Defining levels of care in cardiogenic shock.

Background: Expert opinion and professional society statements have called for multi-tier care systems for the management of cardiogenic shock (CS). However, little is known about how to pragmatically define centers with different levels of care (LOC) for CS. Methods: Eleven of 23 hospitals within our healthcare system sharing a common electronic health record were classified as different LOC according to their highest mechanical circulatory support (MCS) capabilities: Level 1 (L-1)-durable left ventricular assist device, Level 1A (L-1A)-extracorporeal membrane oxygenation, Level 2 (L-2)-intra-aortic balloon pump and percutaneous ventricular assist device; and Level 3 (L-3)-no MCS. All adult patients treated for CS (International Classification of Diseases, ICD-10 code R57.0) between 2016 and 2022 were included. Etiologies of CS were identified using associated diagnostic codes. Management strategies and outcomes across LOC were compared. Results: Higher LOC centers had higher volumes: L-1 (n = 1): 2,831 patients, L-1A (n = 4): 3,452, L-2 (n = 1): 340, and L-3 (n = 5): 780. Emergency room admissions were more common in lower LOC (96% at L-3 vs. 46% L-1; p < 0.001), while hospital transfers were predominant at higher LOC (40% at L-1 vs. 2.7% at L-3; p < 0.001). Men comprised 61% of the cohort. Patients were younger in the higher LOC [69 (60-78) years at L-1 vs. 77 (67-85) years at L-3; p < 0.001]. Patients with acute myocardial infarction (AMI)-CS and acute heart failure (AHF)-CS were concentrated in higher LOC centers while other etiologies of CS were more common in L-2 and L-3 (p < 0.001). Cardiac arrest on admission was more prevalent in lower LOC centers (L-1: 2.8% vs. L-3: 12.1%; p < 0.001). Patients with AMI-CS received more percutaneous coronary intervention in lower LOC (51% L-2 vs. 29% L-1; p < 0.01) but more coronary arterial bypass graft surgery at higher LOC (L-1: 42% vs. L-1A: 23%; p < 0.001). MCS use was consistent across levels for AMI-CS but was more frequent in higher LOC for AHF-CS patients (L-1: 28% vs. L-2: 10%; p < 0.001). Despite increasing in-hospital mortality with decreasing LOC, no significant difference was seen after multivariable adjustment. Conclusion: This is the first report describing a pragmatic classification of LOC for CS which, based on MCS capabilities, can discriminate between centers with distinct demographics, practice patterns, and outcomes. This classification may serve as the basis for future research and the creation of CS systems of care.

Effect of Torsemide Versus Furosemide on Symptoms and Quality of Life Among Patients Hospitalized for Heart Failure: The TRANSFORM-HF Randomized Clinical Trial.

BACKGROUND: Loop diuretics are a primary therapy for the symptomatic treatment of heart failure (HF), but whether torsemide improves patient symptoms and quality of life better than furosemide remains unknown. As prespecified secondary end points, the TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) compared the effect of torsemide versus furosemide on patient-reported outcomes among patients with HF. METHODS: TRANSFORM-HF was an open-label, pragmatic, randomized trial of 2859 patients hospitalized for HF (regardless of ejection fraction) across 60 hospitals in the United States. Patients were randomly assigned in a 1:1 ratio to a loop diuretic strategy of torsemide or furosemide with investigator-selected dosage. This report examined effects on prespecified secondary end points, which included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; assessed as adjusted mean difference in change from baseline; range, 0-100 with 100 indicating best health status; clinically important difference, ≥5 points) and Patient Health Questionnaire-2 (range, 0-6; score ≥3 supporting evaluation for depression) over 12 months. RESULTS: Baseline data were available for 2787 (97.5%) patients for KCCQ-CSS and 2624 (91.8%) patients for Patient Health Questionnaire-2. Median (interquartile range) baseline KCCQ-CSS was 42 (27-60) in the torsemide group and 40 (24-59) in the furosemide group. At 12 months, there was no significant difference between torsemide and furosemide in change from baseline in KCCQ-CSS (adjusted mean difference, 0.06 [95% CI, -2.26 to 2.37]; P=0.96) or the proportion of patients with Patient Health Questionnaire-2 score ≥3 (15.1% versus 13.2%: P=0.34). Results for KCCQ-CSS were similar at 1 month (adjusted mean difference, 1.36 [95% CI, -0.64 to 3.36]; P=0.18) and 6-month follow-up (adjusted mean difference, -0.37 [95% CI, -2.52 to 1.78]; P=0.73), and across subgroups by ejection fraction phenotype, New York Heart Association class at randomization, and loop diuretic agent before hospitalization. Irrespective of baseline KCCQ-CSS tertile, there was no significant difference between torsemide and furosemide on change in KCCQ-CSS, all-cause mortality, or all-cause hospitalization. CONCLUSIONS: Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 months. The effects of torsemide and furosemide on patient-reported outcomes were similar regardless of ejection fraction, previous loop diuretic use, and baseline health status. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03296813.

