End-stage Hypertrophic Cardiomyopathy Research Articles

Influencing and prognostic factors of end-stage hypertrophic cardiomyopathy.

End-stage hypertrophic cardiomyopathy (ES-HCM) is a disease with severe complications and a poor prognosis. This study aimed to explore the influencing and prognostic factors of ES-HCM. A total of 1282 patients with HCM who were hospitalized for the first time at Fujian Medical University Union Hospital between 1 January 2013 and 30 September 2021 were recorded. The patients with HCM and left ventricular ejection fraction (LVEF)<50% were defined as having ES-HCM, and a control group (LVEF≥50%) was generated from the collected medical records of HCM. The patients were matched in a ratio of 4:1 based on age and sex. Logistic regression analysis was used to determine the influencing factors of ES-HCM. Kaplan-Meier survival analysis was performed to analyse the clinical outcomes of ES-HCM patients. A total of 250 inpatients with HCM were enrolled in the study; 50 patients had ES-HCM, and 200 had HCM with LVEF≥50%. The mean age of the patients at enrolment was 62.5±10.3years, and 215 patients (215/250, 86.0%) were male. The median follow-up time of the patients was 2.8 (1.4-5.4) years. The incidence of all-cause death and cardiovascular death in patients with ES-HCM was higher than those in patients with HCM and LVEF≥50% (22/50 [44.0%] vs. 13/200 [6.5%]; 12/50 [24.0%] vs. 4/200 [2.0%], all P<0.001). Multivariate logistic regression analysis showed that the influencing factors associated with ES-HCM included age at first symptom onset (odds ratio [OR]=0.95, 95% CI [0.90, 1.00], P=0.042), New York Heart Association (NYHA) class (OR=7.73, 95% CI [2.93, 20.41], P<0.001), heart rate (OR=1.07, 95% CI [1.02, 1.12], P=0.003), QRS duration (OR=1.03, 95% CI [1.00, 1.05], P=0.020), left ventricular end-diastolic diameter (LVEDD) (OR=1.15, 95% CI [1.04, 1.28], P=0.006), left atrial anteroposterior diameter (LAD) (OR=1.13, 95% CI [1.03, 1.24], P=0.012), and maximum left ventricular wall thickness (MLVWT) (OR=0.80, 95% CI [0.68, 0.93], P=0.005). Among the 50 patients with ES-HCM, NYHA class (P<0.001) and heart rate (P=0.017) were each associated with a higher likelihood and earlier occurrence of heart transplantation or all-cause mortality in univariate analyses. The influencing factors for ES-HCM included the age at first symptom onset, NYHA class, heart rate, QRS duration, LVEDD, LAD, and MLVWT. Both NYHA class and heart rate were related to the prognosis of ES-HCM.

Patterns of Left Ventricular Remodelling in Children and Young Patients with Hypertrophic Cardiomyopathy.

Introduction: The aim of this study was to evaluate the age at onset, clinical course, and patterns of left ventricular (LV) remodelling during follow-up in children and young patients with hypertrophic cardiomyopathy (HCM). Methods: We included consecutive patients with sarcomeric or non-syndromic HCM below 18 years old. Three pre-specified patterns of LV remodelling were assessed: maximal LV wall thickness (MLVWT) thickening; MLVWT thinning with preserved LV ejection fraction; and MLVWT thinning with progressive reduction in LV ejection fraction (hypokinetic end-stage evolution). Results: Fifty-three patients with sarcomeric/non-syndromic HCM (mean age 9.4 ± 5.5 years, 68% male) fulfilled the inclusion criteria. In total, 32 patients (60%) showed LV remodelling: 3 patients (6%) exhibited MLVWT thinning; 16 patients (30%) showed MLVWT thickening; and 13 patients (24%) progressed to hypokinetic end-stage HCM. Twenty-one patients (40%) had no LV remodelling during follow-up. In multivariate analysis, MLVWT was a predictor of the hypokinetic end-stage remodelling pattern during follow-up (OR 1.17 [95%CI 1.01-1.36] per 1 mm increase, p-value 0.043), regardless of sarcomeric variants and New York Heart Association class. Two patients with sarcomeric HCM, showing a pattern of MLVWT regression during childhood, experienced progression during adolescence. Conclusions: Different patterns of LV remodelling were observed in a cohort of children with sarcomeric/non-syndromic HCM. Interestingly, a pattern of progressive MLVWT thinning during childhood, with new progression of MLVWT during adolescence, was noted. A better understanding of the remodelling mechanisms in children with sarcomeric HCM may be relevant to defining the timing and possible efficacy of new targeted therapies in the preclinical stage of the disease.

