[Current role of cardiac magnetic resonance (CMR) in diagnosis and therapy of myocardial diseases]. / Aktueller Stellenwert der Kardio-MRT in Diagnostik und Therapie.

Cardiac magnetic resonance is the only imaging modality, that allows for characterising myocardial tissue with respect to fibrosis and edema. It has therefore become gold standard in diagnosing myocardial inflammation by combining scar, fibrosis and edema imaging. Recent developements in T1- and T2 mapping have improved diagnostic accuracy and prognostic information.

Enhancement of cardiac lymphangiogenesis by transplantation of CD34+VEGFR-3+ endothelial progenitor cells and sustained release of VEGF-C.

Impairment of cardiac lymphatic vessels leads to cardiac lymphedema. Recent studies have suggested that stimulation of lymphangiogenesis may reduce cardiac lymphedema. However, effects of lymphatic endothelial progenitor cells (LEPCs) on cardiac lymphangiogenesis are poorly understood. Therefore, this study investigated effectiveness of LEPC transplantation and VEGF-C release with self-assembling peptide (SAP) on cardiac lymphangiogenesis after myocardial infarction (MI). CD34+VEGFR-3+ EPCs isolated from rat bone marrow differentiated into lymphatic endothelial cells after VEGF-C induction. VEGF-C also stimulated the cells to incorporate into the lymphatic capillary-like structures. The functionalized SAP could adhere with the cells and released VEGF-C sustainedly. In the condition of hypoxia and serum deprivation or abdominal pouch assay, the SAP hydrogel protected the cells from apoptosis and necrosis. At 4 weeks after intramyocardial transplantation of the cells and VEGF-C loaded with SAP hydrogel in rat MI models, cardiac lymphangiogenesis was increased, cardiac edema and reverse remodeling were reduced, and cardiac function was improved significantly. Delivery with SAP hydrogel favored survival of the engrafted cells. VEGF-C released from the hydrogel promoted differentiation and incorporation of the cells as well as growth of pre-existed lymphatic vessels. Cardiac lymphangiogenesis was beneficial for elimination of the inflammatory cells in the infarcted myocardium. Moreover, angiogenesis and myocardial regeneration were enhanced after reduction of lymphedema. These results demonstrate that the combined delivery of LEPCs and VEGF-C with the functionalized SAP promotes cardiac lymphangiogenesis and repair of the infarcted myocardium effectively. This study represents a novel therapy for relieving myocardial edema in cardiovascular diseases.

Controlled decongestion by Reprieve therapy in acute heart failure: results of the TARGET-1 and TARGET-2 studies.

AIMS: Safe and effective decongestion is the main goal of therapy in acute heart failure (AHF). In the non-randomized, prospective TARGET-1 and TARGET-2 studies (NCT03897842), we investigated whether adding the Reprieve System® (which continuously monitors urine output and delivers a matched volume of hydration fluid sufficient to maintain the set fluid balance rate) to standard diuretic-based regimen improves decongestion in AHF. METHODS AND RESULTS: The population consisted of 19 patients hospitalized with AHF (mean age 67 ± 10 years, 18 male, ejection fraction 34 ± 15%, median N-terminal pro-B-type natriuretic peptide 4492 pg/mL). Patients served as their own controls: each patient underwent 24 h of standard diuretic therapy followed by 24 h of diuretics with Reprieve therapy (with normal saline used for matched volume replacement). The primary efficacy endpoint of actual fluid loss not exceeding the target fluid loss at the end of therapy was met in all 19 (100%) patients. The mean diuresis during Reprieve therapy was 6284 ± 2679 mL (vs. 1966 ± 1057 mL 24 h before therapy) and 2053 ± 888 mL (24 h after therapy) (both P < 0.0001). At the end of therapy, patient global assessment improved from 7.7 ± 1.1 to 3.0 ± 1.3 points (P < 0.001), central venous pressure decreased from 15.5 ± 5.3 mmHg to 12.8 ± 4.8 mmHg (P < 0.05) and the median urine sodium loss was 9.7 [3-13] mmol/h. The Reprieve therapy was safe, systolic blood pressure remained stable, mean creatinine dropped from 1.45 ± 0.4 mg/dL to 1.26 ± 0.4 mg/dL (P < 0.001) and biomarkers of renal injury did not change during treatment. CONCLUSIONS: The Reprieve System in conjunction with diuretic therapy supports safe and controlled decongestion in AHF.

