Composite Endpoint Of Heart Failure Research Articles

Oral antithrombotic therapy and one-year clinical outcomes among patients with atrial fibrillation in resource-limited settings

BackgroundAtrial fibrillation is associated with increased risk of morbidity and mortality. There's limited data on the outcomes of atrial fibrillation patients in Africa. We aimed at evaluating the clinical outcomes and their associated factors in patients with atrial fibrillation on antithrombotic therapy in Douala. MethodsThe Douala atrial fibrillation registry is a prospective, observational cohort study of patients with atrial fibrillation followed by cardiovascular specialists in 3 specialized care centres. From January to April 2018, all patients with electrocardiographic diagnosis of atrial fibrillation, aged 21 years or older, were included in the registry provided their consent. The composite endpoint of heart failure, stroke, major bleeding, hospitalisation and mortality as well as their individual occurrence were assessed at 12 months. ResultsOf 113 participants that were included, 6(5.3%) were lost to follow-up. The mean age was 70 ± 12 years, with a female predominance (68%). After a mean follow-up time of 12.2 ± 0.7 months, 51 patients (47.7%) had at least one outcome. Hospitalisation, all-cause mortality, heart failure, stroke and major bleeding rates were 33.3%, 16.8%, 15.2%, 4.8% and 2.9% respectively. There was no significant difference in the composite outcome and mortality according to the antithrombotic treatment. Previous heart failure [aHR = 3.07, 95% CI (1.48–6.36) p = 0.003], new onset atrial fibrillation [aHR= 4.00, 95% CI (0.96–8.19) p < 0.001] and paroxystic atrial fibrillation [aHR= 3.74, 95% CI (1.33–10.53) p = 0.013] were significant predictors of outcome. ConclusionHalf of patients with atrial fibrillation in this registry developed an outcome after one year of follow-up, with heart failure, new onset and paroxystic atrial fibrillation being the main predicting factors. Diagnosing and managing atrial fibrillation in patients with heart disease should therefore be considered as a key priority.

Long-term outcomes in a randomized controlled trial of multimodality imaging-guided left ventricular lead placement in cardiac resynchronization therapy.

This study aims to investigate the long-term occurrence of the composite endpoint of heart failure (HF) hospitalization or all-cause death (primary endpoint) in patients randomized to cardiac resynchronization therapy (CRT) using individualized multimodality imaging-guided left ventricular (LV) lead placement compared with a routine fluoroscopic approach. Furthermore, this study aims to evaluate whether inter-lead electrical delay (IED) is associated with improved response rate of this endpoint. We reviewed follow-up data until November 2020 for all 182 patients included in the ImagingCRT trial for the occurrence of HF hospitalization and all-cause death. During median (inter-quartile range) time to primary endpoint/censuring of 6.7 (3.3-7.9) years, the rate of the primary endpoint was 60% (n = 53) in the imaging group compared with 52% (n = 48) in the control group [hazard ratio (HR) 1.22, 95% confidence interval (CI) 0.83-1.81, P = 0.31]. Neither the risk of HF hospitalization (HR 1.11, 95% CI 0.62-1.99, P = 0.72) nor of all-cause death differed between treatment groups (HR 1.23, 95% CI 0.82-1.85, P = 0.32). The risk of the primary endpoint was significantly reduced among those with IED ≥100 ms when compared with those with IED <100 ms (HR 0.62, 95% CI 0.39-0.98, P = 0.04). In this study, an individualized multimodality imaging-guided strategy targeting LV lead placement towards the latest mechanically activated non-scarred myocardial segment during CRT implantation did not reduce HF hospitalization or all-cause death when compared with routine LV lead placement during long-term follow-up. Targeting the latest electrical activation should be studied as an alternative individualized strategy for optimizing LV lead placement in CRT recipients.

