The prognostic impact of right ventricular-pulmonary arterial coupling in heart failure: a systematic review and meta-analysis.

The echocardiographic tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio is a non-invasive surrogate of right ventricular-pulmonary arterial (RV-PA) coupling which corresponds well with the respective invasively derived index. Recently, a wealth of observational data has arisen, outlining its prognostic value in heart failure (HF) patients. To systematically appraise and quantitatively synthesize the evidence of the prognostic value of TAPSE/PASP ratio in left-sided HF regardless of etiology or left ventricular ejection fraction. A systematic literature review was conducted in electronic databases to identify studies reporting the association of TAPSE/PASP ratio with outcomes in patients with HF and, when appropriate, a random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome of all-cause death or HF hospitalization. Eighteen studies were deemed eligible encompassing 8,699 HF patients. The applied cut-off value for RV-PA uncoupling varied substantially from 0.27 to 0.58 mm/mmHg, and in most studies values lower than the applied cutoff conveyed dismal prognosis. Eleven studies reported appropriate data for meta-analysis. TAPSE/PASP reduction by 1 mm/mmHg was independently associated with all-cause death (pooled aHR=1.32 [1.06-1.65]; p=0.01; I2=56%) and the composite outcome (pooled aHR=3.48 [1.67-7.25]; p<0.001; I2=0%). When a TAPSE/PASP cutoff value of 0.36 mm/mmHg was applied it yielded independent association with all-cause death (pooled aHR=2.84 [2.22-3.64]; p<0.001; I2=82%). RV-PA coupling assessed by echocardiographic TAPSE/PASP ratio appears to be an independent outcome predictor for HF patients.

Left Atrial Myopathy is Associated With Exercise Incapacity and Ventilatory Inefficiency in Hypertrophic Cardiomyopathy.

BACKGROUND: Left atrial (LA) myopathy is an established component of hypertrophic cardiomyopathy (HCM); however, the data about its association with exercise incapacity or ventilatory inefficiency that may be seen in HCM patients are limited. This study aimed to explore the association between LA myopathy, evaluated by echocardiography LA strain, and exercise capacity and ventilatory efficiency, evaluated by cardiopulmonary exercise testing (CPET), in HCM patients. METHODS: This study included 241 consecutive HCM patients (aged 51.2±15.7 years 67.2% male) in sinus rhythm who underwent CPET and transthoracic echocardiography at the same visit. Exercise incapacity (maximal/predicted oxygen consumption [%peakVO2] <80%) and ventilatory inefficiency (ventilation/carbon dioxide output [VE/VCO2] slope >34) were assessed by CPET. Left atrial myopathy was examined by speckle-tracking myocardial deformation parameters: LA reservoir, conduit and booster strain. RESULTS: All three LA strain values were univariate predictors of exercise capacity and ventilatory efficiency. Among them, LA reservoir strain had the higher r correlation coefficient for predicting both %peakVO2 and VE/VCO2 slope. Left atrial reservoir strain, presence of angina and family history of HCM were independent predictors of exercise capacity. Left atrial reservoir strain, male gender and non-sustained ventricular tachycardia were independent predictors of ventilatory efficiency. Left atrial reservoir strain was a significant predictor of %peakVO2<80% with an optimal cut-off value of 27% (sensitivity 87% and specificity 31%) and VE/VCO2>34 with an optimal cut-off value of 18% (sensitivity 71% and specificity 83%). CONCLUSION: Left atrial myopathy, as reflected by the LA strain values, was associated with exercise incapacity and ventilatory inefficiency in HCM individuals. Left atrial reservoir strain was the only common independent predictor of %peakVO2 and VE/VCO2 slope.

Deciphering hypertrophic cardiomyopathy with electrocardiography.

