Threshold crossing of device-based intrathoracic impedance trends identifies relatively increased mortality risk.

AIMS: Threshold crossings of impedance trends detected by implanted devices have been associated with clinically relevant heart failure events, but long-term prognosis of such events has not been demonstrated. The aim of this study is to examine the relationship between alterations in intrathoracic impedance and mortality risk in patients with implantable devices. METHODS AND RESULTS: We reviewed remote monitoring data in the de-identified Medtronic CareLink(®) Discovery Link that captured intrathoracic impedance trends for >6 months. The initial 6 months of the cardiac and impedance trends were used as the observation period to create the patient groups and cross-referenced with the Social Security Death Index for mortality data. In our study cohort of 21 217 patients, 36% experienced impedance threshold crossing within the initial 6 months of monitoring (defined as the 'early threshold crossing' group). Patients with early threshold crossings demonstrated an increased risk of age- and gender-adjusted all-cause mortality [hazard ratio (HR) 2.15, 95% confidence interval (CI) 1.95-2.38, P< 0.0001]. Increased mortality risk remained significant when analysed in subgroups of patients without defibrillator shock (HR 2.10, 95% CI 1.90-2.34, P< 0.0001, n= 1621) or within those patients without device-detectable atrial fibrillation (AF) during the initial 6 months of monitoring (HR 2.09, 95% CI 1.86-2.34, P< 0.0001, n= 17 235). Both the number and the duration of early threshold crossings of impedance trends detectable by implanted devices were associated with increased mortality risk. Furthermore, the improvement of altered impedance trends portends more favourable prognosis. CONCLUSIONS: Threshold crossing of impedance trends detectable by implanted devices is associated with relatively increased mortality risk even after adjusted for demographic, device-detected AF, or defibrillator shocks.

Wild type cardiac amyloidosis: is it time to order a nuclear technetium pyrophosphate SPECT imaging study?

Transthyretin (ATTR) amyloidosis is a debilitating systemic disease often associated with symptomatic cardiac involvement. Diagnosis has dramatically changed with the advent of Technetium-99 m pyrophosphate (Tc-PYP) single-photon emission computed tomography (SPECT). With the ability to diagnose ATTR amyloidosis noninvasively and offer newer therapies, it is increasingly important to identify which patients should be referred for this testing. Relative apical sparing of longitudinal strain on echocardiogram can be potentially used to screen such patients. We sought to describe electrocardiogram (ECG) and echocardiogram (TTE) findings, including relative apical sparing of longitudinal strain, in ATTR amyloidosis patients diagnosed non-invasively with 99mTc-PYP imaging. This was a single-center, retrospective study with 64 patients who underwent 99mTc-PYP imaging between June 2016 and February 2019. Relative apical longitudinal strain was calculated from left ventricular longitudinal strain (LV LS) values. No ECG parameters were meaningfully associated with of 99 m Tc-PYP positive patients. LV mass index (p = 0.001), IVSd (p < 0.001), and LVPWd (< 0.001) demonstrated a highly significant difference between positive and negative 99mTc-PYP groups. 99mTc-PYP positive patients had a higher relative apical sparing of LV LS (p < 0.001), and notably, no 99mTc-PYP negative patient had a ratio > 1.0. The finding of relative apical sparing of longitudinal strain can reliably guide clinicians in triaging which patients to consider ordering 99mTc-PYP imaging for the noninvasive diagnosis of wild type cardiac amyloidosis. A patient with clinically suggestive features and an LV LS relative apical sparing ratio > 0.8 can be considered for 99mTc-PYP imaging to evaluate for ATTR cardiac amyloidosis.

Clinical Utility of Fluid Volume Assessment in Heart Failure Patients Using Bioimpedance Spectroscopy.

