Correction to: Hypertensive acute heart failure: a critical perspective on definition, epidemiology, pathophysiology, and prognosis-a narrative review: a joint session with the Romanian Society of Cardiology (part II).

Hypertensive acute heart failure (HT-AHF) has historically been recognized as a distinct clinical phenotype of AHF, characterized by acute pulmonary congestion in the context of elevated systolic blood pressure (SBP), typically > 140mmHg. However, emerging evidence has begun to challenge the diagnostic accuracy, clinical utility, and relevance of this category. A main criticism of HT-AHF is its considerable overlap with other AHF clinical profiles, including acute decompensated heart failure (ADHF) and acute pulmonary oedema (APO). Clinical features such as dyspnea and pulmonary congestion are not unique to HT-AHF. Additionally, some HT-AHF patients concurrently fulfill diagnostic criteria for the ADHF phenotype, including a history of HF or signs of volume overload, leading to ambiguity in diagnosis. HT-AHF is associated with very low in-hospital mortality (0-2%) compared to other AHF phenotypes. Notably, there is no robust evidence linking high SBP to poor short- or long-term outcomes, nor are there randomized clinical trials validating distinct management strategies for HT-AHF. Often associated with the management of HT-AHF, vasodilators have shown limited benefit across trials, contributing to a downgrade in guideline recommendations. The relatively favorable short-term prognosis and the lack of a standardized, evidence-based treatment approach weaken the rationale for classifying HT-AHF as a standalone AHF category. Given the heterogeneity of clinical presentations, overlap with other AHF phenotypes, and lack of prognostic distinction or targeted therapy, the term "AHF with high SBP at presentation" offers a more flexible and clinically meaningful descriptor, encouraging a more nuanced approach to treatment.

Background Better characterization of the different pathophysiological mechanisms involved in normotensive and hypertensive acute heart failure (AHF) might help to develop novel individualized treatment strategies. Methods The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring B-type natriuretic peptide (BNP) as well as high-sensitive cardiac troponin T (hs-cTnT) in 1,152 unselected patients presenting with AHF to the emergency department (derivation cohort). Systolic blood pressure (SBP) of 90 - 140 mmHg at presentation was used to define normotensive AHF. Findings regarding hemodynamic cardiac stress and cardiomyocyte injury were validated in a second independent AHF cohort (validation cohort; n=324). Results In the derivation cohort 667 (58%) patients had hypertensive AHF. Hemodynamic cardiac stress, as quantified by BNP levels, was significantly higher in normotensive AHF as compared to hypertensive AHF (1,105 pg/mL versus 827 pg/mL, p<0.001). In addition, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF (41 ng/L versus 33 ng/L, p<0.001). These findings were confirmed in the validation cohort. Table 1. Cardiac stress and myocardial necrosis as quantified by BNP and hs-cTnT plasma concentrations Overall Hypertensive AHF Normotensive AHF p-value BNP in pg/ml, median (IQR) 974 (536–1,712) 827 (448–1,419) 1,105 (611–1,956) <0.001 hs-cTnT in ng/L, median (IQR) 37 (22–67) 33 (19–59) 41 (24–71) <0.001 BNP = B-type natriuretic peptide; hs-cTnT = high-sensitivity cardiac Troponin T; IQR = inter-quartile range. Figure 1 Conclusion Biomarker profiling revealed that the extent of hemodynamic stress and cardiomyocyte injury is different in patients with normotensive and hypertensive AHF. This characterization could help to understand AHF phenotypes better, which in turn may lead to more specific management in future, thus improving the dismal prognosis in these patients. Acknowledgement/Funding European Union, Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel

The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments. The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90-140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324). In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF [1105 (611-1956) versus 827 (448-1419) pg/mL, and 5890 (2959-12,162) versus 4068 (1986-8118) pg/mL, both p < 0.001, respectively]. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF [41 (24-71) versus 33 (19-59) ng/L, p < 0.001]. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31-2.10; p < 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort. Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.

