Inoperable chronic thromboembolic pulmonary hypertension: Evolution of prognosis over 10 years of new emerging therapies.

Therapies for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) include balloon pulmonary angioplasty (BPA) and PH-specific medical therapy. This study compares survival and its predictors before and after the introduction of BPA. BPA was independently associated with survival; however, there was no difference in overall survival between the two cohorts.

Peripheral microvascular function is linked to cardiac involvement on cardiovascular magnetic resonance in systemic sclerosis-related pulmonary arterial hypertension.

AIMS: Systemic sclerosis (SSc) is characterized by vasculopathy, inflammation, and fibrosis, and carries one of the worst prognoses if patients also develop pulmonary arterial hypertension (PAH). Although PAH is a known prognosticator, patients with SSc-PAH demonstrate disproportionately high mortality, presumably due to cardiac involvement. In this cross-sectional study, the relationship between cardiac involvement revealed by cardiovascular magnetic resonance (CMR) and systemic microvascular disease severity measured with nailfold capillaromicroscopy (NCM) in patients with SSc-PAH is evaluated and compared with patients with idiopathic PAH (IPAH). METHODS AND RESULTS: Patients with SSc-PAH and IPAH underwent CMR, echocardiography, and NCM with post-occlusive reactivity hyperaemia (PORH) testing on the same day. CMR imaging included T2 (oedema), native, and post-contrast T1 mapping to measure the extracellular volume fraction (ECV, fibrosis) and adenosine-stress-perfusion imaging measuring the relative myocardial upslope (microvascular coronary perfusion). Measures of peripheral microvascular function were related to CMR indices of oedema, fibrosis, and myocardial perfusion. SSc-PAH patients (n = 20) had higher T2 values and a trend towards a higher ECV, compared with IPAH patients (n = 5), and a lower nailfold capillary density (NCD) and reduced capillary recruitment after PORH. NCD correlated with ECV and T2 (r = -0.443 and -0.464, respectively, P < 0.05 for both) and with markers of diastolic dysfunction on echocardiography. PORH testing, but not NCD, correlated with the relative myocardial upslope (r = 0.421, P < 0.05). CONCLUSION: SSc-PAH patients showed higher markers of cardiac fibrosis and inflammation, compared with IPAH patients. These markers correlated well with peripheral microvascular dysfunction, suggesting that SSc-driven inflammation and vasculopathy concurrently affect peripheral microcirculation and the heart. This may contribute to the disproportionate high mortality in SSc-PAH.

Supraventricular arrhythmia in pregnancy.

The physiological changes during pregnancy predispose a woman for the development of new-onset or recurrent arrhythmia. Supraventricular arrhythmia is the most common form of arrhythmia during pregnancy and, although often benign in nature, can be concerning. We describe three complex cases of supraventricular arrhythmia during pregnancy and review the currently available literature on the subject. In pregnancies complicated by arrhythmia, a plan for follow-up and both maternal and fetal monitoring during pregnancy, delivery and post partum should be made in a multidisciplinary team. Diagnostic modalities should be used as in non-pregnant women if there is an indication. All antiarrhythmic drugs cross the placenta, but when necessary, medical treatment should be used with consideration to the fetus and the mother's altered pharmacodynamics and kinetics. Electrical cardioversion is safe during pregnancy, and electrophysiological study and catheter ablation can be performed in selected patients, preferably with zero-fluoroscopy technique. Sometimes, delivering the fetus (if viable) is the best therapeutic option. In this review, we provide a framework for the workup and clinical management of supraventricular arrhythmias in pregnant women, including cardiac, obstetric and neonatal perspectives.

Long-term monitoring of arrhythmias with cardiovascular implantable electronic devices in patients with cardiac sarcoidosis.

