Impact of exercise on pulmonary artery pressure in patients with heart failure using an ambulatory pulmonary artery pressure monitor.

Background: In this multicenter prospective study, we explored the relationship between pulmonary artery pressure (PAP) at rest and in response to a 6-min walk test (6MWT) in ambulatory patients with heart failure (HF) with an implantable PAP sensor (CardioMEMS, Abbott). Methods: Between 5/2019 and 2/2021, HF patients with a CardioMEMS sensor were recruited from seven sites. PAP was recorded in the supine and seated position at rest and in the seated position immediately post-exercise. Results: In our cohort of 66 patients, mean age was 70 ± 12 years, 67% male, left ventricular ejection fraction (LVEF) < 50% in 53%, mean 6MWT distance was 277 ± 95 meters. Resting seated PAPs were 31 ± 15 mmHg (systolic), 13 ± 8 mmHg (diastolic), and 20 ± 11 mmHg (mean). The pressures were lower in the seated rather than the supine position. After 6MWT, the pressures increased to PAP systolic 37 ± 19 mmHg (p < 0.0001), diastolic 15 ± 10 mmHg (p = 0.006), and mean 24 ± 13 mmHg (p < 0.0001). Patients with elevated PAP diastolic at rest (>15 mmHg) demonstrated a greater increase in post-exercise PAP. Conclusion: The measurement of PAP with CardioMEMS is feasible immediately post-exercise. Despite being well-managed, patients had severely limited functional capacity. We observed a significant increase in PAP with ambulation which was greater in patients with higher baseline pressures.

Survival on Venoarterial Extracorporeal Membrane Oxygenation in Cardiogenic Shock: Which Lactate Is Most Useful?

Prognostic significance of elevated serum lactate in patients on venoarterial extracorporeal membrane oxygenation (ECMO) is widely known. Our objective was to study the utility of lactate measured at different points of time and lactate clearance in predicting the two study endpoints: successful ECMO weaning and hospital survival. Among 238 consecutive patients treated with ECMO, lactic acid was collected before initiating ECMO and then on days 1, 3, 5, and 10 while on ECMO. Out of our cohort, 129 (54.2%) were successfully weaned and 98 (41.2%) were discharged alive. Patients successfully weaned from ECMO had a significantly lower lactic acid level pre-ECMO (p = 0.001), at day 1 (p < 0.001), day 3 (p < 0.001), and day 5 (p = 0.001), compared with unsuccessfully weaned patients. Also, patients who survived hospitalization had significantly lower lactic acid pre-ECMO (p = 0.007), at day 1 (p < 0.001), day 3 (p = 0.001), and day 5 (p = 0.001), compared with those who died in-hospital. With regard to hospital survival, day 3 lactic acid was superior to pre-ECMO lactic acid (p = 0.0385), lactic acid on day 1, lactic acid reduction from pre-ECMO to day 1 (p = 0.0177) and from pre-ECMO to day 3 (p = 0.0361), and a day 3 lactic acid ≤ 1.7 meq/L was the optimal value that predicted hospital survival. On multivariable analysis, day 3 lactic acid independently predicted hospital survival after covariate adjustment (odds ratio [OR], 0.505; 95% confidence interval [CI], 0.290-0.880; p = 0.016). In conclusion, the absolute level of lactic acid while on ECMO support is more important for prognosis than a pre-ECMO level or the magnitude of decline from pre-ECMO to on-ECMO.

Ventricular Assist Devices and Chronic Kidney Replacement Therapy: Technology and Outcomes.

Heart failure and kidney failure are very common conditions, precipitating and exacerbating each other. Left ventricular assist devices (LVADs) represent a relatively new technology for treatment of advanced heart failure. Kidney dysfunction, if present, makes candidate selection for LVADs challenging and contributes to multiple complications while the patients are on an LVAD support. Although kidney function generally improves after LVAD implantation, some patients develop acute and then chronic kidney disease sometimes requiring kidney replacement therapies (KRTs). Overall, chronic KRT in LVAD recipients is feasible and well tolerated, but routine technique of blood pressure monitoring should be adjusted to the continuous blood flow. Both hemodialysis and peritoneal dialysis can be used. Unique challenges for chronic KRT posed by the presence of LVAD are discussed in this review.

Right Atrial Pressure Predicts Mortality Among LVAD Recipients: Analysis of the INTERMACS Database.

