A review of biomarker and imaging monitoring to predict heart failure recovery.

Heart failure is a clinical syndrome caused by structural cardiac abnormalities that lead to increased intracardiac pressures and decreased cardiac output. Following cardiovascular insult or direct myocardial injury, neurohormonal activation triggers hemodynamic changes and cardiac remodeling to preserve cardiac output. While initially adaptive, cardiac remodeling eventually causes pathologic changes in cardiac structure that often compromise cardiac function. Reverse remodeling is the regression of abnormal cardiac chamber geometry and function after myocardial injury. In recent years, several classes of therapeutics have been associated with greater likelihood of reverse remodeling. Heart failure recovery and heart failure remission, terms encompassing the clinical correlates of reverse remodeling, have been associated with improved survival in patients with heart failure with reduced ejection. As such, identifying predictors of heart failure recovery can have important implications for guiding clinical practice and therapeutic innovation. This review addresses the role of biomarkers and imaging monitoring in predicting structural, functional, and clinical recovery in patients with acute and chronic heart failure.

Evolving Presentation of Cardiogenic Shock: A Review of the Medical Literature and Current Practices.

Cardiogenic shock (CS) remains a leading cause of morbidity and mortality among patients with cardiovascular disease. In the past, acute myocardial infarction was the leading cause of CS. However, in recent years, other etiologies, such as decompensated chronic heart failure, arrhythmia, valvular disease, and post-cardiotomy, each with distinct hemodynamic profiles, have risen in prevalence. The number of treatment options, particularly with regard to device-mediated therapy has also increased. In this review, we sought to survey the medical literature and provide an update on current practices.

Geographic variation in the use of continuous outpatient inotrope infusion therapy and beta blockers.

BACKGROUND: Continuous outpatient inotrope infusion therapy (COIIT) can be used as palliative or interim treatment in patients with advanced heart failure (AHF). Despite widespread use, there is a relative lack of data informing best practices. This study aimed to examine whether patterns of COIIT use differed by region and to explore whether observed differences influenced clinical outcomes. METHODS: Retrospective study of AHF patients receiving COIIT from May 2009 through June 2016. The primary outcome was regional difference, the secondary outcome was persistence (duration) on therapy. Cox proportional hazards model was used to calculate hazard ratios for treatment regimens. RESULTS: There were 3,286 patients, mean (SD) age 61.9 (14.4) years and 74.0% (2,433) male. Inotrope selection and beta blocker use varied by region by chi square (χ2 (21) = 166.9, p < 0.001). Persistence was greater on milrinone compared to dobutamine (HR (for discontinuation) 0.54, CI 0.41-0.70, p < 0.001). Concurrent beta-blocker was associated with greater persistence for patients receiving milrinone (HR 0.13, CI 0.08-0.20, p < 0.001) and dobutamine (HR 0.36, CI 0.18-0.71, p < 0.001). CONCLUSIONS: Patterns of COIIT use varied by region, and variations in use were associated with differences in clinical outcomes.

Response by Sex in Patient-Centered Outcomes With Baroreflex Activation Therapy in Systolic Heart Failure.