BACKGROUND: Risk stratification for sudden cardiac death (SCD) in cardiac sarcoidosis (CS) is challenging in patients without overt cardiac symptoms. OBJECTIVE: The purpose of this study was to determine the incidence of ventricular arrhythmias (VAs) and mortality after long-term monitoring with a cardiovascular implantable electronic device (CIED) in CS patients identified after systematic screening of patients with extracardiac sarcoidosis (ECS). METHODS: A retrospective study was performed in 547 predominantly Caucasian patients with ECS screened for cardiac involvement. If CS was diagnosed, risk stratification (high vs low risk) for SCD was performed by a multidisciplinary team. The primary endpoint was defined as sustained VA, appropriate implantable cardioverter-defibrillator (ICD) therapy, or cardiac death. RESULTS: In total, 105 patients were included (mean follow-up 33 ± 16 months). An ICD was implanted in 17 high-risk patients (16.2%), whereas 80 low-risk patients (76.1%) received an implantable loop recorder (ILR). Eight low-risk patients (7.6%) did not receive a device. The primary endpoint occurred in 4.8% (n = 5), with an overall annualized event rate of 1.7%. The annualized event rate was 9.8% in high-risk patients and 0.4% in low-risk patients. Nine low-risk patients received an ICD during follow-up, in 7 patients as a result of the ILR recordings. None of these patients required ICD therapy. CONCLUSION: In CS patients without overt cardiac symptoms at initial presentation the annualized overall event rate was 1.7%; 10% in high-risk patients, but only 0.4% in low-risk patients. In low-risk patients long-term arrhythmia monitoring with an ILR enabled early detection of clinically important arrhythmias without showing impact on prognosis.

Hereditary Hemorrhagic Telangiectasia (HHT) and Survival: The Importance of Systematic Screening and Treatment in HHT Centers of Excellence.

Hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disease, is characterized by telangiectases and arteriovenous malformations (AVMs). Untreated AVMs, especially in the lungs-pulmonary AVMs (PAVMs)-can result in morbidity with a decreased life expectancy. We have investigated whether HHT patients, systematically screened for HHT-related organ involvement and treated if needed, have a similar survival as persons without HHT. We included all individuals screened for HHT between 2004 and 2016 with a genetically or clinically confirmed diagnosis (HHT group) or excluded diagnosis (non-HHT control group). The social security number was used to confirm status as dead or alive in December 2019. We included 717 HHT patients and 471 controls. There was no difference in survival between the HHT and the non-HHT control group. The HHT group had a life expectancy of 75.9 years (95% confidence interval (CI) 73.3-78.6), comparable to the control group (79.3 years, 95% CI 74.8-84.0, Mantel-Cox test: p = 0.29). In conclusion, the life expectancy of HHT patients systematically screened for HHT-related organ involvement and treated if needed in an HHT center of excellence was similar compared to their controls, justifying systematic screening and treatment in HHT patients.

Microtransesophageal Echocardiographic Guidance during Percutaneous Interatrial Septal Closure without General Anaesthesia.

OBJECTIVE: To study the safety and efficacy of microtransesophageal echocardiography (micro-TEE) and TEE during percutaneous atrial septal defect (ASD) and patent foramen ovale (PFO) closure. BACKGROUND: TEE has proven to be safe during ASD and PFO closure under general anaesthesia. Micro-TEE makes it possible to perform these procedures under local anaesthesia. We are the first to describe the safety and efficacy of micro-TEE for percutaneous closure. METHODS: All consecutive patients who underwent ASD and PFO closure between 2013 and 2018 were included. The periprocedural complications were registered. Residual shunts were diagnosed using transthoracic contrast echocardiography (TTCE). All data were compared between the use of TEE or micro-TEE within the ASD and PFO groups separately. RESULTS: In total, 82 patients underwent ASD closure, 46 patients (49.1 ± 15.0 years) with TEE and 36 patients (47.8 ± 12.1 years) using micro-TEE guidance. Median device diameter was, respectively, 26 mm (range 10-40 mm) and 27 mm (range 10-35 mm). PFO closure was performed in 120 patients, 55 patients (48.6 ± 9.2 years, median device diameter 25 mm, range 23-35 mm) with TEE and 65 patients (mean age 51.0 ± 11.8 years, median device diameter 27 mm, range 23-35 mm) using micro-TEE. There were no major periprocedural complications, especially no device embolizations within all groups. Six months after closure, there was no significant difference in left-to-right shunt after ASD closure and no significant difference in right-to-left shunt after PFO closure using TEE or micro-TEE. CONCLUSION: Micro-TEE guidance without general anaesthesia during percutaneous ASD and PFO closure is as safe as TEE, without a significant difference in the residual shunt rate after closure.

Prevalence and diagnostic value of nail fold capillary microscopy in hereditary hemorrhagic telangiectasia: A retrospective study.