INTRODUCTION: Risk stratifying candidates for left ventricular assist device (LVAD) is challenging. While INTERMACS profiles provide some prognostic insights, there is an ongoing search for better tools. We studied pre-LVAD haemodynamic parameters in predicting post-LVAD mortality. METHODS: We analysed the INTERMACS dataset for the ability of right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), pulmonary arterial systolic (PASP) and diastolic pressures (PADP), mean pulmonary artery pressure, transpulmonary gradient, cardiac output, cardiac power output and INTERMACS profiles, all recorded before LVAD implantation, to predict mortality. RESULTS: Among 18,733 patients in the INTERMACS dataset, we found that, RAP was the main significant haemodynamic predictor of mortality (13.1 vs. 14.4 mmHg in survivors and non-survivors, respectively, p<0.001), and a higher RAP also predicted the need for extra-corporeal membrane oxygenation (ECMO) support (p<0.001) and intra-aortic balloon pump (p<0.001). Right atrial pressure had a significantly higher area under the curve (AUC) in predicting mortality compared with PASP (difference between areas 0.0338, p<0.0001), PADP (difference between areas 0.0414, p<0.0001), PCWP (difference between areas 0.0290, p=0.0001) and pulmonary artery pulsatility index (difference between areas 0.0105, p=0.0052). Kaplan Meier survival curves showed that RAP≥13 mmHg was the optimal cut-off value to predict mortality (log-rank p<0.001). On Cox regression analysis, RAP remained an independent predictor of mortality (hazard ratio 1.008, 95% confidence interval 1.003-1.013, p=0.003) after covariate adjustment. According to time of death, a higher RAP remained a significant predictor of mortality at 1 month, 3 months, 6 months, 1 year, and beyond 1 year (all p<0.001). RAP remained a predictor for mortality within INTERMACS profiles. After excluding early deaths (first 3 months), the RAP remained a significant predictor of mortality, while INTERMACS profiles were no longer significant. CONCLUSIONS: In general, haemodynamic variables, as well as other criteria including INTERMACS profiles, are weak predictors of mortality. Right atrial pressure is the main consistent haemodynamic predictor of mortality in LVAD recipients. It outperforms other haemodynamic parameters, and keeps its value within each INTERMACS profile.

Prognostic value of 6-minute walk test and cardiopulmonary exercise test in acute heart failure (from the ESCAPE trial).

Introduction: We aim to study the utility of 6-minute walk distance (6MWD) and cardiopulmonary exercise testing (CPET) in patients with acute systolic heart failure (HF) in predicting post-discharge outcomes. Methods: The ESCAPE trial data was utilized to examine the prognostic role of 6MWD and CPET in predicting 6-month all-cause mortality and rehospitalization in acute HF. Results: The average 6MWD recorded in 271 and 292 patients on admission and discharge was 597 and 765 ft., respectively. Compared with non-survivors, survivors had significantly higher 6MWD on admission (624 vs. 463 ft., P = 0.006) and discharge (789 vs. 636 ft., P = 0.006). Admission and discharge 6MWD had an AUC of 0.629 (P = 0.0047) and 0.628 (P = 0.0093) in predicting mortality. The combination of optimal 6MWD cutoff values of >288 ft. on admission and > 320 ft. on discharge was associated with significantly lower mortality (11.1% vs. 28.3%, OR 0.316, P = 0.002). When dividing the sample into quartiles of increasing walking distance, patients in the 1st quartile had significantly higher mortality on admission (OR 3.59, 95% CI 1.396-9.282, P = 0.008) and discharge (OR 3.66, 95% CI 1.357-9.839, P = 0.01) compared with 4th quartile. P-value for the trend in mortality across quartiles of 6MWD on admission and discharge was 0.016 and 0.047, respectively. Cox proportional hazard analysis revealed that admission (HR 0.632, 95% CI 0.449-0.890, P = 0.009) and discharge 6MWD (HR 0.657, 95% CI 0.467-0.926, P = 0.016) were independent mortality determinants after adjustment for age, creatinine, sodium, systolic blood pressure and NYHA class, all on admission. CPET-derived variables did not predict either outcomes. Conclusion: 6MWD is an independent mortality determinant in advanced systolic HF.

Discharge pulmonary artery pulsatility index predicts morbidity and mortality after acute heart failure: From the ESCAPE trial.