The comprehensive assessment of patients with hypertrophic cardiomyopathy is a complex process, with each step concurrently focusing on confirmation of the diagnosis, differentiation between sarcomeric and non-sarcomeric disease (phenocopy), and prognostication. Novel modalities such as genetic testing and advanced imaging have allowed for substantial advancements in the understanding of this condition and facilitate patient management. However, their availability is at present not universal, and interpretation requires a high level of expertise. In this setting, electrocardiography, a fast and widely available method, still retains a significant role in everyday clinical assessment of this population. In our review, we follow a stepwise approach for the interpretation of each electrocardiographic segment, discussing clinical implications of electrocardiographic patterns in sarcomeric disease, their value in the differential diagnosis from phenocopies, and impact on patient management. Outlining the substantial amount of information to be obtained from a simple tracing, we exhibit how electrocardiography is likely to remain an integral diagnostic tool in the future as well.

Mitral regurgitation impact on left atrial myopathy in hypertrophic cardiomyopathy.

BACKGROUND: Recent studies have shown that mitral regurgitation (MR) represents a major determinant of left atrial (LA) function in patients with heart failure with preserved ejection fraction. The role of MR in determining LA myopathy in hypertrophic cardiomyopathy (HCM) is unknown. The aim of this study was to examine the association of MR with LA myopathy, assessed by LA strain values in HCM patients. METHODS: In total 250 consecutive patients (mean age 51 ± 16 years, 67.2% male) with an established diagnosis of HCM and with sinus rhythm at index echocardiography evaluation were included. LA reservoir, conduit and booster strain were analyzed, besides LA size, left ventricular (LV) systolic and diastolic function. The predictors of LA strain values were identified with linear regression analysis. RESULTS: Significant (more than mild) MR was a significant univariate predictor of all the three LA strain values. In multivariate linear regression analysis, independent predictors of LA reservoir strain were more than mild MR (r = -.23), LV global longitudinal strain (r = -.49), LA volume index (r = -.27) and patient age (r = -.23). Significant MR was also an independent determinant of LA conduit (r = -.17) and booster strain (r = -.12). In patients with LA volume index < 34 ml/m2 more than mild MR was an independent predictor of LA reservoir (r = -.32) and conduit strain (r = -.27), but not LA booster strain. CONCLUSION: Significant MR is associated with LA myopathy independently of the LV diastolic and systolic function and LA size.

A novel quantitative method for assessing the therapeutic response to Tafamidis therapy in patients with cardiac TTR amyloidosis. A preliminary report.

OBJECTIVE: Cardiomyopathy is a common manifestation of transthyretin amyloidosis (ATTR), leading to heart failure, associated with high morbidity and mortality. The aim of this study was to investigate the effect of Tafamidis treatment by means of cardiac radiotracer uptake on myocardial scintigraphy. SUBJECTS AND METHODS: Five male patients, mean age 76.2 years, with wild-type ATTR were included in the protocol. Total body scanning using technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) (in four patients) and technetium-99m-hydroxymethylene diphosphonate (99mTc-HMDP) (in one) was performed pre- and one year post-Tafamidis therapy. A novel quantitation method for assessing radiotracer cardiac uptake was employed. The geometric mean was computed for both cardiac and thigh region of interest (ROI) and the heart-to-thigh (HtT) ratio was assessed by dividing the corresponding geometric mean counts. RESULTS: Heart-to-thigh ratio was improved (decreased) in four of the patients receiving Tafamidis, in keeping with lower uptake to the cardiac region. These patients also demonstrated a relatively favorable clinical response to Tafamidis. The patient evaluated by 99mTc-HMDP exhibited minimal HtT ratio reduction and stable clinical and echocardiographic characteristics. CONCLUSION: Sequential HtT ratio measurements could potentially identify patients with a favorable response to Tafamidis treatment at earlier stages, compared to other imaging modalities or serological biomarkers.

Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies.

BACKGROUND: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. METHODS: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator-treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. RESULTS: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0-7.2] and 5.1 [2.0-9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711-0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642-0.959), and the calibration slope was 1.082 (95% CI, 0.643-1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. CONCLUSIONS: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03058185.

Free Cortisol Is a More Accurate Marker for Adrenal Function and Does Not Correlate with Renal Function in Cirrhosis.