22 Nitroglycerin for Treatment of Acute, Hypertensive Heart Failure: Bolus, Drip or Both?

Acute heart failure (AHF) is a condition commonly affecting elderly patients. Heart failure is classified based on systolic blood pressure (SBP) into hypertensive (SBP ≥ 140 mm Hg), and normotensive (SBP < 140 mm Hg) categories. Differences in the pathophysiological mechanisms associated with each type of AHF may result in varying levels of biomarkers released by the heart during the episode, including N-terminal B-type natriuretic peptide (NT-proBNP), high-sensitivity (hs)-troponin I, and endothelin-1. Currently, there are no studies comparing the levels of cardiac biomarkers between normotensive and hypertensive AHF. Therefore, this study aimed to compare the levels of NT-proBNP, hs-troponin I, and endothelin-1 in patients with hypertensive and normotensive AHF. A cross-sectional study was conducted in 104 patients with AHF (40 hypertensive, 64 normotensive) at M. Djamil General Hospital from August 2021 to November 2022. Clinical characteristics, hemodynamic parameters, and cardiac biomarker levels were assessed and compared between groups. Patients with hypertensive AHF had significantly higher sodium and chloride levels with lower urea levels. Echocardiographic assessment showed higher left ventricular ejection fraction (LVEF) (35.72% vs. 35.25%, P = 0.857), cardiac output (3.0 vs. 2.9 L/min, P = 0.669), and systemic vascular resistance (SVR) (2,276 vs. 2,200, P = 0.693), with lower tricuspid annular plane systolic excursion (TAPSE) (1.7 vs. 1.8 cm, P = 0.717), and estimated right atrial pressure (eRAP) > 8 (87.5% vs. 92.6%, P = 0.517) in normotensive AHF patients compared to hypertensive group, although there was no statistically significant difference between the two groups. The biomarkers test showed higher hs-troponin I levels (281 vs. 72.8 ng/L, P = 0.039) in normotensive AHF than those in hypertensive group. No significant differences were observed in endothelin-1 (12.12 vs. 12.02 pg/L, P = 0.510) and NT-proBNP levels (5,410 vs. 4,712 pg/mL, P = 0.122) between groups. In patients with normotensive AHF, higher levels of hs-troponin I were observed, with no significant differences in other cardiac biomarkers. A higher proportion of males and a lower prevalence of hypertension as a risk factor were also noted in normotensive AHF, although these differences were not statistically significant.

Although acute heart failure (AHF) is a common disease associated with significant symptoms, morbidity and mortality, the diagnosis, risk stratification and treatment of patients with hypertensive acute heart failure (H-AHF) still remain a challenge in modern medicine. Despite great progress in diagnostic and therapeutic modalities, this disease is still accompanied by a high rate of both in-hospital (from 3.8% to 11%) and one-year (from 20% to 36%) mortality. Considering the high rate of rehospitalization (22% to 30% in the first three months), the treatment of this disease represents a major financial blow to the health system of each country. This disease is characterized by heterogeneity in precipitating factors, clinical presentation, therapeutic modalities and prognosis. Since heart decompensation usually occurs quickly (within a few hours) in patients with H-AHF, establishing a rapid diagnosis is of vital importance. In addition to establishing the diagnosis of heart failure itself, it is necessary to see the underlying cause that led to it, especially if it is de novo heart failure. Given that hypertension is a precipitating factor of AHF and in up to 11% of AHF patients, strict control of arterial blood pressure is necessary until target values are reached in order to prevent the occurrence of H-AHF, which is still accompanied by a high rate of both early and long-term mortality.

Role of high-dose intravenous nitrates in hypertensive acute heart failure

To review the key clinical and research questions regarding blood pressure (BP) reduction with vasodilators in the early management of hypertensive acute heart failure (H-AHF). Despite numerous AHF vasodilator clinical trials in the past two decades, virtually none has studied a population where vasoconstriction is the predominant physiology, and with the agents and doses most commonly used in contemporary practice. AHF patients are remarkably heterogenous by vascular tone, and this heterogeneity is not always discernible through BP or clinical exam. Emerging data suggest that diastolic BP may be a stronger correlate of vascular tone in AHF than systolic BP, despite the latter historically serving as a key inclusion criterion for vasodilator clinical trials. Existing data are limited. A clinical trial that evaluates vasodilators in a manner of use consistent with contemporary practice, specifically within the subpopulation of patients with true H-AHF, is greatly needed. Until then, observational data supports long-standing vasodilators such as nitroglycerin, administered by IV bolus, and with goal reduction of SBP ≤25% as a safe first-line approach for patients with severe H-AHF presentations.