Long-term post-transplantation outcomes in patients with hypertrophic cardiomyopathy: Single-center 35-year experience.

Heart transplantation (HT) is the only option for most patients with end-stage heart failure and hypertrophic cardiomyopathy (HCM) who fail medical therapy. Data on the long-term outcomes post-transplant in HCM individuals remain scarce. We analyzed data of 319 adult patients who underwent HT between 1984 and 2019. Patients were followed for cardiac allograft rejection, cardiac allograft vasculopathy (CAV), death, or re-transplantation. Outcomes of 24 patients with HCM, 160 with ischemic, and 135 with dilated cardiomyopathy were compared. During a mean follow-up of 11.6±7.2 (max 27.8), 16.7±8.2 (max 32.7), and 16.1±9.7 (max 34.6) years after HT in hypertrophic, ischemic, and dilated cardiomyopathy groups, respectively: 10-year survival rate was 67%, 62%, 69%, respectively (p=.04). Post-transplantation, HCM individuals more often than the other two studied groups required prolonged inotropic support (37%, 12%, 17%, respectively, p=.02), temporary mechanical circulatory support (45%, 13%, 14%, respectively, p<.01), and renal replacement therapy immediately post-HT (55%, 19%, 24%, respectively, p<.01). No significant inter-group differences were noted in the 10-year freedom from acute allograft rejection (38%, 46%, 43%, respectively, p=.38) or 10-year freedom from CAV (88%, 78%, 81%, respectively, p=.57). The long-term post-transplant prognosis of adult patients with hypertrophic cardiomyopathy is favorable despite more challenging immediate post-HT course.

Clinical characteristics and outcome of end stage hypertrophic cardiomyopathy: Role of age and heart failure phenotypes

BackgroundA minority of patients with hypertrophic cardiomyopathy (HCM) presents advanced heart failure (HF) during their clinical course, in the context of left ventricular (LV) remodeling with reduced LV ejection fraction (LVEF), or of severe diastolic dysfunction without impaired LVEF. Aim of this study was to describe a multicentric end stage (ES) HCM population and analyze clinical course and outcome among its different phenotypes. MethodsData of all HCM patients from 7 Italian referral centres were retrospectively evaluated. ES was diagnosed in presence of: LVEF <50% (ES-rEF) or NYHA functional class ≥II with severe diastolic dysfunction (ES-pEF). Outcomes were: HCM-related and all-cause mortality; combined arrhythmic events; advanced HF treatments. ResultsStudy population included 331 ES patients; 87% presented ES-rEF and 13% ES-pEF. At ES recognition, patients with ES-pEF were more commonly females, had more frequently NYHA III/IV, atrial fibrillation and greater maximal LV wall thickness. Over a median follow-up of 5.6 years, 83 (25%) patients died, 46 (15%) experienced arrhythmic events and (26%) 85 received advanced HF treatments. Incidence of HCM-related and all-cause mortality, and of combined arrhythmic events did not differ in ES-pEF and ES-rEF patients, but ES-pEF patients were less likely to receive advanced HF treatments. Older age at ES recognition was an independent predictor of increased HCM-related mortality (p = 0.01) and reduced access to advanced HF treatments (p < 0.0001). ConclusionsTwo different HCM-ES phenotypes can be recognized, with ES-pEF showing distinctive features at ES recognition and receiving less frequently advanced HF treatments. Older age at ES recognition has a major impact on outcomes.

