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 multi-organ 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 (IVC) 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. VExUS score 3 was associated with in-hospital mortality [OR 8.03, 95% CI (2.25-28.61), p=0.001]. The addition of VExUS score on top of the GWTG-HF score improved the predictability of the model (Δx2=+8.44, p=0.03) for in-hospital mortality, whereas other indices of venous congestion (right atrial function, IVC size) did not. CONCLUSION: Patients admitted with acute HF commonly had severe venous congestion based on VExUS score. VExUS score improved the prediction of in-hospital mortality as compared to other indices of venous congestion.

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.

Differences in Demographics, in-Hospital Management and Short-Term Prognosis in Admissions for Acutely Decompensated Heart Failure to Cardiology vs. Internal Medicine Departments: A Prospective Study.

Heart failure (HF) is among the leading causes of unplanned hospital admissions worldwide. Patients with HF carry a high burden of comorbidities; hence, they are frequently admitted for non-cardiac conditions and managed in Internal Medicine Departments (IMD). The aim of our study was to investigate differences in demographics, in-hospital management, and short-term outcomes of HF patients admitted to IMD vs. cardiology departments (CD). A prospective cohort study enrolling consecutive patients with acutely decompensated HF either as primary or as secondary diagnosis during the index hospitalization was conducted. Our primary endpoint was a combined endpoint of in-hospital mortality and 30-day rehospitalization for HF. A total of 302 patients participated in the study, with 45% of them admitted to IMD. Patients managed by internists were older with less pronounced HF symptoms on admission. In-hospital mortality was higher for patients admitted to IMD vs. CD (21% vs. 6%, p < 0.001). The composite endpoint of in-hospital death and heart failure hospitalizations at 30 days post-discharge was higher for patients admitted to IMD both in univariate [OR: 3.2, 95% CI (1.8-5.7); p < 0.001] and in multivariate analysis [OR 3.74, 95% CI (1.72-8.12); p = 0.001]. In addition, the HF rehospitalization rate at 6 months after discharge was higher in IMD patients [HR 1.65, 95% CI (1.1, 2.4), p = 0.01]. Overall, HF patients admitted to IMD have worse short-term outcomes compared to patients admitted to CD.

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.

The patient pathway in ATTR-CM in Greece and how to improve it: A multidisciplinary perspective.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed disease associated with high mortality rates and the patient journey is characterized by increased complexities. Accurate and timely diagnosis and prompt initiation of disease-modifying treatment constitute the contemporary unmet need in ATTR-CM. ATTR-CM diagnosis is characterized by considerable delays and high rates of misdiagnosis. The majority of patients present themselves to primary care physicians, internists, and cardiologists, and many have undergone repeated medical evaluations before an accurate diagnosis has been made. The disease is diagnosed mainly after the development of heart failure symptoms, reflecting a long course of missed opportunities before diagnosis and disease-modifying treatment initiation. Early referral to experienced centers ensures prompt diagnosis and therapy. Early diagnosis, better care coordination, acceleration of digital transformation and reference networks, encouragement of patient engagement, and implementation of rare disease registries are the key pillars to improve the ATTR-CM patient pathway and achieve important benefits in ATTR-CM outcomes.

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.

Iron therapy and severe arrhythmias in HFrEF: rationale, study design, and baseline results of the RESAFE-HF trial.