Introduction: The pulmonary artery pulsatility index (PAPI) is a newer hemodynamic index used for assessment of right ventricular performance. We hypothesized that PAPI predicts morbidity and mortality in acute systolic heart failure (HF). Methods: The ESCAPE trial was utilized to identify the prognostic value of PAPI at different time points in patients hospitalized with acute systolic HF who received care assisted with central hemodynamic monitoring. Results: Among 167 patients (age 57 years, 71% men), PAPI significantly increased from admission to optimum hemodynamic day (from 2.88 to 4.09, P < 0.001) and final day (from 3.24 to 3.91, P = 0.032), and the magnitude of increase was strongly associated with markers of decongestion. Discharge PAPI was higher among survivors compared to non-survivors (median 3.1 vs. 2.0, P = 0.0008) and among patients who did not require rehospitalization compared to re-hospitalized patients (median 3.33 vs. 2.67, P = 0.017), both at 6-months. Discharge PAPI predicted mortality with AUC of 0.631 (P = 0.0207), rehospitalization (AUC 0.598, P = 0.0303), and composite of death, rehospitalization, cardiac transplant (AUC 0.621, P = 0.0101). An optimal cutoff value of discharge PAPI ≤2 had the highest sensitivity and specificity in predicting 6-month mortality, rehospitalization and the composite endpoint. Discharge PAPI, had a higher (though non-significant) AUC in predicting death and composite endpoint compared to admission PAPI, next day PAPI and optimal day PAPI. Cox proportional hazard analysis showed that discharge PAPI remained an independent predictor of the composite endpoint (hazard ratio 0.890, 95% CI 0.819-0.967, P = 0.006) after covariate adjustment. Conclusions: Discharge PAPI ≤2 is a marker of intermediate-term morbidity and mortality in acute systolic HF.

Association of Serum Albumin and Severity of Pulmonary Embolism.

Background and Objectives: Inflammation is considered a risk factor for venous thromboembolism. The association between inflammatory markers and the severity of acute pulmonary embolism (APE) has not been explored. Methods: We studied the association between two crude markers of inflammation, serum albumin, and red cell distribution width (RDW) and massive versus non-massive APE. Results: Among 552 consecutive cases of CT-angiogram-confirmed APE, a total of 46 cases (8.3%) had massive APE. Despite similar demographics and comorbidities, patients with massive APE had higher frequency of acute kidney injury (P = 0.005), higher lactic acid (P = 0.011), higher troponin (P = 0.001), higher BNP (P < 0.001), higher frequency of RV dilation (P = 0.017) and hypokinesis (P = 0.003), and higher in-hospital mortality (15.2% vs. 2%, P < 0.001). Patients with massive APE had significantly lower albumin level (median (IQR): 2.8 (2.2, 3.0) vs. 3.2 (2.8, 3.6) gm/dL, P < 0.001) and higher RDW (median (IQR): 14.7 (13.8, 17.1) vs. 14.2 (13.3, 15.6), P = 0.006) compared with non-massive APE. ROC curves showed that albumin and RDW had an AUC of 0.750 (P < 0.001) and 0.621 (P = 0.006) in predicting a massive APE, respectively. The optimal cutoff values for albumin and RDW that had the highest combined sensitivity and specificity for predicting APE was ≤3 gm/dL and >14, for albumin and RDW, respectively. Restricted cubic splines showed a significant association between albumin (P = 0.0002) and RDW (P = 0.0446) and the occurrence of massive APE. After adjustment for patients' age, body mass index, white blood cell count, the requirement of antibiotics during hospitalization, diabetes, RDW, and peak creatinine, serum albumin was independently associated with massive APE (OR 0.234, 95% CI 0.129-0.4242, P < 0.001). Conclusion: low serum albumin is associated with massive APE. This association is likely a proxy for higher inflammatory state in massive compared with non-massive APE.

Higher Diuretic Requirements in Acute Heart Failure With Admission Hyponatraemia Versus Normonatraemia.

