Analysis of risk factors for complications in echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation.

BACKGROUND: The feasibility of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for the treatment of hypertrophic obstructive cardiomyopathy (HOCM) has been previously reported. However, limited investigation has been conducted regarding the complications associated with this procedure. OBJECTIVE: This study aims to analyze the risk factors affecting the occurrence of complications during PIMSRA, such as pericardial effusion, ventricular premature beats, and interventricular septal perforation. In this study, the optimal cut-off values for these risk factors are also explored, and corresponding strategies for prevention are proposed. METHODS: A total of 101 patients diagnosed with HOCM who underwent the PIMSRA procedure from 2021 to 2022 were included in this retrospective analysis. Patients were classified into subgroups with or without complications based on procedural records. Univariate and multivariate regression analyses were conducted to identify independent risk factors for complications during the PIMSRA procedure. RESULTS: There were 48 patients with complications and 53 patients without complications. The heart rate at the start of the procedure and the maximum left ventricular outflow tract gradient (LVOTG) were independent risk factors related to PIMSRA complications. The optimal cut-off values for predicting complication occurrence were a heart rate > 49 bpm at the start of the procedure (OR: 3.79, 95% CI: 1.64-8.78, p = 0.002) and a maximum LVOTG > 92 mmHg (OR: 2.57, 95% CI: 1.15-5.75, p = 0.022), respectively. CONCLUSIONS: The occurrence of PIMSRA complications is primarily associated with the heart rate at the start of the procedure and the maximum LVOTG. It is recommended to establish a comprehensive control plan to minimize the risk of complications during PIMSRA procedures.

Making a case for mitochondria in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a well-known manifestation of inherited mitochondrial disease. Still, currently available gene panels do not include mitochondrial genome sequencing. Mitochondrial dysfunction plays a very important role in the pathogenesis of HCM, whether tested positive or negative by the currently available gene panels for HCM. Mitochondrial DNA variations may act as modifiers of disease manifestation in genotype-positive individuals. In genotype-negative individuals, it may be the primary driver of pathogenesis. A recent study has demonstrated that mitochondrial dysfunction is correlated with septal hypertrophy in genotype-negative HCM, which can be amenable to mitochondria-targeted therapy. It is important to consider mitochondrial genome sequencing as part of the genetic evaluation of HCM.

Hypertrophic cardiomyopathy or 'thick heart' is a common heart problem that can lead to abnormal heart rhythm and even heart failure. In older adults, it is often due to high blood pressure that causes the heart to pump against high resistance and hence becoming thick. However, it can occur without high blood pressure, often in young individuals with underlying heart muscle disease. Sometimes, there are many individuals in a family with thick hearts. In these instances, it is likely genetic. The individual may have a faulty gene related to heart muscle function causing the heart to become thick as an adaptation to inefficient heart muscle function. Mitochondria are tiny organelles inside our cells that make energy. When there is mitochondrial damage, heart muscles cannot generate energy efficiently. This can lead to a thick heart as well. Hence, it is important to test mitochondrial genes along with the heart muscle genes to find the cause of thick heart when it is unexplained, or a genetic cause is suspected.

Complete mitochondrial genomes of patients from Thailand with cardiovascular diseases.