OBJECTIVES: The aim of this study was to assess sex differences in the efficacy and safety of baroreflex activation therapy (BAT) in the BeAT-HF (Baroreflex Activation Therapy for Heart Failure) trial. BACKGROUND: Patients were randomized 1:1 to receive guideline-directed medical therapy (GDMT) alone (control group) or BAT plus GDMT. METHODS: Pre-specified subgroup analyses including change from baseline to 6 months in 6-min walk distance (6MWD), quality of life (QoL) assessed using the Minnesota Living With Heart Failure Questionnaire (MLWHQ), New York Heart Association (NYHA) functional class, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were conducted in men versus women. RESULTS: Fifty-three women and 211 men were evaluated. Women had similar baseline NT-proBNP levels, 6MWDs, and percentage of subjects with NYHA functional class III symptoms but poorer MLWHQ scores (mean 62 ± 22 vs. 50 ± 24; p = 0.01) compared with men. Women experienced significant improvement from baseline to 6 months with BAT plus GDMT relative to GDMT alone in MLWHQ score (-34 ± 27 vs. -9 ± 23, respectively; p < 0.01), 6MWD (44 ± 45 m vs. -32 ± 118 m; p < 0.01), and improvement in NYHA functional class (70% vs. 27%; p < 0.01), similar to the responses seen in men, with no significant difference in safety. Women receiving BAT plus GDMT had a significant decrease in NT-proBNP (-43% vs. 7% with GDMT alone; difference -48%; p < 0.01), while in men this decrease was -15% versus 2%, respectively (difference -17%; p = 0.08), with an interaction p value of 0.05. CONCLUSIONS: Women in BeAT-HF had poorer baseline QoL than men but demonstrated similar improvements with BAT in 6MWD, QoL, and NYHA functional class. Women had a significant improvement in NT-proBNP, whereas men did not. (Baroreflex Activation Therapy for Heart Failure [BeAT-HF]; NCT02627196).

Acute pulmonary pressure change after transition to sacubitril/valsartan in patients with heart failure reduced ejection fraction.

AIMS: Sacubitril/valsartan combines renin-angiotensin-aldosterone system inhibition with amplification of natriuretic peptides. In addition to well-described effects, natriuretic peptides exert direct effects on pulmonary vasculature. The effect of sacubitril/valsartan on pulmonary artery pressure (PAP) has not been fully defined. METHODS AND RESULTS: This was a retrospective case-series of PAP changes following transition from angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) to sacubitril/valsartan in patients with heart failure reduced ejection fraction and a previously implanted CardioMEMS™ sensor. Pre-sacubitril/valsartan and post-sacubitril/valsartan PAPs were compared for each patient by examining averaged consecutive daily pressure readings from 1 to 5 days before and after sacubitril/valsartan exposure. PAP changes were also compared between patients based on elevated trans-pulmonary gradients (trans-pulmonary gradient ≥ 12 mmHg) at time of CardioMEMS™ sensor implantation. The cohort included 18 patients, 72% male, mean age 60.1 ± 13.6 years. There was a significant decrease in PAPs associated with transition from ACEI/ARB to sacubitril/valsartan. The median (interquartile range) pre-treatment and post-treatment change in mean, systolic and diastolic PAPs were -3.6 (-9.8, -0.7) mmHg (P < 0.001), -6.5 (-15.0, -2.0) mmHg (P = 0.001), and -2.5 (-5.7, -0.7) (P = 0.001), respectively. The decrease in PAPs was independent of trans-pulmonary gradient (F(1,16) = 0.49, P = 0.49). CONCLUSIONS: In this retrospective case series, transition from ACEI/ARB to sacubitril/valsartan was associated with an early and significant decrease in PAPs.

Tolvaptan vs. furosemide-based diuretic regimens in patients hospitalized for heart failure with hyponatremia (AQUA-AHF).

AIMS: Hyponatremia is associated with poorer outcomes and diuretic response in patients hospitalized for heart failure. This study compared a tolvaptan-based vs. furosemide-based diuretic regimen on short-term clinical responses in hyponatremic acute heart failure. METHODS AND RESULTS: Prospective, randomized, open-label, parallel-group, single-centre study comparing oral tolvaptan vs. continuous infusion furosemide. Thirty-three subjects requiring hospitalization for acute congestive heart failure, and a serum sodium < 135 mmol/L, were randomized to tolvaptan 30 mg orally daily or furosemide 5 mg/h intravenously for initial 24 h, after which treatments could be escalated. Median daily dose throughout was tolvaptan 30 mg and furosemide 120 mg, with four subjects in each group requiring dose escalation. Urine output and net fluid balance were not different between groups at 24 h or subsequent time points up to 96 h. Changes in estimated glomerular filtration rate were comparable. Cystatin C improved at 24 h with tolvaptan compared with furosemide (-6.4 ± 11.8 vs. 4.1 ± 17.2% change, P = 0.036), but the effect was transient. No significant between group differences were seen for NT-proBNP, plasma renin activity, or urinary neutrophil gelatinase-associated lipocalin:Cr. Serum sodium, as well as copeptin levels, increased with tolvaptan compared with furosemide. CONCLUSIONS: Oral tolvaptan was associated with similar, but not superior, diuresis compared with intravenous furosemide for acute heart failure with concomitant hyponatremia.