Abstract 13383: Is Genotype Negative Hypertrophic Cardiomyopathy Really Benign? The Increased Risk of Sudden Death and Advanced Heart Failure in the Absence of Pathogenic Sarcomere Mutations

Introduction: The genetic basis of hypertrophic cardiomyopathy (HCM) is complex, and the genotype-phenotype correlations have not been completely resolved. Patients lacking a pathogenic variant are presumed to have a better prognosis than patients with sarcomeric pathogenic mutations. Aim: We sought to assess the relationship between the genotype status and the adverse clinical events. Methods: Consecutive patients with HCM underwent genetic testing focused on HCM-related genes. Patients with pathogenic or likely pathogenic variants were considered genotype positive (G+), and those without definite disease-causing mutation were considered genotype negative (G-). Patients were followed for 5.2 ±4.9 years for outcomes. Sudden death (SD) events included out-of-hospital cardiac arrests, appropriate ICD interventions, and HCM-related death. Results: Of 988 HCM patients, 212 (21%) were G+, while 776 (79%) were G -. As compared to G-, G+ HCM patients were younger (45 ± 14 vs. 53 ± 13 years), had more extensive LV hypertrophy (maximum wall thickness: 19.6 ± 5 mm vs. 18.4 ± 4 mm, p&lt;0.001), and with no difference in the presence of LVOT obstruction (59% vs. 66%, p=0.06). Despite G- status, 3% of G- patients had extensive scarring on cardiac MRI (≥15% of LV mass; no different from G+, p=0.54). Over follow-up, 66 patients had SD events. While SD events were more common in G+ patients (11.3% vs. 5.4%, p=0.002), the majority of SD events occurred in G- patients (64%). Similarly, end-stage HCM developed 54 patients, more commonly in G+ (9.0% vs. 4.5%, p=0.01), but with majority of events in G- patients (65%). Conclusion: Contrary to certain prevailing views, in this large consecutive genotyped HCM cohort, sarcomere genotype-negative patients (representing a distinctive majority) did not express an entirely benign prognosis. In fact, nearly two-thirds of SD events and end-stage HF progression occurred in G- HCM patients, albeit at somewhat lower rates than in G+ patients. These data do not support that genotype should not be included as a risk marker of adverse arrhythmic and advanced heart failure events.

The Persistent Hazard in Young Children With End-Stage Hypertrophic Cardiomyopathy

The Persistent Hazard in Young Children With End-Stage Hypertrophic Cardiomyopathy

Relation of delayed intrinsicoid deflection of the QRS complex to sudden cardiac death in patients with hypertrophic cardiomyopathy

AimsPredictors of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) do not include ECG variables. Intrinsicoid deflection (ID) represents the early ventricular depolarization on surface ECG. Delayed ID (DID) has been associated with sudden cardiac arrest (SCA) in the community.In a cohort of consecutive patients with HCM, we assessed whether DID predicts SCA or its surrogates. MethodsWe reviewed ECG, clinical and follow-up data of 344 consecutive HCM patients. DID (ID ≥50 ms) was classified as lateral (leads I or aVL), inferior (leads II, III or aVF), and precordial (leads V5 or V6). The endpoint was a combination of SCD, resuscitated SCA or appropriate ICD intervention. ResultsThe SCA group was composed by 2 secondary prevention ICD recipients and 23 patients that reached the endpoint during follow-up (108 ± 73 months). SCA patients had more frequently massive LV hypertrophy (LVH) or end-stage HCM. ECG indexes of LVH were comparable between SCA and controls. SCA patients were more likely to have DID on ECG lateral leads I/aVL (72% vs 44%; p = 0.008). A non significant trend was observed for inferior and V5/V6 leads. DID I/aVL was associated with SCA in multivariate analysis after correction for massive LVH and end-stage disease (HR: 2.86; 95%CI: 1.14–7.13; p = 0.02). ConclusionsIn HCM patients DID is associated with increased risk of SCA. Its prognostic value extends beyond that of LVH. If confirmed in prospective studies, the prognostic power of this ECG marker could be used to refine risk prediction.

Waitlist and Posttransplant Outcomes of Children and Young Adults With Hypertrophic Cardiomyopathy

BackgroundHeart transplantation (HT) is standard therapy for end-stage hypertrophic cardiomyopathy (HCM); however, few studies have described outcomes of older children and young adults with HCM listed for HT. Our objective was to compare waitlist and post–HT outcomes among pediatric and young adult patients with HCM and dilated cardiomyopathy (DCM). MethodsThe Scientific Registry of Transplant Recipients was queried for patients with HCM and DCM listed at ≤25 years of age. Patient characteristics, waitlist and post–HT survival were compared between younger (≤5 years of age) and older (>5 to ≤25 years of age) HCM patients and between HCM and DCM patients. ResultsAmong 6252 patients listed for HT at ≤25 years of age with DCM and HCM, 3926 and 250 were in the older cohort and 1944 and 132 were in the younger cohort, respectively. Older HCM patients were less likely to be critically ill at listing compared with younger HCM patients (P = .0001). Waitlist mortality was similar between HCM and DCM patients in both age cohorts. Post-HT survival in HCM patients was similar between the age cohorts. In the younger cohort, early post-HT survival was worse in HCM compared with DCM (P = .009), with no difference in long-term survival. Survival was similar between the older cohorts. ConclusionsOlder children and young adults with HCM are less critically ill than the younger cohort and show waitlist and post-HT survival similar to DCM patients. The young children with HCM had worse early posttransplantation survival, though long-term survival was same as DCM.