BACKGROUND: The accuracy of diagnosis and clinical implications of the hepatoadrenal syndrome, as currently diagnosed using total cortisol, remain to be validated. AIM: The aim of this study was to assess adrenal function using free cortisol in stable cirrhosis and study the potential implications of any abnormalities for renal and/or cardiac function. METHODS: Sixty-one stable consecutively enrolled patients with cirrhosis underwent assessment of adrenal function using the low-dose short Synacthen test, renal function by 51Cr-EDTA glomerular filtration rate (GFR), and cardiac function by two-dimensional echocardiography. RESULTS: Eleven patients (18%) had total peak cortisol (PC) < 500 nmol/L, but no patient had free PC < 33 nmol/L indicating that diagnosis of AI using total cortisol is not confirmed using free cortisol. Free cortisol did not correlate with GFR or parameters of cardiac function. Patients with higher Child-Pugh class had progressively lower free cortisol. Patients with low GFR < 60 mL/min (N = 22) had more frequently grade II-III diastolic dysfunction (66.7% vs. 17.6%; p = 0.005) and had higher Child-Pugh and MELD score compared to those with normal GFR. CONCLUSIONS: Diagnosis of AI using total cortisol is not confirmed using free cortisol and is thus considered unreliable in cirrhosis. Free cortisol is not associated with renal or cardiac dysfunction. Lower free cortisol in more advanced stages of liver disease might be secondary to decreased synthesis due to lower cholesterol levels. Irrespective of free cortisol, parameters of cardiac dysfunction are associated with renal impairment supporting the cardio-renal hypothesis.

Pathogenic truncating filamin C mutations presenting as acute myocarditis: a case series with insights from cardiac magnetic resonance and histological analysis.

Background: The exact mechanisms underlying the pathogenesis of myocarditis are not always understood, but there is emerging evidence to suggest that genetic factors may play a significant role. Case summary: Herein, we present six cases in which clinical, biochemical, and cardiovascular magnetic resonance data were consistent with myocarditis, and genetic testing subsequently revealed pathogenic filamin C (FLNC) mutations. Three patients presented with ventricular arrhythmias, two with severe biventricular dysfunction, and two suffered sudden cardiac arrest. Three received an implantable cardioverter defibrillator, and one underwent heart transplantation. Cascade testing was useful in identifying other relatives with FLNC mutation. We also present relevant histology results of myocardial specimens showing the presence of lymphocytic infiltration and inflammation, further supporting the potential association between FLNC mutations and a myocarditis phenotype. Discussion: Genetic testing of affected individuals for FLNC mutations and cascade screening in the setting of acute myocarditis may be considered in selected clinical context, such as in acute myocarditis accompanied by severe left ventricular systolic dysfunction, biventricular failure, significant ventricular arrhythmias, or right ventricular involvement.

Multiorgan Congestion Assessment by Venous Excess Ultrasound Score in Acute Heart Failure.

BACKGROUND: This study sought to explore the prevalence and clinical utility of different patterns of multiorgan venous congestion as assessed by the venous excess ultrasound (VExUS) score in hospitalized patients with acute heart failure (HF). METHODS: Consecutive patients admitted for acute HF were prospectively enrolled. Inferior vena cava diameter, hepatic vein, portal vein, and renal vein Doppler waveforms were assessed at admission, and patients were stratified based on VExUS score from 0 to 3, with higher values indicating worse congestion. The clinical score Get with the Guidelines (GWTG)-HF for predicting in-hospital mortality in HF was evaluated. In-hospital mortality was recorded. RESULTS: Two hundred ninety patients admitted with acute HF were included, and 114 (39%) of them were classified as VExUS score 3, which was the most prevalent group. Patients with VExUS score 3 suffered more frequently from chronic atrial fibrillation, chronic kidney disease, and anemia. Parameters independently associated with VExUS score 3 were higher mean E/e' ratio, larger right ventricular size, severe tricuspid regurgitation, and impaired right atrial function. A VExUS score of 3 was associated with in-hospital mortality (odds ratio, 8.03; 95% CI [2.25-28.61], P = .001). The addition of VExUS score on top of the GWTG-HF score improved the predictability of the model (Δx2 = +8.44, P = .03) for in-hospital mortality, whereas other indices of venous congestion (right atrial function, inferior vena cava size) did not. CONCLUSIONS: Patients admitted with acute HF commonly had severe venous congestion based on the VExUS score. The VExUS score improved the prediction of in-hospital mortality compared with other indices of venous congestion.