Simultaneous Heart-Kidney Transplant-Does Hospital Experience With Heart Transplant or Kidney Transplant Have a Greater Impact on Patient Outcomes?

High institutional transplant volume is associated with improved outcomes in isolated heart and kidney transplant. The aim of this study was to assess trends and outcomes of simultaneous heart-kidney transplant (SHKT) nationally, as well as the impact of institutional heart and kidney transplant volume on survival. All adult patients who underwent SHKT between 2005-2019 were identified using the United Network for Organ Sharing (UNOS) database. Annual institutional volumes in single organ transplant were determined. Univariate and multivariable analyses were conducted to assess the impact of demographics, comorbidities, and institutional transplant volumes on 1-year survival. 1564 SHKT were identified, increasing from 54 in 2005 to 221 in 2019. In centers performing SHKT, median annual heart transplant volume was 35.0 (IQR 24.0-56.0) and median annual kidney transplant volume was 166.0 (IQR 89.5-224.0). One-year survival was 88.4%. In multivariable analysis, increasing heart transplant volume, but not kidney transplant volume, was associated with improved 1-year survival. Increasing donor age, dialysis requirement, ischemic times, and bilirubin were also independently associated with reduced 1-year survival. Based on this data, high-volume heart transplant centers may be better equipped with managing SHKT patients than high-volume kidney transplant centers.

Pulmonary Congestion on Lung Ultrasound Predicts Increased Risk of 30-Day Readmission in Heart Failure Patients.

OBJECTIVES: Heart failure exacerbations are a common cause of hospitalizations with a high readmission rate. There are few validated predictors of readmission after treatment for acute decompensated heart failure (ADHF). Lung ultrasound (LUS) is sensitive and specific in the assessment of pulmonary congestion; however, it is not frequently utilized to assess for congestion before discharge. This study assessed the association between number of B-lines, on LUS, at patient discharge and risk of 30-day readmission in patients hospitalized for acute decompensated heart failure (ADHF). METHODS: This was a single-center prospective study of adults admitted to a quaternary care center with a diagnosis of ADHF. At the time of discharge, the patient received an 8-zone LUS exam to evaluate for the presence of B-lines. A zone was considered positive if ≥3 B-lines was present. We assessed the risk of 30-day readmission associated with the number of lung zones positive for B-lines using a log-binomial regression model. RESULTS: Based on data from 200 patients, the risk of 30-day readmission in patients with 2-3 positive lung zones was 1.25 times higher (95% CI: 1.08-1.45), and in patients with 4-8 positive lung zones was 1.50 times higher (95% CI: 1.23-1.82, compared with patients with 0-1 positive zones, after adjusting for discharge blood urea nitrogen, creatinine, and hemoglobin. CONCLUSION: Among patients admitted with ADHF, the presence of B-lines at discharge was associated with a significantly increased risk of 30-day readmission, with greater number of lung zones positive for B-lines corresponding to higher risk.

COVID-19 in recent heart transplant recipients: Clinicopathologic features and early outcomes.