Very long-term prognosis in patients with hypertrophic cardiomyopathy: a longitudinal study with a period of 20years.

AimsWe aim to clarify the prognosis on patients with hypertrophic cardiomyopathy (HCM) for a follow‐up period of more than 10 years.Methods and resultsWe retrospectively analysed 102 consecutive patients with HCM diagnosed by 31 December 2000. Complete and detailed clinical records were obtained for 93 (91%) of the 102 patients. Sixty‐three (68%) of the 93 patients were men, and the mean age of the patients at the initial evaluation was 51.5 ± 13.0 years. During the mean follow‐up period of 19.6 ± 8.1 years (median 20.1 years), HCM‐related deaths occurred in 20 patients (21% [1.1%/year]). HCM‐related adverse events (including HCM‐related deaths and nonfatal HCM‐related events: hospitalization for heart failure, embolic stroke admission, and sustained ventricular tachycardia with haemodynamic instability or appropriate implantable cardioverter‐defibrillator discharge) occurred in 45 patients (48%). The first HCM‐related adverse events occurred in approximately 20% of the patients in every decade, the first decade to the third decade, from the initial evaluation. Forty‐seven patients (51%) had documentation of atrial fibrillation at the last follow‐up. There were seven patients in the end‐stage HCM group at the initial evaluation, and 22 patients (24%) had progression to end‐stage HCM during the follow‐up period.ConclusionsIn our cohort of patients, HCM‐related mortality was relatively favourable. However, approximately half of the patients suffered from HCM‐related adverse events during the follow‐up period of 20 years. It is important for HCM patients to be carefully followed up over the long‐term because HCM is a lifelong disease.

Temporal Changes in Cardiac Morphology and Its Relationship with Clinical Characteristics and Outcomes in Patients with Hypertrophic Cardiomyopathy

In this study, we aimed to assess a large cohort of nonapical hypertrophic cardiomyopathy (HC) patients who have undergone 2 serial cardiac magnetic resonance studies to examine morphological dynamics and their correlation to patient characteristics and clinical outcomes. A total of 214 patients with nonapical HC were enrolled in this study, with 2 sequential cardiac magnetic resonance studies separated by a mean interval of 4.8±2.1years. Progression of indexed left ventricular mass (LVMI) was correlated with lower LVMI at baseline (p<0.00001) and older age >50 years. In terms of maximal wall thickness (MWT), progression was associated with lower baseline MWT and with the presence of LV outflow tract obstruction. No association was demonstrated between the degree of progression of LVMI or MWT and baseline LV volumes, the severity of mitral regurgitation, gender, or the presence of pathogenic HC variants. Progression of left atrial size was significantly associated with the development of atrial fibrillation (p=0.014; odds ratio 1.18, confidence interval 1.03 to 1.35) and admission for heart failure (p=0.018; odds ratio 1.18, confidence interval 1.03 to 1.36). No correlation was demonstrated between changes in LV mass or MWT and clinical outcomes of admission for heart failure, progression to New York Heart Association 2/3, progression to end-stage HC, or implantable cardioverter-defibrillator implantation. In conclusion, our study provides novel insights into the natural history of HC from a morphological perspective. It shows that HC is a dynamic disease in which LV morphology and hypertrophy extent change over time, with the presence of risk factors associated with disease progression.