Acute dilated cardiomyopathy in the setting of catastrophic antiphospholipid syndrome and thrombotic microangiopathy: A case series and review.

Catastrophic antiphospholipid antibody syndrome (CAPS) is a rare form of antiphospholipid syndrome, an autoimmune condition characterized by vascular thromboses, pregnancy loss, and antiphospholipid (aPL) antibodies. Diagnosis of CAPS relies on thrombosis of at least three different organs systems over 1 week, histopathological evidence of small vessel occlusion, and high aPL antibody titers. In a subset of precipitating circumstances, activation or disruption of endothelial cells in the microvasculature may occur along with cardiomyopathy. We present two cases of CAPS-associated dilated cardiomyopathy at our institution, focusing on disease management, pathophysiology, and treatment. These patients were of Southeastern Asian descent, raising the possibility of genetic polymorphisms contributing to the development of cardiomyopathy. Both met CAPS criteria and both demonstrated clinicopathologic thrombotic microangiopathy (TMA) and complement activation and developed severe dilated cardiomyopathy with shock. Complement activation plays an important role in the development of CAPS and may be important in the pathogenesis of CAPS-associated cardiomyopathy. Clinical suspicion for TMA as a pathophysiologic mechanism of unexplained heart failure in CAPS is important and increased awareness of cardiac side effects is necessary so that early treatment can be initiated to halt further cardiac and systemic complications.

Churg-Strauss Syndrome Presenting as Acute Necrotizing Eosinophilic Myocarditis: Concise Review of the Literature.

BACKGROUND: Acute eosinophilic myocarditis (EM) is a rare form of heart failure that is characterized by myocardial eosinophilic infiltration usually in association with peripheral eosinophilia. The underlying cause is variable and can include allergic reactions, parasitic infection, idiopathic hypereosinophilic syndrome, malignancy, Loeffler's syndrome, Churg-Strauss syndrome (CSS), early giant cell myocarditis and malignancy. The course is potentially fatal, and early diagnosis and treatment with steroids is essential. CONCLUSION: Here, we present an illustrative case of eosinophilic myocarditis secondary to CSS followed by a brief review of epidemiology, pathogenesis, diagnosis and treatment of both disease entities.

Myxedema Heart Disease: A Rare Disease Entity: Case Report and Brief Review of the Literature.

BACKGROUND: Myxedema heart disease is an extremely rare disease entity and should be suspected in patients with unexplained heart failure refractory to conventional treatment. Myxedema coma with co- existent heart disease is not well known and very few cases have been reported. CONCLUSION: Here, we present an interesting case of myxedema coma with severe valvular cardiomyopathy followed by a concise review of the literature with special emphasis on epidemiology, pathophysiology, diagnosis and therapeutic modalities.

Chronic heart failure management and remote haemodynamic monitoring.

Heart failure (HF) has a large societal and economic burden and is expected to increase in magnitude and complexity over the ensuing years. A number of telemonitoring strategies exploring remote monitoring and management of clinical signs and symptoms of congestion in HF have had equivocal results. Early studies of remote haemodynamic monitoring showed promise, but issues with device integrity and implantation-associated adverse events hindered progress. Nonetheless, these early studies established that haemodynamic congestion precedes clinical congestion by several weeks and that remote monitoring of intracardiac pressures may be a viable and practical management strategy. Recently, the safety and efficacy of remote pulmonary artery pressure-guided HF management was established in a prospective, single-blind trial where randomisation to active pressure-guided HF management reduced future HF hospitalisations. Subsequent commercial use studies reinforced the utility of this technology and post hoc analyses suggest that tight haemodynamic management of patients with HF may be an additional pillar of therapy alongside established guideline-directed medical and device therapy. Currently, there is active exploration into utilisation of this technology and management paradigm for the timing of implantation of durable left ventricular assist devices (LVAD) and even optimisation of LVAD therapy. Several ongoing clinical trials will help clarify the extent and utility of this strategy along the spectrum of patient with HF from individuals with chronic, stable HF to those with more advanced disease requiring heart replacement therapy.