Abnormal vasculature is a key feature of hereditary hemorrhagic telangiectasia (HHT) and can also present in the nail fold capillary beds. However, the exact prevalence and the clinical diagnostic value in HHT are still largely unknown. The nail fold can be easily and noninvasively inspected with a capillary microscope. We therefore retrospectively assessed the prevalence and diagnostic value of abnormal nail fold capillaries in all patients who were screened between January 2000 and July 2017 for the presence of HHT and underwent capillary microscopy in St Antonius Hospital, The Netherlands. Capillary microscopy results and clinical characteristics were extracted from medical files and the prevalence of abnormal nail fold capillaries was calculated and the diagnostic value of the Curaçao criteria with and without capillary microscopy results was assessed. Of the 1761 individuals screened, 923 (52%) were diagnosed with a clinical and/or genetic HHT diagnosis. In these patients, capillary microscopy was normal in 23% (n = 218), enlarged loops were seen in 11% (n = 99), and giant loops in 66% (n = 606). The sensitivity and specificity of the Curaçao criteria for the diagnosis of HHT without capillary microscopy results were 96% and 90%, respectively. The addition of the presence of giant loops to the Curaçao criteria led to a small increase in sensitivity to 97% without affecting the specificity. In conclusion, the prevalence of nail fold abnormalities in patients with HHT is high. Capillary microscopy can be a useful, easy, and noninvasive diagnostic tool in HHT.

An Elderly Woman With Recurrent Transient Loss of Consciousness Preceded by Hallucinatory Attacks.

We report a patient with transient loss of consciousness preceded by hallucinations caused by cardiac syncope. The diagnosis was confirmed by simultaneous video-electrocardiogram-electroencephalogram recording of an event. The attacks no longer occurred after pacemaker implantation. Clinical features helpful in guiding decision making in transient loss of consciousness are discussed. (Level of Difficulty: Beginner.).

Assessment of Predictors of Left Atrial Volume Response to a Transcatheter InterAtrial Shunt Device (from the REDUCE LAP-HF Trial).

In patients with heart failure and preserved or mildly reduced ejection fractions (EF ≥40%), implantation of an interatrial shunt device (IASD) resulted in heterogenous changes of the left atrial (LA) volume. Baseline characteristics that correlate with a favorable decrease in LA volume are unknown. We hypothesized that a larger ratio of left to right atrial volume at baseline would correlate strongly with LA volume decongestion following IASD implantation. Reduce Elevated LA Pressure in Patients With Heart Failure was a multicenter study of the safety and feasibility of IASD implantation. Sixty-four patients with EF ≥40% underwent device implantation along with baseline conventional echocardiograms, speckle tracking echocardiography, and resting and exercise hemodynamics. Higher LA compliance (-4.2%, p = 0.048) and right atrial reservoir strain (-0.8%, p = 0.005) were independently associated with a percent decrease in the systolic LA volume index from baseline to 6-months. In conclusion, greater LA volume reduction following IASD implantation is associated with higher baseline compliance of the left atrium and higher reservoir strain of the right atrium.

Non-vitamin K antagonist oral anticoagulants in adults with a Fontan circulation: are they safe.

Background: In Fontan patients with atrial arrhythmias (AA), non-vitamin K antagonist oral anticoagulants(NOACs) have a class III recommendation according to the Pediatric & Congenital Electrophysiology Society (PACES)/Heart Rhythm Society (HRS) guideline in 2014, due to lack of data on outcomes as opposed to evidence of harm. To address this gap in data, we investigated the safety and efficacy of NOACs in adults with a Fontan circulation in a worldwide study. Methods: This is an international multicentre prospective cohort study, using data from the NOTE (non-vitamin K antagonist oral anticoagulants for thromboembolic prevention in patients with congenital heart disease) registry. The study population comprised consecutive adults with a Fontan circulation using NOACs. Follow-up took place at 6 months and yearly thereafter. The primary endpoints were thromboembolism and major bleeding. Secondary endpoint was minor bleeding. Results: From April 2014 onward, 74 patients (mean age 32±10 years (range 18-68), 54% male) with a Fontan circulation using NOACs were included. During a median follow-up of 1.2 (IQR 0.8-2.0) years, three thromboembolic events (2.9 per 100 patient-years (95% CI 0.7 to 7.6)) and three major bleedings (2.9 per 100 patient-years (95% CI 0.7 to 7.6)) occurred in five atriopulmonary Fontan and one total cavopulmonary connection Fontan patients with AA. Fifteen patients experienced minor bleeding episodes (15.8 per 100 patient-years (95% CI 9.1 to 25.2)). In patients (n=37) using vitamin K antagonists (VKAs) prior to the initiation of NOAC, annual incidence of historical thromboembolic events and major bleeding were 2.4% (95% CI 0.4% to 7.4%) (n = 2) and 1.2% (95% CI 0.7% to 5.1%) (n = 1), respectively. Conclusions: In this review of the largest Fontan cohort using NOACs with prospective follow-up, NOACs appear to be well tolerated and their efficacy and safety during short-term follow-up seem comparable to VKAs. Longer term data are required to confirm these promising short-term results.

