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The aim of the present study was to evaluate, in patients with hypertrophic cardiomyopathy (HC), the association between late gadolinium enhancement and clinical end points, such as nonsustained ventricular tachycardia, arrhythmic risk factors, New York Heart Association class, symptoms, and left ventricular functional parameters. A total of 20 normal subjects (mean age 38 years, 16 men) and 100 patients with HC (mean age 46 years, 70 men) were enrolled in the present study. In the late gadolinium enhancement images, the extent of unenhanced, mildly enhanced, and higher enhanced myocardium was measured. Higher enhancement was present in 80% of the HC population and was significantly greater in patients with a New York Heart Association class >1. Mild enhancement was present in all the patients with HC. Receiver operating characteristic analysis revealed that a cutoff of >4.9% of mild enhancement had 100% sensitivity and 86% specificity to predict the occurrence of nonsustained ventricular tachycardia, and a cutoff of >2.4% of hyperenhancement had 77% sensitivity and 96% specificity. In conclusion, late gadolinium enhancement was associated with nonsustained ventricular tachycardia, arrhythmic risk factors, and worse New York Heart Association class.

Introduction Hypertrophic cardiomyopathy (HCM) patients with apical aneurysm have a largely unfavourable clinical course, and are often unrecognised because echocardiography is limited in the assessment of the left ventricular (LV) apex. The aim of this study is the identification of electrocardiographic (ECG) abnormalities associated with the development of apical aneurysm in HCM patients. Materials and methods Electrocardiographic features were assessed in 14 HCM patients who had a good-quality baseline ECG recorded before and after the diagnosis of apical aneurysm. Results During follow-up (8.8±7.5years), the following ECG changes were observed: increase in QRS-complex duration (87±12ms to 118±34ms, p=0.006), QRS-complex fragmentation, decrease in QRS-complex amplitude (SV 1 +RV 5-6 , from 41±18mm to 26±11mm, p=0.015), ST-segment elevation in V 4 –V 6 (J-point in V 5 , from −0.9±1.3mm to +0.7±1.3, p=0.003), positivisation of negative T waves in V 3 -V 6 (T-wave depth in V 5 , from −3.4±6.6 to +3.1±4.1, p=0.005). Conclusions HCM patients who develop LV apical aneurysm exhibit distinctive ECG changes along with apical remodelling. Suggestive ECGs should lead the physician to study LV apex by nonstandard echocardiographic views, and perform MRI.

Cardiovascular magnetic resonance (CMR) with extensive late gadolinium enhancement (LGE) is a novel marker for increased risk for sudden death (SD) in patients with hypertrophic cardiomyopathy (HC). Small focal areas of LGE confined to the region of right ventricular (RV) insertion to ventricular septum (VS) have emerged as a frequent and highly visible CMR imaging pattern of uncertain significance. The aim of this study was to evaluate the prognostic significance of LGE confined to the RV insertion area in patients with HC. CMR was performed in 1,293 consecutive patients with HC from 7 HC centers, followed for 3.4 ± 1.7 years. Of 1,293 patients (47 ± 14 years), 134 (10%) had LGE present only in the anterior and/or inferior areas of the RV insertion to VS, occupying 3.7 ± 2.9% of left ventricular myocardium. Neither the presence nor extent of LGE in these isolated areas was a predictor of adverse HC-related risk, including SD (adjusted hazard ratio 0.82, 95% confidence interval 0.45 to 1.50, p = 0.53; adjusted hazard ratio 1.16/10% increase in LGE, 95% confidence interval 0.29 to 4.65, p = 0.83, respectively). Histopathology in 20 HC hearts show the insertion areas of RV attachment to be composed of a greatly expanded extracellular space characterized predominantly by interstitial-type fibrosis and interspersed disorganized myocyte patterns and architecture. In conclusion, LGE confined to the insertion areas of RV to VS was associated with low risk of adverse events (including SD). Gadolinium pooling in this region of the left ventricle does not reflect myocyte death and repair with replacement fibrosis or scarring.