Abstract 13932: Association Between Layer-Specific Global Longitudinal Strain and Cardiovascular Events After Coronary Artery Bypass Grafting

Introduction: Sectionalized quantification of layer-specific global longitudinal strain (GLS) has recently become available with new technological advancements. We sought to investigate the prognostic value of layer-specific strain in patients undergoing coronary artery bypass grafting (CABG). Methods: This retrospective cohort study comprised patients undergoing isolated CABG between 2006 and 2011. The patients were followed through nation-wide registries for the composite endpoint of heart failure (HF) or cardiovascular death (CVD) (HF/CVD). Multivariable Cox regression models adjusted for clinical and echocardiographic baseline characteristics, as well as European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) were used to assess the association between layer-specific GLS and the endpoint. Results: Of 641 patients included (mean age 67 years, 84% male), 62 experienced the composite of outcome (HF: n=30, CVD: n=38) during a median follow-up of 3.8 years. Patients who developed the outcome during follow-up had reduced layer-specific GLS in all layers (GLSendo: -14.3% vs. -16.3; GLSww: -12.2 vs. -13.9; GLSepi: -10.7 vs. -12.2). Additionally, all layer-specific GLS parameters were predictors of outcome in unadjusted models (GLSendo: HR=1.11 (1.05-1.17); GLSww: HR=1.13 (1.06-1.21); GLSepi: HR=1.15 (1.07-1.24), per 1% absolute decrease). The risk of the endpoint increased linearly with decreasing absolute GLS for all layers ( Figure 1 ). These findings were unchanged in multivariable models. Patients with reduced GLS in any layer had a higher risk of HF/CVD, however, the risk was highest for those with reduced epicardial GLS (HR=2.60 (1.46-4.66), p=0.001). Conclusions: Layer-specific GLS is an independent prognosticator of cardiovascular events after CABG. Reduced epicardial GLS poses the highest risk of HF/CVD.

Rate of Heart Failure Following Atrial Fibrillation According to Presence of Family History of Dilated Cardiomyopathy or Heart Failure: A Nationwide Study.

BackgroundIt is poorly understood why some patients with atrial fibrillation develop heart failure (HF) and others do not. We examined the rate of developing HF in patients with atrial fibrillation with and without first‐degree family members with HF or dilated cardiomyopathy (DCM).Methods and ResultsUsing Danish nationwide registries, patients born after 1942 diagnosed with atrial fibrillation in the period 2005 to 2015 were identified and followed for up to 5 years. Patients with pre‐existing HF, DCM, and/or ischemic heart disease diagnoses were excluded. Exposure was defined as a first‐degree relative with HF or DCM. The rate of developing the composite end point of HF or death, and the components, was estimated with multivariable Cox proportional hazard regression models. We included 10 605 patients. A total of 17% had a family member with DCM/HF. Having a family member with HF/DCM was associated with an increased 5‐year risk of the composite of HF/death (cumulative incidence, 9.2% [95% CI, 7.8–10.7] versus 5.6% [95% CI, 5.0–6.1]; adjusted hazard ratio [HR] 1.36 [95% CI, 1.13–1.64]). (HF 8.4% [95% CI, 7.0–9.8] versus 4.5% [95% CI, 4.1–5.0]); (adjusted HR, 1.49 [95% CI, 1.22–1.82]). However, familial HF/DCM was not significantly associated with an increased 5‐year risk and rate of death (0.8% [95% CI, 0.4–1.2] versus 1.1% [95% CI, 0.8–1.3]); (adjusted HR, 0.80 [95% CI, 0.46–1.39]).ConclusionsIn patients with incident atrial fibrillation without prior ischemic heart disease or HF diagnoses, 1 of 6 had a first‐degree relative with HF, and having such a family history of HF/DCM was associated with an 87% increase in 5‐year incidence of HF compared with those without.

Prevalence and Significance of Patient Prosthesis Mismatch Following Edwards SAPIEN XT and SAPIEN 3 Transcatheter Aortic Valve Replacement.