Several previous studies have reported that both variation and haplogroups of mitochondrial (mt) DNA were associated with various kinds of diseases, including cardiovascular diseases, in different populations, but such studies have not been carried out in Thailand. Here, we sequenced complete mtDNA genomes from 82 patients diagnosed with three types of cardiovascular disease, i.e., Hypertrophic Cardiomyopathy (HCM) (n = 26), Long Q-T Syndrome (LQTS) (n = 7) and Brugada Syndrome (BrS) (n = 49) and compared these with 750 previously published mitogenome sequences from interviewed normal individuals as a control group. Both patient and control groups are from the same geographic region of northeastern Thailand. We found 9, 2, and 5 novel mutations that were not both damaging and deleterious in HCM, LQTS, and BrS patients, respectively. Haplogroup R9c was significantly associated with HCM (P = 0.0032; OR = 62.42; 95%CI = 6.892-903.4) while haplogroup M12b was significantly associated with LQTS (P = 0.0039; OR = 32.93; 95% CI = 5.784-199.6). None of the haplogroups was found to be significantly associated with BrS. A significantly higher density of mtDNA variants in the rRNA genes was found in patients with HCM and BrS (P < 0.001) than in those with LQTS or the control group. Effects of detected SNPs in either protein coding or tRNA genes of all the mitogenome sequences were also predicted. Interestingly, three SNPs in two tRNA genes (MT-TA m.5618T>C and m.5631G>A heteroplasmic variants in two BrS patients and MT-TQ m.4392C>T novel homoplasmic variant in a HCM patient) were predicted to alter tRNA secondary structure, possibly leading to abnormal tRNA function.

Investigation of coagulation and proteomics profiles in symptomatic feline hypertrophic cardiomyopathy and healthy control cats.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a crucial heart disease in cats. The clinical manifestations of HCM comprise pulmonary edema, dyspnea, syncope, arterial thromboembolism (ATE), and sudden cardiac death. D-dimer and prothrombin time (PT) are powerful biomarkers used to assess coagulation function. Dysregulation in these two biomarkers may be associated with HCM in cats. This study aims to assess D-dimer levels, PT, and proteomic profiling in healthy cats in comparison to cats with symptomatic HCM. RESULTS: Twenty-nine client-owned cats with HCM were enrolled, including 15 healthy control and 14 symptomatic HCM cats. The D-dimer concentration and PT were examined. Proteomic analysis was conducted by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In symptomatic cats, D-dimer levels were statistically significantly higher (mean ± SEM: 372.19 ng/ml ± 58.28) than in healthy cats (mean ± SEM: 208.54 ng/ml ± 10.92) with P-value of less than 0.01, while PT was statistically significantly lower in symptomatic cats (mean ± SEM: 9.8 s ± 0.15) compared to healthy cats (mean ± SEM: 11.08 s ± 0.23) with P-value of less than 0.0001. The proteomics analysis revealed upregulation of integrin subunit alpha M (ITGAM), elongin B (ELOB), and fibrillin 2 (FBN2) and downregulation of zinc finger protein 316 (ZNF316) and ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) in symptomatic HCM cats. In addition, protein-drug interaction analysis identified the Ras signaling pathway and PI3K-Akt signaling pathway. CONCLUSIONS: Cats with symptomatic HCM have higher D-dimer and lower PT than healthy cats. Proteomic profiles may be used as potential biomarkers for the detection and management of HCM in cats. The use of D-dimer as a biomarker for HCM detection and the use of proteomic profiling for a better understanding of disease mechanisms remain to be further studied in cats.

Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing.

BACKGROUND: Patients with refractory, symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy have few therapeutic options. Right ventricular pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized that site-specific pacing would reduce LVMCO gradients and improve symptoms. METHODS: Patients with symptomatic-drug-refractory LVMCO were recruited for a randomized, blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical right ventricular pacing sites were assessed during an invasive hemodynamic study of multisite pacing. Patient-specific pacing-site and atrioventricular delays, defining PPoP, were selected on the basis of LVMCO gradient reduction and acceptable pacing parameters. Patients were randomized to 6 months of active PPoP or backup pacing in a crossover design. The primary outcome examined invasive gradient change with best-site pacing. Secondary outcomes assessed quality of life and exercise following randomization to PPoP. RESULTS: A total of 17 patients were recruited; 16 of whom met primary end points. Baseline New York Heart Association was 3±0.6, despite optimal medical therapy. Hemodynamic effects were assessed during pacing at the right ventricular apex and at a mean of 8 LV sites. The gradients in all 16 patients fell with pacing, with maximum gradient reduction achieved via LV pacing in 14 (88%) patients and right ventricular apex in 2. The mean baseline gradient of 80±29 mm Hg fell to 31±21 mm Hg with best-site pacing, a 60% reduction (P<0.0001). One cardiac vein perforation occurred in 1 case, and 15 subjects entered crossover; 2 withdrawals occurred during crossover. Of the 13 completing crossover, 9 (69%) chose active pacing in PPoP configuration as preferred setting. PPoP was associated with improved 6-minute walking test performance (328.5±99.9 versus 285.8±105.5 m; P=0.018); other outcome measures also indicated benefit with PPoP. CONCLUSIONS: In a randomized placebo-controlled trial, PPoP reduces obstruction and improves exercise performance in severely symptomatic patients with LVMCO. REGISTRATION: URL: https://clinicaltrials.gov/study; Unique Identifier: NCT03450252.