Transcatheter Tricuspid Valve Interventions: An Emerging Field.

PURPOSE OF REVIEW: This review aims to provide an updated overview and a clinical perspective on novel transcatheter tricuspid valve interventions (TTVI), highlighting potential challenges and future directions. RECENT FINDINGS: Severe tricuspid regurgitation (TR) is a predictor of mortality. However, a sizeable number of patients remain untreated until the end-stage when cardiac surgery presents a prohibitive risk. The emergent need in finding a treatment for patients with TR, deemed for surgery options, has encouraged the development of TTVI. These procedures mimic classical surgery techniques and are mainly divided in four categories: annuloplasty and coaptation devices, edge-to-edge techniques and transcatheter tricuspid valve replacement. Early studies showed promising results, but long-term follow-up data are not available. For patients with severe TR and high surgical risk, several percutaneous options are available. However, these therapies are in a growing phase and bigger studies and long term follow-up are needed to prove their efficacy.

Percutaneous patent foramen ovale closure using the Occlutech Figulla device: More than 1,300 patient-years of follow up.

OBJECTIVE: To evaluate the safety and efficacy of the Occlutech patent foramen ovale (PFO) device at long-term follow-up (FU). BACKGROUND: The Occlutech device has been proven safe and effective six-months after percutaneous PFO closure. We describe the safety and efficacy after more than 1,300 patient-years of FU. METHODS: All consecutive patients who underwent PFO closure between October 2008 and December 2015 were included. All complications were registered. Residual right-to-left shunt (RLS) was diagnosed using contrast transthoracic echocardiography and graded as minimal, moderate, or severe. RESULTS: In total, 250 patients (mean age 53.5 ± 10.7 years, 46.8% female) underwent percutaneous PFO closure using the Occlutech device. Mean FU was 5.9 ± 1.8 years, a total of 1,345 patient-years. Transient ischemic attack (TIA) or stroke was the main indication for closure (89.6%). Implantation was successful in 100%, no major complications occurred. Minor complications were inguinal hematoma in 16 patients (6.4%), pericardial effusion without the need for intervention in one patient (0.4%) and a supraventricular tachycardia in one patient (0.4%). A moderate or large shunt at one-year follow up was present in 5.9%. A cerebrovascular vascular event occurred in 2.0% at 1-year FU (four TIA, one stroke) and in 7.4% at long-term FU (nine TIA, eight stroke). The total cerebrovascular event rate (TIA and CVA) was 0.02% per patient-year of FU, with a stroke rate of 0.01%. CONCLUSION: The Occlutech device appears to be safe at long-term FU with a very low annual cerebrovascular event rate and a low moderate to large shunt rate at 1-year FU.

Effect of Losartan on Right Ventricular Dysfunction: Results From the Double-Blind, Randomized REDEFINE Trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) in Adults With Repaired Tetralogy of Fallot.

BACKGROUND: The effect of angiotensin II receptor blockers on right ventricular (RV) function is still unknown. Angiotensin II receptor blockers are beneficial in patients with acquired left ventricular dysfunction, and recent findings have suggested a favorable effect in symptomatic patients with systemic RV dysfunction. The current study aimed to determine the effect of losartan, an angiotensin II receptor blocker, on subpulmonary RV dysfunction in adults after repaired tetralogy of Fallot. METHODS: The REDEFINE trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) is an investigator-initiated, multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled study. Adults with repaired tetralogy of Fallot and RV dysfunction (RV ejection fraction [EF] <50%) but without severe valvular dysfunction were eligible. Patients were randomly assigned between losartan (150 mg daily) and placebo with target treatment duration between 18 and 24 months. The primary outcome was RV EF change, determined by cardiovascular MRI in intention-to-treat analysis. RESULTS: Of 95 included patients, 47 patients received 150 mg losartan daily (age, 38.0±12.4 years; 74% male), and 48 patients received placebo (age, 40.6±11.4 years; 63% male). Overall, RV EF did not change in patients allocated to losartan (n=42) (44.4±5.1% to 45.2±5.0%) and placebo (n=46) (43.2±6.3% to 43.6±6.9%). Losartan did not significantly improve RV EF in comparison with placebo (+0.51%; 95% confidence interval, -1.0 to +2.0; P=0.50). No significant treatment effects were found on secondary outcomes: left ventricular EF, peak aerobic exercise capacity, and N-terminal pro-brain natriuretic peptide (P>0.30 for all). In predefined subgroup analyses, losartan did not have a statistically significant impact on RV EF in subgroups with symptoms, restrictive RV, RV EF<40%, pulmonary valve replacement, or QRS fragmentation. However, in a post hoc analysis, losartan was associated with improved RV EF in a subgroup (n=30) with nonrestrictive RV and incomplete remodeling (QRS fragmentation and previous pulmonary valve replacement) (+2.7%; 95% confidence interval, +0.1 to +5.4; P=0.045). CONCLUSIONS: Losartan had no significant effect on RV dysfunction or secondary outcome parameters in repaired tetralogy of Fallot. Future larger studies may determine whether there might be a role for losartan in specific vulnerable subgroups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02010905.

