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Sodium and fluid restriction has traditionally been advocated in patients with heart failure (HF) due to their sodium and water avid state. However, most evidence regarding the altered sodium handling, fluid homeostasis and congestion‐related signs and symptoms in patients with HF originates from untreated patient cohorts and physiological investigations. Recent data challenge the beneficial role of dietary sodium and fluid restriction in HF. Consequently, the European Society of Cardiology HF guidelines have gradually downgraded these recommendations over time, now advising for the limitation of salt intake to no more than 5 g/day in patients with HF, while contemplating fluid restriction of 1.5–2 L/day only in selected patients. Therefore, the objective of this clinical consensus statement is to provide advice on fluid and sodium intake in patients with acute and chronic HF, based on contemporary evidence and expert opinion. [ABSTRACT FROM AUTHOR]

Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter‐defibrillators and long‐term mechanical support. For others, more evidence is still needed before large‐scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device‐provided therapy and also device‐guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care. [ABSTRACT FROM AUTHOR]

Thiazides on the other hand might be particularly useful as an add-on to boost loop diuretic efficacy when patients are chronically on higher doses of loop diuretics (distal nephron remodelling) and perhaps when there is a higher eGFR. Adding upfront acetazolamide can prevent the development of loop diuretic-induced metabolic alkalosis and the associated loop diuretic resistance and shorten length of stay.[14] If despite optimization of loop diuretics, true diuretic resistance is present (low diuretic response and residual congestion), a combinational diuretic approach should be considered. B This article refers to 'Combining loop and thiazide diuretics for acute heart failure across the estimated glomerular filtration rate spectrum: A post-hoc analysis of the CLOROTIC trial' by J.C. Trullàs I et al i ., published in this issue on pages 1784-1793. b Acute heart failure (AHF) remains one of the most frequent reasons for admissions in patients older than 65 years of age. [Extracted from the article]

Aims: To describe the baseline characteristics of participants in the Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial and compare these with other contemporary diuretic trials in acute heart failure (AHF).Methods and Results: ADVOR recruited 519 patients with AHF, clinically evident volume overload, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and maintenance loop diuretic therapy prior to admission. All participants received standardized loop diuretics and were randomized towards once daily intravenous acetazolamide (500 mg) versus placebo, stratified according to study centre and left ventricular ejection fraction (LVEF) (≤40% vs. >40%). The primary endpoint was successful decongestion assessed by a dedicated score indicating no more than trace oedema and no other signs of congestion after three consecutive days of treatment without need for escalating treatment. Mean age was 78 years, 63% were men, mean LVEF was 43%, and median NT-proBNP 6173 pg/ml. The median clinical congestion score was 4 with an EuroQol-5 dimensions health utility index of 0.6. Patients with LVEF ≤40% were more often male, had more ischaemic heart disease, higher levels of NT-proBNP and less atrial fibrillation. Compared with diuretic trials in AHF, patients enrolled in ADVOR were considerably older with higher NT-proBNP levels, reflecting the real-world clinical situation.Conclusion: ADVOR is the largest randomized diuretic trial in AHF, investigating acetazolamide to improve decongestion on top of standardized loop diuretics. The elderly enrolled population with poor quality of life provides a good representation of the real-world AHF population. The pragmatic design will provide novel insights in the diuretic treatment of patients with AHF. [ABSTRACT FROM AUTHOR]

Novel pharmacologic treatment options reduce mortality and morbidity in a cost‐effective manner in patients with heart failure (HF). Undisputedly, the effective implementation of these agents is an essential element of good clinical practice, which is endorsed by the European Society of Cardiology (ESC) guidelines on acute and chronic HF. Yet, physicians struggle to implement these therapies as they have to balance the true and/or perceived risks versus their substantial benefits in clinical practice. Any worsening of biomarkers of renal function is often perceived as being disadvantageous and is in clinical practice one of the most common reasons for ineffective drug implementation. However, even in this context, they clearly reduce mortality and morbidity in HF with reduced ejection fraction (HFrEF) patients, even in patients with poor renal function. Furthermore these agents are also beneficial in HF with mildly reduced ejection fraction (HFmrEF) and sodium–glucose cotransporter 2 (SGLT2) inhibitors more recently demonstrated a beneficial effect in HF with preserved ejection fraction (HFpEF). The emerge of several new classes (angiotensin receptor–neprilysin inhibitor [ARNI], SGLT2 inhibitors, vericiguat, omecamtiv mecarbil) and the recommendation by the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic HF of early initiation and titration of quadruple disease‐modifying therapies (ARNI/angiotensin‐converting enzyme inhibitor + beta‐blocker + mineralocorticoid receptor antagonist and SGLT2 inhibitor) in HFrEF increases the likelihood of treatment‐induced changes in renal function. This may be (incorrectly) perceived as deleterious, resulting in inertia of starting and uptitrating these lifesaving therapies. Therefore, the objective of this consensus document is to provide advice of the effect HF drugs on renal function. [ABSTRACT FROM AUTHOR]

Layer 2: Heart failure courses HFA exam The HFA exam is for professionals specializing in HF. Study material is the upcoming HFA Textbook of Heart Failure (Oxford University Press 2022), annual HFA congress, as well as the HFA guideline and consensus documents. Heart failure (HF) is a devastating chronic and disabling disease with a wide variety of pharmaceutical and device treatment options which are becoming increasingly complex to implement. HF specialists of tomorrow heart failure masterclass The HF specialists of tomorrow (HoT members) are the HF specialists in the early stages of their career (<40 years). [Extracted from the article]

The article focuses on the treatment of iron deficiency in heart failure patients, highlighting its prevalence in this population and its negative impact on functional status and cardiac function. It discusses previous trials involving intravenous iron supplementation and presents the results of the Ferric Carboxymaltose in Heart Failure With Iron Deficiency (HEART-FID) trial, which evaluated the efficacy of ferric carboxymaltose in heart failure patients with iron deficiency.