A personalized mRNA signature for predicting hypertrophic cardiomyopathy applying machine learning methods.

Hypertrophic cardiomyopathy (HCM) may lead to cardiac dysfunction and sudden death. This study was designed to develop a HCM signature applying bioinformatics and machine learning methods. Data of HCM and normal tissues were obtained from public databases to screen differentially expressed genes (DEGs) using the R software limma package. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed for enrichment analysis of HCM-associated DEGs. Hub genes for HCM were determined using weighted gene co-expression network analysis (WGCNA) together with two machine learning algorithms (SVM-RFE and LASSO). Finally, we introduced a zebrafish model to simulate changes in the hub genes in the HCM and to observe their effects on cardiac disease development. The mRNA expression data from a total of 106 HCM tissues and 39 normal samples were collected and we screened 157 DEGs. Enrichment analysis showed that immune pathways played an important role in the pathogenesis of HCM. Three hub genes (FCN3, MYH6 and RASD1) were identified using WGCNA, SVM-RFE, and LASSO analysis. In a zebrafish model, knockdown of MYH6 and RASD1 resulted in cardiac malformations with reduced ventricular capacity and heart rate, which validated the clinical significance of these genes in the diagnosis of HCM. Based on machine learning algorithms, our study created a signature with potential impact on cardiac function and cardiac quality index for HCM. The current findings had important implications for the early diagnosis and treatment of HCM.

Microcirculatory dysfunction in hypertrophic cardiomyopathy with chest pain assessed by angiography-derived microcirculatory resistance.

Chest pain, a common initial symptom in hypertrophic cardiomyopathy (HCM) patients, is closely linked to myocardial ischemia, despite the absence of significant coronary artery stenosis. This study explored microvascular dysfunction in HCM patients by employing angiography-derived microcirculatory resistance (AMR) as a novel tool for comprehensive assessment. This retrospective analysis included HCM patients with chest pain as the primary symptom and control patients without cardiac hypertrophy during the same period. The AMR was computed through angiography, providing a wire-free and adenosine-free index for evaluating microcirculatory function. Propensity score matching ensured balanced demographics between groups. This study also investigated the correlation between the AMR and clinical outcomes by utilizing echocardiography and follow-up data. After matching, 76 HCM patients and 152 controls were analyzed. While there was no significant difference in the incidence of epicardial coronary stenosis, the AMR of three epicardial coronary arteries was markedly greater in HCM patients. The criterion of an AMR ≥ 250 mmHg*s/m was that 65.7% of HCM patients experienced coronary microvascular dysfunction (CMD). Independent risk factors for CMD included increased left ventricular (LV) wall thickness (OR = 1.209, 95% CI 1.013-1.443, p = 0.036). Furthermore, an AMR_LAD ≥ 250 mmHg*s/m had an increased cumulative risk of the endpoint (log-rank p = 0.023) and was an independent risk factor for the endpoint (HR = 11.64, 95% CI 1.13-120.03, p = 0.039), providing valuable prognostic insights.

