Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

ECG in the clinical and prognostic evaluation of patients with pulmonary arterial hypertension: an underestimated value

Background: Pulmonary arterial hypertension (PAH) is a rare disease leading to right ventricular (RV) failure and manifests in decreasing exercise tolerance. Our study aimed to assess the usefulness of electrocardiographic parameters reflecting right heart hypertrophy as predictors of clinical status in PAH. Methods: The retrospective analysis included 26 patients, mean 49 ± 17 years of age, diagnosed with PAH, and eligible to undergo cardiopulmonary exercise test (CPET). The relations between ECG values and parameters obtained in procedures such as six-minute walk test (6-MWT), echocardiography, right heart catheterization (RHC), and CPET were analyzed. Results: P-wave amplitude in lead II correlated positively with CPET parameter of respiratory response: minute ventilation to carbon dioxide production slope (VE/VCO 2 slope; r  = 0.436, p  = 0.029) and echocardiographic estimated RA pressure (RAP; r  = 0.504, p  = 0.02). RV Sokolow-Lyon index (RVSLI) positively correlated with echocardiographic parameters reflecting RV function, overload, and afterload–tricuspid regurgitation pressure gradient (TRPG; r  = 0.788, p  < 0.001), RV free wall thickness ( r  = 0.738, p  < 0.001), and mean pulmonary arterial pressure (mPAP ECHO ; r  = 0.62, p  = 0.0016), respectively, as well as VE/VCO 2 slope ( r  = 0.593, p  = 0.001) and mPAP assessed directly in RHC (mPAP RHC ; r  = 0.469, p  = 0.0497). R-wave in lead aVR correlated positively with TRPG ( r  = 0.719, p  < 0.001), mPAP ECHO ( r  = 0.446, p  = 0.033), and several hemodynamic criteria of PAH diagnosis: positively with mPAP RHC ( r  = 0.505, p  = 0.033) and pulmonary vascular resistance ( r  = 0.554, p  = 0.026) and negatively with pulmonary capillary wedge pressure ( r  = −0.646, p  = 0.004). QRS duration correlated positively with estimated RAP ( r  = 0.589, p  = 0.004), vena cava inferior diameter ( r  = 0.506, p  = 0.016), and RA area ( r  = 0.679, p  = 0.002) and negatively with parameters of exercise capacity: peak VO 2 ( r  = −0.486, p  = 0.012), CPET maximum load ( r  = − 0.439, p  = 0.025), and 6-MWT distance ( r  = −0.430, p  = 0.046). ROC curves to detect intermediate/high 1-year mortality risk (based on ESC criteria) indicate RVSLI (cut-off point: 1.57 mV, AUC: 0.771) and QRS duration (cut-off points: 0.09 s, AUC: 703 and 0.1 s, AUC: 0.759) as relevant predictors. Conclusion: Electrocardiography appears to be an important and underappreciated tool in PAH assessment. ECG corresponds with clinical parameters reflecting PAH severity

Predicting Mortality in Patients with Atrial Fibrillation and Obstructive Chronic Coronary Syndrome: The Bialystok Coronary Project

Over the next decades, the prevalence of atrial fibrillation (AF) is estimated to double. Our aim was to investigate the causes of the long-term mortality in relation to the diagnosis of atrial fibrillation (AF) and chronic coronary syndrome (CCS). The analysed population consisted of 7367 consecutive patients referred for elective coronary angiography enrolled in a large single-centre retrospective registry, out of whom 1484 had AF and 2881 were diagnosed with obstructive CCS. During follow-up (median = 2029 days), 1201 patients died. The highest all-cause death was seen in AF(+)/CCS(+) [194/527; 36.8%], followed by AF(+)/CCS(−) [210/957; 21.9%], AF(−)/CCS(+) [(459/2354; 19.5%)] subgroups. AF ([HR](AC) = 1.48, 95%CI, 1.09–2.01; HR(CV) = 1.34, 95%CI, 1.07–1.68) and obstructive CCS (HR(AC) = 1.90, 95%CI, 1.56–2.31; HR(CV) = 2.27, 95%CI, 1.94–2.65) together with age, male gender, heart failure, obstructive pulmonary disease, diabetes were predictors of both all-cause and CV mortality. The main findings are as follow among patients referred for elective coronary angiography, both AF and obstructive CCS are strong and independent predictors of the long-term mortality. Mortality of AF without CCS was at least as high as non-AF patients with CCS. CV deaths were more frequent than non-CV deaths in AF patients with CCS compared to those with either AF or CCS alone

