Israel Medical Association Journal

Background: Most dyspneic patients in internal medicine departments have co-morbidities that interfere with the clinical diagnosis. The role of brain natriuretic peptide (BNP) levels is well-established in the acute setting but not in hospitalized patients.

Objectives: To evaluate the additive value of BNP tests in patients with dyspnea admitted to medical wards who did not respond to initial treatment.

Methods: We searched the records of patients who were hospitalized in the department of internal medicine D at Sheba Medical Center during 2012 and were tested for BNP in the ward. Data collected included co-morbidity, medical treatments, diagnosis at presentation and discharge, lab results including BNP, re-hospitalization, and mortality at one year following hospitalization.

Results: BNP results were found for 169 patients. BNP was taken 1.7 ± 2.7 days after hospitalization. According to BNP levels, dividing the patients into tertiles revealed three equally distributed groups with a distinctive character. The higher tertile was associated with higher rates of cardiac co-morbidities, including heart failure, but not chronic obstructive pulmonary disease. Higher BNP levels were related to one-year re-hospitalization and mortality. In addition, higher BNP levels were associated with higher rates of in-admission diagnosis change.

Conclusions: BNP levels during hospitalization in internal medicine wards are significantly related to cardiac illness, the existence of heart failure, and patient prognosis. Thus, BNP can be a useful tool in managing dyspneic patients in this setting.

Pneumonia patients are susceptible to autonomic nervous system changes. Ultrashort HRV (usHRV) is the measurement of cyclic changes in heart rate over a period < 5 minutes.

Objectives: To describe usHRV in patients with pneumonia and assess the correlation with mortality.

Methods: We conducted a retrospective analysis, which included patients diagnosed with pneumonia in the emergency department (ED). UsHRV indices were calculated from a 10-second ED electrocardiogram and correlated with mortality utilizing logistic and Cox regressions.

Results: The study comprised 240 patients. Mortality rates over 30, 90, and 365 days were 13%, 18%, and 30%, respectively. usHRV frequency-domain parameters had significant univariate correlations with mortality. Normalized low frequency (LF) and high frequency (HF) were correlated with 30-, 90-, and 365-day mortality in an opposite direction (odds ratio [OR] 0.094, P = 0.028 vs. OR 4.589, P =0.064; OR 0.052, P = 0.002 vs. OR 6.975, P =0.008; OR 0.055, P < 0.001 vs. OR 7.931, P < 0.001; respectively). Survival analysis was conducted for a follow-up median period of 5.86 years (interquartile range 0.65–9.77 years). Univariate Cox proportional hazard regression revealed time-domain indices with significant correlation with survival (SDNN and RMSSD; hazard ratio [HR] 1.005, 1.005; P = 0.032, P = 0.005; respectively) as well as frequency-domain parameters (normalized LF, HF, LF/HF ratio, and total power; HR 0.102, 5.002, 0.683, 0.997, respectively; P < 0.001).

Conclusions: usHRV may predict mortality in pneumonia patients and serve as a novel risk stratification tool.

Background: Current guidelines for the treatment of heart failure with reduced ejection fraction (HFrEF) are based on studies that have excluded or underrepresented older patients.

Objectives: To assess the value of guideline directed medical therapy (GDMT) in HFrEF patients 80 years of age and older.

Methods: A single-center retrospective study included patients hospitalized with a first and primary diagnosis of acute decompensated heart failure (ADHF) and ejection fraction (EF) of ≤ 40%. Patients 80 years of age and older were stratified into two groups: GDMT, defined as treatment at hospital discharge with at least two drugs of the following groups: beta-blockers, angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or mineralocorticoid antagonists; and a personalized medicine group, which included patients who were treated with up to one of these drug groups. The primary outcomes were 90-day all-cause mortality, 90-day rehospitalization, and 3-years mortality.

Results: The study included 1152 patients with HFrEF. 254 (22%) patients who were at least 80 years old. Of the group, 123 were GDMT at discharge. When GDMT group was compared to the personalized medicine group, there were no statistically significant differences in terms 90-day mortality (17% vs. 13%, P = 0.169), 90-day readmission (51 % vs. 45.6%, P = 0.27), or 3-year mortality (64.5% vs. 63.3%, P = 0.915).

