Chronotropic incompetence (CI) is generally defined as the inability to increase the heart rate (HR) adequately during exercise to match cardiac output to metabolic demands. In patients with heart failure (HF), however, this definition is unsuitable because metabolic demands are unmatched to cardiac output in both conditions. Moreover, HR dynamics in patients with HF differ from those in healthy subjects and may be affected by β-blocking medication. Nevertheless, it has been demonstrated that CI in HF is associated with reduced functional capacity and poor survival. During exercise, the normal heart increases both stroke volume and HR, whereas in the failing heart, contractility reserve is lost, thus rendering increases in cardiac output primarily dependent on cardioacceleration. Consequently, insufficient cardioacceleration because of CI may be considered a major limiting factor in the exercise capacity of patients with HF. Despite the profound effects of CI in this specific population, the issue has drawn limited attention during the past years and is often overlooked in clinical practice. This might partly be caused by a lack of standardized approach to diagnose the disease, further complicated by changes in HR dynamics in the HF population, which render reference values derived from a normal population invalid. Cardiac implantable electronic devices (implantable cardioverter defibrillator; cardiac resynchronization therapy) now offer a unique opportunity to study HR dynamics and provide treatment options for CI by rate-adaptive pacing using an incorporated sensor that measures physical activity. This review provides an overview of disease mechanisms, diagnostic strategies, clinical consequences, and state-of-the-art device therapy for CI in HF.

Aims Patients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality. Methods and results We used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existing heart disease and in-hospital mortality. A total of 16 511 patients with COVID-19 were included (21.1% aged 66–75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male, and often had other comorbid conditions when compared with those without. Mortality was higher in patients with cardiac disease (29.7%; n = 1545 vs. 15.9%; n = 1797). However, following multivariable adjustment, this difference was not significant [adjusted risk ratio (aRR) 1.08, 95% confidence interval (CI) 1.02–1.15; P = 0.12 (corrected for multiple testing)]. Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure (aRR 1.19, 95% CI 1.10–1.30; P < 0.018) particularly for severe (New York Heart Association class III/IV) heart failure (aRR 1.41, 95% CI 1.20–1.64; P < 0.018). None of the other heart disease subtypes, including ischaemic heart disease, remained significant after multivariable adjustment. Serious cardiac complications were diagnosed in <1% of patients. Conclusion Considerable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare during hospitalization.

Impaired left atrial emptying fraction (LAEF) is an important predictor of mortality in patients with heart failure. As it may reflect increased LV wall stress, it might predict ventricular arrhythmia (VA) specifically. This study evaluated the predictive value of LAEF assessed with cardiovascular magnetic resonance (CMR) imaging with respect to appropriate device therapy (ADT) for VA and compared its role with CMR assessed scar size and other risk factors. In total, 229 patients (68% male, 63 ± 10 years, 61% ischemic cardiomyopathy) with LV ejection fraction ≤35% who underwent CMR and implantable cardioverter defibrillator (ICD) implantation for primary prevention in 2005 to 2012 were included. CMR was used to quantify LV volumes and function. LV scar size was quantified when late gadolinium enhancement was available (n = 166). Maximum and minimum left atrial volumes and LAEF were calculated using the biplane area-length method. The occurrence of ADT and mortality was assessed during a median follow-up of 3.9 years. Sixty-two patients (27%) received ADT. Univariable Cox analysis showed that male gender, creatinine level, minimum left atrial volume, LAEF, and total scar size were significant predictors of ADT. In multivariable Cox analysis, LAEF (hazard ratio 0.75 per 10%, p <0.01), and scar size (hazard ratio 1.03 per g, p = 0.03) remained the only independent predictors of ADT. Patients with both LAEF > median and scar size < median were at low risk (13% ADT at 5 years), whereas those with LAEF < median and scar size > median experienced 40% ADT at 5 years (log-rank p = 0.01). In conclusion, LAEF independently predicts ADT in patients with primary prevention ICDs. Combined assessment of LAEF and scar size identifies a group with low risk of ADT. Therefore, LAEF assessment could assist in risk stratification for VA to select patients with the highest benefit from ICD implantation.

Aims In non-ischaemic dilated cardiomyopathy (DCM), concomitant right ventricular (RV) dysfunction is frequently observed. This study sought to determine the correlation of RV dysfunction with several cardiac magnetic resonance (CMR) imaging characteristics in patients with DCM, and the prognostic value of RV dysfunction on all-cause mortality and ventricular arrhythmias (VA) was evaluated. Methods and results Consecutive patients with DCM and left ventricular (LV) dysfunction (ejection fraction < 50%) on CMR were included retrospectively. Left atrial (LA), LV, and RV volumes and function were quantified. RV systolic dysfunction was defined as RVEF<45%. The presence and pattern of late gadolinium enhancement (LGE) on CMR were assessed visually. Septal midwall LGE was defined as midmyocardial stripe-like or patchy hyperenhancement in the septal segments, and the extent was quantified using the full width at half maximum method. Primary endpoint was a composite of all-cause mortality and VA, including resuscitated cardiac arrest, sustained VA, and appropriate implantable cardioverter defibrillator therapy. Secondary endpoints were time to all-cause mortality alone and time to VA alone. A total of 216 DCM patients were included (42% female, age 58 ± 14 years). Mean RVEF was 46 ± 12%, and RV dysfunction was present in 38%. RVEF was moderately correlated with LA dilation (LA minimal volume ρ = À0.38, P < 0.001) and strongly correlated with LA and LV dysfunction (LA emptying fraction r = 0.58, P < 0.001 and LVEF ρ = 0.52, P < 0.001). Septal midwall LGE was more often observed in patients with RV dysfunction compared with patients with preserved RV function (respectively 40% vs. 26%, P = 0.04). No correlation was found between RVEF and the extent of septal midwall LGE (ρ = À0.12, P = 0.34). During a median follow-up of 2.2 years [IQR 1.6-2.8], 30 patients experienced the primary endpoint. RV dysfunction was significantly associated with shorter time to the composite primary endpoint (HR 3.19 [95% CI 1.49-6.84], P < 0.01) and to the secondary endpoint of VA alone (HR 6.48 [95% CI 1.83-22.98], P < 0.01). There was a trend towards increased mortality when RV dysfunction was present (HR 2.54 [95% CI 0.99-6.57], P = 0.05). Conclusions Right ventricular dysfunction was predominantly observed in patients with DCM with advanced heart failure and pronounced myocardial remodelling, defined as increased LV and LA dilation and dysfunction and the presence of septal midwall LGE on CMR. During follow-up, RV dysfunction was associated with shorter time to all-cause mortality and ventricular arrhythmic events.