Tricuspid annuloplasty concomitant with mitral valve surgery: Effects on right ventricular remodeling

ObjectivesTricuspid valve annuloplasty (TVP) has been advocated concomitantly with left-sided cardiac surgery in case of more than moderate tricuspid regurgitation (TR) or tricuspid annular dilation (TAD) (diameter >40 mm or 21 mm/m²) even in the absence of significant TR. Data on postoperative right ventricular (RV) remodeling are lacking in such patients.MethodsPreoperative and postoperative echocardiography data from 45 consecutive TVP procedures, performed in mitral valve surgery in a single tertiary center, were retrospectively analyzed and compared with a propensity-matched control group of 33 procedures without concomitant TVP. RV function and geometry was analyzed by measuring RV size, fractional area change, and end-diastolic sphericity index (RVSI = long-axis length/short-axis width) and compared at baseline versus follow-up.ResultsAt a mean follow-up of 5 months, a favorable change in RV geometry was observed in TVP patients (RVSI increased from 1.99 ± 0.33 to 2.21 ± 0.42; P = .001), whereas the opposite was observed in the control group (RVSI decreased from 2.34 ± 0.52 to 2.17 ± 0.13; P = .05). Only in control patients, indexed RV end-diastolic area increased significantly (P = .003). In TVP patients, when comparing patients with baseline more than moderate TR (n = 13) to patients with isolated TAD (n = 32), there was a significant decrease in RV end-diastolic area only in the group with more than moderate TR (from 12.9 ± 3.5 cm2/m2 to 10.3 ± 1.9 cm2/m2; P = .009).ConclusionsAdding TVP to mitral valve surgery in patients with more than moderate TR or TAD leads to favorable changes in RV geometry and prevents postoperative RV dilation. This is most pronounced in patients with more than moderate TR at baseline

Prognostic Role of Cardiac Power Index in Ambulatory Patients with Advanced Heart Failure

BACKGROUND: Cardiac pump function is often quantified by left ventricular ejection fraction by various imaging modalities. As the heart is commonly conceptualized as a hydraulic pump, cardiac power describes the hydraulic function of the heart. We aim to describe the prognostic value of resting cardiac power index (CPI) in ambulatory patients with advanced heart failure. METHODS AND RESULTS: We calculated CPI in 495 sequential ambulatory patients with advanced heart failure who underwent invasive haemodynamic assessment with longitudinal follow-up of adverse outcomes (all-cause mortality, cardiac transplantation, or ventricular assist device placement). The median CPI was 0.44 W/m(2) (interquartile range 0.37, 0.52). Over a median of 3.3 years, there were 117 deaths, 104 transplants, and 20 ventricular assist device placements in our cohort. Diminished CPI (\u3c0.44 W/m(2) ) was associated with increased adverse outcomes [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.8-3.1, P \u3c 0.0001). The prognostic value of CPI remained significant after adjustment for age, gender, pulmonary capillary wedge pressure, cardiac index, pulmonary vascular resistance, left ventricular ejection fraction, and creatinine [HR 1.5, 95% CI 1.03-2.3, P = 0.04). Furthermore, CPI can risk stratify independently of peak oxygen consumption (HR 2.2, 95% CI 1.4-3.4, P = 0.0003). CONCLUSION: Resting cardiac power index provides independent and incremental prediction in adverse outcomes beyond traditional haemodynamic and cardio-renal risk factors

Heart failure is associated with accelerated age related metabolic bone disease

Background:The heart failure (HF)-syndrome is associated with neuro-hormonal activation, chronic kidney disease (CKD), inflammation and alterations in the phosphorus-metabolism, all of which are involved in regulation of mineral bone density. However, the role of HF as an independent factor associated with metabolic bone disease (MBD) remains unclear. Methods:HF-patients undergoing dual X-ray absorptiometry (DEXA) were matched in a 1:2 fashion against age and gender matched controls without HF, to determine the proportion of osteoporosis (T-score <-2.5). HF-status was tested against known predictors of MBD. Correlation analysis and Z-score analysis were used to assess the impact of HF on age-related bone demineralisation. Results:A total of 190 HF-patients (age = 80 +/- 10 years, female = 61%) were age and gender matched to 380 controls. HF-patients had a higher proportion of osteoporosis (26 vs 17%;p = .007). HF patients had a lower averaged mineral bone density expressed in g/cm(2) (p = .030), T-scores (p = .001) and Z-scores (p <.001). After adjusting for the individual osteoporosis risk-factors of the FRAX-score, difference in baseline features, kidney function and phosphorus-metabolism alterations, heart failure remained independently associated with a lower averaged T-score (Adjusted beta= -0.189;p = .017). Heart failure was associated with an accelerated age-related decline in mineral bone density (p = .0418). Therapies with ACE-I or ARBs and beta-blockers associated with ameliorated bone demineralisation (p = .023, respectivelyp = .029), while loop diuretic associated with worsened bone demineralization (p <.001). Conclusion:Heart failure independently associates with MBD and higher prevalence of osteoporosis. Heart failure aggravates the aged related loss in mineral bone density while treatment with neuro-hormonal blockers seemed to ameliorate this finding

