TSH Variations in Chronic Heart Failure Outpatients: Clinical Correlates and Outcomes.

BACKGROUND: Hypothyroidism is a frequently observed comorbidity in patients with chronic heart failure (CHF), possibly giving rise to unfavorable outcomes. AIM: The aim of the study was to evaluate the impact of TSH changes over time on cardiac function and prognosis of outpatients with CHF. METHODS: Patients underwent clinical, electrocardiographic, and echocardiographic evaluations at baseline and after 12 months. Moreover, blood chemistry tests were performed to evaluate renal function, cardiac biomarkers, fT3, fT4, and TSH levels. Based on TSH serum levels, patients were retrospectively classified into four categories: Group 1, patients with improved thyroid function at one-year follow up vs. baseline; Group 2, patients with stable and mildly high TSH values (3.74 - 10 mUI/L); Group 3, patients with worsening thyroid function; Euthyroid patients Group, TSH levels within the normal range of reference at baseline as well as at 12 months follow-up. We considered as end-points: one-year changes of laboratory and echocardiographic parameters; hospitalizations due to worsening of HF (acute decompensated heart failure - ADHF); death for all causes. RESULTS: Among 257 patients, 174 (67.7%) were euthyroid at baseline and after 12 months. Group 1 patients (n. 22, 8.6%) showed a significant improvement in systolic and diastolic function, filling pressures, NT-proBNP and Galectin-3. Group 2 patients (n. 34, 13.2%) did not exhibit significant modifications in studied parameters. Group 3 patients (n. 27, 10.5%) showed worsening of diastolic function and NT-proBNP and a greater risk of ADHF (HR: 2.12; 95%CI: 1.20-3.74; p: 0.009) and death (HR: 4.05; 95%CI: 2.01-8.15; p<0.001). CONCLUSION: In patients with CHF, changes in thyroid function over time influenced echocardiographic parameters and biomarkers reflecting modifications of cardiac function and prognosis, thus suggesting the clinical relevance of thyroid deficiency screening and correction.

Eligibility of outpatients with chronic heart failure for sodium-glucose co-transporter-2 inhibitors.

AIMS: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have been shown to have a relevant role in the prevention of hospitalizations for heart failure and improvement in the life expectancy of patients with diabetes and outpatients with chronic heart failure (CHF) with reduced left ventricular ejection fraction, independently from the presence of type 2 diabetes mellitus (T2DM). The aim of our study was to evaluate in a real-world population the number of outpatients with CHF who meet the enrolment criteria of the main randomized controlled trials (RCT) published in the last 5 years and consequently identify the percentage of patients who could potential benefit from SGLT2i therapy. METHODS AND RESULTS: We retrospectively evaluated all consecutive outpatients referred for CHF. The diagnosis of T2DM was according to the latest European Society of Cardiology Guidelines. Clinical characteristics considered for the enrolment in the RCTs were recorded. We enrolled 515 patients, 384 (75%) of whom had a left ventricular ejection fraction (LVEF) ≤ 40%, 82 (16%) had pre-diabetes, and 187 (36%) had diabetes. Most of the patients with LVEF ≤ 40% met the criteria for the DAPA-HF trial (65%), and this percentage was even higher if the serum level of N-terminal pro-brain natriuretic peptide was not considered. A high percentage of patients with diabetes and LVEF > 40% met the criteria for the DECLARE (39%), CANVAS (47%), and EMPA-REG (30%) trials. Patients meeting the enrolment criteria of RCTs evaluating SGLT2i were also characterized by a high risk of heart failure events during follow-up. CONCLUSIONS: In spite of a low number of patients actually treated with SGLT2i, we observed that a high prevalence of patients with CHF met the clinical characteristics of RCTs that have demonstrated a beneficial effect of SGLT2i.

Baseline and incident hypochloremia in chronic heart failure outpatients: Clinical correlates and prognostic role.

BACKGROUND: Electrolyte serum disorders are associated with poor outcome in chronic heart failure. The aim of this study sought to identify the main driver of incident hypochloremia in chronic HF (CHF) outpatients and to determine the prognostic value of baseline and incident hypochloremia. METHODS: Consecutive CHF outpatients were enrolled and clinical, laboratoristic and echocardiographic evaluations were performed at baseline and repeated yearly in a subgroup of patients. Baseline and incident hypochloremia were evaluated. During an up to 5-year follow-up, all-cause mortality was the primary end-point for outcome. RESULTS: Among 506 patients enrolled, 120 patients died during follow-up. At baseline, hypochloremia was present in 10% of patients and it was associated with mortality at univariate (HR: 3.25; 95%CI: 2.04-5.18; p<0.001) and at multivariate analysis (HR 2.14; 95%CI: 1.23-3.63; p: 0.005) after correction for well-established CHF prognostic markers. Among patients with repeated evaluations and without baseline hypochloremia, in 13% of these, incident hypochloremia occurred during follow-up and furosemide equivalent daily dose was its first determinant (HR for 1 mg/die: 1.008; 95%CI: 1.004-1.013; p<0.001) at forward stepwise logistic regression analysis. Finally, incident hypochloremia was associated with mortality at univariate (HR: 4.69; 95%CI: 2.69-8.19; p<0.001) as well as at multivariate analysis (HR: 2.97; 95%CI: 1.48-5.94; p: 0.002). CONCLUSIONS: In CHF outpatients baseline and incident hypochloremia are independently associated with all-cause mortality, thus highlighting the prognostic role of serum chloride levels which are generally unconsidered. Future studies should evaluate if the strict monitoring and correction of hypochloremia could exert a beneficial effect on prognosis.

