Hemodynamic Response to Acute Volume Load and Endomyocardial NO-synthase Gene Expression in Heart Transplant Recipients.

A pulmonary capillary wedge pressure (PCWP) >18 mm Hg following volume load has been proposed as a partition value for the detection of heart failure with preserved ejection fraction. As hemodynamic changes in filling pressures (FP) have been attributed to a nitric oxide (NO)-mediated rightward shift of the pressure-volume relationship, we investigated the hemodynamic response to volume load in heart transplant recipients (HTx) and examined the role of inducible NO synthase (iNOS) gene expression on diastolic function changes. Methods: In 36 HTx, FPs were measured before and after volume load, following which Starling curves were constructed using PCWP and cardiac index (CI). Patients were categorized into those with normal (group A, n = 21) and abnormal hemodynamics (group B, n = 15, PCWP >15 mm Hg at rest or >18 mm Hg following volume load). For the establishment of the potential role of NO, endomyocardial iNOS gene expression level was measured. Results: Except for PCWP (P < 0.001) and mean pulmonary artery pressure (P < 0.001) no differences in age, baseline characteristics, and ejection fraction were observed between both groups, and volume load significantly increased PCWP in both groups (group A: P < 0.001 and group B: P < 0.001) without any change in heart rate. Interestingly, volume load significantly increased CI in group A (P < 0.001) but not in group B (P = 0.654), and the Starling curves revealed a higher CI at any given PCWP in group A together with significantly higher iNOS gene expression (P = 0.009). Conclusions: In HTx, volume load increases FP and unmasks the presence of left ventricular diastolic dysfunction. Interestingly, following saline load group B shows a blunted Starling response, with higher PCWP and lack of CI increase at any given PCWP. The higher iNOS gene expression level in group A suggests a potential role of NO as mediator of diastolic function.

Acetazolamide in Decompensated Heart Failure with Volume Overload trial (ADVOR): baseline characteristics.

AIMS: To describe the baseline characteristics of participants in the Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial and compare these with other contemporary diuretic trials in acute heart failure (AHF). METHODS AND RESULTS: ADVOR recruited 519 patients with AHF, clinically evident volume overload, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and maintenance loop diuretic therapy prior to admission. All participants received standardized loop diuretics and were randomized towards once daily intravenous acetazolamide (500 mg) versus placebo, stratified according to study centre and left ventricular ejection fraction (LVEF) (≤40% vs. >40%). The primary endpoint was successful decongestion assessed by a dedicated score indicating no more than trace oedema and no other signs of congestion after three consecutive days of treatment without need for escalating treatment. Mean age was 78 years, 63% were men, mean LVEF was 43%, and median NT-proBNP 6173 pg/ml. The median clinical congestion score was 4 with an EuroQol-5 dimensions health utility index of 0.6. Patients with LVEF ≤40% were more often male, had more ischaemic heart disease, higher levels of NT-proBNP and less atrial fibrillation. Compared with diuretic trials in AHF, patients enrolled in ADVOR were considerably older with higher NT-proBNP levels, reflecting the real-world clinical situation. CONCLUSION: ADVOR is the largest randomized diuretic trial in AHF, investigating acetazolamide to improve decongestion on top of standardized loop diuretics. The elderly enrolled population with poor quality of life provides a good representation of the real-world AHF population. The pragmatic design will provide novel insights in the diuretic treatment of patients with AHF.

Simplified Assessment of the Index of Microvascular Resistance.