BACKGROUND: The impact of COVID-19 on heart transplant (HTx) recipients remains unclear, particularly in the early post-transplant period. METHODS: We share novel insights from our experience in five HTx patients with COVID-19 (three within 2 months post-transplant) from our institution at the epicenter of the pandemic. RESULTS: All five exhibited moderate (requiring hospitalization, n = 3) or severe (requiring ICU and/or mechanical ventilation, n = 2) illness. Both cases with severe illness were transplanted approximately 6 weeks before presentation and acquired COVID-19 through community spread. All five patients were on immunosuppressive therapy with mycophenolate mofetil (MMF) and tacrolimus, and three that were transplanted within the prior 2 months were additionally on prednisone. The two cases with severe illness had profound lymphopenia with markedly elevated C-reactive protein, procalcitonin, and ferritin. All had bilateral ground-glass opacities on chest imaging. MMF was discontinued in all five, and both severe cases received convalescent plasma. All three recent transplants underwent routine endomyocardial biopsies, revealing mild (n = 1) or no acute cellular rejection (n = 2), and no visible viral particles on electron microscopy. Within 30 days of admission, the two cases with severe illness remain hospitalized but have clinically improved, while the other three have been discharged. CONCLUSIONS: COVID-19 appears to negatively impact outcomes early after heart transplantation.

Left Ventricular Assist Devices and the Kidney.

Left ventricular assist devices (LVADs) are common and implantation carries risk of AKI. LVADs are used as a bridge to heart transplantation or as destination therapy. Patients with refractory heart failure that develop chronic cardiorenal syndrome and CKD often improve after LVAD placement. Nevertheless, reversibility of CKD is hard to predict. After LVAD placement, significant GFR increases may be followed by a late return to near baseline GFR levels, and in some patients, a decline in GFR. In this review, we discuss changes in GFR after LVAD placement, the incidence of AKI and associated mortality after LVAD placement, the management of AKI requiring RRT, and lastly, we review salient features about cardiorenal syndrome learned from the LVAD experience. In light of the growing number of patients using LVADs as a destination therapy, it is important to understand the effect of these devices on the kidney. Additional research and long-term data are required to better understand the relationship between the LVAD and the kidney.

Angiotensin II antagonism is associated with reduced risk for gastrointestinal bleeding caused by arteriovenous malformations in patients with left ventricular assist devices.

BACKGROUND: Angiogenesis is implicated in formation of gastrointestinal arteriovenous malformations (AVMs). Angiotensin II signaling is involved in angiogenesis through the vascular endothelial growth factor (VEGF) and angiopoietin-2 pathways. We hypothesized that angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) therapy would be associated with a reduced risk of all-cause gastrointestinal bleeding (GIB) and AVM-associated GIB in patients with left ventricular assist devices (LVADs). METHODS: We reviewed records of all adult patients receiving a continuous-flow LVAD (HeartMate II or HeartWare HVAD) at Johns Hopkins Hospital between January 2004 and December 2014. Of 192 patients, 131 were included for final analyses. Logistic regression analysis adjusting for demographic, cardiovascular, and laboratory variables was used to assess the association of ACEI or ARB therapy with GIB. RESULTS: Of 131 patients, 100 received ACEI or ARB therapy during LVAD support. Of the 31 patients who did not receive ACEI or ARB, 15 experienced GIB (48%), with 9 caused by AVMs (29%). Of 100 patients who received ACEI or ARB therapy, 24 experienced GIB (24%), with 9 caused by AVMs (9%). Logistic regression hazards model demonstrated that ACEI or ARB therapy was independently associated with a reduced risk for all-cause GIB (odds ratio 0.29, 95% confidence interval 0.12-0.72) and AVM-related GIB (odds ratio 0.23, 95% confidence interval 0.07-0.71). CONCLUSIONS: Angiotensin II antagonism is associated with a reduced risk of AVM-related GIB in patients with LVADs. This association is independent of age, sex, blood pressure, renal function, international normalized ratio, LVAD type, and cardiomyopathy etiology.

Associations of Preimplant Red Blood Cell Distribution Width with Clinical Outcomes Among Individuals with Left Ventricular Assist Devices.