P295 EXERCISE OXYGEN KINETIC IN HYPERTROPHIC CARDIOMYOPATHY: RESULTS FROM A MULTICENTER CARDIOPULMONARY EXERCISE TESTING STUDY

Abstract Aims Reduced cardiac output (CO) has been considered crucial in symptoms’ genesis in hypertrophic cardiomyopathy (HCM). We evaluated the cardiopulmonary exercise testing (CPET) response in HCM focusing on parameters strongly associated with stroke volume (SV) and cardiac output (CO), such as oxygen uptake (VO2) and O2–pulse, considering both their absolute values and temporal behavior during physical exercise. Methods and Results We enrolled 312 non–end stage HCM patients, divided according to left ventricle outflow tract obstruction (LVOTO) at rest or during Valsalva maneuver (72% with LVOTO&amp;lt;30; 10% between 30 and 49 and 18% ≥ 50mmHg). Peak VO2 (percent of predicted), O2–pulse and ventilation to carbon dioxide production (VE/VCO2) slope did not change across LVOTO groups. Ninety–six (31%) HCM patients presented an abnormal O2–pulse temporal behavior, irrespective of LVOTO values. These patients showed lower peak systolic pressure, workload (106±45 vs. 130±49W), VO2 (74±17 vs. 80±20%) and O2–pulse (12 [9–14] vs. 14 [11–17]ml/beat), with higher VE/VCO2 slope (28 [25–31] vs. 27 [24–31]) (p &amp;lt; 0.005 for all). Only 2 patients had an abnormal VO2/work slope. Conclusion None of CPET parameters, either as absolute values or dynamic relationships, were associated with LVOTO. Differently, an abnormal O2–pulse exercise behavior, which is strongly related to inadequate SV during exercise, correlates with reduced functional capacity (peak and anaerobic threshold VO2 and workload) and increased VE/VCO2 slope, helping identifying more advanced disease irrespectively of LVOTO. Adding O2–pulse kinetics evaluation to standard CPET could lead to a potential incremental benefit in terms of HCM prognostic stratification and, then, therapeutic management.

Single Nucleus RNA-sequencing Reveals Altered Intercellular Communication and Dendritic Cell Activation in Nonobstructive Hypertrophic Cardiomyopathy.

End stage, nonobstructive hypertrophic cardiomyopathy (HCM) is an intractable condition with no disease-specific therapies. To gain insights into the pathogenesis of nonobstructive HCM, we performed single nucleus RNA-sequencing (snRNA-seq) on human HCM hearts explanted at the time of cardiac transplantation and organ donor hearts serving as controls. Differential gene expression analysis revealed 64 differentially expressed genes linked to specific cell types and molecular functions. Analysis of ligand-receptor pair gene expression to delineate potential intercellular communication revealed significant reductions in expressed ligand-receptor pairs likely affecting the extracellular matrix, growth factor binding, peptidase regulator activity, platelet-derived growth factor binding and protease binding in the HCM tissue. Changes in Integrin-β1 receptor expression were responsible for many observed changes related to extracellular matrix interactions, by increasing in dendritic, smooth muscle and pericyte cells while decreasing in endothelial and fibroblast cells, suggesting potential mechanisms for fibrosis and microvascular disease in HCM and a potential role for dendritic cells. In contrast, there was an increase in ligand-receptor pair expression associated with adenylate cyclase binding, calcium channel molecular functions, channel inhibitor activity, ion channel inhibitor activity, phosphatase activator activity, protein kinase activator activity and titin binding, suggesting important shifts in various signaling cascades in nonobstructive, end stage HCM.

MicroRNAs as Biomarkers in Hypertrophic Cardiomyopathy: Current State of the Art.

Hypertrophic Cardiomyopathy (HCM) is the most common inherited Cardiomyopathy. The hallmark of HCM is myocardial fibrosis that contributes to heart failure, arrhythmias and sudden cardiac death. Currently, there are no reliable serum biomarkers for the detection of myocardial fibrosis, while cardiac magnetic resonance (CMR) is an imaging technique to detect myocardial fibrosis. MicroRNAs (miRNAs) have been increasingly suggested as biomarkers in cardiovascular diseases. However, in HCM there is as yet no identified and verified specific circulating miRNA signature. We conducted a review of the literature to identify the studies that indicate the possible roles of miRNAs in HCM. From studies in transgenic mice with HCM, miR-1, -133 may identify HCM in the early asymptomatic phase. Human miR-29a could be used as a circulating biomarker for detection of both myocardial hypertrophy and fibrosis in HCM, while it could also have a possible additional role in discrimination of hypertrophic obstructive cardiomyopathy from non-obstructive HCM. Additionally, miR-29a-3p is associated with diffuse myocardial fibrosis in HCM, while miR-1-3p could discriminate end-stage HCM from dilated cardiomyopathy and left ventricle dilation. Another role of miRNAs could also be the contribution in the differential diagnosis between HCM and phenocopies. Moreover, miRNA- targeted therapy (miR-133 mimics) is promising in inhibiting cardiac hypertrophy, but this is still in the early stages. A more reliable and specific signature of miRNAs is expected with forthcoming studies in samples from HCM patients and correlation of miRNAs with CMR and serum markers of fibrosis may implicate novel diagnostic and therapeutic pathways.

