Contemporary use of devices in chronic heart failure in the Netherlands

Aims: Despite previous surveys regarding device implantation rates in heart failure (HF), insight into the real-world management with devices is scarce. Therefore, we investigated device implantation rates in HF with reduced left ventricular ejection fraction (LVEF) in 34 Dutch centres. Methods and results: A cross-sectional outpatient registry was conducted in 6666 patients with LVEF < 50% and with information about device implantation available [74 (66–81) years of age; 64% male]. Patients were classified into conventional pacemakers (PM, n = 562), implantable cardioverter defibrillato

The combination of carboxy-terminal propeptide of procollagen type I blood levels and late gadolinium enhancement at cardiac magnetic resonance provides additional prognostic information in idiopathic dilated cardiomyopathy - A multilevel assessment of myocardial fibrosis in dilated cardiomyopathy

Aims To determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients. Methods and results We quantified fibrosis in 209 DCM patients at three levels: (i) non-invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino-terminal propeptide of procollagen type III (PIIINP) and carboxy-terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life-threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90-6.60; P < 0.001 and PICP 1.02, 95% CI 1.01-1.03; P = 0.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test P = 0.007) and reclassification (net reclassification index: 0.28, P = 0.02; and integrated discrimination improvement index: 0.139, P = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (log-rank P < 0.001). RNA-sequencing and gene enrichment analysis of EMB showed an increased expression of pro-fibrotic and pro-inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE-/PICP-). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles. Conclusion The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro-fibrotic and pro-inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP

Balance of active, passive, and anatomical cardiac properties in doxorubicin-induced heart failure

Late-onset heart failure (HF) is a known side effect of doxorubicin chemotherapy. Typically, patients are diagnosed when already at an irreversible stage of HF, which allows few or no treatment options. Identifying the causes of compromised cardiac function in this patient group may improve early patient diagnosis and support treatment selection. To link doxorubicin-induced changes in cardiac cellular and tissue mechanical properties to overall cardiac function, we apply a multi-scale biophysical biomechanics model of the heart to measure the plausibility of changes in model parameters representing the passive, active, or anatomical properties of the left ventricle for reproducing measured patient phenotypes. We create representative models of healthy controls (N= 10) and patients with HF induced by (N= 22) or unrelated to (N= 25) doxorubicin therapy. The model predicts that HF in the absence of doxorubicin is characterized by a 2- to 3-fold stiffness increase, decreased tension (0-20%), and ventricular dilation (of order 10-30%). HF due to doxorubicin was similar but showed stronger bias toward reduced active contraction (10-30%) and less dilation (0-20%). We find that changes in active, passive, and anatomical properties all play a role in doxorubicin-induced cardiotoxicity phenotypes. Differences in parameter changes between patient groups are consistent with doxorubicin cardiotoxicity having a greater dependence on reduced cellular contraction and less anatomical remodeling than HF not caused by doxorubicin.</p

Implications of Genetic Testing in Dilated Cardiomyopathy

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Comprehensive Cardiovascular Magnetic Resonance‐Derived Myocardial Strain Analysis Provides Independent Prognostic Value in Acute Myocarditis

Background Late gadolinium enhancement and left ventricular (LV) ejection fraction on cardiovascular magnetic resonance (CMR) are prognostic markers, but their predictive value for incident heart failure or life‐threatening arrhythmias in acute myocarditis patients is limited. CMR‐derived feature tracking provides a more sensitive analysis of myocardial function and may improve risk stratification in myocarditis. In this study, the prognostic value of LV, right ventricular, and left atrial strain in acute myocarditis patients is evaluated. Methods and Results In this multicenter retrospective study, patients with CMR‐proven acute myocarditis were included. The primary end point was occurrence of major adverse cardiovascular events: all‐cause mortality, heart transplantation, heart failure hospitalizations, and life threatening arrhythmias. LV global longitudinal strain, global circumferential strain and global radial strain, right ventricular‐global longitudinal strain and left atrial strain were measured. Unadjusted and adjusted cox proportional hazard regression analysis were performed. In total, 162 CMR‐proven myocarditis patients were included (41 ± 17 years, 75% men). Mean LV ejection fraction was 51 ± 12%, and 144 (89%) patients had presence of late gadolinium enhancement. Major adverse cardiovascular events occurred in 29 (18%) patients during a follow‐up of 5.5 (2.2–8.3) years. All LV strain parameters were independent predictors of outcome beyond clinical features, LV ejection fraction and late gadolinium enhancement (LV‐global longitudinal strain: hazard ratio [HR] 1.07, P=0.02; LV‐global circumferential strain: HR 1.15, P=0.02; LV‐global radial strain: HR 0.98, P=0.03), but right ventricular or left atrial strain did not predict outcome. Conclusions CMR‐derived LV strain analysis provides independent prognostic value on top of clinical parameters, LV ejection fraction and late gadolinium enhancement in acute myocarditis patients, while left atrial and right ventricular strain seem to be of less importance

