[Hypertrophic cardiomyopathy]. / Hypertrophe Kardiomyopathie.

Hypertrophic cardiomyopathy is the most common genetically determined cardiac disease with a prevalence of 0.2-0.6%. The most important pathophysiological phenomenon is dynamic obstruction predominantly of the left ventricular outflow tract in 70% of the patients. Clinical symptoms (e.g. dyspnea, angina pectoris and syncope) are extremely variable depending on changes in preload and afterload and an increased risk of sudden cardiac death particularly in younger patients. The diagnostic measures should be carried out with respect to a prognostic and symptomatic treatment with implantation of an implantable cardioverter defibrillator (ICD) in cases of increased risk of sudden cardiac death. When medication treatment fails, first-line treatment consists of septal ablation and surgical myectomy as a supplementary measure, depending on the underlying morphology and experience of the surgeon.

Retrofitting the Heart: Explaining the Enigmatic Septal Thickening in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy is the most common genetic cardiac disease and is characterized by left ventricular hypertrophy. Although this hypertrophy often associates with sarcomeric gene mutations, nongenetic factors also contribute to the disease, leading to diastolic dysfunction. Notably, this dysfunction manifests before hypertrophy and is linked to hypercontractility, as well as nonuniform contraction and relaxation (myofibril asynchrony) of the myocardium. Although the distribution of hypertrophy in hypertrophic cardiomyopathy can vary both between and within individuals, in most cases, it is primarily confined to the interventricular septum. The reasons for septal thickening remain largely unknown. In this article, we propose that alterations in muscle fiber geometry, present from birth, dictate the septal shape. When combined with hypercontractility and exacerbated by left ventricular outflow tract obstruction, these factors predispose the septum to an isometric type of contraction during systole, consequently constraining its mobility. This contraction, or more accurately, this focal increase in biomechanical stress, prompts the septum to adapt and undergo remodeling. Drawing a parallel, this is reminiscent of how earthquake-resistant buildings are retrofitted with vibration dampers to absorb the majority of the shock motion and load. Similarly, the heart adapts by synthesizing viscoelastic elements such as microtubules, titin, desmin, collagen, and intercalated disc components. This pronounced remodeling in the cytoskeletal structure leads to noticeable septal hypertrophy. This structural adaptation acts as a protective measure against damage by attenuating myofibril shortening while reducing cavity tension according to Laplace Law. By examining these events, we provide a coherent explanation for the septum's predisposition toward hypertrophy.

Non-invasive estimation of left ventricular systolic peak pressure: a prerequisite to calculate myocardial work in hypertrophic obstructive cardiomyopathy.

AIMS: Myocardial work (MyW) is an echocardiographically derived parameter to estimate myocardial performance. The calculation of MyW utilizes pressure strain loops from global longitudinal strain and brachial blood pressure (BP) as a surrogate of left ventricular systolic pressure (LVSP). Since LVSP cannot be equated with BP in hypertrophic obstructive cardiomyopathy (HOCM), we explored whether LVSP can be derived non-invasively by combining Doppler gradients and BP. METHODS AND RESULTS: We studied 20 consecutive patients (8 women, 12 men; mean age 57.0 ± 13.9 years; NYHA 2.1 ± 0.8; maximal septal thickness 24.7 ± 6.3 mm) with indication for first alcohol septal ablation. All measurements were performed simultaneously in the catheterization laboratory (CathLab)-invasively: ascending aortic and LV pressures; non-invasively: BP, maximal (CWmax) and mean (CWmean) Doppler gradients.LVSP was 188.9 ± 38.5 mmHg. Mean gradients of both methods were comparable (CathLab 34.3 ± 13.4 mmHg vs. CW 31.0 ± 13.7 mmHg). Maximal gradient was higher in echocardiography (64.5 ± 28.8 mmHg) compared with CathLab (54.8 ± 24.0 mmHg; P < 0.05). Adding BP (143.1 ± 20.6 mmHg) to CWmax resulted in higher (207.7 ± 38.0 mmHg; P < 0.001), whereas adding BP to CWmean in lower (174.1 ± 26.1 mmHg; P < 0.01) derived LVSP compared with measured LVSP. However, adding BP to averaged CWmax and CWmean resulted in comparable results for measured and derived LVSP (190.9 ± 31.6 mmHg) yielding a favourable correlation (r = 0.87, P < 0.001) and a good level of agreement in the Bland-Altman plot. CONCLUSION: Non-invasive estimation of LVSP in HOCM is feasible by combining conventional BP and averaged CWmean and CWmax gradients. Hereby, a more reliable estimation of MyW in HOCM may be feasible.