AIMS: The Iron Intravenous Therapy in Reducing the burden of Severe Arrhythmias in HFrEF (RESAFE-HF) registry study aims to provide real-word evidence on the impact of intravenous ferric carboxymaltose (FCM) on the arrhythmic burden of patients with heart failure with reduced ejection fraction (HFrEF), iron deficiency (ID), and implanted cardiac implantable electronic devices (CIEDs). METHODS AND RESULTS: The RESAFE-HF (NCT04974021) study was designed as a prospective, single-centre, and open-label registry study with baseline, 3, 6, and 12 month visits. Adult patients with HFrEF and CIEDs scheduled to receive IV FCM as treatment for ID as part of clinical practice were eligible to participate. The primary endpoint is the composite iron-related endpoint of haemoglobin ≥ 12 g/dL, ferritin ≥ 50 ng/L, and transferrin saturation > 20%. Secondary endpoints include unplanned HF-related hospitalizations, ventricular tachyarrhythmias detected by CIEDs and Holter monitors, echocardiographic markers, functional status (VO2 max and 6 min walk test), blood biomarkers, and quality of life. In total, 106 patients with a median age of 72 years (14.4) were included. The majority were male (84.9%), whereas 92.5% of patients were categorized to New York Heart Association II/III. Patients' arrhythmic burden prior to FCM administration was significant-19 patients (17.9%) received appropriate CIED therapy for termination of ventricular tachyarrhythmia in the preceding 12 months, and 75.5% of patients have frequent, repetitive multiform premature ventricular contractions. CONCLUSIONS: The RESAFE-HF trial is expected to provide evidence on the effect of treating ID with FCM in HFrEF based on real-world data. Special focus will be given on the arrhythmic burden post-FCM administration.

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.

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.

The predictive value of left ventricular and left atrial mechanics for atrial fibrillation and heart failure in hypertrophic cardiomyopathy: a prospective cohort study.

Atrial fibrillation (AF) and heart failure (HF) represent clinical turning points, altering the natural history of HCM and influencing long-term outcome of the disease. The aim of this study was to evaluate the ability of left ventricular (LV) and left atrial (LA) myocardial deformation parameters to predict new-onset AF and HF outcomes in patients with HCM. This was a prospective study that included HCM patients without severe valvular heart disease, prior myocardial infarction or history of AF. The study sample consisted of 250 patients (mean age 50.8 ± 15.8, 67.2% male). Two-dimensional (2D) speckle tracking deformation parameters including global longitudinal strain (GLS), radial strain, circumferential strain, LA reservoir strain (LAεres), LA conduit strain (LAεcon) and LA booster strain(LAεboost) were examined. During a mean follow-up of 2.5 ± 1.2 years, 44 patients developed new-onset AF. All the LV and LA deformation parameters were significant univariate predictors of AF. GLS and LAεres had the highest C statistic among the LV and LA functional indices. In multivariable analysis, only LAεres remained an independent predictor of the arrhythmia (HR 0.91, 95% CI 0.85-0.98, p: 0.008). Similarly, GLS and LAεres had the highest predictive value among the 2D speckle tracking parameters for HF outcomes. LAεres remained an independent predictor after adjusting for significant covariates. GLS and LAεres demonstrated high predictive value for the development of AF and HF in HCM. LAεres was the only independent predictor of both outcomes.Clinical trial registration: ClinicalTrials.gov identifier: NCT04112511.

Prognostic role of left ventricular apical aneurysm in hypertrophic cardiomyopathy: A systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to systematically review and quantitatively synthesize existing evidence about the prognostic value of LV apical aneurysm in patients with HCM. BACKGROUND: Hypertrophic cardiomyopathy (HCM) represents a common inherited heart disease associated with enormous diversity in morphologic expression and clinical course. With the increasing penetration of advanced high resolution cardiovascular imaging into routine HCM practice, a subset of HCM patients with left ventricular (LV) apical aneurysm have become more widely recognized. METHODS: Medline was searched for studies describing the prognostic implication of LV apical aneurysm in patients with HCM. In the main analysis the combined endpoint of major HCM-related outcomes was assessed. Separate analyses for sudden cardiac death (SCD) events and thromboembolic events were also performed. RESULTS: Six studies comprising of 2382 patients met the inclusion criteria. In the pooled analysis, the presence of LV apical aneurysm was significantly associated with major adverse outcomes (pooled OR: 5.13, 95 CI: 2.85 to 9.23, I2:31%), increased risk of SCD arrhythmic events (pooled OR: 4.67, 95% CI: 2.30 to 9.48, I2: 38%) and thromboembolic events (pooled OR: 6.30, 95% CI: 1.52 to 26.19, I2: 66%). CONCLUSIONS: These data demonstrate that LV apical aneurysm in HCM patients is associated with an increased risk for SCD events and thromboembolism. This finding might encourage the inclusion of LV apical aneurysm into the HCM SCD risk stratification algorithm as a novel risk marker that supports consideration for primary prevention implantable cardioverter defibrillator and anticoagulation for stroke prophylaxis.

