Sodium-glucose linked transporter type 2 (SGLT-2) inhibition has been shown to reduce cardiovascular mortality in heart failure independently of glycemic control and prevents the onset of atrial ...arrhythmias, a common co-morbidity in heart failure with preserved ejection fraction (HFpEF). The mechanism behind these effects is not fully understood, and it remains unclear if they could be further enhanced by additional SGLT-1 inhibition. We investigated the effects of chronic treatment with the dual SGLT-1&2 inhibitor sotagliflozin on left atrial (LA) remodeling and cellular arrhythmogenesis (i.e. atrial cardiomyopathy) in a metabolic syndrome-related rat model of HFpEF.
17 week-old ZSF-1 obese rats, a metabolic syndrome-related model of HFpEF, and wild type rats (Wistar Kyoto), were fed 30 mg/kg/d sotagliflozin for 6 weeks. At 23 weeks, LA were imaged in-vivo by echocardiography. In-vitro, Ca
transients (CaT; electrically stimulated, caffeine-induced) and spontaneous Ca
release were recorded by ratiometric microscopy using Ca
-sensitive fluorescent dyes (Fura-2) during various experimental protocols. Mitochondrial structure (dye: Mitotracker), Ca
buffer capacity (dye: Rhod-2), mitochondrial depolarization (dye: TMRE) and production of reactive oxygen species (dye: H2DCF) were visualized by confocal microscopy. Statistical analysis was performed with 2-way analysis of variance followed by post-hoc Bonferroni and student's t-test, as applicable.
Sotagliflozin ameliorated LA enlargement in HFpEF in-vivo. In-vitro, LA cardiomyocytes in HFpEF showed an increased incidence and amplitude of arrhythmic spontaneous Ca
release events (SCaEs). Sotagliflozin significantly reduced the magnitude of SCaEs, while their frequency was unaffected. Sotagliflozin lowered diastolic Ca
of CaT at baseline and in response to glucose influx, possibly related to a ~ 50% increase of sodium sodium-calcium exchanger (NCX) forward-mode activity. Sotagliflozin prevented mitochondrial swelling and enhanced mitochondrial Ca
buffer capacity in HFpEF. Sotagliflozin improved mitochondrial fission and reactive oxygen species (ROS) production during glucose starvation and averted Ca
accumulation upon glycolytic inhibition.
The SGLT-1&2 inhibitor sotagliflozin ameliorated LA remodeling in metabolic HFpEF. It also improved distinct features of Ca
-mediated cellular arrhythmogenesis in-vitro (i.e. magnitude of SCaEs, mitochondrial Ca
buffer capacity, diastolic Ca
accumulation, NCX activity). The safety and efficacy of combined SGLT-1&2 inhibition for the treatment and/or prevention of atrial cardiomyopathy associated arrhythmias should be further evaluated in clinical trials.
The treatment of neonates with irreparable heart valve dysfunction remains an unsolved problem because there are no heart valve implants that grow. Therefore, neonates with heart valve implants are ...committed to recurrent implant exchanges until an adult-sized valve can fit.
To deliver the first heart valve implant that grows.
Case report from a pediatric referral center, with follow-up for more than 1 year. Participants were a recipient neonate with persistent truncus arteriosus and irreparable truncal valve dysfunction and a donor neonate with hypoxic-ischemic brain injury.
First-in-human transplant of the part of the heart containing the aortic and pulmonary valves.
Transplanted valve growth and hemodynamic function.
Echocardiography demonstrated adaptive growth and excellent hemodynamic function of the partial heart transplant valves.
In this child, partial heart transplant delivered growing heart valve implants with a good outcome at age 1 year. Partial heart transplants may improve the treatment of neonates with irreparable heart valve dysfunction.
Despite progressively uncommon in Western countries, rheumatic heart disease still portrays a significant global burden. In elderly or high‐surgical risk patients, plurivalvular disease may require a ...complex percutaneous approach. Transcatheter aortic valve implantation (TAVI) in patients with previous monoleaflet mitral prosthesis is challenging due to interference between the aortic valve and the rigid mitral mechanical prosthesis “ring.” Prior cases report the use of CoreValve or Edwards Sapien aortic valves in patients with adequate mitro‐aortic distance. Performing a second major procedure, such as tricuspid valve‐in‐valve (TVIV), sequentially during a single percutaneous intervention, increases treatment complexity. An 83‐year‐old woman with rheumatic heart disease, with previous implantation of a Bjork–Shiley monoleaflet mitral prosthesis, and Carpentier‐Edwards 29 tricuspid bioprosthesis presented with decompensated heart failure due to severe aortic stenosis and tricuspid bioprosthesis stenosis. After HeartTeam discussion, the patient was deemed as inoperable due to a prohibitive surgical risk. As an alternative, a TAVI (Navitor FlexNav) and a transcatheter TVIV replacement (Edwards Sapiens 3 Ultra) were discussed and proposed, with both techniques being performed sequentially in a single procedure. TAVI in a patient with a previous monoleaflet mitral mechanical prosthesis and TVIV may be a feasible approach in inoperable patients with plurivalvular disease.