Low-grade systemic inflammation and left ventricular dysfunction in hypertensive compared to non-hypertensive hypertrophic cardiomyopathy.

BACKGROUND: Arterial hypertension (HTN) is associated with excess mortality in hypertrophic cardiomyopathy (HCM), but underlying mechanisms are largely elusive. The objective of this study was to investigate the association between HTN and markers of left ventricular (LV) dysfunction and low-grade systemic inflammation in a HCM cohort. METHODS: This was a single-center cross-sectional case-control study comparing echocardiographic and plasma-derived indices of LV dysfunction and low-grade systemic inflammation between 30 adult patients with HCM and HTN (HTN+) and 30 sex- and age-matched HCM patients without HTN (HTN-). Echocardiographic measures were assessed using post-processing analyses by blinded investigators. RESULTS: Mean age of the study population was 55.1 ± 10.4 years, 30% were women. Echocardiographic measures of systolic and diastolic dysfunction, including speckle-tracking derived parameters, did not differ between HTN+ and HTN-. Moreover, levels of N-terminal pro B-type natriuretic peptide were balanced between cases and controls. Compared with HTN-, HTN+ patients exhibited a higher white blood cell count [8.1 ± 1.8 109/l vs. 6.4 ± 1.6 109/l; p < 0.001] as well as higher plasma levels of interleukin-6 [2.8 pg/ml (2.0, 5.4) vs. 2.1 pg/ml (1.5, 3.4); p = 0.008] and high-sensitivity C-reactive protein [2.6 mg/l (1.4, 6.5) vs. 1.1 mg/l (0.9, 2.4); p = 0.004]. CONCLUSION: This study demonstrates that HTN is associated with indices of low-grade systemic inflammation among HCM patients. Moreover, this analysis indicates that the adverse impact of HTN in HCM patients is a consequence of systemic effects rather than alterations of cardiac function, as measures of LV systolic and diastolic dysfunction did not differ between HTN+ and HTN-.

Spatial relationship between mitral valve and ventricular septum assessed by resting echocardiography to diagnose left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

AIMS: Echocardiographic diagnosis of left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) often requires extensive provocative manoeuvers. We investigated, whether echocardiography-derived parameters obtained at rest can aid to determine the presence of LVOTO in persons with HCM. METHODS AND RESULTS: Consecutive patients with HCM admitted to a referral centre underwent standardized transthoracic echocardiographic examination including provocative manoeuvers. Under resting conditions, the length of mitral leaflets and distances between mitral valve coordinates and ventricular walls were blindly measured in parasternal long axis (PLAX) and apical three-chamber (3ch) views, both at early and late systole. Among 142 patients (mean age 59 ± 13 years, 42% women), 68 (42%) had resting or provocable LVOTO with maximal LVOT gradients ≥30 mmHg. Late-systolic distance between mitral leaflet tip and ventricular septum (TIS) was measurable in 137 participants (96%) in 3ch view and independently associated with LVOTO in multivariable logistic regression analysis. The area under the ROC curve of TIS for the identification of LVOTO was 0.91 [95% confidence interval (CI) 0.87-0.96]. TIS ≤ 14 mm yielded 97% sensitivity and 57% specificity regarding LVOTO. TIS >14 mm ruled out LVOTO with a negative predictive value of 95%. TIS ≤9 mm ruled in LVOTO with a positive predictive value of 92% (sensitivity 73%, specificity 95%). Among 43 patients with TIS between 10 and 14 mm, 35% had LVOTO. CONCLUSION: In our study, the novel echocardiographic parameter TIS showed high negative and positive predictive values for LVOTO in HCM. These exploratory results await confirmation in larger collectives and prospective investigations.

Age-related survival after alcohol septal ablation in hypertrophic obstructive cardiomyopathy.