BackgroundSevere patient prosthesis mismatch (sPPM) after surgical aortic valve replacement is associated with worse outcomes. Limited data exists on the impact of sPPM on outcomes after transcatheter aortic valve replacement (TAVR), especially regarding the newer generation valves. The aim of this study was to evaluate the incidence, determinants, and outcomes of sPPM in patients undergoing TAVR with Edwards SAPIEN XT (ES XT) and Edwards SAPIEN 3 (ES3) valves (Edwards Lifesciences, Irvine, CA, USA).MethodsWe retrospectively reviewed 366 patients who underwent TAVR with ES XT (n = 114) or ES3 (n = 252) valves between July 2012 and June 2018. sPPM was defined as indexed effective orifice area (iEOA) <0.65 cm2/m2. Kaplan-Meier survival estimates were used to determine outcomes.ResultsMultivariate linear regression analysis was utilized to determine potential independent effects of PPM on outcomes. sPPM was present in 40 (11%) of the patients [8 (7%) ES XT and 32 (13%) ES3] and was associated with female sex, smaller left ventricular outflow tract (LVOT) diameter and aortic valve annular area, absence of prior coronary artery bypass graft (CABG) surgery, shorter height, higher body mass index, and smaller pre-TAVR valve area (all p < 0.05). Among those with ES3 valves, the incidence of sPPM was inversely proportional to the valve size (50%, 25%, 5% and 3% for 20-, 23-, 26- and 29-mm valve sizes, respectively; p < 0.001). At a mean follow-up period of 3.5 ± 1.5 years, there was no difference in all-cause mortality (22.5% vs. 25.6%, p = 0.89) or a composite endpoint of heart failure, arrhythmias, stroke, and myocardial infarction (30% vs. 34%, p = 0.24) in those with or without sPPM.ConclusionES3 was associated with a higher incidence of sPPM, particularly with smaller valve sizes. However, the presence of sPPM as defined by iEOA was not an independent predictor of adverse outcomes in patients undergoing TAVR within an intermediate follow-up period.

Diastolic function assessed with speckle tracking over a decade and its prognostic value: The Copenhagen City Heart Study.

The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) may be a more accurate measure of LV filling pressure then ratio of early filling pressure to early tissue velocity. The aim of the study was to investigate the impact of age, sex, obesity, smoking, hypertension, hypercholesterolemia, diabetes, physical activity level, socioeconomic, and psychosocial status on E/e'sr over a decade. Additionally, the predictive value of ΔE/e'sr on future major adverse cardiovascular events (MACE) has never been explored. The study included 623 participants from the general population, who participated in the 4th and 5th Copenhagen City Heart Study (CCHS4 and CCHS5). Examinations were median 10years apart. MACE was the composite endpoint of heart failure, myocardial infarction, and all-cause death. Follow-up time was median 5.7years, and 43 (7%) experienced MACE. Mean age was 51±14years, and 43% were male. Mean ΔE/e'sr was 2.1±23.0cm. After multivariable adjustment for demographic, clinical, and biochemistry variables, high age (stand. β-coef.=.24, P<.001) and mean arterial blood pressure (MAP) (stand. β-coef.=.17, P<.001) were significantly associated with an accelerated increase in E/e'sr In multivariable Cox regression, E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of MACE (HR=1.20, 95%CI [1.01; 1.42] per 10cm increase for both). ΔE/e'sr did only provide incremental prognostic value to change in left atrial volume index of the conventional diastolic measurements. In the general population, age and MAP were predictors of an accelerated increase in E/e'sr over a decade. E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of future MACE.

Insights from Cardiopulmonary Exercise Testing in Pediatric Patients with Hypertrophic Cardiomyopathy.

The usefulness of cardiopulmonary exercise test (CPET) in adult hypertrophic cardiomyopathy (HCM) patients is well-known, whereas its role in pediatric HCM patients has not yet been explored. The present study investigates possible insights from a CPET assessment in a cohort of pediatric HCM outpatients in terms of functional and prognostic assessment. Sixty consecutive pediatric HCM outpatients aged <18 years old were enrolled, each of them undergoing a full clinical assessment including a CPET; a group of 60 healthy subjects served as controls. A unique composite end-point of heart failure (HF) related and sudden cardiac death (SCD) or SCD-equivalent events was also explored. During a median follow-up of 53 months (25th–75th: 13–84 months), a total of 13 HF- and 7 SCD-related first events were collected. Compared to controls, HCM patients showed an impaired functional capacity with most of them showing peak oxygen uptake (pVO2) values of <80% of the predicted, clearly discrepant with functional New York Heart Association class assessment. The composite end-point occurred more frequently in patients with the worst CPETs’ profiles. At the univariate analysis, pVO2% was the variable with the strongest association with adverse events at follow-up (C-index = 0.72, p = 0.025) and a cut-off value equal to 60% was the most accurate in identifying those patients at the highest risk. In a pediatric HCM subset, the CPET assessment allows a true functional capacity estimation and it might be helpful in identifying early those patients at high risk of events.