Metabolic remodeling and calcium handling abnormality in induced pluripotent stem cell-derived cardiomyocytes in dilated phase of hypertrophic cardiomyopathy with MYBPC3 frameshift mutation.

Hypertrophic cardiomyopathy (HCM) is an inherited disorder characterized by left ventricular hypertrophy and diastolic dysfunction, and increases the risk of arrhythmias and heart failure. Some patients with HCM develop a dilated phase of hypertrophic cardiomyopathy (D-HCM) and have poor prognosis; however, its pathogenesis is unclear and few pathological models exist. This study established disease-specific human induced pluripotent stem cells (iPSCs) from a patient with D-HCM harboring a mutation in MYBPC3 (c.1377delC), a common causative gene of HCM, and investigated the associated pathophysiological mechanisms using disease-specific iPSC-derived cardiomyocytes (iPSC-CMs). We confirmed the expression of pluripotent markers and the ability to differentiate into three germ layers in D-HCM patient-derived iPSCs (D-HCM iPSCs). D-HCM iPSC-CMs exhibited disrupted myocardial sarcomere structures and an increased number of damaged mitochondria. Ca2+ imaging showed increased abnormal Ca2+ signaling and prolonged decay time in D-HCM iPSC-CMs. Cell metabolic analysis revealed increased basal respiration, maximal respiration, and spare-respiratory capacity in D-HCM iPSC-CMs. RNA sequencing also showed an increased expression of mitochondrial electron transport system-related genes. D-HCM iPSC-CMs showed abnormal Ca2+ handling and hypermetabolic state, similar to that previously reported for HCM patient-derived iPSC-CMs. Although further studies are required, this is expected to be a useful pathological model for D-HCM.

Identification of differentially expressed genes to predict the risk of heart failure in older patients with hypertrophic cardiomyopathy.

AIM: Hypertrophic cardiomyopathy (HCM) is a common heart disease. Old people with HCM are at high risk of heart failure (HF). This study aimed to identify differentially expressed genes (DEGs) to evaluate the risk of HF in older patients with HCM. METHODS: GSE89714 and GSE116250 were downloaded from Gene Expression Omnibus (GEO) database, and DEGs were identified by using limma R package with P < 0.05 and logFC> 1 as cut off. Protein-protein interaction (PPI) network, Genome Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the identified DEGs. NetworkAnalyst online tool was applied for Gene Set Enrichment Analysis (GSEA) analysis. RESULTS: We identified 124 overlap DEGs from the 2 datasets. PPI network showed that COL1A1, COL3A1, COL1A2, BGN, COL5A1, LUM, TGFB2, FMOD, ASPN, and COL14A1 were the top ten genes related to HCM and HF compared with control. Functional and pathway analyses showed that the overlap genes were mainly related to ECM-receptor interaction, ECM organization, Focal adhesion, PI3K-Akt signaling, TGF-beta signaling, and Platelet activation signaling and aggregation. Among the overlap genes, COL5A1 and LUM were significantly upregulated, while TGFB2, FMOD, ASPN, and COL14A1 were significantly downregulated in HF dataset compared with HCM dataset. CONCLUSIONS: Bioinformatics-based analysis revealed potential genes associated with HCM and HF, which could be utilized to evaluate the risk of HF in older patients with HCM.

Two cardiac myosin inhibitors in the treatment of obstructive hypertrophic cardiomyopathy.

A key area of therapeutic progress in obstructive hypertrophic cardiomyopathy revolves around the emergence of cardiac myosin inhibitors, of which mavacamten and aficamten represent the first and second molecules. We summarize the key research evidence, including many similarities and potential differences between various clinical trials studying these molecules.

Myocardial injury mimicking acute myocardial infarction due to coronavirus infection in adults with pre-existing apical hypertrophic cardiomyopathy.