AIMS: Since its introduction, alcohol septal ablation (PTSMA) was discussed as treatment option only in elderly symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). We report on long-term follow-up after PTSMA with respect to patient's age. METHODS AND RESULTS: Between May 2000 and June 2017, we treated 952 consecutive HOCM patients with PTSMA; 133 (14.0%) patients were <40 years of age (Group A; mean age 30.3 ± 7.6; 26.3% female), 422 (44.3%) patients were between ≥40 and <60 years of age (Group B; mean age 50.6 ± 5.8; 27.0% female), and 397 (41.7%) patients were ≥60 years of age (Group C; 69.7 ± 6.1; 60.2% female). After PTSMA, need of pacemaker implantation was lowest in Group A (3.8%, P < 0.01 each) compared with Group B (9.2%) and Group C (14.1%) during hospital stay. One patient in Groups A and C died during hospital stay, each. Follow-up was longer in Group A (7.4 ± 5.5 years) compared with Group C (5.6 ± 4.8 years; P < 0.001) and comparable with Group B (6.5 ± 5.1 years). Mortality was highest in Group C (13.1%; P < 0.0001 each) compared with Group A (1.5%) and Group B (4.3%). In Group A, no patient died from cardiac reason, whereas five patients died from cardiac reasons in Group B and seven patients in Group C. Sudden cardiac death was not observed in Group A, whereas three patients in Group B and one patient in Group C suffered sudden cardiac death. CONCLUSIONS: Mortality after PTSMA is predominantly due to non-cardiac reasons and mainly observed in elderly patients. Survival in young patients is not affected by cardiac mortality. In experienced centres with careful patient selection, PTSMA is safe in young patients.

Sex-related differences in symptomatic patients with hypertrophic obstructive cardiomyopathy - Time for a new definition?

INTRODUCTION: Sex-related differences in diagnosis and treatment of hypertrophic obstructive cardiomyopathy (HOCM) are still unclear. Therefore, we analyzed baseline characteristics of symptomatic patients with indication for alcohol septal ablation (PTSMA) with respect to gender. METHODS AND RESULTS: Between 05/2000 and 06/2017 indication for PTSMA was seen in 1014 patients (420 (41.4%) women and 594 (58.6%) men). Women were older (61.4 ± 15.0 vs. 51.8 ± 13.6 years; p < 0.00001) and suffered more often from dyspnea NYHA III/IV (81.4% vs. 67.7%; p < 0.001), whereas angina pectoris and syncopes were comparable. Echocardiographic gradients were comparable in women (66.4 ± 39.1 mmHg at rest and 106.5 ± 46.6 mmHg at Valsalva) and men (62.7 ± 38.8 mmHg at rest and 103.7 ± 42.7 mmHg at Valsalva). Women had smaller absolute diameter of the left atrium (LA) (44.4 ± 6.9 vs. 47.2 ± 6.5 mm; p < 0.0001), septal thickness (IVS) (20.5 ± 4.1 vs. 21.4 ± 4.5 mm; p < 0.01), and left ventricular posterior wall thickness (LVPW) (12.7 ± 2.8 vs. 13.6 ± 2.9 mm; p < 0.0001). But, indexed for BSA the relationship reversed in LA (25.2 ± 4.3 mm/m2 in women vs. 23.1 ± 3.4 mm/m2), IVS (11.7 ± 2.7 mm/m2 in women vs. 10.6 ± 2.5 mm/m2) and LVPW (7.3 ± 1.7 mm/m2 in women vs. 6.7 ± 1.6 mm/m2), p < 0.00001 each. CONCLUSION: Women with HOCM and indication for PTSMA are older and more symptomatic with advanced disease progression. Reconsideration of disease definition and awareness maybe necessary in order to avoid delayed diagnosis and treatment of HOCM in women.

Hypertrophic Obstructive Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is caused by mutations in a number of genes. Its prevalence is 0.2% to 0.6%. METHODS: This review is based on publications retrieved by a selective literature search and on the authors' clinical experi- ence. RESULTS: 70% of patients with HCM suffer from the obstructive type of the condition, clinically characterized by highly dynamic and variable manifestations in the form of dyspnea, angina pectoris, and stress-dependent presyncope and syn- cope. Younger patients are at particular risk of sudden cardiac death; thus, all patients need not only symptomatic treatment, but also risk assessment, which can be difficult in individual cases. Left ventricular obstruction, which usually causes symptoms, is treated medically at first, with either a beta- blocker or verapamil. If medical treatment fails, two invasive treatments are available, surgical myectomy and percu- taneous septum ablation. Both of these require a high level of expertise. If performed successfully, they lead to sustained gradient reduction and clinical improvement. Septum ablation is associated with low perioperative and peri-interventional mortality but necessitates permanent pacemaker implantation in 10-20% of patients. CONCLUSION: In the absence of evidence from randomized comparison trials, a suitable method of reducing the gradient should be determined by an HCM team in conjunction with each individual patient. Important criteria for decision-making include the anatomical findings and any accompanying illnesses.

Survival After Alcohol Septal Ablation in Patients With Hypertrophic Obstructive Cardiomyopathy.