Clinical characteristics and natural history of hypertrophic cardiomyopathy with midventricular obstruction.

BACKGROUND: The prevalence, clinical characteristics and natural history of patients with hypertrophic cardiomyopathy (HCM) and midventricular obstruction (MVO) have not been adequately studied. METHODS AND RESULTS: A single-center cohort consisting of 423 patients (mean age, 49.3±17.2 years; 66.2% male) was thoroughly followed up for a median of 84 months (7 years; range, 6-480 months). MVO, characterized by the echocardiographic appearance of midventricular muscular apposition with a simultaneous mid-cavitary gradient ≥30mmHg, was identified in 34 patients (8%). Patients with MVO tended to be more symptomatic during their initial evaluation (>90% presented with NYHA class ≥II) compared to the rest of the HCM cohort. Apical aneurysm formation was identified in more than one-fourth of patients with MVO (26.5%), being a characteristic of the group. On multivariate Cox regression hazard analysis, presence of MVO strongly predicted progression to end-stage (burnt out) HCM and related heart failure (HF) deaths (hazard ratio, [HR], 2.62; 95% confidence interval [CI]: 1.2-8.8; P=0.047), as well as sudden death and associated lethal arrhythmic events (HR, 3.3; 95% CI: 1.26-8.85; P=0.016). CONCLUSIONS: MVO is a distinct phenotype of HCM associated with unfavorable prognosis in terms of end-stage HCM, sudden death and lethal arrhythmic events. The high adverse outcome rate necessitates early recognition of MVO and appropriate therapeutic interventions.

Wild-Type Transthyretin Amyloid Cardiomyopathy: The Gordian-Knot of Novel Therapeutic Regimens.

Wild-type TTR amyloidosis (wtATTR) represents a disease difficult to diagnose with poor prognosis. Increased clinical suspicion is key, allowing for timely diagnosis. Until recently, only off-label therapies were available but recent introduction of disease specific therapy has shown potential to alter the natural history of the disease. Tafamidis, the only currently approved drug for the therapy of wtATTR, provided significantly better survival and quality of life. However, not all subgroups of patients derived equal benefit. This, along with the increased cost of treatment raised question on whether treatment should be invariably administered through the wtATTR population. This review aims to summarize current evidence on the natural history and staging systems for wtATTR, as well as available treatment options. Special consideration is given to the selection process of patients who would be expected to gain maximum benefit from tafamidis treatment, based on an ethical and cost-effective point of view.

Prevalence, characteristics, and natural history of apical phenotype in a large cohort of patients with hypertrophic cardiomyopathy.

BACKGROUND: Apical hypertrophic cardiomyopathy (ApHCM) is a variant of hypertrophic cardiomyopathy (HCM) with distinct imaging and clinical characteristics. Data on the prognosis of this HCM subgroup appear conflicting. Our study aims to clarify the natural history of ApHCM and identify predictors of outcomes. MATERIALS AND METHODS: A total of 856 patients with HCM were retrospectively examined. ApHCM was defined as asymmetric left ventricular hypertrophy confined predominantly at the apex, either isolated (pure ApHCM type) or with co-existent hypertrophy of the interventricular septum (mixed ApHCM). Echocardiographic, clinical, and survival data were compared between individuals with ApHCM and non-ApHCM. RESULTS: A total of 143 (16.7%) patients were diagnosed with ApHCM. Compared with non-ApHCM, subjects with apical HCM were diagnosed at an older age and had better echocardiographic indices and more comorbidities at baseline. Apical aneurysms were more prevalent among the ApHCM phenotype (6.3% vs. 1.7%, p = 0.003). During a mean follow-up of 6 ± 3 years, ApHCM was characterized by lower all-cause, cardiovascular, heart failure-related mortality, and ventricular arrhythmic events compared with non-ApHCM. Multivariate analysis identified atrial fibrillation and HCM risk-sudden cardiac death (SCD) as independent predictors of the composite outcome of overall mortality and hospitalizations for cardiovascular reasons (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.9-9.5 for atrial fibrillation and HR 1.2, 95% CI 1.02-1.3 for HCM risk-SCD) in ApHCM. CONCLUSIONS: ApHCM exhibited a lower rate of all-cause mortality and arrhythmic events in the middle-aged population of patients with HCM. Atrial fibrillation and HCM risk-sudden cardiac death were independent predictors of a composite of overall mortality and cardiovascular hospitalizations among those with ApHCM.