Reasons for Guideline Nonadherence at Heart Failure Discharge.

Background Cardiology has advanced guideline development and quality measurement. Recognizing the substantial benefits of guideline-directed medical therapy, this study aims to measure and explain apparent deviations in heart failure ( HF ) guideline adherence by clinicians at hospital discharge and describe any impact on readmission rates. Methods and Results The extent of decongestion and prescription of neurohormonal therapy were recorded prospectively for 226 HF discharges, including 132 (58%) from an academic hospital and 94 (42%) from a community hospital. Among all discharges, 25% were discharged with residual congestion (30% academic versus 18% community, P=0.070). Among discharges of patients with HF with reduced ejection fraction, 37% (45% academic versus 18% community, P<0.001) were discharged without ß-blocker therapy or with lower doses than at admission. Moreover, 46% of patients with HF with reduced ejection fraction (48% academic versus 39% community, P=0.390) were discharged without an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker or with lower doses than at admission. Renal dysfunction was the most common reason for discharge with congestion, and hypotension the most common reason for discharge with no or decreased neurohormonal therapy. There was a trend toward higher 90-day readmission rates after discharge with residual congestion. Conclusions Clinicians frequently deviate from guidelines in both academic and community hospitals; however, this deviation may not always indicate poor quality. Application of guidelines recommended for stable populations is increasingly limited for hospitalized patients by hypotension, renal dysfunction, and inotrope use. Patients with renal dysfunction, hypotension, and recent inotrope use merit further study to determine best practices and possibly to adjust quality metrics for HF severity.

CMR Native T1 Mapping Allows Differentiation of Reversible Versus Irreversible Myocardial Damage in ST-Segment-Elevation Myocardial Infarction: An OxAMI Study (Oxford Acute Myocardial Infarction).

BACKGROUND: CMR T1 mapping is a quantitative imaging technique allowing the assessment of myocardial injury early after ST-segment-elevation myocardial infarction. We sought to investigate the ability of acute native T1 mapping to differentiate reversible and irreversible myocardial injury and its predictive value for left ventricular remodeling. METHODS AND RESULTS: Sixty ST-segment-elevation myocardial infarction patients underwent acute and 6-month 3T CMR, including cine, T2-weighted (T2W) imaging, native shortened modified look-locker inversion recovery T1 mapping, rest first pass perfusion, and late gadolinium enhancement. T1 cutoff values for oedematous versus necrotic myocardium were identified as 1251 ms and 1400 ms, respectively, with prediction accuracy of 96.7% (95% confidence interval, 82.8% to 99.9%). Using the proposed threshold of 1400 ms, the volume of irreversibly damaged tissue was in good agreement with the 6-month late gadolinium enhancement volume (r=0.99) and correlated strongly with the log area under the curve troponin (r=0.80) and strongly with 6-month ejection fraction (r=-0.73). Acute T1 values were a strong predictor of 6-month wall thickening compared with late gadolinium enhancement. CONCLUSIONS: Acute native shortened modified look-locker inversion recovery T1 mapping differentiates reversible and irreversible myocardial injury, and it is a strong predictor of left ventricular remodeling in ST-segment-elevation myocardial infarction. A single CMR acquisition of native T1 mapping could potentially represent a fast, safe, and accurate method for early stratification of acute patients in need of more aggressive treatment. Further confirmatory studies will be needed.

Impacts of nicorandil on infarct myocardium in comparison with nitrate: assessed by cardiac magnetic resonance imaging.