Mineralcorticoid Receptor Antagonist Withdrawal for Hyperkalemia and Mortality in Patients with Heart Failure.

BACKGROUND: Hyperkalemia is one of the most frequent side effects related to renin-angiotensin-aldosterone system (RAAS) inhibition, and can influence optimization of heart failure (HF) therapy. AIM: To evaluate the occurrence of hyperkalemia in a series of outpatients with chronic HF and its relationship with RAAS inhibitor therapy. METHOD: We evaluated consecutive outpatients with HF and a reduced left ventricular ejection fraction. The incidence of hyperkalemia and consequent changes in RAAS inhibitor therapy were evaluated for each patient. RESULTS: A history of hyperkalemia or at least 1 episode of hyperkalemia during follow-up was observed in 104 of 351 patients. Hyperkalemia mainly influenced mineralocorticoid receptor antagonist (MRA) therapy and, among patients with hyperkalemia, not taking MRA was associated with a greater risk of death on univariate analysis (HR = 6.39; 95% CI 2.76-14.79, p < 0.001) and multivariate analysis (HR = 5.24; 95% CI 1.87-14.72, p = 0.002) after correction for age, ischemic cardiomyopathy, diabetes, systolic arterial pressure, New York Heart Association class 3, left ventricular ejection fraction, presence of hyponatremia, glomerular filtration rate calculated by the EPI formula, and presence of N-terminal pro-B-type natriuretic peptide >1,000 pg/mL. CONCLUSION: The occurrence of hyperkalemia is common among outpatients with HF and it is the main cause of MRA withdrawal, which is associated with a worse prognosis. In this setting, the possibility of managing hyperkalemia using new classes of drugs could allow continuation of MRA therapy.

Thyroid Disorders and Prognosis in Chronic Heart Failure: A Long-Term Follow-Up Study.

BACKGROUND: Thyroid disorders may have a negative impact on the prognosis of patients affected by chronic heart failure (CHF). OBJECTIVE: The aim of the current study was to evaluate the prognostic role of all thyroid disorders over a long term follow-up in a single centre large sample of CHF outpatients. METHODS: In all patients, the function of the thyroid was evaluated at the enrolment and during the follow- up. On the basis of free triiodothyronine (T3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) serum levels, patients were classified into one of the following four categories: euthyroid subjects, patients affected by hypothyroidism, low T3 (LT3) syndrome and hyperthyroidism. During the follow-up, death for all causes was assessed as primary end-point, whereas time to the first hospitalization for heart failure worsening was the secondary end-point analyzed. RESULTS: Among 762 patients, 190 patients were affected by hypothyroidism (Hypo). LT3 syndrome was diagnosed in 15 patients and 59 patients were affected by hyperthyroidism (Hyper). During a long term follow-up (5.1±3.7 years), 303 patients died. Patients with Hypo showed an increased risk of death as well as of hospitalization due to heart failure worsening at univariate regression analysis. At multivariate regression analysis, Hypo remained associated with hospitalization after correction for age >75 years, ischemic aetiology, diabetes, therapy with ACE-inhibitors or ARBs, therapy with betablockers and with aldosterone antagonists, NYHA class 3, systolic arterial pressure <95 mmHg, left ventricular ejection fraction <30%, estimated glomerular filtration rate <60 ml/min, hyponatremia and NTproBNP> 1000 pg/ml. At multivariate analysis, the independent association with death was significant only for the subgroup of patients with TSH >10 mIU/L. LT3 was independently associated with both heart failure hospitalization and death, whereas Hyper was not associated with any of the two considered end-points. CONCLUSION: Hypo is associated with a worse prognosis over a long-term follow-up. The association with heart failure hospitalization is not dependent on the baseline TSH levels, whereas the association with death is significant only when TSH >10 mIU/L. Finally, Hyper does not have any association with a worse prognosis.

Hemodynamic Surveillance of Ventricular Pacing Effectiveness with the Transvalvular Impedance Sensor.

