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

BACKGROUND: A 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. METHODS: Data 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. RESULTS: Study 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). CONCLUSIONS: Two 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.

Real-world candidacy to mavacamten in a contemporary hypertrophic obstructive cardiomyopathy population.

AIMS: In the EXPLORER-HCM trial, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved functional capacity of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients. We sought to define the potential use of mavacamten by comparing real-world HOCM patients with those enrolled in EXPLORER-HCM and assessing their eligibility to treatment. METHODS AND RESULTS: We collected information on HOCM patients followed up at 25 Italian HCM outpatient clinics and with significant LVOTO (i.e. gradient ≥30 mmHg at rest or ≥50 mmHg after Valsalva manoeuvre or exercise) despite pharmacological or non-pharmacological therapy. Pharmacological or non-pharmacological therapy resolved LVOTO in 1044 (61.2%) of the 1706 HOCM patients under active follow-up, whereas 662 patients (38.8%) had persistent LVOTO. Compared to the EXPLORER-HCM trial population, these real-world HOCM patients were older (62.1 ± 14.3 vs. 58.5 ± 12.2 years, p = 0.02), had a lower body mass index (26.8 ± 5.3 vs. 29.7 ± 4.9 kg/m2 , p < 0.0001) and a more frequent history of atrial fibrillation (21.5% vs. 9.8%, p = 0.027). At echocardiography, they had lower left ventricular ejection fraction (LVEF, 66 ± 7% vs. 74 ± 6%, p < 0.0001), higher left ventricular outflow tract gradients at rest (60 ± 27 vs. 52 ± 29 mmHg, p = 0.003), and larger left atrial volume index (49 ± 16 vs. 40 ± 12 ml/m2 , p < 0.0001). Overall, 324 (48.9%) would have been eligible for enrolment in the EXPLORER-HCM trial and 339 (51.2%) for treatment with mavacamten according to European guidelines. CONCLUSIONS: Real-world HOCM patients differ from the EXPLORER-HCM population for their older age, lower LVEF and larger atrial volume, potentially reflecting a more advanced stage of the disease. About half of real-world HOCM patients were found eligible to mavacamten.

Heart failure patients with improved ejection fraction: Insights from the MECKI score database.

AIMS: Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF). METHODS AND RESULTS: A total of 7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow-up of 1490 days). We analysed clinical, laboratory, electrocardiographic, echocardiographic, exercise, and survival data from HFimpEF (n = 1504) and pHFrEF (n = 6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. HFimpEF patients had lower HF severity: left ventricular ejection fraction 44.0 [41.0-47.0] versus 29.7 [24.1-34.5]%, B-type natriuretic peptide 122 [65-296] versus 373 [152-888] pg/ml, haemoglobin 13.5 [12.2-14.6] versus 13.7 [12.5-14.7] g/dl, renal function by the Modification of Diet in Renal Disease equation 72.0 [56.7-89.3] versus 70.4 [54.5-85.3] ml/min, peak oxygen uptake 62.2 [50.7-74.1] versus 52.6 [41.8-64.3]% predicted, minute ventilation-to-carbon dioxide output slope 30.0 [26.9-34.4] versus 32.1 [28.0-38.0] in HFimpEF and pHFrEF, respectively (p < 0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person-years for HFimpEF and pHFrEF, respectively (p < 0.001). Kaplan-Meier analysis showed that HFimpEF had better a long-term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan-Meier curves showed the same prognosis. CONCLUSIONS: Heart failure with improved ejection fraction represents a peculiar group of HF patients whose clinical, laboratory, electrocardiographic, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome.

Does moderate hyperkalemia influence survival in HF? Insights from the MECKI score data base.

BACKGROUND: The prognostic role of moderate hyperkalemia in reduced ejection fraction (HFrEF) patients is still controversial. Despite this, it affects the use of renin-angiotensin-aldosterone system inhibitors (RAASi) with therapy down-titration or discontinuation. OBJECTIVES: Aim of the study was to assess the prognostic impact of moderate hyperkalemia in chronic HFrEF optimally treated patients. METHODS AND RESULTS: We retrospectively analyzed MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) database, with median follow-up of 4.2 [IQR 1.9-7.5] years. Data on K+ levels were available in 7087 cases. Patients with K+ plasma level ≥ 5.6 mEq/L and < 4 mEq/L were excluded. Remaining patients were categorized into normal >4 and < 5 mEq/L (n = 4826, 68%) and moderately high ≥5.0 and ≤ 5.5 mEq/L (n = 496, 7%) K+. Then patients were matched by propensity score in 484 couplets of patients. MECKI score value was 7% [IQR 3.1-14.1%] and 7.3% [IQR 3.4-15%] (p = 0.678) in patients with normal and moderately high K+ values while cardiovascular mortality events at two years follow-up were 41 (4.2%) and 33 (3.4%) (p = 0.333) in each group respectively. CONCLUSIONS: Moderate hyperkalemia does not influence patients' outcome in a large cohort of ambulatory HFrEF patients.