Abstract Objective Substantial controversy surrounds the choice between a mechanical versus bioprosthetic prosthesis for aortic valve replacement (AVR), based on age. This study aims to investigate ...national trends and in-hospital outcomes of the 2 prosthesis choices. Methods All patients aged >18 years in the National Inpatient Sample who received an AVR between 1998 and 2011 were considered. Valve-type use was examined by patient, procedural, and hospital characteristics, after which we matched patients based on their propensity score for receiving a bioprosthetic valve and compared their in-hospital outcomes. Results Bioprosthetic valves comprised 53.3% of 767,375 implanted valves, an increase in use from 37.7% in the period 1998 to 2001 to 63.6% in the period 2007 to 2011. The median age was 74 years for patients receiving bioprosthetic valves, and 67 years for those receiving mechanical valves. Use of bioprosthetic valves increased across all age groups, most markedly in patients age 55 to 64 years. Compared with patients receiving mechanical valves, these patients had a higher incidence of renal disease (8.0% vs 4.2%), coronary artery disease (58.5% vs 50.5%), concomitant coronary artery bypass grafting (46.7% vs 41.9%), and having surgery in a high-volume (>250 cases per year) center (31.3% vs 18.5%). Patients receiving bioprosthetic valves had a higher occurrence of in-hospital complications (55.9% vs 48.6%), but lower in-hospital mortality (4.4% vs 4.9%) than patients receiving mechanical valves. This difference was confirmed in propensity-matched analyses (complications: 52.7% vs 51.5%; mortality: 4.3% vs 5.2%). Conclusions Use of bioprosthetic valves in AVR increased dramatically from 1998 to 2011, particularly in patients age 55 to 64 years. Prosthesis selection varied significantly by facility, with low-volume facilities favoring mechanical valves. Aortic valve replacement with a bioprosthetic valve, compared with a mechanical valve, was associated with lower in-hospital mortality.
Heart failure (HF) represents the leading cause of morbidity and mortality in adult patients with congenital heart disease. The nature of underlying congenital heart disease has bearing on timing and ...severity of HF and impacts on short- and long-term outcomes. HF can be subclinical, underscoring the need for close follow-up at tertiary centres with timely management of target hemodynamic lesions. Drug therapies have an effect in systemic left ventricle failure and are employed in acute HF for symptomatic relief. Data on elective drug therapy for the failing systemic right ventricle and/or Fontan circulation is currently lacking. Drugs such as angiotensin receptor blockers with neprilysin inhibitors or sodium-glucose co-transporter-2 inhibitors may show benefit. Cardiac resynchronization therapy, in appropriately selected patients, is considered a treatment option. Mechanical circulatory support and transplantation remain the last resource in highly selected patients. As the congenital heart disease population continues to grow and age, both outpatient and inpatient service for HF will continue to play a major role in the care of adult patients with congenital heart disease.
Main illustration. Strategic overview of the management of heart failure in adult congenital heart disease; ACEI angiotensin-converting enzyme inhibitors; ARNI angiotensin receptor blockers with neprilysin inhibitors; CV cardiovascular; CRT cardiac resynchronization therapy; EF ejection fraction; ERA endothelin receptor antagonist; HF heart failure; ICD implantable cardioverter defibrillator; LBBB left bundle branch block; LV left ventricle, MCS mechanical circulatory support; MRA mineralocorticoid receptor antagonists; NYHA FC New York Heart Association functional class; PAH pulmonary arterial hypertension; PDE5I phosphodiesterase type 5 inhibitor; RV right ventricle; SR sinus rhythm. Display omitted
•Heart failure is the leading cause of morbidity and mortality in adult patients with congenital heart disease•Adult patients with congenital heart disease have approximately 25% risk of death within 1year following their first heart failure admission•Diagnosis and treatment of heart failure is challenged due to heterogeneous underlying mechanisms and should be provided in a tertiary setting
The advent of direct‐acting antiviral therapy for hepatitis C virus (HCV) has generated tremendous interest in transplanting organs from HCV‐infected donors. We conducted a single‐arm trial of ...orthotopic heart transplantation (OHT) from HCV‐infected donors into uninfected recipients, followed by elbasvir/grazoprevir treatment after recipient HCV was first detected (NCT03146741; sponsor: Merck). We enrolled OHT candidates aged 40‐65 years; left ventricular assist device (LVAD) support and liver disease were exclusions. We accepted hearts from HCV‐genotype 1 donors. From May 16, 2017 to May 10, 2018, 20 patients consented for screening and enrolled, and 10 (median age 52.5 years; 80% male) underwent OHT. The median wait from UNOS opt‐in for HCV nucleic‐acid‐test (NAT)+ donor offers to OHT was 39 days (interquartile range IQR 17‐57). The median donor age was 34 years (IQR 31‐37). Initial recipient HCV RNA levels ranged from 25 IU/mL to 40 million IU/mL, but all 10 patients had rapid decline in HCV NAT after elbasvir/grazoprevir treatment. Nine recipients achieved sustained virologic response at 12 weeks (SVR‐12). The 10th recipient had a positive cross‐match, experienced antibody‐mediated rejection and multi‐organ failure, and died on day 79. No serious adverse events occurred from HCV transmission or treatment. These short‐term results suggest that HCV‐negative candidates transplanted with HCV‐infected hearts have acceptable outcomes.