Abstract 14482: Apparent Resistant Hypertension is a Marker of Risk: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Apparent resistant hypertension (ARH) is a common marker of risk in patients with established cardiovascular disease. We ascertained the prevalence and prognostic significance of ARH in patients without prior cardiovascular disease. Methods: This prospective observational cohort study included 9669 community-based participants without a history of heart failure, myocardial infarction, or stroke, who completed the Atherosclerosis Risk in Communities (ARIC) study visit 4 between 1996-1998. The definition of ARH was blood pressure (BP) above goal (traditional goal &lt;140/90mmHg, more stringent goal &lt;130/80mmHg) despite use of ≥3 antihypertensive drug classes, or any BP with ≥4 antihypertensive drug classes. Participants with controlled hypertension (CH), defined as BP at goal with use of 1-3 antihypertensive drug classes, constituted the reference group. The outcome was a composite endpoint of heart failure, myocardial infarction, stroke, or death. Cox regression models were adjusted for age, sex, race, BMI, heart rate, smoking, eGFR, LDL, HDL, triglycerides, glucose, and diabetes. Results: Applying the traditional BP goal, 154/9669 participants (1.6%) had ARH, and there were 2311 participants with CH (23.9%). Using the more stringent BP goal, 218/9669 participants (2.3%) had ARH, and 1523 participants (15.8 %) had CH. The median follow-up time was 19 years. Apparent resistant hypertension was associated with an increased risk for the composite endpoint (adjusted hazard ratio 1.58 [95% CI 1.32-1.90] with the traditional BP goal, and adjusted hazard ratio 1.51 [95% CI 1.28-1.79] with the more stringent BP goal). Conclusions: Apparent resistant hypertension had a low prevalence but was independently associated with adverse outcome during long term follow-up, compared to controlled hypertension and even compared to uncontrolled hypertension. This was observed for both traditional and more stringent BP goals.

LA Mechanics in Decompensated Heart Failure: Insights From Strain Echocardiography With Invasive Hemodynamics

ObjectivesThe aim of this study was to assess the effect of congestion and decongestive therapy on left atrial (LA) mechanics and to determine the relationship between LA improvement after decongestive therapy and clinical outcome in immediate or chronic heart failure with reduced ejection fraction (HFrEF). BackgroundLA mechanics are affected by volume/pressure overload in decompensated HFrEF. MethodsA total of 31 patients with HFrEF and immediate heart failure (age 64 ± 15 years, 74% male, left ventricular ejection fraction 20 ± 12%) underwent serial echocardiography during decongestive therapy with simultaneous hemodynamic monitoring. LA function was assessed by strain (rate) imaging. Patients were re-evaluated 6 weeks after discharge and prospectively followed up for the composite endpoint of heart failure readmission and all-cause mortality. ResultsLA reservoir function was markedly reduced at baseline and improved with decongestion (peak atrial longitudinal strain from 6.4 ± 2.2% to 8.8 ± 3.0% and strain rate from 0.29 ± 0.11 s–1 to 0.38 ± 0.13 s–1), independent of changes in left ventricular global longitudinal strain, LA end-diastolic volume, and mitral regurgitation severity (p < 0.001). Both measures continued to rise at 6 weeks (up to 13.4 ± 6.1% and 0.50 ± 0.19 s–1, respectively; p < 0.001). LA pump strain rate only increased 6 weeks after discharge (–0.25 ± 0.12 s–1 to –0.55 ± 0.29 s–1; p < 0.010). Changes in LA mechanics correlated with changes in wedge pressure (r = –0.61; p < 0.001). Lower peak atrial longitudinal strain values after decongestion were associated with increased risk for the composite endpoint of heart failure and mortality (p < 0.019). ConclusionsLA reservoir and booster function, while severely impaired during immediate decompensation, significantly improve during and after decongestive therapy. Poor LA reservoir function after decongestion is associated with worse outcome.

The Progress and Significance of QRS Duration by Electrocardiography in Hypoplastic Left Heart Syndrome.