Conclusions: Adherence to guidelines in the older adult population may not have the same effect as in younger patients who were studied in the randomized clinical trials. Larger prospective studies are needed to further address this issue.

Background: Advanced heart failure (HF) carries a high rate of recurrent HF hospitalizations and a very high mortality rate. Mechanical devices and heart transplantation are limited to a select few. Dialysis may be a good alternative for advanced HF patients with volume overload despite maximal pharmacological therapy.

Objectives: To assess the net clinical outcome of peritoneal dialysis or hemodialysis in patients with advanced HF.

Methods: We analyzed all advanced HF patients who were referred for dialysis due to volume overload in our institution. Patients were followed for complications, HF hospitalizations, and survival.

Results: We assessed 35 patients; 10 (29%) underwent peritoneal dialysis and 25 (71%) underwent hemodialysis; 71% were male; median (interquartile range) age was 74 (67–78) years. Estimated glomerular filtration rate was 20 (13–32) ml/min per 1.73 m². New York Heart Association functional capacity was III. Median follow-up time was 719 days (interquartile range 658–780). One-year mortality rate was 8/35 (23%) and overall mortality rate was 16/35 (46%). Three patients (9%) died during the first year due to line or peritoneal dialysis related sepsis, and 6 (17%) died during the entire follow-up. The median number of HF hospitalizations was significantly reduced during the year on dialysis compared to the year prior to dialysis (0.0 [0.0–1.0] vs. 2.0 [0.0–3.0], P < 0.001).

Conclusions: Dialysis is reasonably safe and significantly reduced HF hospitalization in advanced HF patients. Dialysis could be a good alternative for advanced HF patients with intractable volume overload.

Background: Cancer patients with heart failure (HF) and severe mitral regurgitation (MR) are often considered to be at risk for surgical mitral valve repair/replacement. Severe MR inducing symptomatic HF may prevent delivery of potentially cardiotoxic chemotherapy and complicate fluid management with other cancer treatments.

Objectives: To evaluate the outcome of percutaneous mitral valve repair (PMVR) in oncology patients with HF and significant MR.

Methods: Our study comprised 145 patients who underwent PMVR, MitraClip, at Hadassah Medical Center between August 2015 and September 2019, including 28 patients who had active or history of cancer. Data from 28 cancer patients were compared to 117 no-cancer patients from the cohort.

Results: There was no significant difference in the mean age of cancer patients and no-cancer patients (76 vs. 80 years, P = 0.16); 67% of the patients had secondary (functional) MR. Among cancer patients, 21 had solid tumor and 7 had hematologic malignancies. Nine patients (32%) had active malignancy at the time of PMVR. The mean short-term risk score of the patients was similar in the two groups, as were both 30-day and 1-year mortality rates (7% vs. 4%, P = 0.52) and (29% vs. 16%, P = 0.13), respectively.

Conclusion: PMVR in cancer patients is associated with similar 30-day and 1-year survival rate compared with patients without cancer. PMVR should be considered for cancer patients presenting with HF and severe MR and despite their malignancy. This approach may allow cancer patients to safely receive planned oncological treatment

Background: The diagnosis of atrial fibrillation (AFIB) related cardiomyopathy relies on ruling out other causes for heart failure and on recovery of left ventricular (LV) function following return to sinus rhythm (SR). The pathophysiology underlying this pathology is multifactorial and not as completely known as the factors associated with functional recovery following the restoration of SR.

Objectives: To identify clinical and echocardiographic factors associated with LV systolic function improvement following electrical cardioversion (CV) or after catheter ablation in patients with reduced ejection fraction (EF) related to AFIB and normal LV function at baseline.

Methods: The study included patients with preserved EF at baseline while in SR whose LVEF had reduced while in AFIB and improved LVEF following CV. We compared patients who had improved LVEF to normal baseline to those who did not.

Results: Eighty-six patients with AFIB had evidence of reduced LV systolic function and improved EF following return to SR. Fifty-five (64%) returned their EF to baseline. Patients with a history of ischemic heart disease (IHD), worse LV function, and larger LV size during AFIB were less likely to return to normal LV function. Multivariant analysis revealed that younger patients with slower ventricular response, a history of IHD, larger LV size, and more significant deterioration of LVEF during AFIB were less likely to recover their EF to baseline values.