BACKGROUND: To validate a simplified invasive method for the calculation of the index of microvascular resistance (IMR). METHODS: This is a prospective, single-center study of patients with chronic coronary syndromes presenting with nonobstructive coronary artery disease. IMR was obtained using both intravenous (IV) adenosine and intracoronary (IC) papaverine. Each IMR measurement was obtained in duplicate. The primary objective was the agreement between IMR acquired using adenosine and papaverine. Secondary objectives include reproducibility of IMR and time required for the IMR measurement. RESULTS: One hundred and sixteen IMR measurements were performed in 29 patients. The mean age was 68.8 ± 7.24 years, and 27.6% was diabetics. IMR values were similar between papaverine and adenosine (17.7 ± 7.26 and 20.1 ± 8.6, p=0.25; Passing-Bablok coefficient A 0.58, 95% CI -2.42 to 3.53; coefficient B 0.90, 95% CI -0.74 to 1.07). The reproducibility of IMR was excellent with both adenosine and papaverine (ICC 0.78, 95% CI 0.63 to 0.88 and ICC 0.93, 95% CI 0.87 to 0.97). The time needed for microvascular assessment was significantly shortened by the use of IC papaverine (3.23 (2.84, 3.78) mins vs. 5.48 (4.94, 7.09) mins, p < 0.0001). CONCLUSION: IMR can be reliably measured using IC papaverine with similar results compared to intravenous infusion of adenosine with increased reproducibility and reduced procedural time. This approach simplifies the invasive assessment of the coronary microcirculation in the catheterization laboratory.

Left-Sided Implantation of a Defibrillator Lead in Persistent Left Superior Vena Cava.

Persistent left superior vena cava (PLSVC) is a congenital venous abnormality, characterized by an enlarged coronary sinus, in most cases without haemodynamic consequences. We report the case of a patient with systolic heart failure undergoing implantation of a defibrillator lead through a PLSVC which was diagnosed at the moment of implantation. LEARNING POINTS: Persistent left superior vena cava (PLSVC) can be incidentally diagnosed during a procedure such as a left-sided central venous line or pacemaker implantation, and can be confirmed by manual contrast injection during the procedure.An enlarged coronary sinus on echocardiography should raise suspicion of PLSVC which can be confirmed by administration of echo-contrast or agitated saline in the left arm.Although lead implantation through a PLSVC is technically feasible, difficulties in lead positioning may be encountered because of the acute angle between the origin of the coronary sinus and the tricuspid valve.

DISENGAGE Registry.

BACKGROUND: During fractional flow reserve (FFR) measurement, the simple presence of the guiding catheter (GC) within the coronary ostium might create artificial ostial stenosis, affecting the hyperemic flow. We aimed to investigate whether selective GC engagement of the coronary ostium might impede hyperemic flow, and therefore impact FFR measurements and related clinical decision-making. METHODS: In the DISENGAGE (Determination of Fractional Flow Reserve in Intermediate Coronary Stenosis With Guiding Catheter Disengagement) registry, FFR was prospectively measured twice (with GC engaged [FFReng] and disengaged [FFRdis]) in 202 intermediate stenoses of 173 patients. We assessed (1) whether ΔFFReng-FFRdis was significantly different from the intrinsic variability of repeated FFR measurements (test-retest repeatability); (2) whether the extent of ΔFFReng-FFRdis could be clinically significant and therefore able to impact clinical decision-making; and (3) whether ΔFFReng-FFRdis related to the stenosis location, that is, proximal and middle versus distal coronary segments. RESULTS: Overall, FFR significantly changed after GC disengagement: FFReng 0.84±0.08 versus FFRdis 0.80±0.09, P<0.001. Particularly, in 38 stenoses (19%) with FFR values in the 0.81 to 0.85 range, GC disengagement was associated with a shift from above to below the 0.80 clinical cutoff, resulting into a change of the treatment strategy from medical therapy to percutaneous coronary intervention. The impact of GC disengagement was significantly more pronounced with stenoses located in proximal and middle as compared with distal coronary segments (ΔFFReng-FFRdis, proximal and middle 0.04±0.03 versus distal segments 0.03±0.03; P=0.042). CONCLUSIONS: GC disengagement results in a shift of FFR values from above to below the clinical cutoff FFR value of 0.80 in 1 out of 5 measurements. This occurs mostly when the stenosis is located in proximal and middle coronary segments and the FFR value is close to the cutoff value.

Fatal Ischaemic Stroke During COVID-19 and Acute Lung Injury.

Severe COVID-19 may predispose to both venous and arterial thrombosis. We describe a patient with acute ischaemic stroke while suffering from COVID-19 and respiratory failure, necessitating mechanical ventilation. Deep sedation may delay diagnosis. LEARNING POINTS: A thrombotic stroke can complicate severe COVID-19.Prolonged deep sedation during mechanical ventilation of COVID-19 patients may delay the diagnosis of stroke.The hypercoagulability and a thrombo-inflammatory response in COVID-19 is characterized by an increase in D-dimers and fibrinogen.