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.

Cardiovascular magnetic resonance as a complementary method to transthoracic echocardiography for aortic valve area estimation in patients with aortic stenosis: A systematic review and meta-analysis.

BACKGROUND: Aortic stenosis (AS) is the most common valvular heart disease. While two-dimensional transthoracic echocardiography (2D-TTE) is the standard imaging modality for AS assessment, cardiac magnetic resonance (CMR) offers a reliable and reproducible alternative. The aim of this study was to compare AVA measurements as determined by TTE and CMR in patients with AS. METHODS: Electronic databases were searched to identify studies comparing TTE continuity equation to CMR planimetry for AVA assessment. A meta-analysis of mean difference was conducted by using the random effects model. Sensitivity analysis was performed after excluding studies reporting AVA indexed to body surface area (BSA). Heterogeneity was assessed with I2. RESULTS: A total of 12 studies, encompassing 621 patients, were included in our systematic review. In the pooled analysis, measurements of AVA by CMR planimetry were found to be significantly higher than those calculated by the continuity equation in TTE (pooled mean difference: 0.09, 95% confidence intervals (CI): 0.01, 0.17, and I2: 93%). The results remained significant, albeit with moderate heterogeneity this time, after excluding the analysis measurements of AVA indexed to BSA (pooled mean difference: 0.08, 95% CI: 0.03 to 0.13, and I2 = 61%). CONCLUSIONS: CMR planimetry slightly overestimates AVA compared to TTE continuity equation. Although, 2D-TTE should be the primary imaging modality for the estimation of AVA, CMR may be useful when there is discrepancy with the clinical assessment or when TTE results are discordant or difficult to obtain.

Atrial fibrillation in hypertrophic cardiomyopathy: A turning point towards increased morbidity and mortality.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmic event in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to identify the clinical impact and prognostic significance of AF on a large cohort of patients with HCM. METHODS: Echocardiographic and clinical correlates, risk factors for AF and thromboembolic stroke and the prognostic significance of AF were evaluated in 509 patients with an established diagnosis of HCM. RESULTS: A total of 119 patients (23.4%) were diagnosed with AF during the index evaluation visit. AF patients had a higher prevalence of stroke and presented with worse functional impairment. Left atrial diameter (LA size) was a common independent predictor of the arrhythmia (OR: 2.2, 95% CI 1.6-3.3) and thromboembolic stroke (OR: 1.6, 95% CI 1.01-2.40). AF was an important risk factor for overall mortality (HR=3.4, 95% CI: 1.7-6.5), HCM-related mortality (HR=3.9, 95% CI: 1.8-8.2) and heart failure-related mortality (HR=6.0, 95% CI: 2.0-17.9), even after adjusting for statistically significant clinical and demographic risk factors. However, AF did not affect the risk for sudden death. CONCLUSIONS: LA size is an independent predictor of both AF and thromboembolic stroke. Moreover, patients with AF, regardless of type, have significantly higher mortality rates than patients without AF.

Implantable cardioverter defibrillators for primary prevention of sudden death in hypertrophic cardiomyopathy.