Conclusions: Patients with worse LV function and larger left ventricle during AFIB are less likely to return their baseline LV function following the restoration of sinus rhythm.

Background: Systemic sclerosis (SSc) is a connective tissue disease that may affect the heart and the autonomic nervous system (ANS). There is little knowledge regarding the degree of ANS involvement in SSc patients with unknown cardiac disease.

Objectives: To evaluate cardiac and pupillary autonomic functions in patients before cardiac involvement has emerged.

Methods: The study comprised 19 patients with SSc and 29 healthy controls. Heart rate variability (HRV) analysis for time and frequency domains, as well as deep breathing test and Ewing maneuvers, were performed in all patients. Automated pupillometry for the evaluation of pupillary diameter and pupillary light reflex was completed in 8 SSc patients and 21 controls.

Results: Both groups had similar characteristics, except for medications that were more commonly or solely prescribed for SSc patients. Compared with control subjects, the SSc patients had significantly lower HRV parameters of NN50 (15.8 ± 24.4 vs. 33.9 ± 33.1, P = 0.03), pNN50 (4.9 ± 7.4% vs.10.8 ± 10.8%, P = 0.03), and triangular index (11.7 ± 3.4 vs. 15.7 ± 5.8, P = 0.02). Abnormal adaptive responses in heart rate changes were recorded during deep breathing tests and Ewing maneuvers. There was no significant difference in any of the pupillometric indices or other HRV parameters within groups.

Conclusions: SSc patients may manifest cardiac autonomic dysfunction, while their autonomic pupillary function is seemingly spared. The role of certain medications, the significance of differential organ involvement, as well as the prognostic value of our findings should be evaluated in future studies

Background: Heart failure with preserved ejection fraction (HFpEF) is a common clinical entity, with a mechanism that appears to involve endothelial dysfunction of the cardiac microcirculation. Endothelial progenitor cells (EPC) are bone marrow derived cells that are able to differentiate into functional endothelial cells and participate in endothelial surface repair.

Objectives: To compare the level and function of EPCs in patients with HFpEF compared with heart failure with reduced ejection fraction (HFrEF) and control subjects.

Methods: We enrolled 21 patients with HFpEF (LVEF ≥ 50%, age 74.5 ± 9.9 years, 43% men, 48% diabetes), 20 patients with HFrEF (LVEF < 40%, age 70 ± 11.5 years, 90% men, 60% diabetes), and 11 control subjects with cardiovascular risk factors (age 53.3 ± 6.1years, 90% men, 64% diabetes). Circulating EPC levels were evaluated by expression of vascular endothelial growth factor receptor-2 (VEGFR-2), CD34, and CD133 by flow-cytometry. EPCs colony forming units (CFUs) were quantified after 7 days in culture.

Results: The proportion of cells that co-expressed VEGFR-2 and CD34 or VEGFR-2 and CD133 was similar among the HFpEF and HFrEF groups, and significantly lower than in the control group. The number of EPC-CFUs was also similar among the two heart failure groups and significantly lower than the control group.

Conclusions: Patients with HFpEF, like HFrEF, have significant reduction in EPC level and function.

Background: Many countries have adopted a mandatory routine pulse oximetry screening of newborn infants to identify babies with otherwise asymptomatic critical congenital heart disease (CCHD).

Objectives: To describe the current status of pulse oximetry CCHD screening in Israel, with a special emphasis on the experience of the Shaare Zedek Medical Center.

Methods: We review the difficulties of the Israeli Medical system with adopting the SaO₂ screening, and the preliminary results of the screening at the Shaare Zedek Medical Center, both in terms of protocol compliance and CCHD detection.

Results: Large scale protocol cannot be implemented in one day, and regular quality assessment programs must take place in order to improve protocol compliance and identify the reasons for protocol failures.

Conclusions: Quality control reviews should be conducted soon after implementation of the screening to allow for prompt diagnosis and quick resolution

Background: In 2006, the International Society for Heart and Lung Transplantation amended the guidelines for the upper age limit of heart transplantation (HTx) from 55 years to 70 years and older for carefully selected patients. However, the relation of age to outcomes following of HTx has not been well studied.