Background Objectives Methods Results Conclusions Severe first‐degree atrioventricular (AV) block may produce symptoms similar to heart failure due to AV dyssynchrony, a syndrome termed AV dromotropathy. According to guidelines, it should be considered for permanent pacemaker implantation, yet evidence supporting this treatment is scarce.This study aimed to determine the impact of AV‐optimized conduction system pacing (CSP) in patients with symptomatic severe first‐degree AV block and echocardiographic signs of AV dyssynchrony.Patients with symptomatic first‐degree AV block (PR > 250 ms), preserved left ventricular ejection fraction, narrow QRS, and AV dyssynchrony were included in the study. In a single‐blind cross‐over design, patients were randomized to AV sequential CSP or backup VVI pacing with a base rate of 40 bpm. We compared exercise capacity, echocardiographic parameters, and symptom occurrence at the end of 3 months of each period.Fourteen patients completed the study. During the AV‐optimized CSP compared to the backup pacing period, patients achieved a higher workload on exercise test (147.2 ± 50.9 vs. 140.7 ± 55.8 W; p = .032), with a trend towards higher peak VO2 (23.3 ± 7.1 vs. 22.8 ± 7.1 mL/min/kg; p = .224), and higher left ventricular stroke volume (LVSV 74.5 ± 13.8 vs. 66.4 ± 12.5 mL; p < .001). Symptomatic improvement was recorded, with fewer patients reporting general tiredness and 71% of patients preferring the AV‐optimized CSP (p = .008).AV‐optimized CSP could improve symptoms, exercise capacity and LVSV in patients with severe first‐degree AV block. [ABSTRACT FROM AUTHOR]

Importantly, SGLT2i act as a smart diuretic through incremental osmotic diuresis, thereby increasing plasma osmolality more compared to classical diuretic therapy, which should improve plasma refill rate considerably ( I Figure i 1). B This article refers to 'Effects of empagliflozin on renal sodium and glucose handling in patients with acute heart failure' by E.M. Boorsma I et al i ., published in this issue on pages 68-78. b The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) recommend sodium-glucose co-transporter 2 inhibitors (SGLT2i) to be used in type 2 diabetes mellitus patients with either established cardiovascular (CV) disease or at high CV risk in order to prevent or delay the onset of and hospitalizations for heart failure (HF).1 Based upon randomized prospective trials, dapagliflozin and empagliflozin are now also recommended in symptomatic patients with HF and reduced ejection fraction, on guideline-directed medical therapy, regardless of the presence of type 2 diabetes mellitus.2-4 At present, the mechanisms underlying the beneficial CV and renal effects of SGLT2i are not completely understood and several, not mutually exclusive, mechanisms have been proposed.1 In this issue of the Journal, Boorsma I et al i .5 describe the effects of empagliflozin on renal sodium and glucose handling in a pre-defined sub-analysis of the EMPA-RESPONSE-AHF trial. Indeed, the current study nicely corroborates previous findings as the direct increase in plasma osmolality induced by SGLT2i should further facilitate the effect of tissue water mobilization if they are provided on top of standard loop diuretic therapy. [Extracted from the article]

Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heart failure hospitalization rates and all-cause mortality. Nevertheless, up to two-thirds of eligible patients are not referred for CRT. Furthermore, post-implantation follow-up is often fragmented and suboptimal, hampering the potential maximal treatment effect. This joint position statement from three European Society of Cardiology Associations, Heart Failure Association (HFA), European Heart Rhythm Association (EHRA) and European Association of Cardiovascular Imaging (EACVI), focuses on optimized implementation of CRT. We offer theoretical and practical strategies to achieve more comprehensive CRT referral and post-procedural care by focusing on four actionable domains: (i) overcoming CRT under-utilization, (ii) better understanding of pre-implant characteristics, (iii) abandoning the term 'non-response' and replacing this by the concept of disease modification, and (iv) implementing a dedicated post-implant CRT care pathway. [ABSTRACT FROM AUTHOR]

Aims: Incorporation of remote monitoring of pulmonary artery pressure and vital signs has been demonstrated to reduce heart failure (HF) hospitalization and all-cause mortality in selected symptomatic HF patients. The aim of this study is to investigate the safety and accuracy of the new CordellaTM Pulmonary Artery Pressure Sensor (Endotronix, Inc., Chicago, IL, USA) and the usability of the comprehensive CordellaTM Heart Failure System (CHFS).Methods and Results: Multicentre, open-label, first-in-human, feasibility study to evaluate the CHFS and the safety and accuracy of the Cordella™ Pulmonary Artery Pressure Sensor in 15 patients with New York Heart Association class III HF. All patients were successfully implanted with the Cordella Pulmonary Artery Pressure Sensor, without sensor failure. No device system-related complications, defined as invasive treatment, device explant or death, occurred. The primary efficacy endpoint of a mean pulmonary artery pressure at 90 days was met in all but one patients with a cohort difference of 2.7 mmHg (Cordella Sensor 22.5 ± 11.8 mmHg, Swan-Ganz catheter 25.2 ± 8.5 mmHg). One patient did not go through the 90-day right heart catheterization for safety reasons. Patient adherence to daily measurement, transmission of vital signs and pulmonary artery pressure sensor readings were recorded 99% of the time.Conclusion: The initial experience of the CHFS incorporating comprehensive vital signs and pulmonary artery pressure monitoring enables safe and accurate monitoring of HF status. [ABSTRACT FROM AUTHOR]