Paroxysmal Atrial Fibrillation in the Course of Acute Pulmonary Embolism: Clinical Significance and Impact on Prognosis

The relationship and clinical implications of atrial fibrillation (AF) in acute pulmonary embolism (PE) are poorly investigated. We aimed to analyze clinical characteristics and prognosis in PE patients with paroxysmal AF episode. Methods. From the 391 patients with PE 31 subjects with paroxysmal AF were selected. This group was compared with patients with PE and sinus rhythm (SR) and 32 patients with PE and permanent AF. Results. Paroxysmal AF patients were the oldest. Concomitant DVT varies between groups: paroxysmal AF 32.3%, SR 49.5%, and permanent AF 28.1% (p=0.02). The stroke history frequency was 4.6% SR, 12.9% paroxysmal AF, and 21.9% permanent AF (p<0.001). Paroxysmal AF comparing to permanent AF and SR individuals had higher estimated SPAP (56 versus 48 versus 47 mmHg, p=0.01) and shorter ACT (58 versus 65 versus 70 ms, p=0.04). Patients with AF were more often classified into high-risk group according to revised Geneva score and sPESI than SR patients. In-hospital mortality was lower in SR (5%) and paroxysmal AF (6.5%) compared to permanent AF group (25%) (p<0.001). Conclusions. Patients with PE-associated paroxysmal AF constitute a separate population. More severe impairment of the parameters reflecting RV afterload may indicate relation between PE severity and paroxysmal AF episode. Paroxysmal AF has no impact on short-term mortality

Echocardiographic Assessment of Right Ventricular–Arterial Coupling in Predicting Prognosis of Pulmonary Arterial Hypertension Patients

In response to an increased afterload in pulmonary arterial hypertension (PAH), the right ventricle (RV) adapts by remodeling and increasing contractility. The idea of coupling refers to maintaining a relatively constant relationship between ventricular contractility and afterload. Twenty-eight stable PAH patients (mean age 49.5 ± 15.5 years) were enrolled into the study. The follow-up time of this study was 58 months, and the combined endpoint (CEP) was defined as death or clinical deterioration. We used echo TAPSE as a surrogate of RV contractility and estimated systolic pulmonary artery pressure (sPAP) reflecting RV afterload. Ventricular–arterial coupling was evaluated by the ratio between these two parameters (TAPSE/sPAP). In the PAH group, the mean pulmonary artery pressure (mPAP) was 47.29 ± 15.3 mmHg. The mean echo-estimated TAPSE/sPAP was 0.34 ± 0.19 mm/mmHg and was comparable in value and prognostic usefulness to the parameter derived from magnetic resonance and catheterization (ROC analysis). Patients who had CEP (n = 21) had a significantly higher mPAP (53.11 ± 17.11 mmHg vs. 34.86 ± 8.49 mmHg, p = 0.03) and lower TAPSE/sPAP (0.30 ± 0.21 vs. 0.43 ± 0.23, p = 0.04). Patients with a TAPSE/sPAP lower than 0.25 mm/mmHg had worse prognosis, with log-rank test p = 0.001. the echocardiographic estimation of TAPSE/sPAP offers an easy, reliable, non-invasive prognostic parameter for the comprehensive assessment of hemodynamic adaptation in PAH patients