Background— Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death in the young, although not all patients eligible for sudden death prevention with an implantable cardioverter-defibrillator are identified. Contrast-enhanced cardiovascular magnetic resonance with late gadolinium enhancement (LGE) has emerged as an in vivo marker of myocardial fibrosis, although its role in stratifying sudden death risk in subgroups of HCM patients remains incompletely understood. Methods and Results— We assessed the relation between LGE and cardiovascular outcomes in 1293 HCM patients referred for cardiovascular magnetic resonance and followed up for a median of 3.3 years. Sudden cardiac death (SCD) events (including appropriate defibrillator interventions) occurred in 37 patients (3%). A continuous relationship was evident between LGE by percent left ventricular mass and SCD event risk in HCM patients ( P =0.001). Extent of LGE was associated with an increased risk of SCD events (adjusted hazard ratio, 1.46/10% increase in LGE; P =0.002), even after adjustment for other relevant disease variables. LGE of ≥15% of LV mass demonstrated a 2-fold increase in SCD event risk in those patients otherwise considered to be at lower risk, with an estimated likelihood for SCD events of 6% at 5 years. Performance of the SCD event risk model was enhanced by LGE (net reclassification index, 12.9%; 95% confidence interval, 0.3–38.3). Absence of LGE was associated with lower risk for SCD events (adjusted hazard ratio, 0.39; P =0.02). Extent of LGE also predicted the development of end-stage HCM with systolic dysfunction (adjusted hazard ratio, 1.80/10% increase in LGE; P Conclusions— Extensive LGE measured by quantitative contrast enhanced CMR provides additional information for assessing SCD event risk among HCM patients, particularly patients otherwise judged to be at low risk.

End-stage hypertrophic cardiomyopathy (ES-HC) has an ominous prognosis. Whether genotype can influence ES-HC occurrence is unresolved. We assessed the spectrum and clinical correlates of HC-associated mutations in a large multicenter cohort with end-stage ES-HC. Sequencing analysis of 8 sarcomere genes (MYH7, MYBPC3, TNNI3, TNNT2, TPM1, MYL2, MYL3, and ACTC1) and 2 metabolic genes (PRKAG2 and LAMP2) was performed in 156 ES-HC patients with left ventricular (LV) ejection fraction (EF)

Patients with hypertrophic cardiomyopathy (HC) are reported to have a mortality rate of about 1.0% per year, and those patients without sudden death risk factors and with no or mild symptoms are generally considered to have a benign clinical presentation. However, the risk of sudden death and the outcome in this latter subgroup have not been investigated systematically and remain unresolved. We assessed the risk of sudden death and outcome in 653 consecutive patients with HC without risk factors and with no or mild symptoms. Over a median follow-up of 5.3 years, 35 patients (5.4%) died of HC-related causes. Mean age at death was 46 ± 20 years in patients who died suddenly and 66 ± 15 and 72 ± 9 years, respectively, in patients who died of heart failure or stroke. Event rate was 0.6% per year for sudden death, 0.2% per year for heart failure death, and 0.1% per year for stroke-related death. Sudden death risk was independently and inversely related to age, and risk of heart failure or stroke death was directly related to age (p = 0.020). At 10 years after the initial evaluation, sudden death risk was 5.9%, with sudden death rate being the lowest (0.3% per year) in patients with normal left atrial dimension (≤40 mm). In conclusion, in patients with HC without conventional risk factors and with no or mild symptoms, the risk of sudden death was not negligible, with an event rate of 0.6% per year. Heart failure and stroke-related death were less common and largely confined to older patients. These results underscore the need for a more accurate assessment of the sudden death risk in patients with HC. © 2014 Elsevier Inc. All rights reserved.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) studies in patients with coronary artery disease report higher risk of ventricular tachycardia/fibrillation (VT/VF) early post-implant, potentially related to local proarrhythmic effects of ICD leads. OBJECTIVE: To characterize early and long-term risk of ICD discharge for VT/VF in a large hypertrophic cardiomyopathy (HCM) cohort. METHODS: By using HCM multicenter registry data, we compared long-term risk of VT/VF subsequent to an early post-implant period (a priori defined as within 3 months of implant) between patients with or without VT/VF within 3 months after ICD implantation. RESULTS: Over a median follow-up of 4.3 years, 109 of 506 (22%) patients with HCM who received ICDs received at least 1 ICD discharge for VT/VF. Risk of first ICD discharge for VT/VF was highest in the first year post-implant (10.8% per person-year; 95% confidence interval 7.9-13.8) and particularly in the first 3 months (17.0% per person-year; 95% confidence interval 9.8-24.3). Patients with early VT/VF (≤3 months post-implant) were older, and more commonly had secondary prevention ICDs following cardiac arrest or systolic dysfunction (end-stage HCM with ejection fraction