Appropriate interpretation of changes in markers of kidney function is essential during the treatment of acute and chronic heart failure. Historically, kidney function was primarily assessed by serum creatinine and the calculation of estimated glomerular filtration rate. An increase in serum creatinine, also termed worsening renal function, commonly occurs in patients with heart failure, especially during acute heart failure episodes. Even though worsening renal function is associated with worse outcome on a population level, the interpretation of such changes within the appropriate clinical context helps to correctly assess risk and determine further treatment strategies. Additionally, it is becoming increasingly recognized that assessment of kidney function is more than just glomerular filtration rate alone. As such, a better evaluation of sodium and water handling by the renal tubules allows to determine the efficiency of loop diuretics (loop diuretic response and efficiency). Also, though neurohumoral blockers may induce modest deteriorations in glomerular filtration rate, their use is associated with improved long-term outcome. Therefore, a better understanding of the role of cardio-renal interactions in heart failure in symptom development, disease progression and prognosis is essential. Indeed, perhaps even misinterpretation of kidney function is a leading cause of not attaining decongestion in acute heart failure and insufficient dosing of guideline-directed medical therapy in general. This position paper of the Heart Failure Association Working Group on Cardio-Renal Dysfunction aims at improving insights into the interpretation of renal function assessment in the different heart failure states, with the goal of improving heart failure care. [ABSTRACT FROM AUTHOR]

Secondary mitral regurgitation (MR) is the result of intrinsic dysfunction of the failing left ventricle (LV) in the absence of organic mitral valve dysfunction. The authors prospectively included symptomatic patients with heart failure with a baseline LVEF between 25% and 50%, despite optimal medical therapy with an ACE-I/ARB and -blocker and significant secondary MR, defined as an effective regurgitant orifice area (EROA) >0.1 cm SP 2 sp . Perhaps it is important to recognize that LVEF is a less precise marker of LV function in the presence of severe MR, because the regurgitant volume diminishes the LV end-systolic volume, thereby increasing LVEF. [Extracted from the article]

The vast majority of acute heart failure episodes are characterized by increasing symptoms and signs of congestion with volume overload. The goal of therapy in those patients is the relief of congestion through achieving a state of euvolaemia, mainly through the use of diuretic therapy. The appropriate use of diuretics however remains challenging, especially when worsening renal function, diuretic resistance and electrolyte disturbances occur. This position paper focuses on the use of diuretics in heart failure with congestion. The manuscript addresses frequently encountered challenges, such as (i) evaluation of congestion and clinical euvolaemia, (ii) assessment of diuretic response/resistance in the treatment of acute heart failure, (iii) an approach towards stepped pharmacologic diuretic strategies, based upon diuretic response, and (iv) management of common electrolyte disturbances. Recommendations are made in line with available guidelines, evidence and expert opinion. [ABSTRACT FROM AUTHOR]

Aims: Decisive evidence on the optimal diuretic agent, dosing schedule, and administration route is lacking in acute heart failure (AHF) with congestion. The Acetazolamide in Decompensated heart failure with Volume OveRload (ADVOR) trial is designed to test the hypothesis that the carbonic anhydrase inhibitor acetazolamide, a potent inhibitor of proximal tubular sodium reabsorption, improves decongestion when combined with loop diuretic therapy in AHF, potentially leading to better clinical outcomes.Methods: The ADVOR trial is set up as a multicentre, randomized, double-blind, placebo-controlled study, aiming to recruit 519 patients with AHF and clinically evident volume overload. All study participants receive high-dose intravenous loop diuretics as background therapy and are randomized towards intravenous acetazolamide at a dose of 500 mg once daily vs. placebo, stratified according to including study centre and ejection fraction (< 40% vs. ≥ 40%). The primary endpoint is successful decongestion with no more than trace oedema assessed on the third morning after hospital admission, with good diuretic efficacy defined as a urine output > 3.5 L during the first 30-48 h of decongestive treatment. Secondary endpoints include all-cause mortality or heart failure readmission after 3 months, length of hospital stay for the index admission, and longitudinal changes in the EuroQol-5 dimensions questionnaire.Conclusion: ADVOR will investigate if acetazolamide combined with loop diuretic therapy improves decongestion in AHF with volume overload. [ABSTRACT FROM AUTHOR]

Abdominal congestion may play an important role in the cardiorenal syndrome and has been demonstrated to drive disease progression. An animal model for abdominal congestion, without other culprit mechanisms that are often present in patients such as low cardiac output or chronic kidney disease, might be interesting to allow a better study of the pathophysiology of the cardiorenal syndrome. The objective of this study was to develop a clinically relevant and valid rat model with abdominal venous congestion and without pre-existing heart and/or kidney dysfunction. To do so, a permanent surgical constriction (20 Gauge) of the thoracic inferior vena cava (IVC) was applied in male Sprague Dawley rats (IVCc, n = 7), which were compared to sham-operated rats (SHAM, n = 6). Twelve weeks after surgery, abdominal venous pressure (mean: 13.8 vs 4.9 mmHg, p < 0.01), plasma creatinine (p < 0.05), plasma cystatin c (p < 0.01), urinary albumin (p < 0.05), glomerular surface area (p < 0.01) and width of Bowman’s space (p < 0.05) of the IVCc group were significantly increased compared to the SHAM group for a comparable absolute body weight between groups (559 vs 530g, respectively, p = 0.73). Conventional cardiac echocardiographic and hemodynamic parameters did not differ significantly between both groups, indicating that cardiac function was not compromised by the surgery. In conclusion, we demonstrate that constriction of the thoracic IVC in adult rats is feasible and significantly increases the abdominal venous pressure to a clinically relevant level, thereby inducing abdominal venous congestion. [ABSTRACT FROM AUTHOR]

Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field. [ABSTRACT FROM AUTHOR]

Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field. [ABSTRACT FROM AUTHOR]

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 0.44W/m2 (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 (<0.44W/m2) was associated with increased adverse outcomes [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.8-3.1, P <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. [ABSTRACT FROM AUTHOR]

These issues underscore the importance of randomized clinical trials with parallel group allocation, and blinded analysis of patient-orientated clinical outcomes including in pre-specified subgroups focusing on patients lying outside the current guidelines. We are delighted to be given the opportunity to respond to the letter by Puvrez I et al i . and clarify the current role of imaging in the selection of patients for cardiac resynchronization therapy (CRT). [Extracted from the article]