Exploring the Prognostic Performance of MECKI Score in Heart Failure Patients with Non-Valvular Atrial Fibrillation Treated with Edoxaban.

INTRODUCTION: Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF. MATERIALS AND METHODS: This study included consecutive outpatients with HF and NVAF treated with edoxaban (n = 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry (n = 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation. RESULTS: Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively, p = 0.452). The two populations' survival appeared non-significantly different at the 2-year follow-up. CONCLUSIONS: this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients.

Left Heart Disease Phenotype in Elderly Patients with Pulmonary Arterial Hypertension: Insights from the Italian PATRIARCA Registry.

Pulmonary arterial hypertension (PAH) in the elderly is often associated with left heart disease (LHD), prompting concerns about the use of pulmonary vasodilators. The PATRIARCA registry enrolled ≥70 year-old PAH or chronic thromboembolic pulmonary hypertension (CTEPH) patients at 11 Italian centers from 1 December 2019 through 15 September 2022. After excluding those with CTEPH, post-capillary PH at the diagnostic right heart catheterization (RHC), and/or incomplete data, 23 (33%) of a total of 69 subjects met the criteria proposed in the AMBITION trial to suspect LHD. Diabetes [9 (39%) vs. 6 (13%), p = 0.01] and chronic kidney disease [14 (61%) vs. 12 (26%), p = 0.003] were more common, and the last RHC pulmonary artery wedge pressure [14 ± 5 vs. 10 ± 3 mmHg, p < 0.001] was higher and pulmonary vascular resistance [5.56 ± 3.31 vs. 8.30 ± 4.80, p = 0.02] was lower in LHD than non-LHD patients. However, PAH therapy was similar, with 13 (57%) and 23 (50%) subjects, respectively, taking two oral drugs. PAH medication patterns remained comparable between LHD and non-LHD patients also when the former [37, 54%] were identified by atrial fibrillation and echocardiographic features of LHD, in addition to the AMBITION criteria. In this real-world snapshot, elderly PAH patients were treated with pulmonary vasodilators, including combinations, despite a remarkable prevalence of a LHD phenotype.

Pick Your Threshold: A Comparison Among Different Methods of Anaerobic Threshold Evaluation in Heart Failure Prognostic Assessment.

BACKGROUND: In clinical practice, anaerobic threshold (AT) is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). AT of oxygen uptake (V.O2; V.O2AT) has been reported as an absolute value (V.O2ATabs), as a percentage of predicted peak V.O2 (V.O2AT%peak_pred), or as a percentage of observed peak V.O2 (V.O2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing. RESEARCH QUESTION: What is the prognostic power of these different ways to report AT? STUDY DESIGN AND METHODS: In this observational cohort study, we screened data of 7,746 patients with HF with a history of reduced ejection fraction (< 40%) recruited between 1998 and 2020 and enrolled in the Metabolic Exercise Combined With Cardiac and Kidney Indexes register. All patients underwent a maximum cardiopulmonary exercise test, executed using a ramp protocol on an electronically braked cycle ergometer. RESULTS: This study considered 6,157 patients with HF with identified AT. Follow-up was median, 4.2 years (25th-75th percentiles, 1.9-5.0 years). Both V.O2ATabs (mean ± SD, 823 ± 305 mL/min) and V.O2AT%peak_pred (mean ± SD, 39.6 ± 13.9%), but not V.O2AT%peak_obs (mean ± SD, 69.2 ± 17.7%), well stratified the population regarding prognosis (composite end point: cardiovascular death, urgent heart transplant, or left ventricular assist device). Comparing area under the receiver operating characteristic curve (AUC) values, V.O2ATabs (0.680) and V.O2AT%peak_pred (0.688) performed similarly, whereas V.O2AT%peak_obs (0.538) was significantly weaker (P < .001). Moreover, the V.O2AT%peak_pred AUC value was the only one performing as well as the AUC based on peak V.O2 (0.710), with an even a higher AUC (0.637 vs 0.618, respectively) in the group with severe HF (peak V.O2 < 12 mL/min/kg). Finally, the combination of V.O2AT%peak_pred with peak V.O2 and V. per CO2 production shows the highest prognostic power. INTERPRETATION: In HF, V.O2AT%peak_pred is the best way to report V.O2 at AT in relationship to prognosis, with a prognostic power comparable to that of peak V.O2 and, remarkably, in patients with severe HF.