Differences in clinical features of hypertrophic cardiomyopathy with or without left ventricular enlargement.

Few studies have focused on the clinical features of hypertrophic cardiomyopathy (HCM) with enlarged left ventricle (ELV). In this study, participants were patients with HCM (n=170), who were divided into two groups [ELV and normal left ventricle (NLV)] according to left ventricle size. Age at diagnosis, sex, complications, electrocardiogram (ECG), symptoms, drug treatment, and echocardiographic parameters were compared between the NLV (n=153) and ELV (n=17) groups. The incidence of end-stage HCM (ES-HCM) among all HCM patients was 5.29%, while that of ELV was 10.0%. For all patients with HCM and those with asymmetric septal HCM (ASHCM), there were more males with ELV than NLV. Of the patients with HCM and ASHCM, left ventricular ejection fraction (LVEF) was significantly lower in the ELV group than the NLV group; accordingly, the rates of diuretics use in the ELV group were higher than those in the NLV group. Among apical HCM (ApHCM) patients, the left atrial diameter (LAd), incidence of atrial fibrillation (Af) or ST-T change, and rate of angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) use were all higher in the ELV group compared to the NLV group. These findings suggest that the prevalence of ES-HCM in HCM patients with ELV was higher than those with NLV. Additionally, ELV is more common in men than women and there are differences in the clinical features of different types of HCM with ELV.

Post-Heart Transplant Outcomes in Patients with Hypertrophic Cardiomyopathy (HCM) before and after the 2018 UNOS Heart Allocation Policy Change

<h3>Purpose</h3> Patients with end-stage HCM, the most common genetic cardiovascular condition, often require heart transplant (HT) but there is limited data assessing outcomes. We sought to assess the effect of the 2018 UNOS Heart Allocation policy changes on patients with HCM which increased prioritization for this population. <h3>Methods</h3> 128 patients with HCM received HT in the year before and after the UNOS policy changes. Pre- (n=65) and post-policy (n=63) cohorts were identified using the UNOS registry. Baseline characteristics were compared using standard statistical analysis. 30- and 180-day outcomes were evaluated using Kaplan Meier survival analysis as well as univariate and multivariate Cox proportional hazards modeling. <h3>Results</h3> Baseline characteristics were similar for both groups, but differed in median [IQR] distance (nm) from donor and treatment center (pre: 91 [17, 253]; post: 245 [100.5, 393]; p=0.002) and median PA pressure (mm/Hg) at registration (pre: 38 [30, 49.2]; post: 45 [31, 58], p=0.036). Donor characteristics differed in mean BMI (pre: 26.1 (SD 7.2); post: 28.9 [SD 7.2]). Pre- and post-policy 30-day survival was 100% (CI 100%, 100%) and 95% (CI 90%, 100%) respectively. Pre- and post- 180-day survival was 94% (CI 88%, 100%) and 90% (CI 83%, 98%). Cox univariate hazard ratio (HR) following the UNOS change was 1.62 (CI 0.46, 5.73, p=0.5). Multivariate Cox proportional HR adjusted for recipient age, donor age, serum creatinine, total bilirubin, ischemic time, pre-transplant dialysis, ventilator and ECMO status was 1.54 (CI 0.39, 6.09, p=0.5). <h3>Conclusion</h3> UNOS policy changes did not adversely affect survival at 30 and 180 days for patients with HCM receiving HT. Additional research is needed to evaluate the effects these policy changes have on patients with HCM.