Cardiac sarcoidosis: challenges in clinical practice.

PURPOSE OF REVIEW: To address the current recommendations for screening, diagnosis, and treatment of cardiac sarcoidosis and the difficulties to put these recommendations into clinical practice. RECENT FINDINGS: The incidence of cardiac sarcoidosis appears to be higher than earlier reported, probably because of improved imaging techniques. Late gadolinium enhancement with cardiac MRI (LGE-CMR) and fluorodeoxyglucose positron emission tomography obtained a central role in the diagnostic algorithm and monitoring of disease activity. New techniques are being investigated: T1 and T2 mapping for early detection in CMR, a sarcoid-specific tracer in PET, integrated positron emission tomography/MRI scanners, and assessment of scar with LGE in cardiac computed tomography. Isolated cardiac sarcoidosis is an increasingly recognized phenotype, but still an enormous challenge in clinical practice. The prognostic value of (and extent of) LGE-CMR should be taken into account for risk assessment and internal cardiac defbrillator therapy, even in patients with preserved left ventricular function. Unfortunately, randomized controlled trials to guide immunosuppressive therapy are still lacking. A multidisciplinary approach to diagnose and treat cardiac sarcoidosis patients in specialized centers is strongly recommendable. SUMMARY: Cardiac sarcoidosis is increasingly recognized because of improved imaging techniques; however, treatment of cardiac sarcoidosis is still mainly based on expert opinion.

Right vEntricular Dysfunction in tEtralogy of Fallot: INhibition of the rEnin-angiotensin-aldosterone system (REDEFINE) trial: Rationale and design of a randomized, double-blind, placebo-controlled clinical trial.

Renin-angiotensin-aldosterone system (RAAS) inhibition with angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors is beneficial in patients with acquired left ventricular dysfunction. Adult patients with tetralogy of Fallot (TOF) with right ventricular (RV) dysfunction are at high risk for heart failure, arrhythmias, and sudden cardiac death. However, the efficacy of RAAS inhibition has not been established in these patients. METHODS: The REDEFINE is an investigator-initiated, multicenter, prospective, randomized, double-blind, placebo-controlled trial to study the effects of the angiotensin II receptor blocker losartan (target dosage of 150 mg once daily) in adult patients with TOF. Patients with RV dysfunction in the absence of severe valvular dysfunction are eligible for inclusion. The primary end point is the change in RV ejection fraction after 18 to 24 months, as measured by cardiovascular magnetic resonance imaging. In addition, laboratory measurements, echocardiography, and cardiopulmonary exercise testing are performed. CONCLUSION: The REDEFINE trial will study the effects of RAAS inhibition with losartan in TOF patients with RV dysfunction.

QRS fragmentation is superior to QRS duration in predicting mortality in adults with tetralogy of Fallot.