Heart Rate in Patients with SARS-CoV-2 Infection: Prevalence of High Values at Discharge and Relationship with Disease Severity.

The most common arrhythmia associated with COronaVIrus-related Disease (COVID) infection is sinus tachycardia. It is not known if high Heart Rate (HR) in COVID is simply a marker of higher systemic response to sepsis or if its persistence could be related to a long-term autonomic dysfunction. The aim of our work is to assess the prevalence of elevated HR at discharge in patients hospitalized for COVID-19 and to evaluate the variables associated with it. We enrolled 697 cases of SARS-CoV2 infection admitted in our hospital after February 21 and discharged within 23 July 2020. We collected data on clinical history, vital signs, laboratory tests and pharmacological treatment. Severe disease was defined as the need for Intensive Care Unit (ICU) admission and/or mechanical ventilation. Median age was 59 years (first-third quartile 49, 74), and male was the prevalent gender (60.1%). 84.6% of the subjects showed a SARS-CoV-2 related pneumonia, and 13.2% resulted in a severe disease. Mean HR at admission was 90 ± 18 bpm with a mean decrease of 10 bpm to discharge. Only 5.5% of subjects presented HR > 100 bpm at discharge. Significant predictors of discharge HR at multiple linear model were admission HR (mean increase = ß = 0.17 per bpm, 95% CI 0.11; 0.22, p < 0.001), haemoglobin (ß = -0.64 per g/dL, 95% CI -1.19; -0.09, p = 0.023) and severe disease (ß = 8.42, 95% CI 5.39; 11.45, p < 0.001). High HR at discharge in COVID-19 patients is not such a frequent consequence, but when it occurs it seems strongly related to a severe course of the disease.

Nonresponse to Acute Vasodilator Challenge and Prognosis in Heart Failure With Pulmonary Hypertension.

BACKGROUND: An acute vasodilator challenge is recommended in patients with heart failure and pulmonary hypertension during heart transplant evaluation. The aim of the study was to assess which hemodynamic parameters are associated with nonresponsiveness to the challenge. METHODS AND RESULTS: This study is a retrospective analysis of 402 patients with heart failure with pulmonary hypertension who underwent right heart catheterization and a pulmonary vasodilator challenge. Among the 140 who fulfilled the transplant guidelines eligibility criteria for the vasodilator challenge, 38 were responders and 102 nonresponders. At multivariable analysis, a diastolic blood pressure of <70 mm Hg, pulmonary vascular resistance of >5 Woods units, and pulmonary artery compliance of <1.2 mL/mm Hg were independently associated with poor response to vasodilator challenge (all P < .001). The presence of any 2 of these 3 conditions was associated with a 90% probability of being a nonresponder. The covariate-adjusted hemodynamic predictors of death in the entire population were a low baseline systolic blood pressure (P = .0017) and a low baseline right ventricular stroke work index (P = .0395). CONCLUSIONS: In patients with heart failure and pulmonary hypertension, low pulmonary arterial compliance, high pulmonary vascular resistance, and low diastolic blood pressure predict the nonresponsiveness to acute vasodilator challenge whilst a poor right ventricular function predicts a dismal prognosis.

Clinical and prognostic impact of chronotropic incompetence in patients with hypertrophic cardiomyopathy.