A Simple Algorithm for a Clinical step-by-step Approach in the Management of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease with an autosomal dominant pattern and a reported prevalence of about 0.2%. In this review, we present a simple algorithm for the management of first diagnosed HCM patients. Initially, the clinical examination, medical and detailed family history and the ECG are essential. The etiological diagnosis of left ventricular hypertrophy is important in order to differentiate HCM due to sarcomeric genes mutation from other phenocopies, such as cardiac amyloidosis. The next step consists of the cardiovascular imaging and ambulatory electrocardiography. Cardiopulmonary exercise testing may also be considered if available. All of the above provide evidence for the critical step of the risk stratification of patients for sudden cardiac death. The therapeutic strategy, with respect to obstructive and nonobstructive disease, arrhythmias and end-stage HCM is also described.

Elevation of high-sensitivity cardiac troponin T and left ventricular remodelling in hypertrophic cardiomyopathy.

AimsHypertrophic cardiomyopathy (HCM) is generally associated with mild disability and normal life expectancy. On the other hand, once the end‐stage phase of HCM characterized by left ventricular (LV) ejection fraction < 50% is established, patients with this subtype have a poor prognosis. This study clarifies the clinical parameters associated with progression to end‐stage HCM.Methods and resultsWe retrospectively studied 157 HCM patients (age 59.9 ± 14.2 years, 104 men) with preserved LV systolic function in whom subsequent echocardiographic data were obtained for a period of >1 year. HCM progressed to end‐stage HCM in 13 patients (8.3%) of the 157 patients during a mean follow‐up period of 6.3 ± 2.8 years. Compared with patients who did not reach end‐stage HCM at the last evaluation, patients with progression to the end‐stage phase had lower ejection fraction, larger LV size, more enlarged left atrial diameter, longer follow‐up period, and higher frequency of an elevated concentration of high‐sensitivity cardiac troponin T (hs‐cTnT; >0.014 ng/mL) at registration. Multivariate analysis revealed that elevated hs‐cTnT was a significant predictor independent of lower LV ejection fraction for progression to end‐stage HCM. Furthermore, in patients with elevated hs‐cTnT levels, LV ejection fraction became significantly lower, LV end‐diastolic diameter increased, and LV wall thickness decreased during the follow‐up period, whereas those parameters did not change in the normal hs‐cTnT group.ConclusionsIn patients with HCM, an elevated hs‐cTnT was associated with progression of LV remodelling, and this biomarker can be useful for predicting progression to the end‐stage phase.

Use of sacubitril/valsartan as 'bridge to transplant'in patients with end-stage hypertrophic cardiomyopathy.

The endstage or burned-out phase is an uncommon but challenging clinical evolution of hypertrophic cardiomyopathy (HCM). The management of end-stage HCM is empirically based on the use of drugs approved for heart failure with reduced ejection fraction; however, cardiac transplantation often represents the best option to improve survival. In our case, we describe the use of sacubitril/valsartan as a 'bridge to transplant' in a patient with end-stage HCM. After introducing the drug, enhancements in functional capacity, a reduction in natriuretic peptides and an increase in left ventricular ejection fraction occurred. Given their improved volume of oxygen consumption (VO2)peak and hemodynamic parameters, our patient was left off the waiting list for cardiac transplant and continues to be regularly followed-up with every 3months.

Telehealth monitoring for hypertrophic cardiomyopathy and amyloid cardiomyopathy patients: lessons from the coronavirus disease 2019 lockdown in Italy.