Left ventricular assist devices (LVADs) are increasingly used for end-stage heart failure. However, post-LVAD complications are potentially devastating and remain unpredictable. The red blood cell distribution width (RDW) is a predictor of adverse events in patients with heart failure but has not been studied in the LVAD population. We reviewed laboratory results and clinical outcomes for all continuous flow LVADs implanted from 2004 to June 2014 (N = 188). Cox proportional hazards models adjusted for demographic, cardiovascular, and laboratory variables were used to assess association of preimplant RDW tertiles with mortality, gastrointestinal bleed, infection, pump thrombosis, and stroke more than 1 year of follow-up. Compared with the lowest tertile (RDW < 15.7%), the higher two tertiles (RDW 15.7-18% and RDW >18.1%) had significantly higher risks of mortality (hazard ratio (HR) 6.95 [confidence interval: 2.67-18.10] and HR 4.61 [1.74-12.21], respectively) after full adjustment. Preimplant RDW was not statistically associated with our secondary outcomes. In conclusion, higher preimplant RDW is independently associated with an increased risk of postimplant mortality and infection. Future studies are needed to understand the prognostic ability of RDW and to understand the biologic mechanism underlying this association.

Cardiac Index Declines During Long-Term Left Ventricular Device Support.

To investigate longitudinal trends in valvular and ventricular function with long-term left ventricular assist device (LVAD) therapy, we analyzed hemodynamic and echocardiographic data of patients with at least 2 years of continuous LVAD support. All 130 patients who underwent HeartMate II implantation at our institution between 2005 and 2012 were reviewed. Twenty patients had hemodynamic and echocardiographic evaluations in both the early (0-6 months) and late (2-3 years) postoperative period. Patients on inotropic therapy or temporary mechanical support were excluded. The average times of early and late hemodynamic evaluations were 59 ± 41 days and 889 ± 160 days, respectively. Cardiac index (CI) declined by an average of 0.4 L/min/m2 (P = 0.04) with concomitant increase in pulmonary capillary wedge pressure (PCWP; P = 0.02). The right atrial pressure to PCWP (RAP:PCWP) ratio decreased during LVAD support suggesting improvement in right ventricular function. While there was an increase in degree of aortic insufficiency (AI) at the late follow-up period (P = 0.008), dichotomization by median decline in CI (-0.4 L/min/m2 ) indicated no difference in prevalence of AI among the groups. CI declined in patients with HeartMate II after 2 years of continuous support. An increase in preload and afterload was observed in those with the greatest decline in CI.

Right ventricular afterload sensitivity dramatically increases after left ventricular assist device implantation: A multi-center hemodynamic analysis.

BACKGROUND: Right ventricular (RV) failure is a source of morbidity and mortality after left ventricular assist device (LVAD) implantation. In this study we sought to define hemodynamic changes in afterload and RV adaptation to afterload both early after implantation and with prolonged LVAD support. METHODS: We reviewed right heart catheterization (RHC) data from participants who underwent continuous-flow LVAD implantation at our institutions (n = 244), excluding those on inotropic or vasopressor agents, pulmonary vasodilators or additional mechanical support at any RHC assessment. Hemodynamic data were assessed at 5 time intervals: (1) pre-LVAD (within 6 months); (2) early post-LVAD (0 to 6 months); (3) 7 to 12 months; (4) 13 to 18 months; and (5) very late post-LVAD (18 to 36 months). RESULTS: Sixty participants met the inclusion criteria. All measures of right ventricular load (effective arterial elastance, pulmonary vascular compliance and pulmonary vascular resistance) improved between the pre- and early post-LVAD time periods. Despite decreasing load and pulmonary artery wedge pressure (PAWP), RAP remained unchanged and the RAP:PAWP ratio worsened early post-LVAD (0.44 [0.38, 0.63] vs 0.77 [0.59, 1.0], p < 0.001), suggesting a worsening of RV adaptation to load. With continued LVAD support, both RV load and RAP:PAWP decreased in a steep, linear and dependent manner. CONCLUSIONS: Despite reducing RV load, LVAD implantation leads to worsened RV adaptation. With continued LVAD support, both RV afterload and RV adaptation improve, and their relationship remains constant over time post-LVAD. These findings suggest the RV afterload sensitivity increases after LVAD implantation, which has major clinical implications for patients struggling with RV failure.