Patients with hypoplastic left heart syndrome (HLHS) are now surviving through to Fontan palliation and beyond, however, with increased morbidity and mortality. Prolonged QRSd has become one of the predictors of morbidity and mortality in certain congenital heart diseases. There is limited data characterizing the QRSd in patients with HLHS. We aimed to describe the changes in QRSd at various times during the lifetime and to evaluate whether QRSd correlates with a higher risk of developing a composite endpoint of heart failure, heart transplant, or death. We conducted a retrospective chart review of patients with HLHS who survived Fontan palliation. QRSd was measured on ECGs at various stages pre- and postsurgical palliations and subsequently at 5year intervals. Patients with a composite endpoint were compared to those without. A total of 89 patients were included in the final analysis. The QRSd increased significantly with time from 68.7 ± 9.0ms prior to Norwood to 91.0 ± 14.0ms immediately following Fontan and 104.7 ± 13.6ms 15years after Fontan (p < 0.001). The composite endpoint was observed in 28 patients (31.4%). The time trends of QRSd differ so that the patients having the composite endpoint experienced a greater increase in QRSd over time (p = 0.009). Ever having a QRSd of 120ms or more predicted the composite endpoint with 93% specificity. The area under the curve of the receiver operator curve analysis was 0.596. A Cox regression analysis demonstrated that QRS duration > 120ms was independently related to a greater frequency of composite endpoint and this was confirmed by a Kaplan-Meier analysis (p = 0.011). This study unveils a novel relationship between QRSd of 120ms or more with the composite endpoint. Despite the low sensitivity, this finding on a routine surveillance ECG could help identify HLHS Fontan patients at risk for heart failure, heart transplant, or death.

P5447Prognostic significance of carboxy-terminal telopeptide (ICTP) and Caspase-3 in patients with non-ischemic dilated cardiomyopathy

Abstract Background Non-ischemic dilated cardiomyopathy (niDCM) is a common debilitating disease leading to heart failure and poor prognosis. Therefore, a reliable diagnosis of niDCM and search of prognostic biomarkers is a task of paramount importance preventing final destruction of myocardium and improving the outcomes of the disease. The aim of the study was to evaluate the prognostic value of carboxy-terminal telopeptide (ICTP), a marker of myocardial collagen I degradation, and Caspase-3, a marker of apoptosis, in serum and endomyocardium biopsies (EMBs) of patients with niDCM. Methods 34 consecutive patients (male 25 (78%); 43.83±12.17 years) with niDCM (average of left ventricle (LV) end-diastolic diameter 6.94±0.78 cm, LV ejection fraction 24.97±6.93%, mean pulmonary capillary wedge pressure 32.9±8.7 mmHg) were enrolled in the study. The levels of ICTP and Caspase-3 in patients' serum and EMBs were measured by ELISA. After a follow-up period of 5 years, 18 patients (53%) have reached the primary composite end-point of heart failure: 6 patients (17.6%) died, 6 patients (17.6%) had heart transplantation and 6 patients (17.6%) underwent left ventricle assist device implantation. Results Univariate Cox proportional hazard model and ROC curve analysis identified levels of ICTP and Caspase-3 in serum as predictors of composite end-point (Table 1). However, the levels of ICTP and Caspase-3 in EMBs had no prognostic value. The cut-off values of serum biomarkers for prediction of the outcome were 13.43 pg/mg protein (sensitivity 67%; specificity 81%) for ICTP and 10.21 pg/mg protein (sensitivity 53%; specificity 87%) for Caspase-3. Univariate Cox regression analysis revealed that patients with higher levels of ICTP and Caspase-3 than cut-off values in serum had higher risk of reaching the composite end-point compared to the patients with lower cut-off values (HR 4.4 (95% CI: 1.6–12.1) and 3.15 (95% CI: 1.2–8.29), respectively). Kaplan-Meier survival analysis demonstrated that patients with serum Caspase-3 and ICTP levels above cut-off values had significantly worse outcome (p=0.01 and p=0.002, respectively). Table 1 Biomarkers (pg/mg protein) Mean ± SD HR (95% CI) p-value AUC (95% CI) ICTP in serum 15.26±10.59 1.052 (1.013–1.093) 0.009 0.71 (0.53–0.89) ICTP in EMB 132±295 0.999 (0.998–1.001) 0.56 0.45 (0.28–0.61) Caspase-3 in serum 7.78±9.86 1.047 (1.002–1.093) 0.04 0.69 (0.51–0.87) Caspase-3 in EMB 283±282 1 (0.998–1.002) 0.92 0.50 (0.28–0.72) Conclusion The findings show that increased serum levels of Caspase-3 and ICTP are significantly associated with poor outcome in patients with niDCM. Acknowledgement/Funding the Research Council of Lithuania (Grants nos. MIP-086/2012 and MIP-011/2014), the European Union, EU-FP7, SARCOSI Project (no. 291834)

