup ICD experienced a notably low rate of arrhythmic death. Most recurrences proved nonlethal.