BACKGROUND: Although QRS duration >180 ms has prognostic value in adults with tetralogy of Fallot (TOF), its sensitivity to predict mortality is low. Fragmented QRS complexes, a simple measurement on ECG, are related to myocardial fibrosis and dysfunction in patients with TOF. Our objective was to determine whether QRS fragmentation predicts major outcomes in TOF. METHODS: This multicentre study included adult patients with TOF from a prospective registry. Notches in the QRS complex in ≥2 contiguous leads on a 12-lead ECG, not related to bundle branch block, were defined as QRS fragmentation, which was classified as none, moderate (≤4 leads) or severe (≥5 leads). The primary and secondary outcomes were all-cause mortality and clinical ventricular arrhythmia, respectively. RESULTS: A total of 794 adult patients with TOF (median age 27 years, 55% male; 52% no QRS fragmentation, 32% moderate, 16% severe) were included. During long-term (median 10.4 years) follow-up, 46 (6%) patients died and 35 (4%) patients had ventricular arrhythmias. Overall, 10-year survival was 98% in patients without fragmented QRS complexes, 93% in patients with moderate QRS fragmentation and 81% in patients with severe QRS fragmentation. In multivariable Cox hazards regression analysis, extent of QRS fragmentation (HR: 2.24/class, 95% CI 1.48 to 3.40, p<0.001) remained independently predictive for mortality, whereas QRS duration was not predictive (p=0.85). The extent of QRS fragmentation was also independently predictive for ventricular arrhythmia (HR: 2.00/class, 95% CI 1.26 to 3.16, p=0.003). CONCLUSIONS: The extent of QRS fragmentation is superior to QRS duration in predicting mortality in adult patients with TOF and may be used in risk stratification.

Patent Foramen Ovale With Atrial Septal Aneurysm Is Strongly Associated With Migraine With Aura: A Large Observational Study.

BACKGROUND: A patent foramen ovale (PFO) with atrial septal aneurysm (ASA) has been identified as a risk factor for cryptogenic stroke. Patients with migraine with aura (MA) appear to be at risk for silent brain infarction, which might be related to the presence of a PFO. However, the association between MA and PFO with ASA has never been reported. We examined this association in a large observational study. METHODS AND RESULTS: Patients (>18 years) who underwent an agitated saline transesophageal echocardiography (cTEE) at our outpatient clinics within a timeframe of 4 years were eligible to be included. Before cTEE they received a validated headache questionnaire. Two neurologists diagnosed migraine with or without aura according to the International Headache Criteria. A total of 889 patients (mean age 56.4±14.3 years, 41.7% women) were included. A PFO was present in 23.2%, an isolated ASA in 2.7%, and a PFO with ASA in 6.9%. The occurrence of migraine was 18.9%; the occurrence of MA was 8.1%. The prevalence of PFO with ASA was significantly higher in patients with MA compared to patients without migraine (18.1% vs 6.1%; OR 3.72, 95% CI 1.86-7.44, P<0.001). However, a PFO without ASA was not significantly associated with MA (OR 1.50, 95% CI 0.79-2.82, P=0.21). Interestingly, a PFO with ASA was strongly associated with MA (OR 2.71, 95% CI 1.23-5.95, P=0.01). CONCLUSION: In this large observational study, PFO with ASA was significantly associated with MA only. PFO closure studies should focus on this specific intra-atrial anomaly.

One-Year Outcomes After Transcatheter Insertion of an Interatrial Shunt Device for the Management of Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction has a complex pathophysiology and remains a therapeutic challenge. Elevated left atrial pressure, particularly during exercise, is a key contributor to morbidity and mortality. Preliminary analyses have demonstrated that a novel interatrial septal shunt device that allows shunting to reduce the left atrial pressure provides clinical and hemodynamic benefit at 6 months. Given the chronicity of heart failure with preserved ejection fraction, evidence of longer-term benefit is required. METHODS AND RESULTS: Patients (n=64) with left ventricular ejection fraction ≥40%, New York Heart Association class II-IV, elevated pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during supine bicycle exercise) participated in the open-label study of the interatrial septal shunt device. One year after interatrial septal shunt device implantation, there were sustained improvements in New York Heart Association class (P<0.001), quality of life (Minnesota Living with Heart Failure score, P<0.001), and 6-minute walk distance (P<0.01). Echocardiography showed a small, stable reduction in left ventricular end-diastolic volume index (P<0.001), with a concomitant small stable increase in the right ventricular end-diastolic volume index (P<0.001). Invasive hemodynamic studies performed in a subset of patients demonstrated a sustained reduction in the workload corrected exercise pulmonary capillary wedge pressure (P<0.01). Survival at 1 year was 95%, and there was no evidence of device-related complications. CONCLUSIONS: These results provide evidence of safety and sustained clinical benefit in heart failure with preserved ejection fraction patients 1 year after interatrial septal shunt device implantation. Randomized, blinded studies are underway to confirm these observations. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01913613.