Prognostic Role of Pulmonary Arterial Capacitance in Advanced Heart Failure

Background—Right ventricular (RV) dysfunction frequently occurs and independently prognosticates in left-sided heart failure. It is not clear which RV afterload measure has the greatest impact on RV function and prognosis. We examined the determinants, prognostic role, and response to treatment of pulmonary arterial capacitance (PAC, ratio of stroke volume over pulmonary pulse pressure), in relation to pulmonary vascular resistance (PVR) in heart failure. Methods and Results—We reviewed 724 consecutive patients with heart failure who underwent right heart catheterization between 2000 and 2005. Changes in PAC were explored in an independent cohort of 75 subjects treated for acute decompensated heart failure. PAC showed a strong inverse relation with PVR (r=−0.64) and wedge pressure (r=−0.73), and provides stronger prediction of significant RV failure than PVR (area under the curve ROC 0.74 versus 0.67, respectively, P=0.003). During a mean follow-up of 3.2±2.2 years, both lower PAC (P\u3c0.0001) and higher PVR (P\u3c0.0001) portend more adverse clinical events (all-cause mortality and cardiac transplantation). In multivariate analysis, PAC (but not PVR) remains an independent predictor (Hazard ratio=0.92 [95% CI: 0.84–1.0, P=0.037]). Treatment of heart failure resulted in a decrease in PVR (270±165 to 211±88 dynes·s–1·cm–5, P=0.002), a larger increase in PAC (1.65±0.64 to 2.61±1.42 mL/mm Hg, P\u3c0.0001), leading to an increase in pulmonary arterial time constant (PVR×PAC) (0.29±0.12 to 0.37±0.15 second, P\u3c0.0001). Conclusions—PAC bundles the effects of PVR and left-sided filling pressures on RV afterload, explaining its strong relation with RV dysfunction, poor long-term prognosis, and response to therapy

Differential Response to Cardiac Resynchronization Therapy and Clinical Outcomes According to QRS Morphology and QRS Duration

ObjectivesThe goal of this study was to examine the relative impact of QRS morphology and duration in echocardiographic responses to cardiac resynchronization therapy (CRT) and clinical outcomes.BackgroundAt least one-third of all patients treated with CRT fail to derive benefit. Patients without left bundle branch block (LBBB) or patients with smaller QRS duration (QRSd) respond less or not at all to CRT.MethodsWe retrospectively assessed baseline characteristics, clinical and echocardiographic response, and outcomes of all patients who received CRT at our institution between December 2003 and July 2007. Patients were stratified into 4 groups according to their baseline QRS morphology and QRSd.ResultsA total of 496 patients were included in the study; 216 (43.5%) had LBBB and a QRSd ≥150 ms, 85 (17.1%) had LBBB and QRSd <150 ms, 92 (18.5%) had non-LBBB and a QRSd ≥150 ms, and 103 (20.8%) had non-LBBB and QRSd <150 ms. Echocardiographic response (change in ejection fraction) was better in patients with LBBB and QRSd ≥150 ms (12 ± 12%) than in those with LBBB and QRSd <150 ms (8 ± 10%), non-LBBB and QRSd ≥150 ms (5 ± 9%), and non-LBBB and QRSd <150 ms (3 ± 11%) (p < 0.0001). In a multivariate stepwise model with change in ejection fraction as the dependent variable, the presented classification was the most important independent variable (p = 0.0003). Long-term survival was better in LBBB patients with QRSd ≥150 ms (p = 0.02), but this difference was not significant after adjustment for other baseline characteristics (p = 0.15).ConclusionsQRS morphology is a more important baseline electrocardiographic determinant of CRT response than QRSd

