Trajectories of Kidney Function in Heart Failure Over a 15-Year Follow-Up: Clinical Profiling and Mortality.

BACKGROUND: Limited data are available on the long-term trajectory of estimated glomerular filtration rate (eGFR) in patients with chronic heart failure. OBJECTIVES: The authors evaluated eGFR dynamics using the 2009 Chronic Kidney Disease Epidemiology Collaboration equation and its prognostic significance in a real-world cohort over a 15-year follow-up. METHODS: A prospective observational registry of ambulatory heart failure outpatients was conducted, with regular eGFR assessments at baseline and on a 3-month schedule for ≤15 years. Urgent kidney function assessments were excluded. Locally weighted error sum of squares curves were plotted for predefined subgroups. Multivariable longitudinal Cox regression analyses were conducted to assess associations with all-cause and cardiovascular death. RESULTS: A total of 2,672 patients were enrolled consecutively between August 2001 and December 2021. The average age was 66.8 ± 12.6 years, and 69.8% were men. Among 40,970 creatinine measurements, 28,634 were used for eGFR analysis, averaging 10.7 ± 8.5 per patient. Over the study period, a significant decline in eGFR was observed in the entire cohort, with a slope of -1.70 mL/min/1.73 m2 per year (95% CI: -1.75 to -1.66 mL/min/1.73 m2 per year). Older patients, those with diabetes, a preserved ejection fraction, a higher baseline eGFR, elevated hospitalization rates, and those who died during follow-up experienced more pronounced decreases in the eGFR. Moreover, the decrease in kidney function correlated independently with all-cause mortality and cardiovascular death. CONCLUSIONS: These findings highlight the sustained decline in eGFR over 15 years in patients with heart failure, with variations based on clinical characteristics, and emphasize the importance of regular eGFR monitoring in this population.

Sudden Cardiac Death in Heart Failure: A 20-Year Perspective From a Mediterranean Cohort.

BACKGROUND: The prediction of sudden cardiac death (SCD) in heart failure (HF) remains an unmet need. The aim of our study was to assess the prevalence of SCD over 20 years in outpatients with HF managed in a Mediterranean multidisciplinary HF Clinic, and to compare the proportion of SCD (SCD/all-cause death) to the expected proportional occurrence based on the validated Seattle Proportional Risk Model (SPRM) score. METHODS AND RESULTS: This prospective observational registry study included 2772 outpatients with HF admitted between August 2001 and May 2021. Patients were included when the cause of death was known and SPRM score was available. Over the 20-year study period, 1351 patients (48.7%) died during a median follow-up period of 3.8 years (interquartile range 1.6-7.6). Among these patients, the proportion of SCD out of the total of deaths was 13.6%, whereas the predicted by SPRM was 39.6%. This lower proportion of SCD was observed independently of left ventricular ejection fraction, ischemic etiology, and the presence of an implantable cardiac defibrillator. CONCLUSIONS: In a Mediterranean cohort of outpatients with HF, the proportion of SCD was lower than expected based on the SPRM score. Future studies should investigate to what extend epidemiological and guideline-directed medical therapy patterns influence SCD.

Mortality Risk Prediction Dynamics After Heart Failure Treatment Optimization: Repeat Risk Assessment Using Online Risk Calculators.

Objectives: Heart failure (HF) management has significantly improved over the past two decades, leading to better survival. This study aimed to assess changes in predicted mortality risk after 12 months of management in a multidisciplinary HF clinic. Materials and Methods: Out of 1,032 consecutive HF outpatients admitted from March-2012 to November-2018, 357 completed the 12-months follow-up and had N-terminal pro-B-type natriuretic peptide (NTproBNP), high sensitivity troponin T (hs-TnT), and interleukin-1 receptor-like-1 (known as ST2) measurements available both at baseline and follow-up. Three contemporary risk scores were used: MAGGIC-HF, Seattle HF Model (SHFM), and the Barcelona Bio-HF (BCN Bio-HF) calculator, which incorporates the three above mentioned biomarkers. The predicted risk of all-cause death at 1 and 3 years was calculated at baseline and re-evaluated after 12 months. Results: A significant decline in predicted 1-and 3-year mortality risk was observed at 12 months: MAGGIC ~16%, SHFM ~22% and BCN Bio-HF ~15%. In the HF with reduced ejection fraction (HFrEF) subgroup guideline-directed medical therapy led to a complete normalization of left ventricular ejection fraction (≥50%) in almost a third of the patients and to a partial normalization (41-49%) in 30% of them. Repeated risk assessment after 12 months with SHFM and BCN Bio-HF provided adequate discrimination for all-cause 3-year mortality (C-Index: MAGGIC-HF 0.762, SHFM 0.781 and BCN Bio-HF 0.791). Conclusion: Mortality risk declines in patients with HF managed for 12 months in a multidisciplinary HF clinic. Repeating the mortality risk assessment after optimizing the HF treatment is recommended, particularly in the HFrEF subgroup.