In this pilot study, we compared the infarct and edema size in acute myocardial infarction (MI) patients treated by nicorandil with those treated by nitrate, using cardiac magnetic resonance (CMR) imaging. Fifty-two acute MI patients who underwent emergency percutaneous coronary intervention (PCI) were enrolled, and were assigned to receive nicorandil or nitrate at random just before reperfusion. For the assessment of infarct and edema areas, short-axis delayed enhancement (DE) and T2-weight (T2w) CMR images were acquired 6.1 ± 2.4 days after the onset of MI. A significant correlation was observed between the peak creatinine kinase (CK) level and the infarct size on DE CMR (r = 0.62, p < 0.05), as well as the edema size on T2w CMR (r = 0.70, p < 0.05) in patients treated by nicorandil (28 patients). A similar correlation was seen between the peak CK level and the infarct size on DE CMR (r = 0.84, p < 0.05), as well as the edema size on T2w CMR (r = 0.84, p < 0.05) in patients treated by nitrate (24 patients). The maximum CK level was significantly lower in patients treated by nicorandil rather than nitrate (1991 ± 1402, 2785 ± 2121 IU/L, respectively, p = 0.03). Both the edema size on T2w CMR and the infarct size on DE CMR were significantly smaller in patients treated by nicorandil rather than nitrate (17.7 ± 9.9, 21.9 ± 13.7 %; p = 0.03, 10.3 ± 6.0, 12.7 ± 6.9 %, p = 0.03, respectively). The presence and amount of microvascular obstruction were significantly smaller in patients treated by nicorandil rather than nitrate (39.2, 64.7 %; p = 0.03; 2.2 ± 1.3, 3.4 ± 1.5 cm(2); p = 0.02, respectively). Using CMR imaging, we demonstrated that the complementary use of intravenously and intracoronary administered nicorandil during PCI favorably acts more on the damaged myocardium after MI than nitrate. We need a further powered prospective study on the use of nicorandil.

Behind a mask: tricks, pitfalls, and prejudices for noninvasive ventilation.

It is difficult to exactly date the beginning of mechanical ventilation, but there are no doubts that noninvasive ventilation (NIV) was the first method of ventilatory support in clinical practice. The technique had a sudden increase in popularity, so that it is now considered, according to criteria of evidence-based medicine, the first-line treatment for an episode of acute respiratory failure in 4 pathologies (the Fabulous Four): COPD exacerbation, cardiogenic pulmonary edema, pulmonary infiltrates in immunocompromised patients, and in the weaning of extubated COPD patients. The so-called emerging applications are those for which the evidence has not achieved level A, mainly because the number or sample size of the published studies does not allow conclusive meta-analysis. These emerging applications are the post-surgical period, palliation of dyspnea, asthma attack, obesity hypoventilation syndrome, and to prevent extubation failure. Potentially "risky business" uses include for respiratory failure from pandemic diseases and ARDS, where probably the "secret" for success is early use. Healthcare is rich in evidence-based innovations, yet even when such innovations are implemented successfully in one location, they often disseminate slowly, if at all, so their clinical use remains limited and heterogeneous. The low rate of NIV use in some hospitals relates to lack of knowledge about or experience with NIV, insufficient confidence in the technique, lack of NIV equipment, and inadequate funding. But NIV use has been increasing around the world, thanks partly to improved technologies. The skill and confidence of clinicians in NIV have improved with time and experience, but NIV is and should remain a team effort, rather than the property of a single local "champion," because, overall, NIV is beautiful!

Clinical course and predictive value of congestion during hospitalization in patients admitted for worsening signs and symptoms of heart failure with reduced ejection fraction: findings from the EVEREST trial.