The Transvalvular Impedance (TVI) is derived between atrial and ventricular pacing electrodes. A sharp TVI increase in systole is an ejection marker, allowing the hemodynamic surveillance of ventricular stimulation effectiveness in pacemaker patients. At routine follow-up checks, the ventricular threshold test was managed by the stimulator with the supervision of a physician, who monitored the surface ECG. When the energy scan resulted in capture loss, the TVI system must detect the failure and increase the output voltage. A TVI signal suitable to this purpose was present in 85% of the tested patients. A total of 230 capture failures, induced in 115 patients in both supine and sitting upright positions, were all promptly recognized by real-time TVI analysis (100% sensitivity). The procedure was never interrupted by the physician, as the automatic energy regulation ensured full patient's safety. The pulse energy was then set at 4 times the threshold to test the alarm specificity during daily activity (sitting, standing up, and walking). The median prevalence of false alarms was 0.336%. The study shows that TVI-based ejection assessment is a valuable approach to the verification of pacing reliability and the autoregulation of ventricular stimulation energy.

Atrial fibrillation in recipients of cardiac resynchronization therapy device: 1-year results of the randomized MASCOT trial.

BACKGROUND: Atrial fibrillation (AF) is associated with increased morbidity and mortality in patients suffering from heart failure (HF). Patients in New York Heart Association HF classes III or IV, with systolic dysfunction and a wide QRS, are candidates for cardiac resynchronization therapy (CRT), and might benefit from atrial overdrive pacing (AOP). METHODS: The Management of Atrial fibrillation Suppression in AF-HF COmorbidity Therapy (MASCOT) trial enrolled 409 CRT device recipients (79% men), who were randomly assigned to AOP ON (n = 197), versus AOP OFF (n = 197) and followed up for 1 year. Their mean age was 68 +/- 10 years, left ventricular ejection fraction 25 +/- 6%, QRS duration 163 +/- 29 milliseconds. New York Heart Association class III was present in 86% of patients and 19% had a history of paroxysmal AF. The primary study end point was incidence of permanent AF at 1 year. RESULTS: Atrial overdrive pacing increased the percentage of atrial pacing from 30% to 80% (P < .0001), was well tolerated, and did not interfere with (a) delivery of CRT (95% mean ventricular pacing in both groups), (b) response to CRT (70% responders in the control vs 67% in the treatment group), or (c) cardiac function (left ventricular ejection fraction increased from 24.5% +/- 6.2% to 32.7% +/- 10.9% in the control and from 25.8% +/- 6.8% to 33.1% +/- 12.6% in the treatment group). The incidence of permanent AF was 3.3% in both groups. By logistic regression analysis, a history of AF (P < .001) and absence of antiarrhythmic drugs (P = .002) were associated with permanent AF. CONCLUSIONS: In this first trial of a specific AF prevention algorithm in CRT recipients, AOP was safe and did not worsen HF. The prevention algorithm did not lower the 1-year incidence of AF.

A randomized comparison of amiodarone and class IC antiarrhythmic drugs to treat atrial fibrillation in patients paced for sinus node disease: the Prevention Investigation and Treatment: A Group for Observation and Research on Atrial arrhythmias (PITAGORA) trial.

BACKGROUND: Rhythm control is an important goal in the treatment of recurrent atrial tachyarrhythmias (AT). The PITAGORA study was a randomized trial in patients paced for sinus node disease (SND), designed to test the noninferiority of class IC antiarrhythmic drugs (AADs) to amiodarone in terms of a primary end point composed of death, permanent AT, cardiovascular hospitalization, atrial cardioversion, or AAD change. METHODS: Randomization was stratified to assign 2 patients to amiodarone and 2 patients to class IC AADs: propafenone or flecainide. One hundred seventy-six patients (46% men, 72 +/- 8 years) were enrolled. Device diagnostics continuously monitored AT recurrences and duration. RESULTS: In a mean follow-up of 20 +/- 9 months, the primary end point occurred in 23 (30.7%) of 75 class IC patients and in 28 (40.0%) of 70 amiodarone patients. The absolute difference in the end point incidence (-9.3%; 95% CI between 3.7% and -22.3%) confirmed the noninferiority of class IC to amiodarone (P = .007). Kaplan-Meier 1-year freedom from AT episodes >10 minutes, 1 day, and 7 days was 40%, 73%, and 91% for amiodarone and 28%, 78%, and 86% for class IC AADs (P = nonsignificant). CONCLUSIONS: In patients paced for SND and suffering from AT, class IC AADs proved not to be inferior to amiodarone in terms of the primary composite end point described or end points which were differently composed of mortality, efficacy, or AAD side effects. The AADs studied also showed similar results in terms of symptoms, quality of life, and freedom from AT recurrences.