P4600Intraventricular conduction disturbance and ventricular paced rhythms in patients with acute coronary syndromes

Abstract Introduction Left or right bundle branch block (LBBB or RBBB) and ventricular paced rhythms (PM) difficult the diagnosis and often delay adequate treatment in patients with acute coronary syndromes (ACS). In the past few years, guidelines have placed a greater emphasis on the need for considering urgent revascularization in these patients. Purpose Evaluate initial revascularization strategy and short-term prognostic impact of LBBB, RBBB and PM in patients with ACS. Methods Multicentric observational study of consecutive patients with ACS recorded in the Portuguese Registry of Acute Coronary Syndromes (ProACS) between October 2010 and January 2019. Patients were categorized according to the ECG at admission: LBBB, RBBB, PM and normal QRS morphology. Patients with missing data on the ECG or the primary outcome were excluded. Demographic, clinical data and in-hospital outcomes were analyzed. The association between LBBB, RBBB, PM and in-hospital adverse outcomes was assessed using a logistic regression model. The primary and secondary outcomes were in-hospital mortality and a composite of in-hospital adverse events (heart failure, re-infarction or cardiac arrest), respectively. Results Of the original cohort, 18314 (94.3%) patients were included (mean age 66±13 years, 73.2% male): 243 (1.3%) had PM, 846 (4.6%) had LBBB, 1195 (6.5%) had RBBB and 16030 (87.5%) had normal QRS. Patients with abnormal QRS were significantly older, had more comorbidities, were less frequently diagnosed as ST-elevation MI (LBBB 18%; RBBB 35.1%; PM 7.8%; Normal 44.2%, p&lt;0.001) and considered for urgent reperfusion (LBBB 13%; RBBB 33.6%; PM 5.8%; Normal 41.6%, p&lt;0.001). Among patients who underwent non-urgent coronary angiography, the finding of an occluded culprit coronary artery was not higher compared to patients with normal QRS (Normal 15.2% vs LBBB 14.3%; RBBB 17.4%; PM 11.4%, p&gt;0.05 for difference). Overall in-hospital mortality was 3.4% (LBBB 6.6%; RBBB 8.1%; PM 5.3%; Normal 3.4%; p&lt;0.001) and the composite endpoint of in-hospital adverse events was 17.4% (LBBB 35.6%; RBBB 27.3%; PM 23.5%; Normal 15.6%, p&lt;0.001). After adjusting for cofounding variables, and using normal QRS as reference, only RBBB was shown to be significantly associated with increased in-hospital mortality (OR 1.94; 95% CI 1.43–2.66), p&lt;0.001); and both RBBB (OR 1.75; 95% CI 1.5–2, p&lt;0.001) and LBBB (OR 1.8; 95% CI 1.4–2.3, p&lt;0.001), but not PM, were significantly associated with the composite endpoint of heart failure, re-infarction or cardiac arrest. Conclusion Compared to patients with normal QRS, those with LBBB, RBBB or PM less often undergo urgent revascularization and have higher rates of in-hospital adverse outcomes. In multivariate analysis, RBBB patients are almost two times more likely to die compared to those with normal QRS. LBBB and RBBB were independently associated with increased rates of in-hospital adverse events. PM was not associated with worse in-hospital outcomes.