Hypertrophic cardiomyopathy (HCM) is the most common, heritable cardiovascular disorder and the most frequent cause of sudden cardiac death (SCD) in young adults. Gender disparities with regards to clinical outcomes among HCM patients are not well-defined. We investigated the relationship between

ObjectivesThis study sought to assess the rate of progression of fibrosis by 2 consecutive cardiac magnetic resonance (CMR) examinations and its relation with clinical variables.BackgroundIn hypertrophic cardiomyopathy (HCM) myocardial fibrosis, detected by late gadolinium enhancement (LGE), is associated to a progressive ventricular dysfunction and worse prognosis.MethodsA total of 55 HCM patients (37 males; mean age 43 ± 18 years) underwent 2 CMR examinations (CMR-1 and CMR-2) separated by an interval of 719 ± 410 days. Extent of LGE was measured, and the rate of progression of LGE (LGE-rate) was calculated as the ratio between the increment of LGE (in grams) and the time (months) between the CMR examinations.ResultsAt CMR-1, LGE was detected in 45 subjects, with an extent of 13.3 ± 15.2 g. At CMR-2, 53 (96.4%) patients had LGE, with an extent of 24.6 ± 27.5 g. In 44 patients, LGE extent increased significantly (≥1 g). Patients with apical HCM had higher increments of LGE (p = 0.004) and LGE-rate (p < 0.001) than those with other patterns of hypertrophy. The extent of LGE at CMR-1 and the apical pattern of hypertrophy were independent predictors of the increment of LGE. Patients with worsened New York Heart Association functional class presented higher increase of LGE (p = 0.031) and LGE-rate (p < 0.05) than those with preserved functional status.ConclusionsMyocardial fibrosis in HCM is a progressive and fast phenomenon. LGE increment, related to a worse clinical status, is more extensive in apical hypertrophy than in other patterns.

Background Cardiovascular Magnetic resonance (CMR) with the late gadolinium enhancement (LGE) technique allows the detection of myocardial fibrosis in Hypertrophic cardiomyopathy (HCM). The aim of this study was to compare different methods of automatic quantification of LGE in HCM patients. Methods: Forty HCM patients (mean age 48 y, 30 males) and 20 normal subjects (mean age 38 y, 16 males) underwent CMR, and we compared 3 methods of quantification of LGE: 1) in the SD2 method a region of interest (ROI) was placed within the normal myocardium and enhanced myocardium was considered as having signal intensity >2 SD above the mean of ROI; 2) in the SD6 method enhanced myocardium was defined with a cut-off of 6 SD above mean of ROI; 3) in the RC method a ROI was placed in the background of image, a Rayleigh curve was created using the SD of that ROI and used as ideal curve of distribution of signal intensity of a perfectly nulled myocardium. The maximal signal intensity found in the Rayleigh curve was used as cut-off for enhanced myocardium. Parametric images depicting non enhanced and enhanced myocardium was created using each method. Three investigators assigned a score to each method by the comparison of the original LGE image to the respective parametric map generated. Results Patients with HCM had lower concordance between the measured curve of distribution of signal intensity and the Rayleigh curve than controls (63.7 ± 12.3% vs 92.2 ± 2.3%, p < 0.0001). A cut off of concordance < 82.9% had a 97.1% sensitivity and 92.3% specificity to distinguish HCM from controls. The RC method had higher score than the other methods. The average extent of enhanced myocardium measured by SD6 and Rayleigh curve method was not significant different but SD6 method showed underestimation of enhancement in 12% and overestimation in 5% of patients with HCM. Conclusions Quantification of fibrosis in LGE images with a cut-off derived from the Rayleigh curve is more accurate than using a fixed cut-off.