Baseline diastolic pressure gradient and pressure reduction in chronic heart failure patients implanted with the CardioMEMS™ HF sensor.

AIMS: Remote haemodynamic monitoring (RHM) decreases hospitalization rates in patients with chronic heart failure (HF). Many patients with chronic HF develop pulmonary hypertension (PH) secondary to left heart disease with some acquiring combined pre-capillary and post-capillary PH (Cpc-PH). The efficacy of RHM in achieving pulmonary pressure reductions in patients with Cpc-PH vs. isolated post-capillary PH (Ipc-PH) is unknown. The purpose of this study is to evaluate whether a higher baseline diastolic pressure gradient (DPGbaseline ) measured at the time of CardioMEMS™ HF sensor implantation is associated with lower reductions in pulmonary artery diastolic pressures (PADP). METHODS AND RESULTS: This was a retrospective analysis of 32 patients meeting clinical indications for CardioMEMS™ implantation. DPGbaseline categorized patients as Cpc-PH (DPG ≥ 7 mmHg) or Ipc-PH (DPG < 7 mmHg). Minimum achievable PADP (PADPmin ) and ∆PADP (PADPbaseline  - PADPmin ) were determined. Pearson's correlation analysis and comparison of mean pressure changes were assessed. Median age was 69 years, and median left ventricular ejection fraction (LVEF) was 25%. Eight patients (25%) had a LVEF ≥40%. Twenty-five patients (78%) met criteria for Ipc-PH and seven (22%) for Cpc-PH. Neither PADPmin (ρ = 0.27; P = 0.13) nor ΔPADP (ρ = 0.07; P = 0.72) was correlated with DPGbaseline . A trend towards higher ΔPADP was seen in Cpc-PH vs. Ipc-PH patients (15.2 vs. 9.88 mmHg; P = 0.12). There was a moderate positive correlation between baseline PADP and ΔPADP [ρ = 0.55 (0.26-0.76); P < 0.001]. CONCLUSIONS: Decreased PADP reduction was not seen in Cpc-PH vs. Ipc-PH patients. Higher PADPbaseline was associated with greater ΔPADP. Larger studies are needed to elaborate our findings.

Case Report of Multiembolic Cerebrovascular Event Associated with Ramp Study Echocardiogram.

The incidence of ramp test echocardiogram-associated embolic events in the setting of therapeutic anticoagulation is likely rare and has not been reported. We present such a case in a patient with a HeartMate II left ventricular assist device (LVAD) whose serial head computed tomography images, deteriorating clinical course, and the multiembolic nature of the event suggest causality. If the pretest probability of pump thrombosis in an individual LVAD patient is sufficiently high, the potential risks of performing a ramp study echocardiogram may not be warranted, even in the setting of adequate anticoagulation.

Effects of pressure variation and atrial fibrillation on CardioMEMS™ HF measured pulmonary artery diastolic pressure: comparison of device-averaged and visually inspected waveforms.