BACKGROUND: Diuretic requirements in patients with acute decompensated heart failure (ADHF) and hyponatraemia versus normonatraemia on admission has not been previously explored. METHODS: The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial dataset was utilised to examine the characteristics and diuretic requirements of patients with ADHF with hyponatraemia or normonatraemia on admission. RESULTS: Patients with ADHF and admission hyponatraemia (n = 103, average Na 130.2 meq/L) had a higher degree of congestion evident in higher frequency of jugular venous distension (JVD) >12 cmH2O (p = 0.007), 2+ lower extremity oedema (p = 0.001), and higher right atrial pressure (p = 0.007), compared with normonatraemic patients (n = 327, average Na 138.6 meq/L). Despite a similar baseline furosemide dose in both groups (median 200 mg), the hyponatraemia group received higher in-hospital furosemide (280 vs. 200 mg, in both groups, respectively, p < 0.001) which represented a higher percentage of furosemide utilisation relative to baseline, compared with the normonatraemia group (33% vs 0%, in both groups respectively, p = 0.007). With in-hospital diuresis, the Na level of hyponatraemic subjects started significantly increasing at discharge and up to 6 months after randomisation-all relative to baseline. Hyponatraemic patients had significantly lower systolic blood pressure (SBP) longitudinally at multiple time points compared with normonataremic patients, but it did not further decrease despite the higher furosemide dose in the former group. CONCLUSION: Patients with ADHF and hyponatraemia on admission had a higher degree of congestion and required higher doses of furosemide, compared with normonatraemic subjects. The lower Na and SBP in this instance should not lead to withholding or minimising diuretic dosage which should rather be dictated by volume status.

Serum Albumin as a Biomarker of Pulmonary Sarcoidosis Chronicity.

OBJECTIVES: The duration of sarcoidosis is associated with a higher risk of irreversible pulmonary fibrosis. Sarcoidosis shows diverse clinical presentations, which may lead to a delayed diagnosis due to lack of a specific diagnostic test. Biomarkers of sarcoidosis duration have not been previously explored. MATERIALS AND METHODS: A retrospective study was conducted to investigate independent biomarkers of pulmonary sarcoidosis duration. RESULTS: A total of 108 cases with pulmonary sarcoidosis (mean age 53.4 years; 76.9% females; average duration of sarcoidosis 12 years) were included in the study. We found significant correlation between the duration of sarcoidosis and serum albumin levels (r=-0.414, p=0.0001), sedimentation rate (r=0.375, p=0.001), pulmonary artery systolic pressure (r= 0.468, p=0.003), diffusion capacity (r=-0.334, p=0.002), and age (r=0.492, p=0.0001). A multivariate linear regression analysis revealed that serum albumin levels (ß=-5.242, 95% confidence interval [CI] -8.372 to -2.112, p=0.001) and age (ß=0.367, 95% CI 0.164 to 0.570, p=0.001) were independent correlates of sarcoidosis duration. A receiver operating characteristics curve analysis for prediction of sarcoidosis of a >10 years duration gave an area under curve (AUC) of 0.722 (95% CI 0.620-0.824, p<0.0001) for serum albumin and an AUC of 0.665 (95% CI 0.561-0.768, p<0.004) for age. An albumin level <2.4 gm/dL yielded a 90.5% sensitivity and 98.2% specificity for predicting sarcoidosis of >10 years duration. In comparison, the patient age of 51.5 years yielded a 70.2% sensitivity and 50% specificity for predicting patients with sarcoidosis for >10 years. CONCLUSION: The serum albumin level may be a biomarker of pulmonary sarcoidosis duration and chronicity of disease. Further investigations are required to confirm its predictive ability.

Prevalence, determinants, and correlates of coagulation necrosis and contraction band necrosis in donor hearts.

BACKGROUND: Exploration of pathologic changes in donor hearts and finding the association of pathologic findings with potentially reversible cardiac condition may result in allowing such hearts to recover and be used for transplantation. METHODS: We enrolled consecutive donors from one federally designated Organ Procurement Organization for one calendar year. Hearts rejected for transplantation underwent pathological examination. We studied the association of pathologic findings with the mechanism of death. RESULTS: A total of 81 hearts were rejected for transplantation. The most common pathologic findings were coagulation necrosis (CN) in 17.3% and contraction band necrosis (CBN) in 34.6%. Anoxic brain injury was present in 78.6% of the donors who had CN, and only in 29.9% of those without CN (P = 0.002). CBN was more commonly associated with subarachnoid hemorrhage (17.9% vs 1.9% of donors with and without CBN, P = 0.017). Only hearts with CBN had significantly lower LVEF (P = 0.017). CONCLUSION: Coagulation necrosis and CBN are the most common pathologic findings in the hearts rejected for transplantation. While CN is more prevalent in anoxic brain injury, CBN is more often present in subarachnoid hemorrhage. This may be clinically important because CBN is a pathologic hallmark of catecholamine-induced cardiomyopathy which is potentially reversible.

Response to cardiac resynchronization therapy in non-ischemic cardiomyopathy is unrelated to medical therapy.