Procedural microvascular activation in long lesions treated with bioresorbable vascular scaffolds or everolimus-eluting stents: the PROACTIVE trial.

AIMS: Significant platelet activation after long stented coronary segments has been associated with periprocedural microvascular impairment and myonecrosis. In long lesions treated either with an everolimus-eluting bioresorbable vascular scaffold (BVS) or an everolimus-eluting stent (EES), we aimed to investigate (a) procedure-related microvascular impairment, and (b) the relationship of platelet activation with microvascular function and related myonecrosis. METHODS AND RESULTS: Patients (n=66) undergoing elective percutaneous coronary intervention (PCI) in long lesions were randomised 1:1 to either BVS or EES. The primary endpoint was the difference between groups in changes of pressure-derived corrected index of microvascular resistance (cIMR) after PCI. Periprocedural myonecrosis was assessed by high-sensitivity cardiac troponin T (hs-cTnT), platelet reactivity by high-sensitivity adenosine diphosphate (hs-ADP)-induced platelet reactivity with the Multiplate Analyzer. Post-dilatation was more frequent in the BVS group, with consequent longer procedure time. A significant difference was observed between the two groups in the primary endpoint of ΔcIMR (p=0.04). hs-ADP was not different between the groups at different time points. hs-cTnT significantly increased after PCI, without difference between the groups. CONCLUSIONS: In long lesions, BVS implantation is associated with significant acute reduction in IMR as compared with EES, with no significant interaction with platelet reactivity or periprocedural myonecrosis.

Sacubitril/valsartan in heart failure and end-stage renal insufficiency.

The aim of this report is to describe the feasibility and tolerability of medical treatment with sacubitril/valsartan in a patient treated with hemodialysis. We describe the case of a 67-year-old man with heart failure with reduced ejection fraction due to an ischemic cardiomyopathy and renal insufficiency undergoing hemodialysis. Because of worsening heart failure with no other therapeutic options, a treatment with sacubitril/valsartan was started. Although this patient had a very low systolic blood pressure, he could tolerate a moderate dose of 49/51 mg twice daily. After initiation of sacubitril/valsartan, there was a symptomatic improvement with a clear reduction NT-proBNP, accompanied by a decrease in filling pressures. In conclusion, in this patient with severe heart failure undergoing hemodialysis, treatment with sacubitril/valsartan was feasible, safe, and improved heart failure symptoms.

Serial strain imaging in takotsubo syndrome with concomitant coronary artery disease.

We report a case of takotsubo syndrome (TTS) triggered by herpes encefalitis in the presence of significant triple vessel coronary artery disease (CAD). The typical ECG abnormalities, moderately elevated cardiac enzymes with disproportionally elevated brain natriuretic peptide (BNP) as well as the typical wall motion abnormalities on echocardiography and left ventricular (LV) angiography, were consistent with the diagnosis of TTS with concomitant CAD rather than an acute coronary syndrome. The normalization of the wall motion abnormalities, ejection fraction and longitudinal strain on serial echocardiography all support the diagnosis of takotsubo syndrome, especially in challenging cases.

A rapid evolution from effusive-constrictive to constrictive pericarditis.

We present a case of a 69-year-old woman with constrictive pericarditis preceded by effusive-constrictive pericarditis. Echocardiography on admission revealed a mild pericardial effusion, pericardial thickening and a constrictive physiology in the absence of RV pressure/volume overload suggesting effusive-constrictive pericarditis. Echocardiographic follow-up showed gradual disappearance of the effusion within one month and an important thickening of the visceral and parietal pericardium up to 9 mm. Respiratory variation of the mitral and tricuspid inflow, prominent diastolic septum shift and high mitral annular TDI-velocities were indicative of constrictive pericarditis. Subsequent left/right heart catheterisation 3 months after the initial diagnosis confirmed constrictive pericarditis with elevated diastolic pressures equalized in the four heart chambers, square root sign, respiratory discordant change of the left and right systolic pressures and an inspiratory increase of the right atrial pressure. The patient remained symptomatic under treatment with aspirin and diuretics. A parietal and visceral pericardectomy was successfully performed with a favourable clinical evolution.