Aims: In symptomatic patients with heart failure and reduced ejection fraction (HFrEF), recent international guidelines recommend initiating four major therapeutic classes rather than sequential initiation. It remains unclear how this change in guidelines is perceived by practicing cardiologists versus heart failure (HF) specialists. Methods and results: An independent academic web‐based survey was designed by a group of HF specialists and posted by email and through various social networks to a broad community of cardiologists worldwide 1 year after the publication of the latest European HF guidelines. Overall, 615 cardiologists (38 [32–47] years old, 63% male) completed the survey, of which 58% were working in a university hospital and 26% were HF specialists. The threshold to define HFrEF was ≤40% for 61% of the physicians. Preferred drug prescription for the sequential approach was angiotensin‐converting enzyme inhibitors or angiotensin receptor–neprilysin inhibitors first (74%), beta‐blockers second (55%), mineralocorticoid receptor antagonists third (52%), and sodium–glucose cotransporter 2 inhibitors (53%) fourth. Eighty‐four percent of participants felt that starting all four classes was feasible within the initial hospitalization, and 58% felt that titration is less important than introducing a new class. Age, status in training, and specialization in HF field were the principal characteristics that significantly impacted the answers. Conclusion: In a broad international cardiology community, the 'historical approach' to HFrEF therapies remains the preferred sequencing approach. However, accelerated introduction and uptitration are also major treatment goals. Strategy trials in treatment guidance are needed to further change practices. [ABSTRACT FROM AUTHOR]

Aims ‘Worsening renal function’ (WRF) and ‘improvement in renal function’ (IRF) monitored by changes in serum creatinine are frequently encountered during treatment of acute decompensated heart failure (ADHF). We sought to establish the important haemodynamic determinants of alterations in serum creatinine. Methods and results We reviewed data from 443 patients treated for ADHF with haemodynamic guidance in a single centre. WRF and IRF were defined as a 25% increase or decrease in estimated glomerular filtration rate (eGFR) from time of admission to pulmonary artery catheter removal, respectively. Of the 443 patients, 46 (10%) experienced WRF and 127 (29%) had IRF. Baseline eGFR was lower in patients with IRF when compared with stable patients or those with WRF (45 ± 25 vs. 63 ± 30 vs. 68 ± 27 mL/min/m2, respectively, P < 0.0001). In contrast, the relative decrease in mean blood pressure (BP) was more pronounced in patients with WRF when compared with stable patients or those with IRF (15 ± 15 vs. 9 ± 17 vs. 4 ± 15%, respectively, P = 0.003). With larger decreases in mean BP, there was greater likelihood of experiencing WRF (P = 0.04) but less likelihood of experiencing IRF (P = 0.01). In contrast, the degree of changes in right atrial pressure or cardiac index did not affect the propensity for developing WRF or IRF. There was no difference in adverse clinical outcomes (death, heart transplantation, LV assist device implantation, or readmission) between the three groups (P = 0.56). Conclusion Blood pressure decrease, rather than alterations in cardiac output or central venous pressure, were associated with changes in serum creatinine during treatment of ADHF. [ABSTRACT FROM AUTHOR]

Despite improvement in morbidity and mortality with cardiac resynchronization therapy (CRT), disease progression continues to affect a subset of patients and there is limited effort to identify contributing factors. Our objective was to investigate if a protocol-driven approach incorporated in a management strategy of heart failure immediately after implantation would provide incremental benefits beyond usual care after implantation. We reviewed 114 consecutive patients with CRT implanted from 2005 through 2009 who received usual care after implantation or underwent protocol-driven CRT care after implantation. Preimplantation characteristics in patients receiving usual versus protocol-driven care were similar in left ventricular (LV) dimension (LV internal diastolic diameter 6.2 ± 0.8 vs 6.4 ± 1.0 cm), LV ejection fraction (26 ± 8% vs 25% ± 8%), QRS width, and medication usage. Major adjustments during the protocol-driven approach were uptitration of neurohormonal blockers (64%), echocardiographically guided atrioventricular optimization (50%), heart failure education (42%), arrhythmia management (19%), and LV lead repositioning (7%). Although positive LV remodeling was noted in the 2 groups at 6 months, extent was significantly greater in the protocol-driven approach compared to usual care (change in LV internal diastolic diameter 0.7 ± 0.6 cm vs 0.2 ± 1.2 cm, p = 0.01; change in LV ejection fraction 11 ± 7% vs 7 ± 9%, p = 0.01), which was associated with fewer major adverse events (14% vs 53%, p <0.001). In conclusion, a protocol-driven approach for patients with CRT started immediately after implantation is associated with incremental favorable effects on reverse remodeling and fewer adverse events compared to usual care after implantation. These effects appeared to be driven not only by changes in device settings and arrhythmia management but also by concomitant medication optimization and heart failure education. [ABSTRACT FROM AUTHOR]

Worsening renal function during treatment of acute decompensated heart failure (ADHF) often complicates the treatment course of heart failure. Furthermore, the development of worsening renal function is a strong independent predictor of long-term adverse outcomes. Sometimes referred to as 'cardiorenal syndrome, 'the definition varies widely, and the overall understanding of pathogenesis is limited. This is probably owing to the lack of precision and characterisation of renal compromise during treatment of heart failure. Traditionally, the predominant cause has been attributed to impairment of cardiac output and relative underfilling of arterial perfusion. Emerging data have led to a resurgence of interest in the importance of venous congestion and elevated intra-abdominal pressure rather than confining it to impaired forward cardiac output as the primary driver of renal impairment. These revived concepts may support the role of novel renal-sparing approaches to salt and water removal and renal preservation, but better ways to distinguish haemodynamic versus other nephrotoxic aetiologies are needed. [ABSTRACT FROM AUTHOR]