In spite of advances in our understanding of acute heart failure (AHF) and its different phenotypic expressions, AHF management is still centered on volume removal with intravenous diuretics. This narrative review describes the pathophysiology underlying hypertensive AHF and appraises therapies targeting these mechanisms. Vascular redistribution rather than volume overload may be the primary determinant of elevated cardiac filling pressures and subsequent pulmonary congestion in patients with hypertensive AHF; in these patients, vasodilators should be the predominant treatment. Additional therapy with diuretics in hypertensive AHF should be relegated to the treatment of overt volume overload or persistent congestion in spite of optimized hemodynamics. Intravenous nitroglycerin at high doses can rapidly achieve pulmonary decongestion and reduce downstream critical care needs in these patients. The therapeutic role for synthetic peptides with vasodilator properties has yet to be defined. Evidence supporting both old and new vasodilator therapies is limited by a paucity of well-designed studies and failure to demonstrate improvement in long-term outcomes. Targeted study of this phenotype of AHF is needed before vasodilator therapies become incorporated into treatment guidelines.

Clevidipine in acute heart failure: Results of the A Study of Blood Pressure Control in Acute Heart Failure—A Pilot Study (PRONTO)

Management approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H-AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease that is based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H-AHF.

Clinical and Research Considerations for Patients With Hypertensive Acute Heart Failure: A Consensus Statement from the Society of Academic Emergency Medicine and the Heart Failure Society of America Acute Heart Failure Working Group

BackgroundAfterload reduction with bolus enalaprilat is used by some for management of acute hypertensive heart failure (HF) but existing data on the safety and effectiveness of this practice are limited. The purpose of this study was to evaluate the clinical effects of bolus enalaprilat when administered to patients with acute hypertensive heart failure.FindingsWe performed an IRB-approved retrospective cohort study of patients who presented to the emergency department of a large urban academic hospital. Patients were identified by pharmacy record and included if they received enalaprilat intravenous (IV) bolus in the setting of acute hypertensive HF. A total of 103 patients were included. Patients were hypertensive on presentation (systolic blood pressure [SBP] = 195.2 [SD ± 32.3] mmHg) with significantly elevated mean NT-proBNP levels (3797.8 [SD ± 6523.2] pg/ml). The mean dose of enalaprilat was 1.3 [SD ± 0.7] mg, with most patients (76.7%) receiving a single 1.25 mg bolus. By 3 h post­enalaprilat, SBP had decreased substantially (−30.5 mmHg) with only 2 patients (1.9%) developing hypotension. Renal function was unaffected, with no significant change in serum creatinine by 72 h. In the 30 days post-admission, patients spent an average of 23 [SD ± 7.5] days alive and out of hospital.ConclusionsIn this retrospective cohort of acute hypertensive HF patients, bolus IV enalaprilat resulted in a substantial reduction in systolic BP without adverse effect.

Graves’ disease, a well-known cause of hyperthyroidism, is an autoimmune disease with multi-system involvement. More prevalent among young women, it appears as an uncommon cardiovascular complication during pregnancy, posing a diagnostic challenge, largely owing to difficulty in detecting the complication, because of a low index of suspicion of Graves’ disease presenting during pregnancy. Globally, cardiovascular disease is an important factor for pregnancy-related morbidity and mortality. Here, we report a case of 24 years old primi with Graves’ disease detected for the first time in pregnancy presenting with acute hypertensive left heart failure and severe pre-eclampsia. She was found to have abnormal thyroid function tests compatible with the diagnosis of Graves’ disease. Emphasis is placed on the spectrum of clinical presentations of Graves’ disease, and the importance of considering this thyroid disorder as a possible aetiological factor for such a presentation in pregnancy.

In treating patients with acute hypertensive heart failure we often try preload-reduction therapy using diuretics or vasodilators, but this may frequently produce a considerable decrease in cardiac output, particularly in hypertensive patients with diastolic dysfunction. Therefore, it is important from the clinical standpoint to predict the change in cardiac output following preload-reduction therapy. The objective of this study was to assess whether the change in cardiac output in association with preload-reduction therapy is predictable before treatment by analysis of mitral flow velocity patterns in patients with hypertensive heart failure. Changes in left ventricular volumes and cardiac output in association with preload-reduction therapy and Doppler echocardiographic parameters of the mitral flow velocity pattern before treatment were studied in 18 patients with hypertensive heart failure. Cardiac output increased in six patients with systolic dysfunction (fractional shortening < 25%). In the other 12 patients (those with normal systolic function), the changes in cardiac output were homogenous among the patients. In this subset there was a greater decrease in cardiac output in patients with a shorter deceleration time. Thus, analysis of deceleration time of the early diastolic filling wave before treatment may be useful in estimating the change in cardiac output following preload reduction in patients with hypertensive heart failure due to diastolic dysfunction.