BACKGROUND: A blunted heart rate (HR) response is associated with an impaired peak oxygen uptake (pVO2), a powerful outcome predictor in hypertrophic cardiomyopathy (HCM). The present multicenter study sought to determine the prognostic role for exercise-induced HR response in HCM. METHODS: A total of 681 consecutive HCM outpatients on optimized treatment were recruited. The heart failure (HF) end-point was death due to HF, cardiac transplantation, NYHA III-IV class progression, HF worsening leading to hospitalization and severe functional deterioration leading to septal reduction. The sudden cardiac death (SCD) end-point included SCD, aborted SCD and appropriate implantable cardioverter defibrillator discharges. RESULTS: During a median follow-up of 4.2 years (25-75th centile: 3.9-5.2), 81 patients reached the HF and 23 the SCD end-point. Covariates with independent effects on the HF end-point were left atrial diameter, left ventricular ejection fraction, maximal left ventricular outflow tract gradient and exercise cardiac power (ECP = pVO2∗systolic blood pressure) (C-Index = 0.807) whereas the HCM Risk-SCD score and the ECP remained associated with the SCD end-point (C-Index = 0.674). When the VO2-derived variables were not pursued, peak HR (pHR) re-entered in the multivariate HF model (C-Index = 0.777) and, marginally, in the SCD model (C-index = 0.656). A pHR = 70% of the maximum predicted resulted as the best cut-off value in predicting the HF-related events. CONCLUSIONS: The cardiopulmonary exercise test is pivotal in the HCM management, however the pHR remains a meaningful alternative parameter. A pHR < 70% identified a HCM population at high risk of HF-related events, thus calling for a reappraisal of the chronotropic incompetence threshold in HCM.

Triple Combination Therapies Based on Olmesartan: A Personalized Therapeutic Approach to Improve Blood Pressure Control.

Recent epidemiological surveys have demonstrated that effective and sustained blood pressure (BP) control is achieved in a relatively small proportion of treated hypertensive patients. Indeed, treatment of hypertension represents a key strategy for preventing coronary artery disease, stroke, congestive heart failure and cardiovascular death. Several interventions have been proposed by international guidelines for ameliorating hypertension management and control, mostly including integrated and multi-dimensional pharmacological and non-pharmacological strategies. In particular, numerous evidence demonstrated that a more extensive use of combination therapy may represent a valid therapeutic option for treating hypertensive patients at different risk profile. This strategy has been definitely strengthened by the availability of single pill fixed-dose combinations. Among potential combination therapies, those based on the association of renin-angiotensin system antagonists, thiazide diuretics and calcium channel blockers are very effective in lowering BP levels and well tolerated. We will provide here an overview of clinical evidence supporting the use of triple combination therapy, with a focus on that based on olmesartan medoxomil, a thiazide diuretic (hydrochlorothiazide) and a calcium channel blocker (amlodipine besylate), which is available in multiple dosages. Finally, in view of the recognised importance of single-pill combination therapy for treating hypertension, we will examine the potential benefits of dual (fixed) combination therapy based on olmesartan medoxomil with either thiazide diuretic hydrochlorothiazide or calcium channel blocker amlodipine in terms of efficacy, safety and tolerability profile.

Monotherapy and Dual Combination Therapies Based on Olmesartan: A Comprehensive Strategy to Improve Blood Pressure Control.

Olmesartan medoxomil is an antihypertensive drug of the class of angiotensin II type 1 (AT1) receptor antagonists (or blockers), characterized by tight and prolonged binding to AT1 receptor compared to other molecules within the same class. These characteristics produce effective and sustained blood pressure reductions in hypertensive patients at different cardiovascular risk profile with a good tolerability profile. After a brief description of the pharmacological characteristics of olmesartan, we will provide a thorough overview of the clinical studies that investigated its efficacy and safety in the clinical management of hypertensive patients both in monotherapy and in dual combination therapies with either thiazide diuretics or calcium channel blockers. These studies demonstrated that olmesartan-based antihypertensive strategy may indeed provide sustained BP control over the 24-h period in a wide proportion of hypertensive patients, thus contributing to a substantial progress in hypertension management. Finally, since growing evidence suggest that olmesartan may also exert potential favourable effects at vascular level, thereby antagonizing the vascular inflammatory process involved in the development and progression of atherosclerosis, the main clinical studies addressing this issue will be also discussed.

Cardiopulmonary Exercise Test in Hypertrophic Cardiomyopathy.

Understanding the functional limitation in hypertrophic cardiomyopathy, the most common inherited heart disease, is challenging. In addition to the occurrence of disease-related complications, several factors are potential determinants of exercise limitation, including left ventricular hypertrophy, myocardial fiber disarray, left ventricular outflow tract obstruction, microvascular ischemia, and interstitial fibrosis. Furthermore, drugs commonly used in the daily management of these patients may interfere with exercise capacity, especially those with a negative chronotropic effect. Cardiopulmonary exercise testing can safely and objectively evaluate the functional capacity of these patients and help the physician in understanding the mechanisms that underlie this limitation. Features that reduce exercise capacity may predict progression to heart failure in these patients and even the risk of sudden cardiac death.