Data supporting the use of oral isosorbide dinitrate and/or hydralazine (I/H) as add-on therapy to standard neurohormonal antagonists in advanced decompensated heart failure (ADHF) are limited, especially in the non–African-American population. Our objective was to determine if addition of I/H to standard neurohormonal blockade in patients discharged from the hospital with ADHF is associated with improved hemodynamic profiles and improved clinical outcomes. We reviewed consecutive patients with ADHF admitted from 2003 to 2006 with a cardiac index ≤2.2 L/min/m2 admitted for intensive medical therapy. Patients discharged with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers (control group) were compared with those receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers plus I/H (I/H group). The control (n = 97) and I/H (n = 142) groups had similar demographic characteristics, baseline blood pressure, and renal function. Patients in the I/H group had a significantly higher estimated systemic vascular resistance (1,660 vs 1,452 dynes/cm5, p <0.001) and a lower cardiac index (1.7 vs 1.9 L/min/m2, p <0.001) on admission. The I/H group achieved a similar decrease in intracardiac filling pressures and discharge blood pressures as controls, but had greater improvement in cardiac index and systemic vascular resistance. Use of I/H was associated with a lower rate of all-cause mortality (34% vs 41%, odds ratio 0.65, 95% confidence interval 0.43 to 0.99, p = 0.04) and all-cause mortality/heart failure rehospitalization (70% vs 85%, odds ratio 0.72, 95% confidence interval 0.54 to 0.97, p = 0.03), irrespective of race. In conclusion, the addition of I/H to neurohormonal blockade is associated with a more favorable hemodynamic profile and long-term clinical outcomes in patients discharged with low-output ADHF regardless of race. [Copyright &y& Elsevier]

Objectives: Our aim was to determine the feasibility and value of a protocol-driven approach to patients with cardiac resynchronization therapy (CRT) who did not exhibit a positive response long after implant. Background: Up to one-third of patients with advanced heart failure do not exhibit a positive response to CRT. Methods: A total of 75 consecutive ambulatory patients with persistent advanced heart failure symptoms and/or adverse reverse remodeling and CRT implanted >6 months underwent a comprehensive protocol-driven evaluation to determine the potential reasons for a suboptimal response. Recommendations were made to maximize the potential of CRT, and adverse events were documented. Results: All patients (mean left ventricular [LV] ejection fraction 23 ± 9%, LV end-diastolic volume 275 ± 127 ml) underwent evaluation. Eighty-eight percent of patients had significantly better echocardiographic indexes of LV filling and LV ejection with optimal setting of their CRT compared with a temporary VVI back-up setting. Most patients had identifiable reasons for suboptimal response, including inadequate device settings (47%), suboptimal medical treatment (32%), arrhythmias (32%), inappropriate lead position (21%), or lack of baseline dyssynchrony (9%). Multidisciplinary recommendations led to changes in device settings and/or other therapy modifications in 74% of patients and were associated with fewer adverse events (13% vs. 50%, odds ratio: 0.2 [95% confidence interval: 0.07 to 0.56], p = 0.002) compared with those in which no recommendation could be made. Conclusions: Routine protocol-driven approach to evaluate ambulatory CRT patients who did not exhibit a positive response is feasible, and changes in device settings and/or other therapies after multidisciplinary evaluation may be associated with fewer adverse events. [Copyright &y& Elsevier]

Objectives: Our aim was to determine the potential hemodynamic contributions of cardiac resynchronization therapy (CRT) in patients admitted for advanced decompensated heart failure. Background: CRT restores synchrony of the heart resulting in hemodynamic support that can facilitate the reversal of left ventricular (LV) remodeling in some patients. Methods: A total of 40 consecutive patients with advanced decompensated heart failure and CRT implanted >3 months, admitted due to hemodynamic derangements, underwent simultaneous comprehensive echocardiographic and invasive hemodynamic evaluation under different CRT settings. Results: All patients (mean LV ejection fraction 22 ± 7%, LV end-diastolic volume 323 ± 140 ml, 40% ischemic) had experienced progressive cardiac remodeling despite adequate LV lead positions and continuous biventricular pacing. A significant worsening of hemodynamics was observed immediately when CRT was programmed OFF in the majority (88%) of patients (systolic blood pressure: 105 ± 12 mm Hg to 98 ± 13 mm Hg; pulmonary capillary wedge pressure: 17 ± 6 mm Hg to 21 ± 7 mm Hg; cardiac output: 4.6 ± 1.4 l/min·m2 to 4.0 ± 1.1 l/min·m2; all p < 0.001). Worsening of hemodynamics coincided with reappearance of significant electrical (QRS width 161 ± 29 ms to 202 ± 39 ms, p < 0.001) and intraventricular mechanical dyssynchrony (15 ± 26 ms to 57 ± 41 ms, p < 0.001), together with a significant reduction in diastolic filling time (377 ± 138 ms to 300 ± 118 ms, p < 0.001). Conclusions: Despite progressive cardiac remodeling and decompensation, chronic CRT continues to provide hemodynamic augmentation in the failing heart in most patients. Our data suggest that disease progression may not be explained by diminished beneficial hemodynamic contributions of successful resynchronization. [Copyright &y& Elsevier]

Objectives: To determine whether venous congestion, rather than impairment of cardiac output, is primarily associated with the development of worsening renal function (WRF) in patients with advanced decompensated heart failure (ADHF). Background: Reduced cardiac output is traditionally believed to be the main determinant of WRF in patients with ADHF. Methods: A total of 145 consecutive patients admitted with ADHF treated with intensive medical therapy guided by pulmonary artery catheter were studied. We defined WRF as an increase of serum creatinine ≥0.3 mg/dl during hospitalization. Results: In the study cohort (age 57 ± 14 years, cardiac index 1.9 ± 0.6 l/min/m2, left ventricular ejection fraction 20 ± 8%, serum creatinine 1.7 ± 0.9 mg/dl), 58 patients (40%) developed WRF. Patients who developed WRF had a greater central venous pressure (CVP) on admission (18 ± 7 mm Hg vs. 12 ± 6 mm Hg, p < 0.001) and after intensive medical therapy (11 ± 8 mm Hg vs. 8 ± 5 mm Hg, p = 0.04). The development of WRF occurred less frequently in patients who achieved a CVP <8 mm Hg (p = 0.01). Furthermore, the ability of CVP to stratify risk for development of WRF was apparent across the spectrum of systemic blood pressure, pulmonary capillary wedge pressure, cardiac index, and estimated glomerular filtration rates. Conclusions: Venous congestion is the most important hemodynamic factor driving WRF in decompensated patients with advanced heart failure. [Copyright &y& Elsevier]