Symptoms of apical hypertrophic cardiomyopathy (ApHCM) can mimic acute myocardial infarction (AMI). Following COVID-19 infection, the elevation of troponin in ApHCM might be confusing, due to its similarity with AMI. We report the case of a 64-year-old male patient presenting with exertional dyspnoea and chest discomfort. He had no history of coronary artery disease (CAD), but his swab test was positive for COVID-19. The physical examination was normal. The 12-lead electrocardiogram showed a sinus rhythm of 78 bpm, with deep inverted T waves in leads V2 to V6, I, and aVL, and left ventricular hypertrophy. An Echocardiographic examination showed an 18 mm apical wall thickness of the left ventricle. Laboratory tests revealed elevated hs- Troponin level, but diagnostic coronary angiography was normal. The diagnostic criteria fulfilled apical cardiac hypertrophic cardiomyopathy. Coronavirus can induce atypical cardiovascular symptoms in pre-existing ApHCM. Misdiagnosis and failure to recognize may result in inappropriate therapy and delay in definitive treatment.

[Correlation between coronary artery tortuosity and poor prognosis in patients with septal hypertrophic cardiomyopathy].

Objective: To investigate the incidence of coronary artery tortuosity and its correlation with poor prognosis in patients with septal hypertrophic cardiomyopathy (HCM). Methods: This was a retrospective cohort study. Patients with septal HCM who were hospitalized in Fuwai Central China Cardiovascular Hospital and Zhengzhou University People's Hospital between December 1, 2017 and June 10, 2021 were selected. Non-HCM patients were matched by gender, age, and hypertension as control group. Septal HCM was divided into two groups based on the presence or absence of coronary artery tortuosity. Clinical baseline data and coronary angiography findings were compared using a multifactorial logistic analysis of the risk factors for coronary artery tortuosity. Patients were followed up until July 1, 2022, with the primary outcome being the composite endpoint of malignant arrhythmia, ischemic stroke and all-cause death. Incidence densities were compared between the coronary artery tortuosity and non-coronary artery tortuosity groups of septal HCM patients. The Cox risk-ratio model was used to analyze risk factors for primary outcomes in septal HCM patients. Results: There were 156 patients in the septal HCM group and 156 patients in the control group, both aged (57.0±11.4) years, and 75 (48.1%) were female. The incidence of coronary artery tortuosity was significantly higher in the septal HCM group than in the control group (63.5% vs. 36.5%, P<0.01), and the coronary artery tortuosity score was also higher in the septal HCM group than in the control group (P<0.01). Multiple logistic regression analysis showed that septal HCM was a risk factor for coronary artery tortuosity (OR=3.27, 95%CI: 2.02-5.29, P<0.01). In the septal HCM patients, after (2.5±1.2) years of follow-up, the incidence density of primary outcome was significantly higher in the coronary artery tortuosity group than in the non-coronary artery tortuosity group (P=0.02), while each on-point in coronary artery tortuosity score increased the risk of primary outcome by 53% for septal HCM patients (HR=1.53, 95%CI: 1.26-1.86, P<0.01). Conclusions: Patients with septal HCM are more prone to suffer coronary artery tortuosity and suffer from it to a greater extent. Coronary artery tortuosity is an important risk factor for adverse events in patients with septal HCM.

Ongoing assertion of two-dimensional measurements on differentiation type of left ventricular hypertrophy: Focus on inferior vena cava.