QT spatial dispersion and sudden cardiac death in hypertrophic cardiomyopathy: Time for reappraisal.

BACKGROUND: The 12-lead surface electrocardiographic (ECG) analysis is able to provide independent predictors of prognosis in several cardiovascular settings, including hypertrophic cardiomyopathy (HCM). The present single-center study investigated the possible ability of several ECG-derived variables in stratifying sudden cardiac death (SCD) risk and, possibly, in improving the accuracy of the 2014 European Society of Cardiology guidelines. METHODS: A total of 221 consecutive HCM outpatients were recruited and prospectively followed. All of them underwent a full clinical and instrumental examination, including a 12-lead surface ECG to calculate the dispersion for the following intervals: QRS, Q-Tend (QT), Q-Tpeak (QTp), Tpeak-Tend (TpTe), J-Tpeak (JTp), and J-Tend (JT). The study composite end-point was SCD, aborted SCD, and appropriate implantable cardioverter defibrillator (ICD) interventions. RESULTS: During a median follow-up of 4.4 years (25th-75th interquartile range: 2.4-9.4 years), 23 patients reached the end-point at 5-years (3 SCD, 3 aborted SCD, 17 appropriate ICD interventions). At multivariate analysis, the spatial QT dispersion corrected according to Bazett's formula (QTcd) remains independently associated to the study endpoint over the HCM Risk-SCD score (C-index 0.737). A QTcd cut-off value of 93ms showed the best accuracy in predicting the SCD endpoint within the entire HCM study cohort (sensitivity 56%, specificity 75%, positive predictive value 22%, negative predictive value 97%). CONCLUSION: Our data suggest that the QTcd might be helpful in SCD risk stratification, particularly in those HCM categories classified at low-intermediate SCD risk according to the contemporary guidelines.

Prognostic Implications of Defibrillation Threshold Testing in Patients With Hypertrophic Cardiomyopathy.

INTRODUCTION: In hypertrophic cardiomyopathy (HCM) patients the need for defibrillation threshold (DFT) testing at the time of ICD implantation is debated. Moreover, its prognostic implications have never been explored. In a cohort of HCM patients we sought to (a) investigate factors prompting DFT testing, (b) evaluate ICD efficacy by testing DFT, (c) compare DFT in patients with and without massive LVH, and (d) assess whether DFT testing predicts shock efficacy for spontaneous VT/VF. METHODS AND RESULTS: We retrospectively analyzed a cohort of HCM patients implanted with an ICD. DFT was tested at the discretion of the implanting physician with a 10 J safety margin. During follow-up, ICD interventions were evaluated. The study population included 66 patients. DFT was determined in 25 (38%) patients. Age (HR: 0.95; 95%CI: 0.92-0.98; P = 0.004) and massive LVH (HR: 6.0; 95%CI: 2.03-18.8; P = 0.001) affected the decision to test DFT. DFT was at least 10 J less than maximal ICD output in 25/25. Safety margin was similar among patients with and without massive LVH (15 ± 3 J vs. 14 ± 2 J; P = 0.42). During follow-up (median 53 months) 15 shocks were delivered for 12 VT/VF in 7 patients. One VF ended spontaneously after a failed shock. Of 4 unsuccessful shocks, 2 occurred in 1 patient with DFT testing and 2 were delivered in 2 patients without. All unsuccessful shocks were ≤35 J. CONCLUSION: Young age and massive LVH prompt DFT testing. Contemporary ICDs are safe and effective in HCM patients independently from the magnitude of LVH. DFT testing does not predict shock efficacy for spontaneous VT/VF.

Hypertension in Patients with Heart Failure with Reduced Ejection Fraction.

Hypertension (HTN) is a well-known health problem associated with considerable morbidity and mortality and it is an important risk factor for the development of heart failure (HF). These findings support the need for optimizing the antihypertensive strategies to prevent the progression to HF. Interestingly, the progression from HTN to HF, among other things, may be a consequence of inappropriate over-activation of the renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system (SNS), and the natriuretic peptide system (NPS). In the present review, we will discuss the pathophysiological aspects of the progression from HTN to HF with reduced ejection fraction (HFrEF) and we will focus on the evolution of different pharmacological therapies which are reported to be effective in reducing BP and improving HF outcomes, paying particular attention to the recent trials that have demonstrated the efficacy of the combined therapy of RAAS blockade and Neprilysin (NEP) inhibitor in lowering BP and mediating several beneficial actions within cardiovascular tissues, such as avoiding the worsening of HF.