Broad population studies of patients with stable ambulatory heart failure have associated female gender with better age-adjusted survival. This study investigated whether there are gender-specific differences in clinical presentation, response to intensive medical therapy, and outcomes in patients admitted with advanced (cardiac index <2.4 L/min/m2) decompensated heart failure (ADHF). We reviewed 278 consecutive patients (age 54 ± 12 years, cardiac index 1.7 ± 0.4 L/kg/m2, pulmonary capillary wedge pressure 26 ± 9 mm Hg, serum creatinine 1.4 ± 0.8 mg/dl) with ADHF treated with intensive medical therapy guided by pulmonary artery catheter in a dedicated heart failure intensive care unit from 2000 to 2006. Compared with men (n = 226), women (n = 52) had similar baseline characteristics with the exception of a higher prevalence of nonischemic cause. No differences in medical therapy on admission, during intensive medical therapy, or at discharge were observed. Intensive medical therapy was associated with significant hemodynamic improvement independent of gender. All-cause mortality and heart failure rehospitalization rates were similar between genders. However, adjusted for cause, women with ischemic cardiomyopathy had higher all-cause mortality rates (50% vs 37%, hazard ratio 1.95, 95% confidence interval 0.98 to 3.90, p = 0.05) and those with nonischemic cardiomyopathy had lower all-cause mortality rates (19% vs 40%, hazard ratio 0.40, 95% confidence interval 0.17 to 0.96, p = 0.01) than men. In conclusion, women presenting with ADHF had baseline characteristics and response to therapy similar to men. Overall outcomes were similar between men and women, although subgroup analysis suggested better survival for women with a nonischemic cause. [Copyright &y& Elsevier]

Objectives: This study was designed to examine the safety and efficacy of sodium nitroprusside (SNP) for patients with acute decompensated heart failure (ADHF) and low-output states. Background: Inotropic therapy has been predominantly used in the management of patients with ADHF presenting with low cardiac output. Methods: We reviewed all consecutive patients with ADHF admitted between 2000 and 2005 with a cardiac index ≤2 l/min/m2 for intensive medical therapy including vasoactive drugs. Administration of SNP was chosen by the attending clinician, nonrandomized, and titrated to a target mean arterial pressure of 65 to 70 mm Hg. Results: Compared with control patients (n = 97), cases treated with SNP (n = 78) had significantly higher mean central venous pressure (15 vs. 13 mm Hg; p = 0.001), pulmonary capillary wedge pressure (29 vs. 24 mm Hg; p = 0.001), but similar demographics, medications, and renal function at baseline. Use of SNP was not associated with higher rates of inotropic support or worsening renal function during hospitalization. Patients treated with SNP achieved greater improvement in hemodynamic measurements during hospitalization, had higher rates of oral vasodilator prescription at discharge, and had lower rates of all-cause mortality (29% vs. 44%; odds ratio: 0.48; p = 0.005; 95% confidence interval: 0.29 to 0.80) without increase in rehospitalization rates (58% vs. 56%; p = NS). Conclusions: In patients with advanced, low-output heart failure, vasodilator therapy used in conjunction with optimal current medical therapy during hospitalization might be associated with favorable long-term clinical outcomes irrespective of inotropic support or renal dysfunction and remains an excellent therapeutic choice in hospitalized ADHF patients. [Copyright &y& Elsevier]

Previous heart failure (HF) risk models have included clinical and noninvasive variables and have been derived largely from clinical trial databases or decompensated HF registries. The importance of hemodynamic assessment is less established, particularly in ambulatory patients with advanced HF. In this study, 513 consecutive ambulatory patients (mean age 54 ± 11 years, mean left ventricular ejection fraction 20 ± 9%) with symptomatic HF who underwent diagnostic right-sided cardiac catheterization as part of outpatient assessment from 2000 to 2005 were reviewed. After a total of 1,696 patient-years of follow-up, 139 (27%) patients had died and 116 (23%) had undergone cardiac transplantation. The 1- and 2-year overall survival rates (defined as freedom from death or cardiac transplantation) were 77% and 67%, respectively. Overall, 65% of patients had elevated intracardiac filling pressures, and 40% had cardiac indexes <2.2 L/min/m2. In multivariate analysis, mean pulmonary arterial pressure, cardiac index, and the severity of mitral regurgitation were the 3 strongest predictors of all-cause mortality and cardiac transplantation. Renal dysfunction was also an independent predictor of all-cause mortality. When a clinical model for Cox multivariate analysis of all-cause mortality was compared with a model that also included cardiac index and mean pulmonary arterial pressure, the chi-square score increased from 45 to 69 (p <0.0001). In conclusion, in ambulatory patients with advanced HF, hemodynamic and renal function assessments remain strong independent predictors of all-cause mortality. [Copyright &y& Elsevier]

Objectives: This study sought to determine whether changes in intra-abdominal pressure (IAP) with aggressive diuretic or vasodilator therapy are associated with improvement in renal function in acute decompensated heart failure (ADHF). Background: Elevated IAP (≥8 mm Hg) is associated with intra-abdominal organ dysfunction. There is potential for ascites and visceral edema causing elevated IAP in patients with ADHF. Methods: Forty consecutive patients admitted to a specialized heart failure intensive care unit for management of ADHF with intensive medical therapy were studied. The IAP was measured using a simple transvesical technique at time of admission and before removal of the pulmonary artery catheter. Results: In our study cohort (mean age 59 ± 13 years, mean left ventricular ejection fraction 19 ± 9%, baseline serum creatinine 2.0 ± 0.9 mg/dl), the mean baseline IAP was 8 ± 4 mm Hg, with 24 (60%) patients having elevated IAP. Elevated IAP was associated with worse renal function (p = 0.009). Intensive medical therapy resulted in improvement in both hemodynamic measurements and IAP. A strong correlation (r = 0.77, p < 0.001) was observed between reduction in IAP and improved renal function in patients with baseline elevated IAP. However, changes in IAP or renal function did not correlate with changes in any hemodynamic variable. Conclusions: Elevated IAP is prevalent in patients with ADHF and is associated with impaired renal function. In the setting of intensive medical therapy for ADHF, changes in IAP were better correlated with changes in renal function than any hemodynamic variable. [Copyright &y& Elsevier]