Urinary Sodium Profiling in Chronic Heart Failure to Detect Development of Acute Decompensated Heart Failure

OBJECTIVES This study sought to determine the relationship between urinary sodium (U-na) concentration and the pathophysiologic interaction with the development of acute heart failure (AHF) hospitalization. BACKGROUND No data are available on the longitudinal dynamics of U-na concentration in patients with chronic heart failure (HF), including its temporal relationship with AHF hospitalization. METHODS Stable, chronic HF patients with either reduced or preserved ejection fraction were prospectively included to undergo prospective collection of morning spot U-na samples for 30 consecutive weeks. Linear mixed modeling was used to assess the longitudinal changes in U-na concentration. Patients were followed for the development of the clinical endpoint of AHF. RESULTS A total of 80 chronic HF patients (71 +/- 11 years of age; an N-terminal pro-B-type natriuretic peptide [NT-proBNP] concentration of 771 [interquartile range: 221 to 1,906] ng/l; left ventricular ejection fraction [LVEF] 33 +/- 7%) prospectively submitted weekly pre-diuretic first void morning U-na samples for 30 weeks. A total of 1,970 U-na samples were collected, with mean U-na concentration of 81.6 +/- 41 mmol/l. Sodium excretion remained stable over time on a population level (time effect p = 0.663). However, interindividual differences revealed the presence of high (88 mmol/l U-na [n = 39]) and low (73 mmol/l U-na [n = 41]) sodium excreters. Only younger age was an independent predictor of high sodium excretion (odds ratio [OR]: 0.91; 95% confidence interval [CI]: 0.83 to 1.00; p = 0.045 per year). During 587 +/- 54 days of follow-up, 21 patients were admitted for AHF. Patients who developed AHF had significantly lower U-na concentrations (F-[1.80] = 24.063; p <0.001). The discriminating capacity of U-na concentration to detect AHF persisted after inclusion of NT-proBNP and estimated glomerular filtration rate (eGFR) measurements as random effects (p = 0.041). Furthermore, U-na concentration dropped (U-na = 46 +/- 16 mmol/l vs. 70 +/- 32 mmol/l, respectively; p = 0.003) in the week preceding the hospitalization and returned to the individual's baseline (U-na = 71 +/- 22 mmol/l; p = 0.002) following recompensation, while such early longitudinal changes in weight and dyspnea scores were not apparent in the week preceding decompensation. CONCLUSIONS Overall, U-na concentration remained relatively stable over time, but large interindividual differences existed in stable, chronic HF patients. Patients who developed AHF exhibited a chronically lower U-na concentration and exhibited a further drop in U-na concentration during the week preceding hospitalization. Ambulatory U-na sample collection is feasible and may offer additional prognostic and therapeutic information. (C) 2019 by the American College of Cardiology Foundation

Selective abdominal venous congestion induces adverse renal and hepatic morphological and functional alterations despite a preserved cardiac function

Venous congestion is an important contributor to worsening renal function in heart failure and the cardiorenal syndrome. In patients, it is difficult to study the effects of isolated venous congestion on organ function. In this study, the consequences of isolated abdominal venous congestion on morphology and function of the kidneys, liver and heart were studied in a rat model. Twelve shamoperated (SHAM) male Sprague Dawley rats were compared to eleven inferior vena cava-constricted (IVCc) rats for twenty-one weeks. Abdominal venous pressure was significantly higher in the IVCc versus SHAM group (p < 0.0001). Indices of liver and kidney weight, function and morphology, inflammation as well as collagen deposition were significantly increased in the IVCc compared to SHAM group, (p < 0.05). Echocardiographic and hemodynamic parameters were largely unaffected by abdominal venous congestion. In this rat model of isolated abdominal venous congestion, retrogradely conducted glomerular hypertension without a concomitant change in glomerular filtration rate was observed. Adverse short-term hepatic morphological alterations were developed which explain the observed organ function dysfunction. Importantly, cardiac function remained comparable between both groups. This study provides relevant insight in the pathophysiology of abdominal congestion on organ function

Sodium and potassium changes during decongestion with acetazolamide:A pre-specified analysis from the ADVOR trial