The pilot USHER trial, involving 10 heart recipients, provides important evidence that transplanting hepatitis C virus–infected hearts into uninfected recipients poses reasonable risks and that hepatitis C cure rates are high even in the context of transplant immunosuppression.
Summary Background Chronic heart failure is associated with high mortality and morbidity. Raised resting heart rate is a risk factor for adverse outcomes. We aimed to assess the effect of heart-rate ...reduction by the selective sinus-node inhibitor ivabradine on outcomes in heart failure. Methods Patients were eligible for participation in this randomised, double-blind, placebo-controlled, parallel-group study if they had symptomatic heart failure and a left-ventricular ejection fraction of 35% or lower, were in sinus rhythm with heart rate 70 beats per min or higher, had been admitted to hospital for heart failure within the previous year, and were on stable background treatment including a β blocker if tolerated. Patients were randomly assigned by computer-generated allocation schedule to ivabradine titrated to a maximum of 7·5 mg twice daily or matching placebo. Patients and investigators were masked to treatment allocation. The primary endpoint was the composite of cardiovascular death or hospital admission for worsening heart failure. Analysis was by intention to treat. This trial is registered, number ISRCTN70429960. Findings 6558 patients were randomly assigned to treatment groups (3268 ivabradine, 3290 placebo). Data were available for analysis for 3241 patients in the ivabradine group and 3264 patients allocated placebo. Median follow-up was 22·9 (IQR 18–28) months. 793 (24%) patients in the ivabradine group and 937 (29%) of those taking placebo had a primary endpoint event (HR 0·82, 95% CI 0·75–0·90, p<0·0001). The effects were driven mainly by hospital admissions for worsening heart failure (672 21% placebo vs 514 16% ivabradine; HR 0·74, 0·66–0·83; p<0·0001) and deaths due to heart failure (151 5% vs 113 3%; HR 0·74, 0·58–0·94, p=0·014). Fewer serious adverse events occurred in the ivabradine group (3388 events) than in the placebo group (3847; p=0·025). 150 (5%) of ivabradine patients had symptomatic bradycardia compared with 32 (1%) of the placebo group (p<0·0001). Visual side-effects (phosphenes) were reported by 89 (3%) of patients on ivabradine and 17 (1%) on placebo (p<0·0001). Interpretation Our results support the importance of heart-rate reduction with ivabradine for improvement of clinical outcomes in heart failure and confirm the important role of heart rate in the pathophysiology of this disorder. Funding Servier, France.
Objectives This study sought to determine the frequency and magnitude of impaired systolic deformation in heart failure with preserved ejection fraction (HFpEF). Background Although diastolic ...dysfunction is widely considered a key pathophysiologic mediator of HFpEF, the prevalence of concomitant systolic dysfunction has not been clearly defined. Methods We assessed myocardial systolic and diastolic function in 219 HFpEF patients from a contemporary HFpEF clinical trial. Myocardial deformation was assessed using a vendor-independent 2-dimensional speckle-tracking software. The frequency and severity of impaired deformation was assessed in HFpEF, and compared to 50 normal controls free of cardiovascular disease and to 44 age- and sex-matched hypertensive patients with diastolic dysfunction (hypertensive heart disease) but no HF. Among HFpEF patients, clinical, echocardiographic, and biomarker correlates of left ventricular strain were determined. Results The HFpEF patients had preserved left ventricular ejection fraction and evidence of diastolic dysfunction. Compared to both normal controls and hypertensive heart disease patients, the HFpEF patients demonstrated significantly lower longitudinal strain (LS) (−20.0 ± 2.1 and −17.07 ± 2.04 vs. −14.6 ± 3.3, respectively, p < 0.0001 for both) and circumferential strain (CS) (−27.1 ± 3.1 and −30.1 ± 3.5 vs. −22.9 ± 5.9, respectively; p < 0.0001 for both). In HFpEF, both LS and CS were related to LVEF (LS, R = −0.46; p < 0.0001; CS, R = −0.51; p < 0.0001) but not to standard echocardiographic measures of diastolic function (E' or E/E'). Lower LS was modestly associated with higher NT-proBNP, even after adjustment for 10 baseline covariates including LVEF, measures of diastolic function, and LV filling pressure (multivariable adjusted p = 0.001). Conclusions Strain imaging detects impaired systolic function despite preserved global LVEF in HFpEF that may contribute to the pathophysiology of the HFpEF syndrome. (LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction; NCT00887588 )
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