Objectives: We studied whether functional improvement after cardiac resynchronization therapy (CRT) is associated with reversal of the heart failure (HF) gene program. Background: Cardiac resynchronization therapy improves exercise tolerance and survival in patients with advanced congestive HF and dyssynchrony. Methods: Twenty-four patients referred for CRT underwent left ventricular (LV) endomyocardial biopsies immediately before CRT implantation (baseline). In addition, 17 of them underwent LV endomyocardial biopsy procurement 4 months later (follow-up). In 6 control patients with normal LV function, LV biopsies were obtained at the time of coronary artery bypass grafting. The LV messenger ribonucleic acid (mRNA) levels of contractile and calcium regulatory genes were measured by quantitative real time polymerase chain reaction and normalized for glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The HF patients showing an improvement in New York Heart Association (NYHA) functional class by >1 score and a relative increase in LV ejection fraction ≥25% at 4 months after CRT were considered as responders. Results: The HF patients were characterized by lower LV mRNA levels of α-myosin heavy chain (α-MHC), β-myosin heavy chain (β-MHC), sarcoplasmic reticulum calcium ATPase 2α (SERCA), phospholamban (PLN), and higher brain natriuretic peptide (BNP) mRNA levels as compared with control subjects. Responders to CRT (n = 11) showed an increase in LVEF (p < 0.001), a decrease in left ventricular end-diastolic diameter (p = 0.003), and NYHA functional class (p = 0.002), and a reduction in N-terminal proBNP levels (p = 0.032) as compared with baseline. This was associated with an increase in mRNA levels of α-MHC (p = 0.035), SERCA (p = 0.032), a decrease in BNP mRNA levels (p = 0.002), and an increase in the ratio of α-/β-MHC (p = 0.018) and SERCA/PLN (p = 0.012). No significant changes in molecular profile were observed in nonresponders. Conclusions: In HF patients with electromechanical cardiac dyssynchrony, functional improvement related to CRT is associated with favorable changes in established molecular markers of HF, including genes that regulate contractile function and pathologic hypertrophy. [Copyright &y& Elsevier]

Mitral regurgitation (MR) is highly prevalent among patients with heart failure and preserved ejection fraction (HFpEF). Despite this combination being closely associated with unfavourable outcomes, it remains relatively understudied. This is partly due to the inherent heterogeneity of patients with HFpEF. To address this gap, dissecting HFpEF into mechanism‐based phenotypes may offer a promising avenue for advancing our comprehension of these complex intertwined conditions. This review employs the validated CircAdapt model to explore the haemodynamic implications of moderate to severe MR across a well‐defined spectrum of myocardial disease, characterized by impaired relaxation and reduced myocardial compliance. Both heart failure and mitral valve disease share overlapping symptomatology, primarily attributed to elevated pulmonary pressures. The intricate mechanisms contributing to these elevated pressures are multifaceted, potentially influenced by diastolic dysfunction, left atrial myopathy, and MR. Accurate evaluation of the haemodynamic and clinical impact of MR necessitates a comprehensive approach, taking into account the characteristics of both the left atrium and left ventricle, as well as their intricate interactions, which may currently be underemphasized in diagnostic practice. This holistic assessment is imperative for enhancing our understanding and refining therapeutic strategies within this patient cohort. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) has evolved into an established therapy for patients with chronic heart failure and a wide QRS complex. Data on long-term outcomes over time are scarce and the criteria for implantation remain a subject of investigation. Methods: An international, multicenter, retrospective registry includes 2275 patients who received CRT between 30 November 2000 and 31 December 2019, with a mean follow-up of 3.6 ± 2.7 years. Four time periods were defined, based on landmark trials and guidelines. The combined endpoint was a composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Results: The composite endpoint occurred in 656 patients (29.2%). The mean annual implantation rate tripled from 31.5 ± 17.4/year in the first period to 107.4 ± 62.4/year in the last period. In the adjusted Cox regression analysis, the hazard ratio for the composite endpoint was not statistically different between time periods. When compared to sinus rhythm with left bundle branch block (LBBB), a non-LBBB conduction pattern (sinus rhythm: HR 1.51, 95% CI 1.12–2.03; atrial fibrillation: HR 2.08, 95% CI 1.30–3.33) and a QRS duration below 130 ms (HR 1.64, 95% CI 1.29–2.09) were associated with a higher hazard ratio. Conclusions: Despite innovations, an adjusted regression analysis revealed stable overall survival over time, which can at least partially be explained by a shift in patient characteristics. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Methods and results Conclusion Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all‐cause mortality or hospitalization. Clinicians have traditionally favoured torsemide in the setting of kidney dysfunction due to better oral bioavailability and longer half‐life, but direct supportive evidence is lacking.The TRANSFORM‐HF trial randomized patients hospitalized for HF to a long‐term strategy of torsemide versus furosemide, and enrolled patients across the spectrum of renal function (without dialysis). In this post‐hoc analysis, baseline renal function during the index hospitalization was assessed as categories of estimated glomerular filtration rate (eGFR; <30, 30–<60, ≥60 ml/min/1.73 m2). The interaction between baseline renal function and treatment effect of torsemide versus furosemide was assessed with respect to mortality and hospitalization outcomes, and the change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ‐CSS). Of 2859 patients randomized, 336 (11.8%) had eGFR <30 ml/min/1.73 m2, 1138 (39.8%) had eGFR 30–<60 ml/min/1.73 m2, and 1385 (48.4%) had eGFR ≥60 ml/min/1.73 m2. Baseline eGFR did not modify treatment effects of torsemide versus furosemide on all adverse clinical outcomes including individual components or composites of all‐cause mortality and all‐cause (re)‐hospitalizations, both when assessing eGFR categorically or continuously (p‐value for interaction all >0.108). Similarly, no treatment effect modification by eGFR was found for the change in KCCQ‐CSS (p‐value for interaction all >0.052) when assessing eGFR categorically or continuously.Among patients discharged after hospitalization for HF, there was no significant difference in clinical and patient‐reported outcomes between torsemide and furosemide, irrespective of renal function. [ABSTRACT FROM AUTHOR]