OBJECTIVE: Heart failure (HF) management guided by implantable hemodynamic monitoring reduces hospitalization rates. Hemodynamic data from the CardioMEMS™ HF system includes device-averaged pulmonary artery pressures (PAP) and heart rate. Agreement of device-averaged values compared to the standard method of visual inspection of pressure waveforms at end-expiration is unknown. We evaluated the agreement between device-averaged and visually inspected end-expiratory PAP. APPROACH: Twenty-one patients implanted with the CardioMEMS™ HF system were evaluated. Eight-hundred twenty-three PAP waveforms from the Merlin remote monitoring website were visually inspected and pulmonary artery systolic pressure (PASP) and pulmonary artery diastolic pressure (PADP) at end-expiration were recorded. Waveforms were evaluated for pressure variation (PV), defined as the difference between highest and lowest PASP measurement of ⩾20 mmHg. Bland-Altman analysis quantified differences between device-averaged and visually inspected waveforms. MAIN RESULTS: All patients were NYHA functional class III, mean age was 67 ± 15 years and 15 (71%) had AF. Bland-Altman analysis of all waveforms revealed a mean-difference in PADP of -1.4 mmHg, indicating that visually inspected values were higher than device-averaged values. For PV ⩾20 mmHg, this value increased to -2.8 mmHg. The mean-difference comparing waveforms from patients with or without AF was -1.3 and -1.6 mmHg, respectively. The 95% limits of agreement were >50% wider for waveforms from patients with versus without AF (10.3 versus 6.7 mmHg). SIGNIFICANCE: There is good agreement between device-averaged and visually inspected waveforms when pressure variation is <20 mmHg and for patients without atrial fibrillation.

Tacrolimus-Associated Dilated Cardiomyopathy in Adult Patient After Orthotopic Liver Transplant.

This report presents a case of tacrolimus cardiotoxicity in an adult patient who received tacrolimus immunosuppression for orthotopic liver transplant (OLT). Tacrolimus-associated cardiotoxicity has been described in the literature, however this is the first case to document the development of a dilated cardiomyopathy in a patient shortly after initiating tacrolimus therapy post transplant. With the growing use of tacrolimus in transplant medicine, this case report expands the literature of tacrolimus cardiotoxicity and can aid clinicians in the evaluation and management of patients exposed to this form of immunosuppression.

Heart Failure-Induced Brain Injury.

Heart failure (HF) is a systemic illness with grave implications for bodily functions. The brain, among other vital organs, often suffers insults as a result of HF, and both anatomic and functional brain abnormalities were found in the HF population. This injury was demonstrated across a wide range of clinical conditions and cardiac functions and was shown to affect patients' outcomes. Although reduced cardiac output and high burden of cardiovascular risk factors are the prevailing explanations for these findings, there are data showing the involvement of neurohormonal, nutritional, and inflammatory mechanisms in this complex process. Here, the authors review the suggested pathophysiology behind brain injury in HF, describe its effect on patients' outcomes, offer a diagnostic approach, and discuss possible therapeutic options.

Point-of-Care Technologies for Precision Cardiovascular Care and Clinical Research: National Heart, Lung, and Blood Institute Working Group.

Point-of-care technologies (POC or POCT) are enabling innovative cardiovascular diagnostics that promise to improve patient care across diverse clinical settings. The National Heart, Lung, and Blood Institute convened a working group to discuss POCT in cardiovascular medicine. The multidisciplinary working group, which included clinicians, scientists, engineers, device manufacturers, regulatory officials, and program staff, reviewed the state of the POCT field; discussed opportunities for POCT to improve cardiovascular care, realize the promise of precision medicine, and advance the clinical research enterprise; and identified barriers facing translation and integration of POCT with existing clinical systems. A POCT development roadmap emerged to guide multidisciplinary teams of biomarker scientists, technologists, health care providers, and clinical trialists as they: 1) formulate needs assessments; 2) define device design specifications; 3) develop component technologies and integrated systems; 4) perform iterative pilot testing; and 5) conduct rigorous prospective clinical testing to ensure that POCT solutions have substantial effects on cardiovascular care.

Pan-Cardiac Cycle Fixed Mitral Valve Opening in an LVAD Patient Presenting with Hemorrhagic Shock.

We present the case of a patient with a HeartMate II left ventricular assist device (LVAD) who underwent an elective cholecystectomy and abruptly decompensated on postoperative day 9. We highlight the uncommon echocardiogram finding of mitral valve leaflets fixed widely open throughout the cardiac cycle during an LVAD suction event. Bedside echocardiographic confirmation of a suction event enabled the rapid diagnosis and intervention for hemorrhagic shock before blood tests and radiographic results were available. Acoustic image quality can be limited in LVAD patients, and awareness of this uncommon finding may increase specificity for the echocardiographic diagnosis of LVAD suction events.