Sacubitril/valsartan affects pulmonary arterial pressure in heart failure with preserved ejection fraction and pulmonary hypertension.

AIMS: Prior studies have not fully characterized the haemodynamic effects of the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan in heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF-PH). The aim of the Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device (ARNIMEMS-HFpEF) study is to assess pulmonary artery pressure (PAP) dynamics by means of implanted PAP monitors in patients with HFpEF-PH treated with sacubitril/valsartan. METHODS AND RESULTS: This single-arm, investigator-initiated, interventional study included 14 consecutive ambulatory symptomatic HFpEF-PH patients who underwent CardioMEMS implantation prior to enrolment [mean ejection fraction 60.4 ± 7.2%, baseline mean PAP (mPAP) 33.9 ± 7.6 mmHg]. Daily PAP values were examined during three periods: a 6 week period after CardioMEMS implantation and before sacubitril/valsartan treatment (pre-ARNI), a 6 week period with sacubitril/valsartan treatment (ARNI ON), and a 6 week period of sacubitril/valsartan withdrawal (ARNI OFF). The primary endpoint was change in mPAP with and without sacubitril/valsartan. Secondary endpoints included changes in 6 min walking distance, B-line sum in lung ultrasound, and quality of life (QoL). During the study period, 1717 mPAP measurements were recorded. Between pre-ARNI vs. ARNI ON, mPAP significantly declined by -4.99 mmHg [95% confidence interval (CI) -5.55 to -4.43]. Between ARNI ON vs. ARNI OFF, mPAP significantly increased by +2.84 mmHg [95% CI +2.26 to +3.42]. Between pre-ARNI vs. ARNI ON, we found an improvement in 6 min walking distance, B-lines, and QoL. Mean loop diuretic management did not differ between periods. CONCLUSIONS: Sacubitril/valsartan significantly reduced mPAP in patients with HFpEF-PH, independent of loop diuretic management, together with improvement in functional capacity, lung congestion, and QoL. Sacubitril/valsartan may be a therapeutic alternative in HFpEF-PH.

Ventricular Arrhythmias and Sudden Death in Nonischemic Dilated Cardiomyopathy: Matter of Sex or Scar?

BACKGROUND: To evaluate the association between sex and ventricular arrhythmias (VA) or sudden death (SD) in nonischemic dilated cardiomyopathy, including analysis of potential confounders. METHODS AND RESULTS: Retrospective cohort study of consecutive patients with DCM referred for cardiac magnetic resonance at 2 tertiary hospitals. The primary combined end point encompassed sustained VA, appropriate implantable cardioverter defibrillator therapies, resuscitated cardiac arrest, and SD. We included 1165 patients with median follow-up of 36 months (interquartile range 20-58 months). The majority of patients (66%) were males. Males and females had similar left ventricular ejection fraction, but the prevalence of late gadolinium enhancement (LGE) at cardiac magnetic resonance was significantly higher among males (48% vs 30%, P < .001). Males had higher cumulative incidence of the primary end point (8% vs 4%, P = .02), and male sex was a significant predictor of the primary end point at univariate analysis (hazard ratio 1.93, P = .02). However, LGE had a major confounding effect in the association between sex and the primary outcome: the hazard ratio of male sex adjusted for LGE was 1.29 (P = .37). LGE+ females had significantly higher cumulative incidence of the primary end point than LGE- males (13% vs 1.8%, P < .001). CONCLUSIONS: In patients with DCM, the prevalence of LGE is significantly higher among males, implying a major confounding effect in the association between male sex and VA or SD. LGE+ females have significantly higher risk than LGE- males. These data do not support the inclusion of sex into risk stratification algorithms for VA or SD in DCM.

Genotype-phenotype correlation of LMNA variants involving the Arg541 residue: a case report with multimodality imaging and literature review.

We present a case of atypical LMNA cardiomyopathy associated with the pathogenic variant p.Arg541Ser. The patient had early-onset severe ventricular arrhythmias but atrioventricular conduction was normal. Segmental motion abnormalities and a large transmural scar, mainly apical and lateral, were found at cardiac magnetic resonance, corresponding to areas of severe wall thinning at computed tomography and of low voltages at electroanatomic mapping. Ventricular tachycardia ablation was successful in controlling ventricular arrhythmias. Few other cases described patients with pathogenic variants in the Arg541 residue, and they displayed similar atypical features, suggesting a genotype-phenotype correlation which may have specific prognostic and therapeutic implications.