Hypertrophic cardiomyopathy: a review.

Hypertrophic cardiomyopathy (HCM) is a global disease with cases reported in all continents, affecting people of both genders and of various racial and ethnic origins. Widely accepted as a monogenic disease caused by a mutation in 1 of 13 or more sarcomeric genes, HCM can present catastrophically with sudden cardiac death (SCD) or ventricular arrhythmias or insidiously with symptoms of heart failure. Given the velocity of progress in both the fields of heart failure and HCM, we present a review of the approach to patients with HCM, with particular attention to those with HCM and the clinical syndrome of heart failure.

Temporary mechanical circulatory support: a review of the options, indications, and outcomes.

Cardiogenic shock remains a challenging disease entity and is associated with significant morbidity and mortality. Temporary mechanical circulatory support (MCS) can be implemented in an acute setting to stabilize acutely ill patients with cardiomyopathy in a variety of clinical situations. Currently, several options exist for temporary MCS. We review the indications, contraindications, clinical applications, and evidences for a variety of temporary circulatory support options, including the intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO), CentriMag blood pump, and percutaneous ventricular assist devices (pVADs), specifically the TandemHeart and Impella.

Risk stratification of ambulatory patients with advanced heart failure undergoing evaluation for heart transplantation.

BACKGROUND: Risk stratification of ambulatory heart failure (HF) patients has relied on peak VO(2)<14 ml/kg/min. We investigated whether additional clinical variables might further specify risk of death, ventricular assist device (VAD) implantation (INTERMACS <4) or heart transplantation (HTx, Status 1A or 1B) within 1 year after HTx evaluation. We hypothesized that right ventricular stroke work index (RVSWI), pulmonary capillary wedge pressure (PCWP) and the model for end-stage liver disease-albumin score (MELD-A) would be additive prognostic predictors. METHODS: We retrospectively collected data on 151 ambulatory patients undergoing HTx evaluation. Primary outcomes were defined as HTx, LVAD or death within 1 year after evaluation. RESULTS: Average age in our cohort was 55 ± 11.1 years, 79.1% were male and 39% had an ischemic etiology (LVEF 21 ± 10.5% and peak VO(2) 12.6 ± 3.5 ml/kg/min). Fifty outcomes (33.1%) were observed (27 HTxs, 15 VADs and 8 deaths). Univariate logistic regression showed a significant association of RVSWI (OR 0.47, p = 0.036), PCWP (OR 2.65, p = 0.007) and MELD-A (OR 2.73, p = 0.006) with 1-year events. Stepwise regression showed an independent correlation of RVSWI<5gm-m(2)/beat (OR 6.70, p < 0.01), PCWP>20 mm Hg (OR 5.48, p < 0.01), MELD-A>14 (OR 3.72, p< 0.01) and peak VO(2)<14 ml/kg/min (OR 3.36, p = 0.024) with 1-year events. A scoring system was developed: MELD-A>14 and peak VO(2)<14-1 point each; and PCWP>20 and RVSWI<5-2 points each. A cut-off at≥4 demonstrated a 54% sensitivity and 88% specificity for 1-year events. CONCLUSIONS: Ambulatory HF patients have significant 1-year event rates. Risk stratification based on exercise performance, left-sided congestion, right ventricular dysfunction and liver congestion allows prediction of 1-year prognosis. Our findings support early and timely referral for VAD and/or transplant.

Computed tomography and cardiac magnetic resonance imaging in pulmonary hypertension.

Recent advances in imaging technology have allowed for better temporal and spatial resolution in cardiovascular imaging. The idea of a "one-stop shop" for anatomical and functional cardiopulmonary and vascular assessment in patients with pulmonary hypertension is very appealing since diagnostic, prognostic, and therapeutic response can be measured. Modalities, such as computed tomography (CT) and cardiac magnetic resonance (CMR), are better suited to image the right heart and associated structures in multiple projections allowing for three-dimensional data sets and image reconstruction. This review will focus on the use of CT and CMR in the assessment of the right ventricle and pulmonary structures as they relate to pulmonary vascular disease.