Objectives: To investigate the impact of recipient age on the occurrence of rejections, vasculopathy, and mortality after HTx.

Methods: Study population comprised all consecutive 291 patients who underwent HTx between 1991–2016 and were followed at our center. Patients were categorized by age tertiles: < 46 years (mean 31.4 ± 11.7, range 16–45, n=90), 46–57 years (mean 51.4 ± 3.2, range 46–56, n=92), and ≥ 57 years (mean 61.6 ± 3.4, range 57–73, n=109).

Results: Patients aged ≥ 57 years were more often males and had more pre-HTx co-morbidities including hypertension, diabetes, dyslipidemia, and history of smoking (P < 0.05) compared to the younger age groups. Kaplan-Meier analysis by age tertiles showed the rates of major rejections and vasculopathy at 15 years were similar among the three age groups. Mortality rates at 15 years were directly related to the age groups (39%, 52%, 62% log-rank, P = 0.01). However, the association between age and mortality was no longer statistically significant after multivariate analysis (hazard ratio 1.01, 95% confidence interval 1.00–1.03).

Conclusions: In a contemporary cohort of patients undergoing HTx, recipient age does not significantly impact the risk of major rejections, vasculopathy, and long-term mortality.

Background: Heart failure (HF) patients with reduced ejection fraction (HFrEF) are frequently treated with sub-optimal doses of angiotensin converting enzyme-inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta blockers (BBs).

Objectives: To determine factors associated with attaining upper-range doses in patients with HFrEF.

Methods: We examined treatment in patients with left ventricular ejection fraction (LVEF) ≤ 40% in a community-based, dedicated heart-failure clinic. Upper-range doses were defined as ≥ 75% of target recommended doses by heart failure society guidelines.

Results: The majority of the 215 patients were men (82%); median age at presentation 73 years (interquartile range [IQR] 65–78) and LVEF of 30% (IQR 25–35%). Following the up-titration program, 41% and 35% of patients achieved upper-range doses of ACE-Is/ARBs and BBs, respectively. Higher body mass index (BMI) was the only parameter found to be associated with achieving upper-range doses of ACE-I/ARBs (odds ratio [OR] 1.13, 95% confidence interval [95%CI] 1.05–1.22, P = 0.001). More patients achieved this target as BMI increased, with a sharp decline in the highest obesity category (BMI ≥ 40 m²/kg). Attaining upper-range doses of BBs was associated with pre-existing diabetes mellitus (DM) (OR 2.6, 95%CI 1.34–5.19, P = 0.005); women were associated with attaining lower BBs doses (OR 0.34, 95%CI 0.13–0.90, P = 0.031).

Conclusions: Achieving upper-range doses of ACE-Is/ARBs and BBs in HFrEF outpatients in a treatment up-titration program were associated with greater BMI and DM, respectively. These findings may serve as benchmarks for up-titration programs.

Background: Left ventricular assist devices (LVADs) are used more commonly in patients with advanced-stage heart failure. Some of these patients may require elective or urgent abdominal surgical procedures.

Objectives: To determine the outcomes of the management of LVAD-supported patients who underwent elective and urgent abdominal surgical procedures in our institution.

Methods: A retrospective review was conducted on 93 patients who underwent LVAD implantation between August 2008 and January 2017. All abdominal surgeries in these patients were studied, and their impact on postoperative morbidity and mortality was evaluated.

Results: Ten patients underwent abdominal surgical procedures. Of these procedures, five were emergent and five were elective. The elective cases included one bariatric surgery for morbid obesity, one hiatal hernia repair, two cholecystectomies, and one small bowel resection for a carcinoid tumor. The emergency cases included suspected ischemic colitis, right colectomy for bleeding adenocarcinoma, laparotomy due to intraabdominal bleeding, open cholecystectomy for gangrenous cholecystitis, and laparotomy for sternal and abdominal wall infection. All patients undergoing elective procedures survived. Of the five patients who underwent emergency surgery, three died (60%, P = 0.16) and one presented with major morbidity. One of the two survivors required reintervention. In total, 12 interventions were performed on this group of patients.

Conclusions: It is safe to perform elective abdominal procedures for LVAD-supported patients. The prognosis of these patients undergoing emergency surgery is poor and has high mortality and morbidity rates.