Background: Bioimpedance spectroscopy (BIS) is a non-invasive method used to measure fluid volumes. In this report, we compare BIS measurements from patients with heart failure (HF) to those from healthy adults, and describe how these point-of-care fluid volume assessments may be applied to HF management. Methods and results: Fluid volumes were measured in 64 patients with NYHA class II or III HF and 69 healthy control subjects. BIS parameters including extracellular fluid (ECF), intracellular fluid (ICF), total body water (TBW), and ECF as a percentage of TBW (ECF%TBW) were analyzed. ECF%TBW values for the HF and control populations differed significantly (49.2 ± 3.2% vs. 45.2 ± 2.1%, respectively; p < 0.001); both distributions satisfied criteria for normality. Interquartile ranges did not overlap (46.7-51.0% vs. 43.8-46.4%, respectively; p < 0.001). Subgroup analyses of HF patients who underwent transthoracic echocardiography showed that impedance measurements correlated with inferior vena cava size (Pearson correlation -0.73, p < 0.0001). A case study is presented for illustrative purposes. Conclusions: BIS-measured ECF%TBW values were significantly higher in HF patients as compared to adults without HF. We describe three strata of ECF%TBW (normal, elevated, fluid overload) that may aid in clinical risk stratification and fluid volume monitoring of HF patients. Clinical Trial Registration: COMPARE - www.ClinicalTrials.gov; IMPEL - www.ClinicalTrials.gov; Heart Failure at Home - www.ClinicalTrials.gov, identifier: NCT02939053; NCT02857231; NCT04013373.

Novel doses of sacubitril/valsartan in patients unable to tolerate traditional therapy: Effects on N-terminal pro B-type natriuretic peptide levels.

BACKGROUND: Widespread use of angiotensin receptor blocker and neprilysin inhibitor (ARNI) remains low, and many patients are unable to tolerate the medication due to hypotension at the currently recommended starting dose. HYPOTHESIS: The aim of this study is to assess if lower than standard doses of ARNI, sacubitril/valsartan (S/V), significantly reduces NT-proBNP and leads to any change in diuretic dose, serum potassium, or creatinine. METHODS: In a retrospective study of 278 patients who were started on a low dose S/V at a single medical center, 45 patients were selected for the study cohort. Patients were subcategorized to Group 1 (n = 10): very low dose S/V (half a tab of 24/26 mg BID), Group 2 (n = 10): very low dose titrated to low dose S/V, and Group 3 (n = 25): low dose S/V (24/26 mg BID). NT-proBNP, diuretic dose, serum potassium, and creatinine were compared before and after initiation of S/V. RESULTS: Among all groups, there was a significant reduction in NT-proBNP level (Group 1: p < .01, Group 2: p < .01, and Group 3: p < .001). In addition, there was a significant reduction in diuretic dose across all groups combined (furosemide 53 mg/day vs. 73 mg/day; p = .03), with 17.8% (8/45) patients being able to discontinue their diuretic completely. There was no significant change in potassium or creatinine. CONCLUSIONS: Lower than standard dose of S/V significantly reduces NT-proBNP and diuretic requirement without change in potassium or creatinine, which provides hope that patients who cannot tolerate standard doses of S/V due to hypotension may be able to receive the benefits of S/V therapy.

Stiff Left Atrial Syndrome; Prospects and Possibilities. Retrospective Analysis and Review of the Literature.

OBJECTIVES: Stiff left atrial syndrome is an intriguing clinical phenomena characterized by reduced left atrial compliance, pulmonary venous hypertension and exacerbations of volume overload. We conducted a retrospective review of patients diagnosed with stiff left atrial syndrome at our center. METHODS: All patients admitted to our hospital with volume overload and pulmonary venous hypertension who were diagnosed with stiff left atrial syndrome based on evidence by echocardiogram and right heart catheterization between July 2011 and July 2013 were included in this retrospective review. RESULTS: Twentythree patients (mean age 73 ± 11 years, 39% male and 61% female) were diagnosed with stiff left atrial syndrome at our center. Thirty-five percent had persistent while 39% had permanent atrial fibrillation. Mean duration of atrial fibrillation was 7.6 ± 2.1 years. Forty-three percent of patients had long standing hypertension. There was no mitral regurgitation in 39% of patients while 48% had mild mitral regurgitation. On right heart catheterization, mean right atrial pressure was 12.6±4.8 mm of Hg, mean pulmonary arterial pressure was 33±7.2 mm of Hg, mean pulmonary capillary wedge pressure was 24.8± 4.2mm of Hg while peak V waves were seen at mean of 37.8± 5.3 mm of Hg. Mean left atrial volume index was 49.8±17.1 mL/m 2. After the initial diagnosis with a two year follow- up, there were no readmissions in 65% of patients who were on appropriate diuretic therapy and had regular clinical visits. Frequent readmissions were seen in 35% of patients inspite of appropriate diuretic therapy. All-cause mortality rate was 4.3% at two year follow up. CONCLUSION: In patients with stiff left atrial syndrome, the presence of left atrial dilation, long standing atrial fibrillation and hypertension are the key factors associated with pathogenesis and clinical course. Close follow up and monitoring of volume status is essential to prevent hospital readmissions and improve long term prognosis.