Aims: Sodium restriction was not associated with improved outcomes in heart failure patients in recent trials. The skin might act as a sodium buffer, potentially explaining tolerance to fluctuations in sodium intake without volume overload, but this is insufficiently understood. Therefore, we studied the handling of an increased sodium load in patients with heart failure with reduced ejection fraction (HFrEF). Methods and results: Twenty‐one ambulatory, stable HFrEF patients and 10 healthy controls underwent a 2‐week run‐in phase, followed by a 4‐week period of daily 1.2 g (51 mmol) sodium intake increment. Clinical, echocardiographic, 24‐h urine collection, and bioelectrical impedance data were collected every 2 weeks. Blood volume, skin sodium content, and skin glycosaminoglycan content were assessed before and after sodium loading. Sodium loading did not significantly affect weight, blood pressure, congestion score, N‐terminal pro‐brain natriuretic peptide, echocardiographic indices of congestion, or total body water in HFrEF (all p > 0.09). There was no change in total blood volume (4748 ml vs. 4885 ml; p = 0.327). Natriuresis increased from 150 mmol/24 h to 173 mmol/24 h (p = 0.024), while plasma renin decreased from 286 to 88 μU/L (p = 0.002). There were no significant changes in skin sodium content, total glycosaminoglycan content, or sulfated glycosaminoglycan content (all p > 0.265). Healthy controls had no change in volume status, but a higher increase in natriuresis without any change in renin. Conclusions: Selected HFrEF patients can tolerate sodium loading, with increased renal sodium excretion and decreased neurohormonal activation. [ABSTRACT FROM AUTHOR]

Aim: Cardiac resynchronization therapy (CRT) is a cornerstone in the management of chronic heart failure in patients with a broad or paced QRS. However, data on long‐term outcome after upgrade to CRT are scarce. Methods and results: This international, multicentre retrospective registry included 2275 patients who underwent a de novo or upgrade CRT implantation with a mean follow‐up of 3.6 ± 2.7 years. The primary composite endpoint included all‐cause mortality, heart transplantation, or ventricular assist device implantation. The secondary endpoint was first heart failure admission. Multivariable Cox regression and propensity score matching (PSM) analyses were performed. Patients who underwent CRT upgrade (n = 605, 26.6%) were less likely female (19.7% vs. 28.8%, p < 0.001), more often had ischeemic cardiomyopathy (49.8% vs. 40.2%, p < 0.001), and had worse renal function (median estimated glomerular filtration rate 50.3 ml/min/1.73 m2 [35.8–69.5] vs. 59.9 ml/min/1.73 m2 [43.0–76.5], p < 0.001). The incidence rate of the composite endpoint was 10.8%/year after CRT upgrade versus 7.1%/year for de novo implantations (p < 0.001). PSM for the primary endpoint resulted in 488 pairs. After propensity score matching, upgrade to CRT was associated with a higher chance to reach the composite endpoint (multivariable hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.08–1.70), for both upgrade from pacemaker (multivariable HR 1.33, 95% CI 1.03–1.70) and implantable cardioverter‐defibrillator (ICD) (multivariable HR 1.40, 95% CI 1.01–1.95). PSM for the secondary endpoint resulted in 277 pairs. After PSM, upgrade to CRT was associated with a higher chance for heart failure admission (HR 1.74, 95% CI 1.26–2.41). Conclusion: In this retrospective analysis, the outcome of patients who underwent upgrades to CRT differed significantly from patients who underwent de novo CRT implantation, particularly for upgrades from ICD. Importantly, this difference in outcome does not imply a causal relation between therapy and outcome but rather a difference between two different patient populations. [ABSTRACT FROM AUTHOR]

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 sham-operated (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. [ABSTRACT FROM AUTHOR]

Cardiomyopathies are a significant contributor to cardiovascular morbidity and mortality, mainly due to the development of heart failure and increased risk of sudden cardiac death (SCD). Despite improvement in survival with contemporary treatment, SCD remains an important cause of mortality in cardiomyopathies. It occurs at a rate ranging between 0.15% and 0.7% per year (depending on the cardiomyopathy), which significantly surpasses SCD incidence in the age‐ and sex‐matched general population. The risk of SCD is affected by multiple factors including the aetiology, genetic basis, age, sex, physical exertion, the extent of myocardial disease severity, conduction system abnormalities, and electrical instability, as measured by various metrics. Over the past decades, the knowledge on the mechanisms and risk factors for SCD has substantially improved, allowing for a better‐informed risk stratification. However, unresolved issues still challenge the guidance of SCD prevention in patients with cardiomyopathies. In this review, we aim to provide an in‐depth discussion of the contemporary concepts pertinent to understanding the burden, risk assessment and prevention of SCD in cardiomyopathies (dilated, non‐dilated left ventricular, hypertrophic, arrhythmogenic right ventricular, and restrictive). The review first focuses on SCD incidence in cardiomyopathies and then summarizes established and emerging risk factors for life‐threatening arrhythmias/SCD. Finally, it discusses validated approaches to the risk assessment and evidence‐based measures for SCD prevention in cardiomyopathies, pointing to the gaps in evidence and areas of uncertainties that merit future clarification. [ABSTRACT FROM AUTHOR]