Periostin is overexpressed, correlated with fibrosis and differs among grades of cardiomyocyte hypertrophy in myectomy tissue of patients with hypertrophic cardiomyopathy.

Periostin, a secreted matricellular protein, has been implicated in cardiac extracellular matrix remodeling and fibrosis. Evidence suggest that periostin stimulates cardiomyocyte hypertrophy. The current study aims to investigate the extent of periostin expression in patients with advanced Hypertrophic Cardiomyopathy (HCM) and its correlation with fibrosis and hallmark histopathological features of the disease. Interventricular septal tissue from thirty-nine HCM patients who underwent myectomy and five controls who died from non-cardiac causes was obtained. Staining with Masson's Trichrome and immunohistochemistry were used to localize fibrosis and periostin respectively. The extent of fibrosis and the expression of periostin were defined as the stained percentage of total tissue area using digital pathology software. Periostin expression was higher in HCM patients compared to controls (p<0.0001), positively correlated with the extent of fibrosis (r = 0.82, p<0.001), positively correlated with maximal interventricular septal thickness (Rho = 0.33, p = 0.04) and negatively correlated with LVEF (r = -0.416, p = 0.009). Periostin was approximately co-localized with fibrosis. Mean periostin expression was lower in patients with mild grade cardiomyocyte hypertrophy compared to those with moderate grade (p = 0.049) and lower in patients with mild grade replacement fibrosis compared to moderate grade (p = 0.036). In conclusion, periostin is overexpressed in advanced HCM, correlated with fibrosis and possibly related to cardiomyocyte hypertrophy.

Apical Hypertrophic Cardiomyopathy: Diagnosis, Natural History, and Management.

Apical hypertrophic cardiomyopathy (ApHCM) represents a rare variant of hypertrophic cardiomyopathy (HCM) with distinct phenotypic characteristics. The prevalence of this variant varies according to each study's geographic region. The leading imaging modality for the diagnosis of ApHCM is echocardiography. Cardiac magnetic resonance, however, is the gold standard for ApHCM diagnosis in case of poor acoustic windows or equivocal echocardiographic findings but also in cases of suspected apical aneurysms. The prognosis of ApHCM was reported to be relatively benign, although more recent studies seem to contradict this, demonstrating similar incidence of adverse events compared with the general HCM population. The aim of this review is to summarize the available evidence for the diagnosis of ApHCM, highlight distinctions in comparison to more frequent forms of HCM with regards to its natural history, prognosis, and management strategies.

An overview of heart rhythm disorders and management in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is the most common adult form of muscular dystrophy, presenting with a constellation of systemic findings secondary to a CTG triplet expansion of the noncoding region of the DMPK gene. Cardiac involvement is frequent, with conduction disease and supraventricular and ventricular arrhythmias being the most prevalent cardiac manifestations, often developing from a young age. The development of cardiac arrhythmias has been linked to increased morbidity and mortality, with sudden cardiac death well described. Strategies to mitigate risk of arrhythmic death have been developed. In this review, we outline the current knowledge on the pathophysiology of rhythm abnormalities in patients with myotonic dystrophy and summarize available knowledge on arrhythmic risk stratification. We also review management strategies from an electrophysiological perspective, attempting to underline the substantial unmet need to address residual arrhythmic risks for this population.

Validation of the new American College of Cardiology/American Heart Association Guidelines for the risk stratification of sudden cardiac death in a large Mediterranean cohort with Hypertrophic Cardiomyopathy.