Heart Failure Progression in Hypertrophic Cardiomyopathy　- Possible Insights From Cardiopulmonary Exercise Testing.

BACKGROUND: Heart failure (HF) progression and its complications represent major emergent concerns in hypertrophic cardiomyopathy (HCM). We investigated the possible adjunctive role of cardiopulmonary exercise testing (CPET) in predicting HF-related events. An exercise-derived risk model, theHYPertrophicExercise-derivedRiskHF(HYPERHF), has been developed. METHODS AND RESULTS: A multicenter cohort of 620 consecutive HCM outpatients was recruited and followed (2007 to 2015). The endpoint was death from HF, cardiac transplantation, NYHA III-IV class progression, severe functional deterioration leading to hospitalization for septal reduction, and hospitalization for HF worsening. During a median follow-up of 3.8 years (25-75th centile: 2.3-5.3 years), 84 patients reached the endpoint. Peak circulatory power (peak oxygen consumption * peak systolic blood pressure), ventilatory efficiency and left atrial diameter were independently associated with the endpoint and, accordingly, integrated into the HYPERHFmodel (C index: 0.849; best cutoff value equal to 15%). CONCLUSIONS: CPET is useful in the evaluation of HCM patients. In this context, the HYPERHFscore might allow early identification of those patients at high risk of HF progression and its complications. (Circ J 2016; 80: 2204-2211).

Cardiopulmonary exercise test and sudden cardiac death risk in hypertrophic cardiomyopathy.

BACKGROUND: In hypertrophic cardiomyopathy (HCM), most of the factors associated with the risk of sudden cardiac death (SCD) are also involved in the pathophysiology of exercise limitation. The present multicentre study investigated possible ability of cardiopulmonary exercise test in improving contemporary strategies for SCD risk stratification. METHODS: A total of 623 consecutive outpatients with HCM, from five tertiary Italian HCM centres, were recruited and prospectively followed, between September 2007 and April 2015. The study composite end point was SCD, aborted SCD and appropriate implantable cardioverter defibrillator (ICD) interventions. RESULTS: During a median follow-up of 3.7 years (25th-75th centile: 2.2-5.1 years), 25 patients reached the end point at 5 years (3 SCD, 4 aborted SCD, 18 appropriate ICD interventions). At multivariate analysis, ventilation versus carbon dioxide relation during exercise (VE/VCO2 slope) remains independently associated to the study end point either when challenged with the 2011 American College of Cardiology Foundation/American Heart Association guidelines-derived score (C index 0.748) or with the 2014 European Society of Cardiology guidelines-derived score (C index 0.750). A VE/VCO2 slope cut-off value of 31 showed the best accuracy in predicting the SCD end point within the entire HCM study cohort (sensitivity 64%, specificity 72%, area under the curve 0.72). CONCLUSIONS: Our data suggest that the VE/VCO2 slope might improve SCD risk stratification, particularly in those HCM categories classified at low-intermediate SCD risk according to contemporary guidelines. There is a need for further larger studies, possibly on independent cohorts, to confirm our preliminary findings.

New therapies for arterial hypertension.

Arterial hypertension is the most common chronic disease in developed countries and it is the leading risk factor for stroke, ischemic heart disease, congestive heart failure, chronic renal failure and peripheral artery disease. Its prevalence appears to be about 30-45% of the general population. Recent European guidelines estimate that up to 15-20% of the hypertensive patients are not controlled on a dual antihypertensive combination and they require three or more different antihypertensive drug classes to achieve adequate blood pressure control. The guidelines confirmed that diuretics, beta-blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in combination therapy. Very few antihypertensive agents have reached the market over the last few years, but no new therapeutic class has really emerged. The long-term adherence to cardiovascular drugs is still low in both primary and secondary prevention of cardiovascular diseases. In particular, the issue of compliance is persistently high in hypertension, despite the fixed-dose combination therapy. As a consequence, a cohort of high-risk hypertensive population, represented by patients affected by refractory and resistant hypertension, can be identified. Therefore, the need of controlling BP in high-risk patients may be addressed, in part, by the development of new drugs, devices and procedures that are designed to treat hypertension and comorbidities. In this review we will comprehensively discuss the current literature on recent therapeutic advances in hypertension, including both medical therapy and interventional procedures.