INTRODUCTION: Current guidelines recommend at least 3 months of guideline-directed medical therapy (GDMT) for patients with a new onset of non-ischemic cardiomyopathy (NICM) and left bundle branch block (LBBB) prior to cardiac resynchronization therapy (CRT). For patients who do not receive optimal GDMT, response to CRT is unknown. METHODS: Patients with NICM and LBBB with QRS ≥ 120 ms were identified among all patients who underwent CRT. Patients who received GDMT for ≥ 3 months before CRT were compared to those who did not. Among 38 patients who met inclusion criteria, 24 received optimal GDMT prior to implantation (Group 1) and 14 did not (Group 2). RESULTS: QRS narrowing occurred in Group 1 (160 ± 9 ms to 138 ± 20 ms, P = 0.001) and Group 2 (160 ± 17 ms to 139 ± 30 ms, P = 0.021). Left ventricular ejection fraction (LVEF) improvement occurred in Group 1 (21.3 ± 5.9% to 34.4 ± 13.9%, P < 0.001) and Group 2 (18.8 ± 4.7% to 31.1 ± 13%, P = 0.010). QRS interval and LVEF changes were similar between groups (P = NS). There was a trend towards greater CRT response in women than in men, although differences did not reach statistical significance. CONCLUSION: In patients with NICM and LBBB, CRT is associated with improvements in LV size and function independent of prior GDMT. The ability of resynchronization to improve LVEF without GDMT suggests that CRT without waiting 3 months for GDMT optimization may benefit some patients with NICM and LBBB.

Rise of first follow-up sodium in patients hospitalized with acute heart failure is associated with better outcomes.

INTRODUCTION: The prognostic effect of the direction of change in sodium (Na) level from admission to subsequent check in patients with acute heart failure (HF) has not been previously explored. METHODS: The ESCAPE trial data was utilized to study whether the rise of 1st follow-up Na (at day 3) relative to admission (among patients with admission hyponatremia) is associated with favorable outcomes. The study endpoints were all-cause rehospitalization and a composite of death, rehospitalization and cardiac transplant, both up to 6-month after discharge. RESULTS: Patients with rise of 1st follow-up Na (n = 43) had an average admission Na of 130.1 meq/L which increased to 134 meq/L at day 3 (P < 0.001), while patients without rise of 1st follow up Na (n = 46) had an admission Na of 131 meq/L which decreased to 128.9 meq/L at day 3 (P < 0.001). There was an inverse association between the magnitude of change in Na level from admission to day 3 and the magnitude of change in blood urea nitrogen (BUN, r = -0.304, P = 0.004), creatinine (r = -0.401, P < 0.001) and weight (r = -0.279, P = 0.011) during the same time frame. Among those 89 cases, 56 (63%) were rehospitalized and 70 (79%) experienced the composite endpoint. Patients without rise in 1st follow-up Na had higher frequency of rehospitalization (76.1% vs. 48.8%, univariate Odds ratio (OR) 1.778, 95% CI 1.174-2.693, P = 0.009) and composite endpoint (89.1% vs. 67.4%, univariate OR 1.779, 95% CI 1.208-2.619, P = 0.017), compared with those with Na rise. Cox regression analysis showed that rise in 1st follow-up Na was independently associated with reduced rehospitalization (Hazard ratio (HR) 0.429, 95% CI 0.191-0.960, P = 0.04) and the composite endpoint (HR 0.430, 95% CI 0.201-0.920, P = 0.03) after covariate adjustment. CONCLUSION: Rise of first follow-up Na in patients with HF decompensation and hyponatremia on admission is associated with favorable intermediate-term outcomes.

Internist, anesthesiologist and surgeon use of ketogenic diet.

Ketogenic diet is being increasingly utilized in recent decades because of its success as an effective tool for short and intermediate-term weight loss. Promoting physiological ketosis from a drastically low carbohydrate diet is the fundamental basis for this diet regime. Though debated, these diets have been demonstrated to be effective, at least in the short- to medium terms, to manage excess weight, hyperlipidemia, and other cardiovascular risk factors. We reviewed the cardiovascular, metabolic, anesthetic, and postsurgical profiles in the literature and summarized technical issues of anesthesia and surgery along with long-term changes from published papers. Doubts with ketogenic diet were raised due to possible renal damage caused by significant excretion of nitrogen found in animal models, the effects of acidosis, and the concerns of increasing triglycerides and cholesterol levels. Though current literature supports the efficacy of very low carbohydrate keto-diets their potential negative effects on renal function and acidosis are debated. An increase in nitrogen excretion during protein metabolism in the postoperative period could lead to renal damage. Research on the value of ketogenic diets is emerging because of its value in weight loss and in managing other pathologies.