AIMS: Sudden cardiac death (SCD) may complicate hypertrophic cardiomyopathy (HCM) natural course. Patient selection for implantable cardioverter defibrillator (ICD) therapy in the primary prevention setting is still a challenge. METHODS: Thirty-seven HCM patients with a primary prevention ICD were included. All patients underwent preimplantation SCD risk assessment and semi-annual device interrogation during follow-up. Primary end point was the time to first appropriate ICD intervention including antitachycardia pacing or shock. Inappropriately delivered ICD therapies served as secondary end point. RESULTS: During a median follow-up of 3.1 years, 10 (27%) patients received one or more appropriate ICD therapies. First appropriate ICD intervention rate was 7.2%/year (95% CI: 3.4-13.2) with a 5-year cumulative probability of 29.2 ±â€Š7.4%. No SCD risk marker was significantly associated with the primary end point, whereas event rates were comparable among patients with one, two or three or more SCD risk markers (log-rank P = 0.58). Patients with a history of SCD in first-degree relatives with HCM were at 3.8 times higher risk of experiencing an ICD intervention compared with those with no family history of SCD (HR: 3.8; 95% CI: 1.0-14.1, P = 0.05). Seven (18.9%) patients experienced one or more inappropriate ICD therapies; beta-blocker therapy was associated with 75% fewer inappropriate ICD interventions (HR: 0.15; 95% CI: 0.03-0.89). CONCLUSION: Current criteria identify a subgroup of patients with HCM at increased risk of major arrhythmic events as indicated by high ICD intervention rates. However, no individual risk marker demonstrated superior predictive ability over the others, whereas simple arithmetic summing of risk markers was not associated with increased ICD intervention rates.

An Overview of Pharmacotherapy in Hypertrophic Cardiomyopathy: Current Speculations and Clinical Perspectives.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Its clinical course is variable, ranging from a benign asymptomatic or mildly symptomatic course throughout life, to severe symptoms (dyspnea, angina, palpitations) or cardiovascular events (syncope and thromboembolism). Sudden cardiac death (SCD) remains the most striking manifestation of the disease, affecting a minority of patients. This review focuses on the medical treatments applied according to the symptomatology in obstructive and nonobstructive HCM; a special reference is made to atrial fibrillation and arterial hypertension, which often coexist with the disease. Current literature about the pharmaceutical prevention of SCD is also analyzed and novel pharmacologic agents and approaches that may represent the future management of HCM are critically reviewed. The analysis of interventional techniques that are used in cases of medical treatment failure is avoided. Rather than enumerating clinical studies and guidelines, this review provides a concise and contemporary analysis of HCM pharmacotherapy, developing applicable algorithms for clinicians and highlighting promising future drug regimens.

Feasibility and significance of preclinical diagnosis in hypertrophic cardiomyopathy.

Preclinical diagnosis in hypertrophic cardiomyopathy (HCM) refers to the detection of functional or histopathological abnormalities in subjects who carry any HCM-causing gene mutation, before or even without the development of left ventricular hypertrophy [genotype(+)/phenotype(-)subjects]. The concept that HCM pathology may exist in the absence of left ventricular hypertrophy is quite old but the ability to recognize the presence of early myocardial changes is quite new. Lessons from animal models have shown that in experimental human HCM, myocardial cell mechanical dysfunction precedes histopathological changes, such as myocyte disarray, fibrosis, and hypertrophy. Several clinical reports have demonstrated that the majority of HCM genotype(+)/phenotype(-) subjects display myocardial functional or histopathological changes, such as reduced tissue Doppler imaging-derived systolic and diastolic velocities, abnormal electrocardiogram, cardiac magnetic resonance-visualized myocardial crypts, mitral leaflet elongation, and evidence of a fibrotic state, such as increased type I procollagen synthesis, cardiac magnetic resonance-increased myocardial extracellular volume, and late gadolinium myocardial enhancement. All these signs have been proposed as preclinical markers of HCM. At present the separation of such a group of subjects in the early phase of their disease provides the opportunity to test new therapies to prevent the development of fibrosis, hypertrophy, and dysfunction.