AIMS: Signs and symptoms of congestion are the most common cause for hospitalization for heart failure (HHF). The clinical course and prognostic value of congestion during HHF has not been systemically characterized. METHODS AND RESULTS: A post hoc analysis was performed of the placebo group (n = 2061) of the EVEREST trial, which enrolled patients within 48 h of admission (median ~24 h) for worsening HF with an EF ≤ 40% and two or more signs or symptoms of fluid overload [dyspnoea, oedema, or jugular venous distension (JVD)] for a median follow-up of 9.9 months. Clinician-investigators assessed patients daily for dyspnoea, orthopnoea, fatigue, rales, pedal oedema, and JVD and rated signs and symptoms on a standardized 4-point scale ranging from 0 to 3. A modified composite congestion score (CCS) was calculated by summing the individual scores for orthopnoea, JVD, and pedal oedema. Endpoints were HHF, all-cause mortality (ACM), and ACM + HHF. Multivariable Cox regression models were used to evaluate the risk of CCS at discharge on outcomes at 30 days and for the entire follow-up period. The mean CCS obtained after initial therapy decreased from the mean ± SD of 4.07 ± 1.84 and the median (25th, 75th) of 4 (3, 5) at baseline to 1.11 ± 1.42 and 1 (0, 2) at discharge. At discharge, nearly three-quarters of study participants had a CCS of 0 or 1 and fewer than 10% of patients had a CCS >3. B-type natriuretic peptide (BNP) and amino terminal-proBNP, respectively, decreased from 734 (313, 1523) pg/mL and 4857 (2251, 9642) pg/mL at baseline to 477 (199, 1079) pg/mL, and 2834 (1218, 6075) pg/mL at discharge/Day 7. A CCS at discharge was associated with increased risk (HR/point CCS, 95% CI) for a subset of endpoints at 30 days (HHF: 1.06, 0.95-1.19; ACM: 1.34, 1.14-1.58; and ACM + HHF: 1.13, 1.03-1.25) and all outcomes for the overall study period (HHF: 1.07, 1.01-1.14; ACM: 1.16, 1.09-1.24; and ACM + HHF 1.11, 1.06-1.17). Patients with a CCS of 0 at discharge experienced HHF of 26.2% and ACM of 19.1% during the follow-up. CONCLUSION: Among patients admitted for worsening signs and symptoms of HF and reduced EF, congestion improves substantially during hospitalization in response to standard therapy alone. However, patients with absent or minimal resting signs and symptoms at discharge still experienced a high mortality and readmission rate.

Ischemic preconditioning enhances integrity of coronary endothelial tight junctions.

Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiac TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood-heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs-Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC enhanced the translocation of ZO-2 from cytosol to cytoskeleton. In conclusion, TJs occur in normal mouse heart. IPC preserves the integrity of TJ structure and function that are vulnerable to IR injury.

Edema index established by a segmental multifrequency bioelectrical impedance analysis provides prognostic value in acute heart failure.

OBJECTIVES: A segmental multifrequency bioelectrical impedance analysis (SMBIA) is a noninvasive and reproducible modality for estimating the fluid state. The aim of this study was to test whether the SMBIA-derived edema index provides prognostic value in patients hospitalized due to acute heart failure (AHF). METHODS: To estimate the 6-month prognostic value of the predischarge edema index in patients hospitalized due to AHF, 112 patients were consecutively enrolled. Both predischarge edema index and B-type natriuretic peptide (BNP) were measured. Outcome follow-up focused on heart failure-related and all-cause re-hospitalizations and all events. RESULTS: On the basis of a cutoff value of edema index of 0.390, patients were separated into two groups: edema index more than 0.390 (n = 44) and edema index of 0.390 or less (n = 68). Compared with patients with edema index 0.390 or less, those with edema index of more than 0.390 were older, had lower blood albumin and hemoglobin levels, and had higher predischarge BNP levels, functional class, incidence of diabetes mellitus, valvular cause, and diuretic use. Although edema indexes were correlated with BNP levels (r = 0.47, P < 0.0001), a mismatch was noted in 33 (29%) patients. Univariate and multivariate analysis showed that an edema index of more than 0.390 predicted a higher incidence of heart failure-related re-hospitalization [odds ratio (OR) = 4.14, confidence interval (CI) = 1.05-15.28, P = 0.04] and all events (OR = 3.97, CI = 1.4-11.25, P = 0.01). The edema index provided a prognostic value superior to that of BNP. Reducing the edema index in high-risk patients resulted in fewer heart failure-related re-hospitalizations (OR = 0.81, CI = 0.77-0.84, P < 0.001) and all events (OR = 0.8, CI = 0.76-0.85, P < 0.001). CONCLUSION: Edema index provides 6-month prognostic values in patients hospitalized due to AHF. Reducing the edema index in high-risk patients results in better outcomes.

[Volume regulation in cardiac insufficiency : possibilities of telephone coaching and peritoneal dialysis]. / Volumenregulation bei Herzinsuffizienz : Möglichkeiten des Telefon-Coachings sowie der Peritonealdialyse.