Nonmyocardial production of ST2 protein in human hypertrophy and failure is related to diastolic load.

OBJECTIVES: This study was designed to investigate: 1) relationships between serum ST2 levels and hemodynamic/neurohormonal variables; 2) myocardial ST2 production; and the 3) expression of ST2, membrane-anchored ST2L, and its ligand, interleukin (IL)-33, in myocardium, endothelium, and leukocytes from patients with left ventricular (LV) pressure overload and congestive cardiomyopathy. BACKGROUND: Serum levels of ST2 are elevated in heart failure. The relationship of ST2 to hemodynamic variables, source of ST2, and expression of ST2L and IL-33 in the cardiovascular system are unknown. METHODS: Serum ST2 (pg/ml; median [25th, 75th percentile]) was measured in patients with LV hypertrophy (aortic stenosis) (n = 45), congestive cardiomyopathy (n = 53), and controls (n = 23). ST2 was correlated to N-terminal pro-brain natriuretic peptide, C-reactive protein, and hemodynamic variables. Coronary sinus and arterial blood sampling determined myocardial gradient (production) of ST2. The levels of ST2, ST2L, and IL-33 were measured (reverse transcriptase-polymerase chain reaction) in myocardial biopsies and leukocytes. The ST2 protein production was evaluated in human endothelial cells. The IL-33 protein expression was determined (immunohistochemistry) in coronary artery endothelium. RESULTS: The ST2 protein was elevated in aortic stenosis (103 [65, 165] pg/ml, p < 0.05) and congestive cardiomyopathy (194 [69, 551] pg/ml, p < 0.01) versus controls (49 [4, 89] pg/ml) and correlated with B-type natriuretic peptide (r = 0.5, p < 0.05), C-reactive protein (r = 0.6, p < 0.01), and LV end-diastolic pressure (r = 0.38, p < 0.03). The LV ST2 messenger ribonucleic acid was similar in aortic stenosis and congestive cardiomyopathy versus control (p = NS). No myocardial ST2 protein gradient was observed. Endothelial cells secreted ST2. The IL-33 protein was expressed in coronary artery endothelium. Leukocyte ST2L and IL-33 levels were highly correlated (r = 0.97, p < 0.001). CONCLUSIONS: In human hypertrophy and failure, serum ST2 correlates with the diastolic load. Though the heart, endothelium, and leukocytes express components of ST2/ST2L/IL-33 pathway, the source of circulating serum ST2 is extra-myocardial.

GLU-27 variant of beta2-adrenergic receptor polymorphisms is an independent risk factor for coronary atherosclerotic disease.

OBJECTIVE: Arg16Gly and Gln27Glu polymorphism of beta(2)-adrenergic receptors (beta 2AR) have been associated with several risk factors for coronary atherosclerotic disease (CAD). Nevertheless, conflicting data have been reported concerning their influence on CAD and cardiovascular clinical events. AIM: To investigate whether (a) beta 2AR polymorphisms are associated with CAD; and (b) the potential impact, if any, of these polymorphisms on cardiovascular clinical events in patients presenting with angina-like pain or silent ischemia. METHODS AND RESULTS: We screened 786 consecutive patients referred to cardiac catheterization because of angina-like pain or silent ischemia for Arg16Gly, Gln27Glu, Thr164Ile beta 2AR polymorphisms. Patients were divided in 2 groups according to the presence or absence of CAD at the angiography. Hundred subjects from blood donor center served as controls. Clinical endpoints were evaluated at baseline and up to 6 years follow-up. Glu-27 homozygous genotype and Glu-27 allele (Glu-27, allele frequency: 47% CAD versus 39% NO CAD, p<0.05) were more frequent in patients with CAD. At multivariate analysis, patients carrying Glu-27 allele showed a significantly higher risk of developing CAD (OR: 1.78, 95% CI: 1.21-2.63, p=0.004). At clinical follow-up, a higher incidence of coronary revascularization was noted in Glu-27 homozygotes as compared with Gln-27 homozygote patients. CONCLUSIONS: In patients at high risk for CAD and/or angina-like pain, Glu-27 allele of beta2 adrenergic receptor polymorphism is an independent risk factor for CAD and appears to be associated with higher incidence of myocardial revascularization.