Studies of the standardized, 3D, 16-segments map of the circumferential distribution of T2* values, of cardiovascular magnetic resonance (CMR) in thalassemia major (TM) and thalassemia intermedia (TI) patients and of electrocardiogram (ECG) changes associated with TM, have been carried out. Similarly, the segment-dependent correction map of the T2* values and the artifactual variations in normal subjects and the T2* correction map to correct segmental measurements in patients with different levels of myocardial iron burden have been evaluated. Cardiovascular magnetic resonance can be a suitable guide to cardiac management in TI, as well as in TM; TI patients show lower myocardial iron burden and more pronounced high cardiac output findings than TM patients. Moreover, it is proposed that, due to its good positive predictive value (PPV) and low cost, ECG can be a suitable guide to orient towards CMR examination in TM cases.

Context Recently, the implantable cardioverter-defibrillator (ICD) has been promoted for prevention of sudden death in hypertrophic cardiomyopathy (HCM). However, the effectiveness and appropriate selection of patients for this therapy is incompletely resolved. Objective To study the relationship between clinical risk profile and incidence and efficacy of ICD intervention in HCM. Design, Setting, and Patients Multicenter registry study of ICDs implanted between 1986 and 2003 in 506 unrelated patients with HCM. Patients were judged to be at high risk for sudden death; had received ICDs; underwent evaluation at 42 referral and nonreferral institutions in the United States, Europe, and Australia; and had a mean follow-up of 3.7 (SD, 2.8) years. Measured risk factors for sudden death included family history of sudden death, massive left ventricular hypertrophy, nonsustained ventricular tachycardia on Holter monitoring, and unexplained prior syncope. Main OutcomeMeasure Appropriate ICD intervention terminating ventricular tachycardia or fibrillation. Results The 506 patients were predominately young (mean age, 42 [SD, 17] years) at implantation, and most (439 [87%]) had no or only mildly limiting symptoms. ICD interventions appropriately terminated ventricular tachycardia/fibrillation in 103 patients (20%). Intervention rates were 10.6% per year for secondary prevention after cardiac arrest (5-year cumulative probability, 39% [SD, 5%]), and 3.6% per year for primary prevention (5-year probability, 17% [SD, 2%]). Time to first appropriate discharge was up to 10 years, with a 27% (SD, 7%) probability 5 years or more after implantation. For primary prevention, 18 of the 51 patients with appropriate ICD interventions (35%) had undergone implantation for only a single risk factor; likelihood of appropriate discharge was similar in patients with 1, 2, or 3 or more risk markers (3.83, 2.65, and 4.82 per 100 person-years, respectively; P=.77). The single sudden death due to an arrhythmia (in the absence of advanced heart failure) resulted from ICD malfunction. ICD complications included inappropriate shocks in 136 patients (27%). Conclusions In a high-risk HCM cohort, ICD interventions for life-threatening ventricular tachyarrhythmias were frequent and highly effective in restoring normal rhythm. An important proportion of ICD discharges occurred in primary prevention patients who had undergone implantation for a single risk factor. Therefore, a single marker of high risk for sudden death may be sufficient to justify consideration for prophylactic defibrillator implantation in selected patients with HCM.