Comprehensive Cardiovascular Magnetic Resonance-Derived Myocardial Strain Analysis Provides Independent Prognostic Value in Acute Myocarditis

Background Late gadolinium enhancement and left ventricular (LV) ejection fraction on cardiovascular magnetic resonance (CMR) are prognostic markers, but their predictive value for incident heart failure or life-threatening arrhythmias in acute myocarditis patients is limited. CMR-derived feature tracking provides a more sensitive analysis of myocardial function and may improve risk stratification in myocarditis. In this study, the prognostic value of LV, right ventricular, and left atrial strain in acute myocarditis patients is evaluated. Methods and Results In this multicenter retrospective study, patients with CMR-proven acute myocarditis were included. The primary end point was occurrence of major adverse cardiovascular events: all-cause mortality, heart transplantation, heart failure hospitalizations, and life threatening arrhythmias. LV global longitudinal strain, global circumferential strain and global radial strain, right ventricular-global longitudinal strain and left atrial strain were measured. Unadjusted and adjusted cox proportional hazard regression analysis were performed. In total, 162 CMR-proven myocarditis patients were included (41 ± 17 years, 75% men). Mean LV ejection fraction was 51 ± 12%, and 144 (89%) patients had presence of late gadolinium enhancement. Major adverse cardiovascular events occurred in 29 (18%) patients during a follow-up of 5.5 (2.2-8.3) years. All LV strain parameters were independent predictors of outcome beyond clinical features, LV ejection fraction and late gadolinium enhancement (LV-global longitudinal strain: hazard ratio [HR] 1.07, P=0.02; LV-global circumferential strain: HR 1.15, P=0.02; LV-global radial strain: HR 0.98, P=0.03), but right ventricular or left atrial strain did not predict outcome. Conclusions CMR-derived LV strain analysis provides independent prognostic value on top of clinical parameters, LV ejection fraction and late gadolinium enhancement in acute myocarditis patients, while left atrial and right ventricular strain seem to be of less importance

Left Atrial Reverse Remodeling in Dilated Cardiomyopathy

BACKGROUND: Left atrial (LA) dilation is associated with a worse prognosis in several cardiovascular settings but therapies can promote LA reverse remodeling. We aimed to characterize and define the prognostic implications of LA volume (LAVI) reduction in dilated cardiomyopathy (DCM). METHODS: Consecutive DCM patients from two tertiary care centers, with available echocardiography at baseline and at 1-year follow-up, were retrospectively analyzed. LA dilation was defined as LAVI >34 ml/m2, change in LAVI (ΔLAVI) was defined as the 1-year relative LAVI reduction. The outcome was a composite of death/heart transplantation/heart failure hospitalization (D/HTx/HFH). RESULTS: Five hundred sixty patients were included (age 54±13 years; left ventricular ejection fraction (LVEF) 31±10%, LAVI 45±18 ml/m2). Baseline LAVI had a non-linear association with the risk of D/HTx/HFH, independently from age, LVEF, MR and medical therapy (p<0.01). At 1-year follow-up, LAVI decreased in 374 patients (67%, median ΔLAVI -24%, interquartile range -37% - -11%). Factors independently associated with ΔLAVI were higher baseline LAVI and lower baseline LVEF. After multivariable adjustment, ΔLAVI showed a linear association with the risk of D/HTx/HFH (HR 0.96, 95% 0.93-0.99 per 5% decrease, p=0.042). At 1-year follow-up, patients with a reduction in LAVI greater than 10% and LAVI normalization (i.e. follow-up LAVI ≤34ml/m2) (31% of the overall cohort) were at lower risk of D/HTx/HFH (HR 0.37, 95% C.I. 0.35-0.97, p=0.028). CONCLUSIONS: In a large cohort of DCM, 1-year reduction in LAVI is observed in a number of patients. The association between reduction in LAVI and D/HTx/HFH suggests that LA structural reverse remodeling might be considered an additional parameter useful in the individualized risk stratification of patients with DCM