The severity of LQTS in adulthood can be risk stratified with information regarding genotype, gender, QTc duration, and history of cardiac events. Beta-blockers effectively reduce but do not eliminate the risk of both syncopal and life-threatening cardiac events in adult patients with mutation-confirmed LQTS.

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In LQTS, the timing and frequency of syncope, QTc prolongation, and sex were predictive of risk for aborted cardiac arrest and sudden cardiac death during adolescence. Among patients with recent syncope, beta-blocker treatment was associated with reduced risk.

Background Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome associated with multiple pathophysiologic abnormalities, including left ventricular (LV) diastolic dysfunction, longitudinal LV systolic dysfunction, abnormal ventricular-arterial coupling, pulmonary hypertension, and right ventricular (RV) remodeling/dysfunction. However, the relative prognostic significance of each of these pathophysiologic abnormalities in HFpEF is unknown. Methods and Results We prospectively studied 419 patients with HFpEF using echocardiography and sphygmomanometry to assess HFpEF pathophysiologic markers. Cox proportional hazards analyses were used to determine the associations between pathophysiologic markers and outcomes. Mean age was 65±12 years; 62% were women; 39% were black; comorbidities were common; and study participants met published criteria for HFpEF. RV abnormalities were frequent: 28% had abnormal tricuspid annular plane systolic excursion, 15% had reduced RV fractional area change, and 34% had RV hypertrophy. During a median follow-up time of 18 months, 102 (24%) were hospitalized for HF and 175 (42%) experienced the composite end point of cardiovascular hospitalization or death. Decreased LV compliance, measured as reduced LV end-diastolic volume at an idealized LV end-diastolic pressure of 20 mm Hg (EDV20), and RV remodeling, as indicated by increased RV wall thickness, were the 2 pathophysiologic markers most predictive of worse outcomes: adjusted hazard ratio per 1 SD decrease in EDV20=1.39 (95% confidence interval [CI], 1.10–1.75; P=0.006), and hazard ratio per 1 SD increase in RV wall thickness=1.37 (95% CI, 1.16–1.61; P<0.001). These associations persisted after additional adjustment for markers of HF severity. By contrast, markers of LV relaxation, longitudinal LV systolic dysfunction, and ventricular-arterial coupling were not significantly associated with adverse outcomes. Conclusions In patients with HFpEF, reduced LV compliance and RV remodeling are the strongest pathophysiologic predictors of adverse outcomes.

It is estimated that half of all patients with heart failure (HF) have HF with preserved ejection fraction (HFpEF). Yet this form of HF remains a diagnostic and therapeutic challenge. Differentiating HFpEF from other causes of dyspnoea may require advanced diagnostic methods, such as exercise echocardiography, invasive haemodynamics and investigations for ‘HFpEF mimickers’. While the classification of HF has relied heavily on cut-points in left ventricular ejection fraction (LVEF), recent evidence points towards a gradual shift in underlying mechanisms, phenotypes and response to therapies as LVEF increases. For example, among patients with HF, the proportion of hospitalisations and deaths due to cardiac causes decreases as LVEF increases. Medication classes that are efficacious in HF with reduced ejection fraction (HFrEF) have been less so at higher LVEF ranges, decreasing the risk of HF hospitalisation but not cardiovascular or all-cause death in HFpEF. These observations reflect the burden of non-cardiac comorbidities as LVEF increases and highlight the complex pathophysiological mechanisms, both cardiac and non-cardiac, underpinning HFpEF. Treatment with sodium-glucose cotransporter 2 inhibitors reduces the risk of composite cardiovascular events, driven by a reduction in HF hospitalisations; renin-angiotensin-aldosterone blockers and angiotensin-neprilysin inhibitors result in smaller reductions in HF hospitalisations among patients with HFpEF. Comprehensive management of HFpEF includes exercise as well as treatment of risk factors and comorbidities. Classification based on phenotypes may facilitate a more targeted approach to treatment than LVEF categorisation, which sets arbitrary cut-points when LVEF is a continuum. This narrative review summarises the pathophysiology, diagnosis, classification and management of patients with HFpEF.