BACKGROUND: Alcohol-induced infarction for treatment of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) was discussed as a risk factor for increased cardiac mortality during follow-up. OBJECTIVES: This study sought to report on long-term survival after echo-guided alcohol septal ablation (percutaneous transluminal septal myocardial ablation [PTSMA]) in symptomatic patients with HOCM. METHODS: Between May 2000 and June 2017, PTSMA with alcohol injection was performed in 952 patients (age 55.7 ± 14.9 years; 59.2% men; 73.3% New York Heart Association functional class III or IV; 50.3% syncope; 10.3% sudden cardiac death in family). Clinical follow-up after 6.0 ± 5.0 years was achieved in all patients. RESULTS: We injected 2.1 ± 0.4 cc of alcohol. Maximal creatine kinase rise was 872 ± 489 U/l. Two (0.21%) patients died 3 and 33 days after ablation. Permanent pacemaker was implanted in 100 (10.50%) patients. Echo gradients were acutely reduced from 63.9 ± 38.2 mm Hg to 33.6 ± 29.8 mm Hg at rest and from 104.6 ± 44.0 mm Hg to 56.5 ± 41.0 mm Hg at Valsalva (p < 0.0001, each). During follow-up, 164 (17.2%) patients underwent reablation due to the planned staged procedure, 18 (1.9%) patients underwent surgical myectomy, and 49 (5.10%) patients underwent cardioverter-defibrillator implantation. Seventy patients died: causes of death were identified as noncardiovascular in 50, stroke related in 6, and cardiac in 14 patients. Estimated 5-year survival was 95.8%, estimated 5-year survival free of cardiovascular events was 98.6%, and an estimated 5-year survival free of cardiac events was 98.9%. Corresponding values at 10 years were 88.3%, 96.5%, and 97.0%, and at 15 years were 79.7%, 92.3%, and 96.5%. CONCLUSIONS: In this study, PTSMA could be proofed as a safe procedure with ongoing symptomatic improvement and excellent long-term survival. Therefore, PTSMA is a reasonable alternative to surgical myectomy in HOCM.

[Syncope in hypertrophic (obstructive) cardiomyopathy]. / Synkope bei hypertropher (obstruktiver) Kardiomyopathie.

Hypertrophic cardiomyopathy is the most common genetic cardiac disease. The most important pathophysiological finding is dynamic (outflow tract) obstruction of the left ventricle in about 70% of affected patients. Especially in younger patients, an increased risk of sudden cardiac death has been observed. Syncope and presyncope-in addition to extremely variable cardiac symptoms (dyspnea and angina)-are common. The etiology of syncope is complex. The most important aspect for diagnosis is a detailed history regarding the accompanying circumstances of the syncope. In principle, an attempt must be made to distinguish between rhythmogenic and hemodynamic causes. Diagnostic work-up should be performed under the criteria of a possible prognostic-with implantation of an implantable cardioverter-defibrillator (ICD) in patients at increased risk of sudden cardiac death-and symptomatic therapy. Depending on the underlying morphology and the experience of the surgeon, percutaneous septal ablation and operative myectomy are complementary options for symptomatic treatment if medical therapy with beta-blockers and/or verapamil is inadequate.

Endogenous erythropoietin and the association with inflammation and mortality in diabetic chronic kidney disease.

BACKGROUND AND OBJECTIVES: Anemia and inflammation are prevalent in diabetic patients with chronic kidney disease (CKD). The role of endogenous erythropoietin (EPO) in the pathophysiology of anemia in chronic diseases and its relationship to clinical outcomes remain uncertain. In this cohort study, we aimed to identify factors associated with endogenous EPO levels and investigate their relation to all-cause mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between 2004 and 2005, 215 patients with type 2 diabetes were enrolled. Exclusion criteria included stage renal disease ESRD and any form of anemia therapy. The association of EPO levels with clinical and laboratory variables was investigated by linear regression modeling. Predictors of all-cause mortality were evaluated by Cox proportional hazards analyses. RESULTS: Patients (median age, 67 years; 52% men; median duration of diabetes, 10 years; median estimated GFR, 49 ml/min per 1.73 m²) were followed for up to 7.0 years. Forty-one patients died. Elevated EPO levels were independently associated with elevated C-reactive protein, low ferritin, and hypertension, in a multivariate model that also included age, cardiovascular disease, kidney function, albumin, cholesterol, and hemoglobin. Higher EPO levels were independently predictive for mortality, as were age, low levels of albumin, and cardiovascular disease. CONCLUSIONS: In diabetic patients with CKD, elevated endogenous EPO levels were predictive for mortality and were related mainly to markers of inflammation, independent of kidney function, and despite low hemoglobin levels. Understanding the phenomenon of EPO resistance and iron dysregulation caused by inflammation is crucial for effective and safe treatment of anemia in patients with CKD.