RV dysfunction in pulmonary hypertension is independently related to pulmonary artery stiffness.

OBJECTIVES: This study investigated whether right ventricular (RV) adaptation to chronic pressure overload is associated with pulmonary artery (PA) stiffness beyond the degree of severity of pulmonary hypertension (PH). BACKGROUND: Increased PA stiffness has been associated with reduced survival in PH. The mechanisms for this association remain unclear. METHODS: Right heart catheterization and cardiac magnetic resonance were performed within 1 week in 124 patients with known or suspected chronic PH. Pulmonary vascular resistance index (PVRI) and PA pressures were quantified from right heart catheterization. Cardiac magnetic resonance included standard biventricular cine sequences and main PA flow quantification with phase-contrast imaging. Indexes of PA stiffness (elasticity, distensibility, capacitance, stiffness index beta, and pulse pressure) were quantified combining right heart catheterization and cardiac magnetic resonance data. RV performance and adaptation were measured by RV ejection fraction, right ventricular mass index (RVMI), RV end-systolic volume index, and right ventricular stroke work index (RVSWI). RESULTS: All indexes of PA stiffness were significantly correlated with measures of RV performance (Spearman rho coefficients ranging from -0.20 to 0.61, p < 0.05). Using multivariate regression analysis, PA elasticity, distensibility, and index beta were independently associated with all measures of RV performance after adjusting PVRI (p ≤ 0.024). PA capacitance was independently associated with RV ejection fraction, RVMI, and RVSWI (p < 0.05), whereas PA pulse pressure was associated with RVMI and RVSWI (p ≤ 0.027). Compared with PVRI, PA elasticity, distensibility, capacitance, and index beta explained 15% to 68% of the variability in RV ejection fraction, RVMI, and RV end-systolic volume index. Relative contributions of PA stiffness for RVSWI were 1.2× to 18.0× higher than those of PVRI. CONCLUSIONS: PA stiffness is independently associated with the degree of RV dysfunction, dilation, and hypertrophy in PH. RV adaptation to chronic pressure overload is related not only to the levels of vascular resistance (steady afterload), but also to PA stiffness (pulsatile load).

Exercise performance in patients with pulmonary hypertension linked to cardiac magnetic resonance measures.

BACKGROUND: The 6-minute walk distance (6MWD) is a useful measure of functional class and has been shown to predict mortality in patients with pulmonary hypertension (PH). Determinants of functional class in PH are incompletely understood. We hypothesized that cardiovascular structure and function, as determined by cardiac magnetic resonance (CMR) imaging, and cardiac hemodynamics, as determined by right heart catheterization (RHC), would predict 6MWD in adult patients with PH. METHODS: Forty-three patients (32 women) with PH underwent RHC, CMR and 6MWD testing within a 3-month period. The 6MWD was correlated with RHC and CMR variables using Spearman rho (r) coefficients. These relationships were further evaluated using linear regression analysis. RESULTS: Median 6MWD was 233.2 (interquartile range 161.6 to 338.4) meters. The 6MWD was correlated with pulmonary artery (PA) elasticity (r = 0.42, p = 0.006), PA average blood flow velocity (r = 0.38, p = 0.014), right ventricular stroke volume index (RVSVI; r = 0.41, p = 0.008), left ventricular SVI (LVSVI; r = 0.36, p = 0.018) and RV stroke work index (RVSWI; r = 0.37, p = 0.017). These associations remained significant after adjustment for age, gender, body mass index and the presence of lung disease. Exercise performance did not correlate with commonly measured indices such as ventricular volume, ejection fraction or pulmonary pressure. CONCLUSIONS: Stroke volume index, PA elasticity and PA average blood flow velocity are novel CMR parameters associated with functional class in PH. CMR can provide insights into determinants of exercise performance and may be a useful tool to non-invasively monitor cardiovascular status in patients with PH.