Abstract 17186: Left Atrial Strain Predicts Adverse Outcomes in Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) patients are at increased risk for heart failure (HF), stroke, death, and paroxysmal atrial fibrillation (PAF) development. There is no consensus whether atrial fibrillation (AF) is a marker or mediator of adverse outcomes in HCM patients. Hypothesis: We hypothesized that PAF and left atrial (LA) remodeling predict adverse outcomes in HCM. Methods: Echocardiography (2D and speckle tracking) was used to assess LA size, function, and mechanics in a cohort of HCM patients with history of PAF (PAF group, n=45) and age/gender-matched HCM patients without history of AF (No-AF group; n=59). AF was diagnosed by review of EKGs, event recorder/holter monitor data, and ICD interrogation. Patients were followed for a mean of 53 months for development of the composite endpoint of HF, death, and stroke. Results: Clinical/demographic characteristics were similar in the 2 groups; 67% of PAF group had a CHADS 2 VASC score ≤ 1. The PAF group had higher LA volume, lower LA ejection fraction, and higher E/A ratio (reflecting LV diastolic dysfunction) compared to the No-AF group. LA contractile and reservoir strain/strain rate (SR) were significantly lower in the PAF group (Table 1). Male gender, LA reservoir and conduit strain/SR (not PAF presence) were associated with the development of the composite endpoint in univariate analysis. Only LA conduit and reservoir strain/SR independently predicted the composite endpoint in a multivariate model. Kaplan Meier survival analysis showed greater event-free survival among HCM patients with LA conduit strain &gt;10.2% (Figure 1a) and LA reservoir strain &gt;23.8% (p &lt; 0.01) (Figure 1b). Conclusions: PAF is associated with greater degree of LA myopathy in HCM. LA myopathy assessed by conduit and reservoir strain/SR may be useful for risk stratification for HF, stroke, and death in HCM.

Growth differentiation factor 15 (GDF-15) in patients admitted for acute heart failure: results from the RELAX-AHF study.

Growth differentiation factor 15 (GDF-15) was found to be upregulated in patients with chronic heart failure (HF) and associated with disease severity, however, data on patients with acute heart failure (AHF) is lacking. Levels of GDF-15 were measured at pre-specified time-points (baseline and at days 2, 5, 14, and 60) in patients enrolled in the placebo-controlled RELAXin in Acute Heart Failure (RELAX-AHF) study, which examined the effect of serelaxin in 1161 patients with AHF, systolic blood pressure >125 mmHg, and mild to moderate renal impairment. Neither baseline nor changes in GDF-15 were associated with the degree of dyspnoea or dyspnoea relief. After adjustment for baseline characteristics, baseline GDF-15 was not associated with the composite endpoint of heart failure or renal failure (HF/RF) readmission at 60 days/cardiovascular (CV) death or CV death at 180 days. In contrast, larger increases in GDF-15 levels at days 2 and 14 were associated with a greater risk of 60-day HF/RF rehospitalizations/CV death and CV death at 180 days. Serelaxin treatment was associated with significantly larger decreases of GDF-15 at days 2 and 5 than placebo. In AHF patients enrolled in the RELAX-AHF study, increases in GDF-15 levels, but not baseline measurements, were associated with a greater likelihood of adverse outcomes. Serelaxin administration was associated with greater decreases in GDF-15 compared with placebo.

Abstract 9371: Diuretic Use and the Benefit of Cardiac Resynchronization Therapy to Prevent Heart Failure and Death: Secondary Analysis of Data from MADIT-CRT.

MADIT-CRT demonstrated a reduction in the composite endpoint of heart failure (HF) or death with CRT-D vs. ICD-only therapy in patients with NYHA class I-II, ejection fraction &lt;0.30, and QRS &gt;130ms. Additional predictive variables would aid in selecting patients for preventive CRT-D. We hypothesized that diuretic use at study enrollment might identify patients with more advanced cardiac impairment and incipient HF and thus greater potential for reduction in later overt HF or death with CRT-D. At baseline, 1228 patients were diuretic users and 592 were diuretic non-users. Kaplan-Meier graphs are shown for the two subgroups. Diuretic users showed a relatively high probability of overt HF or death with ICD alone plus a large, highly significant reduction in the risk of this end point with CRT-D therapy. Nonusers had fewer of these events with ICD and modest reduction of borderline statistical significance with CRT-D. As anticipated, the predictive information derived from diuretic use was not unique: when adjusted for imbalances in relevant baseline characteristics (e.g., serum creatinine), diuretic users and non-users experienced similar benefit from CRT-D therapy. Conclusion: in MADIT-CRT, the physician's pre-enrollment decision to use diuretics discriminated between a subgroup achieving a strikingly significant benefit from CRT-D therapy and one receiving little likelihood of benefit. This finding may aid in selecting optimal management for patients resembling MADIT-CRT enrollees.