BACKGROUND: The aim of our study was to assess the performance of the new American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines, with respect to sudden cardiac death (SCD) prevention, in comparison with the established risk score of the European Society of Cardiology (hypertrophic cardiomyopathy [HCM] Risk-SCD), in a large Mediterranean cohort of HCM patients. METHODS: The clinical and imaging characteristics of 784 HCM patients (mean age at first evaluation 52 ± 16 years, 67.2% males) were analyzed retrospectively. The sensitivity, specificity, and negative predictive value for SCD events of the presence of ≥1 risk factor for SCD according to the ACC/AHA Guidelines 2020 and of the HCM Risk-SCD≥6% and HCM Risk-SCD≥4% were estimated during follow-up. RESULTS: During follow-up, 47 (6%) patients suffered an SCD event. The presence of ≥1 major risk factor for SCD according to the new ACC/AHA Guidelines had 96% sensitivity (95% CI 85.5-99.5%) with modest specificity of 59% (95% CI 55-62.2%) and negative predictive value of 99.5% (95% CI 98.2-99.9%). On the contrary, HCM- Risk-SCD≥6% had a relatively low sensitivity (32%, 95% CI 19.1-47.1%) and high specificity of 95% (95% CI 93.1-96.4%), whereas, HCM-Risk-SCD≥4% had sensitivity of 60% (95% CI 44-74%) and specificity of 83.9% (95% CI 80-85.6%). Both the HCM Risk-SCD cut-off values demonstrated lower negative predictive value but higher accuracy than the ACC/AHA algorithm for SCD prediction. CONCLUSION: The novel ACC/AHA proposed algorithm identifies most of the patients with an SCD event with the cost of numerous defibrillator implantations. HCM-Risk-SCD demonstrated higher specificity, whereas its sensitivity and negative predictive value are modest.

Cardiac Outcomes in Adults With Mitochondrial Diseases.

BACKGROUND: Patients with mitochondrial diseases are at risk of heart failure (HF) and arrhythmic major adverse cardiac events (MACE). OBJECTIVES: We developed prediction models to estimate the risk of HF and arrhythmic MACE in this population. METHODS: We determined the incidence and searched for predictors of HF and arrhythmic MACE using Cox regression in 600 adult patients from a multicenter registry with genetically confirmed mitochondrial diseases. RESULTS: Over a median follow-up time of 6.67 years, 29 patients (4.9%) reached the HF endpoint, including 19 hospitalizations for nonterminal HF, 2 cardiac transplantations, and 8 deaths from HF. Thirty others (5.1%) reached the arrhythmic MACE, including 21 with third-degree or type II second-degree atrioventricular blocks, 4 with sinus node dysfunction, and 5 sudden cardiac deaths. Predictors of HF were the m.3243A>G variant (HR: 4.3; 95% CI: 1.8-10.1), conduction defects (HR: 3.0; 95% CI: 1.3-6.9), left ventricular (LV) hypertrophy (HR: 2.6; 95% CI: 1.1-5.8), LV ejection fraction <50% (HR: 10.2; 95% CI: 4.6-22.3), and premature ventricular beats (HR: 4.1; 95% CI: 1.7-9.9). Independent predictors for arrhythmia were single, large-scale mtDNA deletions (HR: 4.3; 95% CI: 1.7-10.4), conduction defects (HR: 6.8; 95% CI: 3.0-15.4), and LV ejection fraction <50% (HR: 2.7; 95% CI: 1.1-7.1). C-indexes of the Cox regression models were 0.91 (95% CI: 0.88-0.95) and 0.80 (95% CI: 0.70-0.90) for the HF and arrhythmic MACE, respectively. CONCLUSIONS: We developed the first prediction models for HF and arrhythmic MACE in patients with mitochondrial diseases using genetic variant type and simple cardiac assessments.

Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis.