To the Editor As a result of the coronavirus disease 2019 (COVID-19) lockdown imposed beginning on 9 March 2020, Italian hospitals were required to postpone or even halt outpatient visits deemed as nonurgent. Methods The Hypertrophic Cardiomyopathy (HCM) Outpatient Clinic at the Ospedale Policlinico San Martino, Genova, regularly follows patients affected by HCM and cardiac amyloidosis. At the beginning of the COVID-19 lockdown an already operating service for patients’ communications (via telephone and E-mail) was implemented, and each patient with a scheduled visit in the forthcoming weeks (up to 15 May 2020) was contacted by a medical trainee to assess urgency related to her/his medical evaluation. According to information collected via the telemedical contact, patients were divided into ‘stable’ (group-A) and ‘potentially unstable’ (group-B). Patients were deemed as ‘potentially unstable’ if one or more of the following were present: signs and/or symptoms of heart failure, in particular if worsening relatively to the precontact condition; known end-stage HCM; heart failure hospitalization(s) and/or more than three outpatients evaluations in the prior 6 months. Those in group-B received weekly telemedical contact to monitor their conditions. Results Forty patients (27 males, median age: 62 years) received a telecontact, of whom 28 were HCM and 12 were cardiac amyloidosis patients. Nineteen patients were deemed as ‘potentially unstable’ (10 cardiac amyloidosis and 9 HCM). The main reason for inclusion in group-B was a recent heart failure hospitalization. Characteristics of patients in group-A versus B are shown in Table 1. As of 7 May 2020 no patients in group-A sought medical attention outside the planned telemedical contacts, and none needed an outpatient visit or hospitalization. In group-B, eight patients needed unplanned medical attention. In four instances, their needs were managed via telecontact without the need for in-person evaluations: two cardiac amyloidosis patients needed optimization of diuretic therapy; two obstructive HCM patients needed optimization of therapy for relief of obstruction. In three other instances, a medical outpatient evaluation was required: two cardiac amyloidosis patients presented worsening heart failure symptoms, and one severely obese HCM patient presented a new-onset atrial fibrillation with high ventricular response. Finally, one cardiac amyloidosis patient required hospitalization due to acute decompensated heart failure.Table 1: Characteristics of patients according to group allocationComment In this series of cardiomyopathy patients managed during the COVID-19 lockdown in Italy, a strategy of telehealth monitoring was feasible and effective, at least in the short term, with even a subset of patients contacted via E-mail. Telemedical contact by trained staff was able to stratify patients in higher and lower heart failure risk. No unplanned medical contact was required by patients deemed at low heart failure risk; moreover, half of the unplanned medical contacts among those at high heart failure risk was managed via repeated telemedical evaluations. Though of course not generalizable to the whole HCM and cardiac amyloidosis cardiomyopathy population, our report may offer suggestions for future management of this increasing cohort of patients. Telemedicine interventions have shown a beneficial effect in the management of heart failure patients.1 In current COVID-19 times, telemedicine served as an emergency tool, yet lessons from its impact on healthcare may be exploited for the future.2 In the case of cardiomyopathies such as HCM or cardiac amyloidosis, telehealth monitoring may be useful, in particular for a specific subset of low-risk patients, such as genotype-positive-phenotype-negative relatives. However, strategies of telehealth monitoring have never been specifically assessed in the case of cardiomyopathies. Implementation of telehealth strategies in Cardiomyopathy Units may help adequate followup for all patients and, at the same time, allow a better allocation of resources for in-hospital visits. Many already available tools may be exploited for telehealth strategies, including: telephone-based follow-up, remote monitoring of devices, use of novel portable devices,3 web-based interactive platforms.4 Telehealth monitoring cannot replace in-hospital in-person medical evaluation, but may be a valid practice in the near future. Acknowledgements Conflicts of interest There are no conflicts of interest.

Sex-specific cardiac remodeling in early and advanced stages of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiac disease with a prevalence of 1:500 to 1:200. While most patients show obstructive HCM and a relatively stable clinical phenotype (stage II), a small group of patients progresses to end-stage HCM (stage IV) within a relatively brief period. Previous research has shown sex-differences in stage II HCM with more diastolic dysfunction in female than in male patients. Moreover, female patients more often show progression to heart failure. Here we investigated if differences in functional and structural properties of the heart may underlie sex-differences in disease progression from stage II to stage IV HCM. Cardiac tissue from stage II and IV patients was obtained during myectomy (n = 54) and heart transplantation (n = 10), respectively. Isometric force was measured in membrane-permeabilized cardiomyocytes to define active and passive myofilament force development. Titin isoform composition was assessed using gel electrophoresis, and the amount of fibrosis and capillary density were determined with histology. In accordance with disease stage-dependent adverse cardiac remodeling end-stage patients showed a thinner interventricular septal wall and larger left ventricular and atrial diameters compared to stage II patients. Cardiomyocyte contractile properties and fibrosis were comparable between stage II and IV, while capillary density was significantly lower in stage IV compared to stage II. Women showed more adverse cellular remodeling compared to men at stage II, evident from more compliant titin, more fibrosis and lower capillary density. However, the disease stage-dependent reduction in capillary density was largest in men. In conclusion, the more severe cellular remodeling in female compared to male stage II patients suggests a more advanced disease stage at the time of myectomy in women. Changes in cardiomyocyte contractile properties do not explain the progression of stage II to stage IV, while reduced capillary density may underlie disease progression to end-stage heart failure.