Volume retention is the hallmark of progressive heart failure, both systolic and diastolic (heart failure with preserved ejection fraction). It represents the cause of the main symptoms (dyspnea, edema, liver synthesis) and also the main target of drug therapy. Antagonizing excessive volume retention is also the most important therapy element. Many patients can be stabilized with sequential nephron blockade (thiazide + loop diuretics) combined with afterload reduction [blockade of the RAAS (renin-angiotensin-aldosterone) system]. Personal patient coaching combined with telemetric components (weight, blood pressure) has evolved as another cornerstone of treatment in heart failure patients. If these measures are insufficient to control volume retention, renal replacement therapy is effective and can improve quality of life. More specifically, aquaresis via peritoneal dialysis has been shown to be effective and adequate to control volume overload. Many patients may qualify for this evolving therapy as it effectively prevents repeat hospitalization for heart failure decompensation, can be performed in an out-patient setting and has a low complication rate, thus significantly improving quality of life.

Cardiovascular magnetic resonance in wet beriberi.

The clinical presentation of beriberi can be quite varied. In the extreme form, profound cardiovascular involvement leads to circulatory collapse and death. This case report is of a 72 year-old male who was admitted to the Neurology inpatient ward with progressive bilateral lower extremity weakness and parasthesia. He subsequently developed pulmonary edema and high output cardiac failure requiring intubation and blood pressure support. With the constellation of peripheral neuropathy, encephalopathy, ophthalmoplegia, unexplained heart failure, and lactic acidosis, thiamine deficiency was suspected. He was empirically initiated on thiamine replacement therapy and his thiamine level pre-therapy was found to be 23 nmol/L (Normal: 80-150 nmol/L), consistent with the diagnosis of beriberi. Cardiovascular magnetic resonance (CMR) showed severe left ventricular systolic dysfunction, markedly increased myocardial T2, and minimal late gadolinium enhancement (LGE). After 5 days of daily 100 mg IV thiamine and supportive care, the hypotension resolved and the patient was extubated and was released from the hospital 3 weeks later. Our case shows via CMR profound myocardial edema associated with wet beriberi.

Impact of manual lymphatic drainage on hemodynamic parameters in patients with heart failure and lower limb edema.

Manual lymphatic drainage (MLD), intermittent sequential pneumatic therapy (ISPT), multilayered bandages (MLB), and compression garments are main techniques in conservative treatment of peripheral lymphedema. Since 1990, it has been thought that ISPT applied to both lower limbs simultaneously should not be used for patients with heart failure because right atrial, pulmonary arterial, and pulmonary wedge pressures may increase to a critical point. In 2005, these same results were observed in patients with heart failure wearing MLB. For these reasons, MLB and ISPT have been contraindicated during lymphedema treatment in cardiac patients. The aim of this study was to determine if we may continue the treatment of lower limb lymphedema using MLD in patients with heart failure. We evaluated hemodynamic parameters using echography during MLD in patients with cardiac disease and obtained circumferential measurements of the edematous limb before and after treatment. MLD treatment significantly decreased the limbs as expected. The heart rate also decreased following MLD in contrast with all other hemodynamic parameters which were not affected by MLD. The findings suggest that there is no contraindication to use MLD in patients with heart failure and lower limb edema.

[Acute intermediate-risk pulmonary embolism with right-sided free-floating intracardiac thrombus, systemic inflammatory reaction syndrome, multiple organ dysfunction syndrome, disseminated intravascular coagulation and acute ischaemia of a limb]. / Ostra zatorowosc plucna posredniego ryzyka z ruchoma skrzeplina w prawym sercu, przebiegajaca z zespolem uogólnionej reakcji zapalnej, zespolem niewydolnosci wielonarzadowej, rozsianym krzepnieciem wewnatrznaczyniowym i ostrym niedokrwieniem konczyny.

A case of a 64 year-old woman admitted to ICCU because of severe dyspnoea and oedema of left lower limb is presented. We diagnosed coincidence of acute pulmonary embolism with right-sided free-floating heart thrombi, systemic inflammatory reaction syndrome, multiple organ dysfunction syndrome, disseminated intravascular coagulation and acute ischaemia of the right lower limb. Due to atypical clinical presentation therapeutic strategies were discussed with ZATPOL registry coordinator. The patient was treated pharmacologically, underwent cardiosurgical evacuation of right-sided intracardiac thrombus and lower limb amputation. At follow up visit 6 months after discharge from hospital she was in good general condition with no complaints.