BACKGROUND: Long-term statin treatment reduces the frequency of cardiovascular events, but safety and efficacy in patients with abnormal liver tests is unclear. We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study population. METHODS: GREACE was a prospective, intention-to-treat study that randomly assigned by a computer-generated randomisation list 1600 patients with coronary heart disease (aged <75 years, with serum concentrations of LDL cholesterol >2·6 mmol/L and triglycerides <4·5 mmol/L) at the Hippokration University Hospital, Thessaloniki, Greece to receive statin or usual care, which could include statins. The primary outcome of our post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests (defined as serum alanine aminotransferase or aspartate aminotransferase concentrations of less than three times the upper limit of normal) compared with patients with abnormal liver tests who did not receive a statin. This risk reduction was compared with that for patients treated (or not) with statin and normal liver tests. FINDINGS: Of 437 patients with moderately abnormal liver tests at baseline, which were possibly associated with non-alcoholic fatty liver disease, 227 who were treated with a statin (mainly atorvastatin 24 mg per day) had substantial improvement in liver tests (p<0·0001) whereas 210 not treated with a statin had further increases of liver enzyme concentrations. Cardiovascular events occurred in 22 (10%) of 227 patients with abnormal liver tests who received statin (3·2 events per 100 patient-years) and 63 (30%) of 210 patients with abnormal liver tests who did not receive statin (10·0 events per 100 patient-years; 68% relative risk reduction, p<0·0001). This cardiovascular disease benefit was greater (p=0·0074) than it was in patients with normal liver tests (90 [14%] events in 653 patients receiving a statin [4·6 per 100 patient-years] vs 117 [23%] in 510 patients not receiving a statin [7·6 per 100 patient-years]; 39% relative risk reduction, p<0·0001). Seven (<1%) of 880 participants who received a statin discontinued statin treatment because of liver-related adverse effects (transaminase concentrations more than three-times the upper limit of normal). INTERPRETATION: Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease. FUNDING: None.

Prognostic value of right ventricular diastolic function indices in hypertrophic cardiomyopathy.

AIMS: Despite the fact that the role of left ventricular diastolic dysfunction in hypertrophic cardiomyopathy (HCM) patients' prognosis has been established, the effect of increased right ventricular (RV) diastolic filling pressures still remains unclear. The purpose of this study was to determine the prognostic significance of transthoracic echocardiographic indices of RV diastolic function (tricuspid inflow and tricuspid annulus tissue Doppler imaging) in HCM patients. METHODS AND RESULTS: We followed up 386 patients diagnosed with HCM (aged 49.3 ± 17.2 years; 65% male) for a median period of 67 months (interquartile range 26-189 months). Primary endpoints were considered mortality due to heart failure (HF) (13 patients) and total cardiovascular (TC) mortality [HF, sudden cardiac death and its equivalents (35 patients)]. Patients presenting with an increased RV E/E(r) ratio (ratio of tricuspid in flow E wave to E(r) wave obtained by tissue Doppler imaging at the lateral tricuspid annulus) had a 1.6 times greater risk for HF mortality [hazard ratio (HR): 1.6, 95% confidence interval (CI): 1.1-2.4, P = 0.03] while patients with shortened tricuspid E wave deceleration time (DTE) had a 1.1 greater risk for SCD (HR: 1.1, 95% CI: 1.01-1.2, P = 0.03). Following ROC analysis, the optimal RV indices' cut-off values for the recognition of our study endpoints were assessed [E/E(r) = 6.88, sensitivity 75%, specificity 77.4%, area under curve (AUC) 0.847, P = 0.017 for HF mortality and DTE < 239 ms, sensitivity 62.5%, specificity 56.7%, AUC 0.642, P = 0.05 for TC mortality]. CONCLUSION: The establishment of RV restrictive physiology appears to have significant predictive value in HCM, regardless of the presence of other detrimental risk factors.

Risk Prediction Models and Scores in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) has historically been linked with sudden cardiac death (SCD). Currently, it is well established that only a subset of patients is at the highest risk stratum for such a catastrophic event. Detection of patients belonging to this high-risk category can allow for timely defibrillator implantation, changing the natural history of HCM. Inversely, device implantation in patients deemed at low risk leads to an unnecessary burden of device complications with no apparent protective benefit. Previous studies have identified a series of markers, now considered established risk factors, with genetic testing and newer imaging allowing for the detection of novel, highly promising indices of increased risk for SCD. Despite the identification of a number of risk factors, there is noticeable discrepancy in the utility of such factors for risk stratification between the current American and European guidelines. We sought to systematically review the data available on these two approaches, presenting their rationale and respective predictive capacity, also discussing the potential of novel markers to augment the precision of currently used risk stratification models for SCD in HCM.