AIMS: Acetazolamide, an inhibitor of proximal tubular sodium reabsorption, leads to more effective decongestion in acute heart failure (AHF). It is unknown whether acetazolamide alters serum sodium and potassium levels on top of loop diuretics and if baseline values modify the treatment effect of acetazolamide.METHODS AND RESULTS: This is a pre-specified sub-analysis of the ADVOR trial that randomized 519 patients with AHF and volume overload in a 1:1 ratio to intravenous acetazolamide or matching placebo on top of standardized intravenous loop diuretics. Mean potassium and sodium levels at randomization were 4.2 ± 0.6 and 139 ± 4 mmol/L in the acetazolamide arm versus 4.2 ± 0.6 and 140 ± 4 mmol/L in the placebo arm. Hypokalaemia (&lt;3.5 mmol/L) on admission was present in 44 (9%) patients and hyponatraemia (≤135 mmol/L) in 82 (16%) patients. After 3 days of treatment, 44 (17%) patients in the acetazolamide arm and 35 (14%) patients in the placebo arm developed hyponatraemia (p = 0.255). Patients randomized to acetazolamide demonstrated a slight decrease in mean potassium levels during decongestion, which was non-significant over time (p = 0.053) and had no significant impact on hypokalaemia incidence (p = 0.061). Severe hypokalaemia (&lt;3.0 mmol/L) occurred in only 7 (1%) patients, similarly distributed between the two treatment arms (p = 0.676). Randomization towards acetazolamide improved decongestive response irrespective of baseline serum sodium and potassium levels.CONCLUSIONS: Acetazolamide on top of standardized loop diuretic therapy does not lead to clinically important hypokalaemia or hyponatraemia and improves decongestion over the entire range of baseline serum potassium and sodium levels.</p

Higher doses of loop diuretics limit uptitration of angiotensin converting enzyme inhibitors in patients with heart failure and reduced ejection fraction

Background: Loop diuretics are frequently prescribed to patients with heart failure and reduced ejection fraction (HFrEF) for the treatment of congestion; however, they might hamper uptitration of inhibitors of the renin–angiotensin system. Methods: Loop diuretic dose at baseline was recorded in 2338 patients with HFrEF enrolled in BIOSTAT-CHF, an international study of HF patients on loop diuretic therapy who were eligible for uptitration of angiotensin-converting enzyme inhibitors (ACEi)/mineralocorticoid receptor antagonists (MRA). The association between loop diuretic dose and uptitration of ACEi/MRA to percentage of target dose was adjusted for a previously published model for likelihood of uptitration and a propensity score. Results: Baseline median loop diuretic dose was 40 [40–100] mg of furosemide or equivalent. Higher doses of loop diuretics were associated with higher NYHA class and higher levels of NT-proBNP, more severe signs and symptoms of congestion, more frequent MRA use, and lower doses of ACEi reached at 3 and 9 months (all P < 0.01). After propensity adjustment, higher doses of loop diuretics remained significantly associated with poorer uptitration of ACEi (Beta per log doubling of loop diuretic dose: − 1.66, P = 0.021), but not with uptitration of MRAs (P = 0.758). Higher doses of loop diuretics were independently associated with an increased risk of all-cause mortality or HF hospitalization [HR per doubling of loop diuretic dose: 1.06 (1.01–1.12), P = 0.021]. Conclusions: Higher doses of loop diuretics limited uptitration of ACEi in patients with HFrEF and were associated with a higher risk of death and/or HF hospitalization, independent of their lower likelihood of uptitration and higher baseline risk. Graphic abstract: This figure was created with images adapted from Servier Medical Art licensed under a Creative Commons Attribution 3.0[Figure not available: see fulltext.]

Acetazolamide in Acute Decompensated Heart Failure with Volume Overload

BACKGROUND: Whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with acute decompensated heart failure with volume overload, is unclear.METHODS: In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro-B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter to receive either intravenous acetazolamide (500 mg once daily) or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose). Randomization was stratified according to the left ventricular ejection fraction (≤40% or &gt;40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy. Secondary end points included a composite of death from any cause or rehospitalization for heart failure during 3 months of follow-up. Safety was also assessed.RESULTS: A total of 519 patients underwent randomization. Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; P&lt;0.001). Death from any cause or rehospitalization for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and in 72 of 259 patients (27.8%) in the placebo group (hazard ratio, 1.07; 95% CI, 0.78 to 1.48). Acetazolamide treatment was associated with higher cumulative urine output and natriuresis, findings consistent with better diuretic efficiency. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups.CONCLUSIONS: The addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion. (Funded by the Belgian Health Care Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788.).</p