BACKGROUND: Left ventricular hypertrophy (LVH), including hypertensive LVH, hypertrophic cardiomyopathy (HCM) and cardiac amyloidosis (CA), is a commonly encountered condition in cardiology practice, presenting challenges in differential diagnosis. In this study, we aimed to investigate the importance of echocardiographic evaluation of the inferior vena cava (IVC) in distinguishing LVH subtypes including hypertensive LVH, HCM, and CA. METHODS: In this retrospective study, patients with common causes of LVH including hypertensive LVH, HCM, and CA were included. The role of echocardiographic evaluation of IVC diameter and collapsibility in distinguishing these causes of LVH was assessed in conjunction with other echocardiographic, clinical, and imaging methods. RESULTS: A total of 211 patients (45% HCM, 43% hypertensive heart disease, and 12% CA) were included in our study. Their mean age was 56.6 years and 62% of them were male. While mean IVC diameter was significantly dilated in CA patients (13.4 mm in hypertensive LVH, 16.0 mm in HCM, and 21.1 mm in CA, p < .001), its collapsibility was reduced (IVC collapsible in 95% of hypertensive patients, 72% of HCM patients, and 12% of CA patients, p < .001). In the analysis of diagnostic probabilities, the presence of both hypovoltage and IVC dilation is significant for CA patients. Although it is not statistically significant, the presence of IVC dilation along with atrial fibrillation supports the diagnosis of HCM. CONCLUSION: In conclusion, although advances in imaging techniques facilitate the diagnosis of LVH, simple echocardiographic methods should never be overlooked. Our study supports the notion that IVC assessment could play an important role in the differential diagnosis of LVH.

Evaluation of the prognostic value of papillary muscle-free strain in patients with hypertrophic cardiomyopathy.

BACKGROUND: The prognosis of hypertrophic cardiomyopathy (HCM) varies from mild disease with a normal life expectancy to heart failure and sudden cardiac death (SCD). The identification of patients who are at high risk for SCD remains challenging. AIMS: In this study, we evaluated the prognostic value of papillary muscle-free strain in HCM patients. METHODS AND RESULTS: Seventy-nine patients with a diagnosis of HCM were included in this study. Patients were divided into low/intermediate-risk (n = 57) and high-risk (n = 22) groups. Two-dimensional (2-D) echocardiography and strain imaging were performed for each patient. The mean age of the study population was 53.85 ± 15.88 years; 47 (59.5%) of them were male. During a mean follow-up duration of 74.45 ± 17.03 months, 12 patients died. A comparison of the low-intermediate and high-SCD risk groups revealed that patients in the high-SCD risk group had greater maximal wall thickness, interventricular septum thickness, posterior wall thickness, and left ventricular mass index (LVMI) and lower (less negative) global longitudinal, anterolateral papillary muscle (ALPM) and posteromedial papillary muscle (PMPM) free strain. Additionally, a history of syncope and ICD implantation were found to be more common in patients with high SCD risk scores. The SCD risk score was positively correlated with the global longitudinal strain, ALPM-free strain, and PMPM-free strain (r = .528, r = .658, and r = .600, respectively; p < .001 for all). Our results showed that the LVMI, presence of syncope, global longitudinal strain, and ALPM-free strain were predictors of death. CONCLUSIONS: Decreased papillary muscle-free strain values might have prognostic value in patients with HCM.

[Bibliometrics Analysis of Studies on Hypertrophic Cardiomyopathy From 2018 to 2022].

Objective To analyze the research progress and hot topics in hypertrophic cardiomyopathy from 2018 to 2022.Methods The publications in the field of hypertrophic cardiomyopathy from January 1,2018 to December 31,2022 were retrieved from Web of Science core collection database and included for a bibliometric analysis.Results A total of 6355 publications were included,with an average citation frequency of 7 times.The year 2021 witnessed the most publications (1406).The analysis with VOSviewer showed that the research on sudden death related to hypertrophic cardiomyopathy,especially the predictive value of late gadolinium-enhanced cardiac MRI in sudden death,was a hot topic.In addition,gene detection and the new drug mavacamten became hot research topics.The United States was the country with the largest number of publications and the highest citation frequency in this field.Chinese scholars produced the second largest number of publications,which,however,included few high-quality research results.Conclusions Risk stratification and prevention of sudden death is still an important and hot research content in the field of hypertrophic cardiomyopathy.Chinese scholars should carry out multi-center cooperation in the future to improve the research results.