Background— End stage (ES) is a recognized part of the hypertrophic cardiomyopathy (HCM) disease spectrum. Frequency, clinical profile and course, and treatment strategies in these patients remain incompletely defined. Methods and Results— Three HCM cohorts comprised 1259 patients, including 44 (3.5%) characterized as ES with systolic dysfunction (ejection fraction P =0.84). Appropriate defibrillator interventions were 10% per year in patients awaiting donor hearts. Most ES patients (n=23; 52%) showed substantial left ventricular (LV) remodeling with cavity dilatation. Less complete remodeling occurred in 21 patients (48%), including 5 with persistence of a nondilated and markedly hypertrophied LV. Pathology and magnetic resonance imaging showed extensive (transmural) fibrosis in 9 of 11 ES patients. At initial evaluation, patients who developed ES were younger with more severe symptoms, had a larger LV cavity, and more frequently had a family history of ES than other HCM patients. Conclusions— ES of nonobstructive HCM has an expanded and more diverse clinical expression than previously appreciated, including occurrence in young patients, heterogeneous patterns of remodeling, frequent association with atrial fibrillation, and impaired LV contractility that precedes cavity dilatation, wall thinning, and heart failure symptoms. ES is an unfavorable complication (mortality rate 11% per year) and a sudden death risk factor; it requires vigilance to permit timely recognition and the necessity for defibrillator implantation and heart transplantation.

Cardiovascular magnetic resonance (CMR) with extensive late gadolinium enhancement (LGE) is a novel marker for increased risk for sudden death in patients with hypertrophic cardiomyopathy (HCM) presumably due to ventricular tachyarrhythmias emanating from areas of replacement fibrosis. Of particular

Incidence of Pulmonary Hypertension (PH) has been described in haemoglobinopathic patients, ranging from 10% to 50%, depending on age, therapy, coexisting left ventricular dysfunction (LVD) and classification of the disease. To determine whether PH can occurs in haemoglobinopathic patients in absence of overt LVD, we studied 1121 pts from 7 Thalassemia Centers in Italy(485 Thalassemia Major (TM), 458 thalassemia intermedia (TI), 178 Sickle Cell or Sickle Thalassemia Disease (SCD),49% males, mean age 30 yrs, range 13–56 yrs). In all pts echocardiographic (Echo) defined ejection fraction (EF%) was > 45% and clinically overt LVD was excluded. A cross-sectional Echo study was performed in order to detect PH that was prospectively defined as mild with tricuspid regurgitant jet velocity (TRV)of at least 2.5 m per second and defined as severe with a TRV> 3.5 m per second. Severe PH was observed in 9 pts, 3 with TM, in 6 with TI and in 1 patients with SCD. Mild PH occurs in 46 patients with TM, in 57 patients with TI and 11 pts with SCD. In the remaining patients, PH was in the normal range (TM 89,9%, TI 86,2% and SCD 93,2% of pts, respectively). In the whole group of hemoglobinopathic pts the incidence of PH (mild plus severe) range from 6.5 % to 13.8% of pts. PH (mild to severe) particularly affects pts with TI (13,8% of pts). | Tricuspid Regurgitant Jet Velocity | Thal Major 485 pts | Thal Int 458 pts | SCD 178 pts | % pts | |:----------------------------------:| ------------------ | ---------------- | ----------- | ----- | | TRV3.5 m/sec | 3 (0.6%) | 6 (1.3%) | 1 (0.9%) | 0.9% | Incidence of PH in TM, TI and SCD Our data support a significant presence of PH in haemoglobinopathic pts (6.2 to 13,8%) even though well treated and without LVD. Considering the pathophisiology of haemoglobinopathies a specific consideration to PH in these diseases is required in order to establish a preventive and therapeutic approach.